Castration-resistant prostate cancer: Where are we going? | Actas Urológicas Españolas (English Edition)

array:24 ["pii" => "S2173578612001394" "issn" => "21735786" "doi" => "10.1016/j.acuroe.2011.10.001" "estado" => "S300" "fechaPublicacion" => "2012-06-01" "aid" => "384" "copyright" => "AEU" "copyrightAnyo" => "2011" "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Actas Urol Esp. 2012;36:367-74" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1071 "formatos" => array:3 [ "EPUB" => 11 "HTML" => 852 "PDF" => 208 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0210480611003883" "issn" => "02104806" "doi" => "10.1016/j.acuro.2011.10.010" "estado" => "S300" "fechaPublicacion" => "2012-06-01" "aid" => "384" "copyright" => "AEU" "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Actas Urol Esp. 2012;36:367-74" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 7624 "formatos" => array:3 [ "EPUB" => 18 "HTML" => 6707 "PDF" => 899 ] ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "Artículo de revisión" "titulo" => "Cáncer de próstata resistente a castración: ¿hacia dónde vamos?" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "367" "paginaFinal" => "374" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Castration-Resistant Prostate Cancer: Where are We Going?" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Alcaraz, R. Medina, P. Maroto, M.Á. Climent, D. Castellano, J. Carles" "autores" => array:6 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Alcaraz" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Medina" ] 2 => array:2 [ "nombre" => "P." "apellidos" => "Maroto" ] 3 => array:2 [ "nombre" => "M.Á." "apellidos" => "Climent" ] 4 => array:2 [ "nombre" => "D." "apellidos" => "Castellano" ] 5 => array:2 [ "nombre" => "J." "apellidos" => "Carles" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173578612001394" "doi" => "10.1016/j.acuroe.2011.10.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578612001394?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480611003883?idApp=UINPBA00004N" "url" => "/02104806/0000003600000006/v2_201304261440/S0210480611003883/v2_201304261440/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173578612001400" "issn" => "21735786" "doi" => "10.1016/j.acuroe.2011.07.006" "estado" => "S300" "fechaPublicacion" => "2012-06-01" "aid" => "363" "copyright" => "AEU" "documento" => "article" "crossmark" => 0 "subdocumento" => "sco" "cita" => "Actas Urol Esp. 2012;36:375-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1229 "formatos" => array:3 [ "EPUB" => 9 "HTML" => 967 "PDF" => 253 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Casuistry" "titulo" => "Is it necessary to place a surgical clamp early in the spermatic cord during testicular examination via inguinal approach?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "375" "paginaFinal" => "378" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "¿Resulta necesaria la colocación de una pinza quirúrgica tempranamente en el cordón espermático durante la exploración testicular por vía inguinal?" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "G. Gueglio, M. Bergero, S. Treiyer, C. Cristallo, M. Isola, O. Damia" "autores" => array:6 [ 0 => array:2 [ "nombre" => "G." "apellidos" => "Gueglio" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Bergero" ] 2 => array:2 [ "nombre" => "S." "apellidos" => "Treiyer" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Cristallo" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Isola" ] 5 => array:2 [ "nombre" => "O." "apellidos" => "Damia" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210480611003342" "doi" => "10.1016/j.acuro.2011.07.018" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480611003342?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578612001400?idApp=UINPBA00004N" "url" => "/21735786/0000003600000006/v1_201304251924/S2173578612001400/v1_201304251924/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173578612001382" "issn" => "21735786" "doi" => "10.1016/j.acuroe.2011.09.003" "estado" => "S300" "fechaPublicacion" => "2012-06-01" "aid" => "389" "copyright" => "AEU" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Actas Urol Esp. 2012;36:361-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1003 "formatos" => array:3 [ "EPUB" => 11 "HTML" => 820 "PDF" => 172 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Major urologic surgical procedures in locally advanced colorectal cancers" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "361" "paginaFinal" => "366" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Procedimientos quirúrgicos urológicos mayores en el cáncer colorrectal localmente avanzado" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C. Göktaş., R. Horuz, M. Yıldırım, G. Faydacı, C. Şahin, S. Albayrak" "autores" => array:6 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Göktaş." ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Horuz" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Yıldırım" ] 3 => array:2 [ "nombre" => "G." "apellidos" => "Faydacı" ] 4 => array:2 [ "nombre" => "C." "apellidos" => "Şahin" ] 5 => array:2 [ "nombre" => "S." "apellidos" => "Albayrak" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210480611003937" "doi" => "10.1016/j.acuro.2011.09.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480611003937?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578612001382?idApp=UINPBA00004N" "url" => "/21735786/0000003600000006/v1_201304251924/S2173578612001382/v1_201304251924/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Review article" "titulo" => "Castration-resistant prostate cancer: Where are we going?" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "367" "paginaFinal" => "374" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Alcaraz, R. Medina, P. Maroto, M.Á. Climent, D. Castellano, J. Carles" "autores" => array:6 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Alcaraz" "email" => array:1 [ 0 => "aalcaraz@clinic.ub.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "R." "apellidos" => "Medina" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "P." "apellidos" => "Maroto" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "M.Á." "apellidos" => "Climent" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "D." "apellidos" => "Castellano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "J." "apellidos" => "Carles" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "aff0030" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Servicio de Urología, IDIBAPS, Hospital Clínic de Barcelona, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Urología, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Oncología, Hospital de Sant Pau, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Oncología, Instituto Valenciano de Oncología, Valencia, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Oncología, Hospital Universitario 12 de Octubre, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Oncología, Instituto de Oncología de la Vall d’Hebron, Barcelona, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Cáncer de próstata resistente a castración: ¿hacia dónde vamos?" ] ] "textoCompleto" => "IntroductionProstate cancer (PCa) is the most common tumor among the western male population if we exclude skin cancer. Its incidence has been increasing, reaching a peak in 1992, decreasing until 1995, and then increasing by 1% annually.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Although the considerable increase in the use of the determination of the prostate specific antigen (PSA) may be one of the reasons for this growth, there may also be genetic and environmental factors involved.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>The incorporation of the PSA determination as an early diagnostic method makes it possible to detect many cases of PCa in localized stages, where surgery or radiotherapy are potentially curative. However, between 20 and 40% of the patients undergoing local treatment will have a biochemical relapse (PSA>0.2ng/ml after surgery), and of those, between 30 and 70% will develop metastases 10 years after local treatment.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> When the PCa progresses after local treatment or is diagnosed in advanced stages, the possibility of healing becomes more complicated. In fact, PCa is the second leading cause of cancer death in the male population in North America and the western world, and the third in developing countries.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>Hormone treatment allows for lasting and effective control of disease-related symptoms in its advanced stage. However, virtually all the patients with metastatic PCa will suffer from progression of their disease when it becomes resistant to androgen suppression.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> This situation is called castration resistance. The term hormone refractory is often used interchangeably, but they represent different disease situations.Traditionally, chemotherapy showed modest efficacy in castration-resistant PCa (CPRC), with response rates of 10–20%, with no impact in increased survival, which was estimated around the year.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> The arrival of docetaxel was a turning point in the treatment of this disease. Docetaxel achieved a higher response rate and improved biochemical control by reducing PSA levels, and, above all, a benefit in metastatic PCa survival on mitoxantrone and prednisone.<a class="elsevierStyleCrossRefs" href="#bib0030">6–8</a> Therefore, the combination of docetaxel and prednisone is the treatment of choice in first line in CRPC. However, there is no clear alternative when progression to docetaxel occurs. Recently, new agents such as cabazitaxel, abiraterone, and sipuleucel have proved able to improve the survival of our patients, both before and after docetaxel, which opens new prospects in the treatment of this disease.This review updates the treatment of metastatic PCa in progression with castration levels of testosterone, how this clinical situation is defined, its prognosis and first-line treatment, and new options of second-line treatment.Definition of the terms castration-resistant prostate cancer/hormone-refractory prostate cancerClassically, the term hormone-refractory PCa (HRPC) was used to define the PCa that experiences a progression in a patient undergoing gonadal androgen deprivation. However, within this concept of HRPC, there is great heterogeneity with different types of patients according to their clinical situation, the PSA elevation, the possibility or not of new hormone treatments, and the presence or absence of metastases. The estimated mean survival ranges from 4 years for a patient with only PSA recurrence to 9–16 months for a symptomatic patient with extensive metastatic disease. Contrary to what has traditionally been thought, PCa progression after gonadal suppression does not necessarily mean that the disease is androgen-independent. Therefore, currently, the term CRPC is more often used to differentiate it from HRPC,<a class="elsevierStyleCrossRef" href="#bib0045">9</a> as the CRPC may still be sensitive to hormone manipulations, while the true HRPC would not respond to any new hormone therapy.The CRPC can respond to second hormone maneuvers such as suppression of antiandrogens, use of corticosteroids or estrogens, or above all, to the incorporation of new drugs with mechanisms of different hormone action, such as the new agents against the androgen receptor, like the MDV3100, or inhibitors of the androgen synthesis through the CYP17 inhibitor pathway, such as abiraterone. Therefore, there would be a PCa independent to castration, but sensitive to hormones, the CRPC, which can be treated with new hormone therapies, different from a PCa totally refractory to hormone treatment, the HRPC. Therefore, a CRPC is currently defined as one that meets the criteria listed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Hormone maneuvers prior to progressionHormone treatment of PCa is based on deprivation of testosterone, which can be accomplished by means of a chemical or surgical castration and associated or not with antiandrogenic treatment. Both hormone manipulations can be used separately or in combination with the so-called complete androgen blockade. When a patient under hormone treatment experiences an elevation of the PSA, the first step to be taken must be to confirm that testosterone levels are in castration range, as testosterone levels higher than desired<a class="elsevierStyleCrossRef" href="#bib0050">10</a> have been described in up to 11% of cases treated by orchiectomy, with similar figures in those treated with LHRH agonists.After making sure that the patient is subjected to a proper castration, before a PSA rise, we have several options such as: (a) withdrawal of antiandrogens;<a class="elsevierStyleCrossRefs" href="#bib0055">11,12</a> (b) addition or substitution of other antiandrogens;<a class="elsevierStyleCrossRef" href="#bib0065">13</a> (c) adrenal suppressive agents, such as ketoconazole<a class="elsevierStyleCrossRef" href="#bib0070">14</a> and corticosteroids;<a class="elsevierStyleCrossRef" href="#bib0075">15</a> (d) estrogens like diethylstilbestrol<a class="elsevierStyleCrossRef" href="#bib0080">16</a> and fosfestrol;<a class="elsevierStyleCrossRef" href="#bib0085">17</a> and (e) new lines of research,<a class="elsevierStyleCrossRef" href="#bib0090">18</a> such as MDV3100 and abiraterone acetate, which provide new therapeutic possibilities and confirm the idea that there is a big difference between the castration-resistant stage and the hormone-resistant stage, opening a new door to research into hormone treatment.Prognostic factorsOne of the main problems of the patients with CRPC is the difficulty to assess the response to a treatment and establish a proper prognosis. We have to take into account that in the patients with HRPC, there will be different groups with very different clinical situation and prognosis. Therefore, we must look for markers that may be useful and provide information on the evolution and prognosis of the disease and can assess the effectiveness of a treatment. Within these indicators, we can differentiate clinical parameters such as pain control, analgesic consumption, quality of life, or overall condition. On the other hand, among analytical factors, such as hemoglobin or LDH levels, there is no doubt that the serum PSA levels are the most interesting tool. In recent years, as a result of constant research, other approaches have been developed such as determination of the number of circulating tumor cells.Serum levels of prostate-specific antigenPSA levels prior to treatment greater than 100 or 150μg/l have been associated with a lower survival, especially when combined with the presence of anemia.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> Other groups have reported that a PSA doubling time greater than 80 days is associated with better treatment outcomes.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> In fact, in large trials like the South West Oncology Group (SWOG 9916)<a class="elsevierStyleCrossRef" href="#bib0105">21</a> or those conducted by the Cancer and Leukemia Group B (CALGB),<a class="elsevierStyleCrossRef" href="#bib0110">22</a> increases in PSA were one of the criteria that made it possible to significantly differentiate the survival of patients. Reciprocally, PSA declines of at least 50% are also used to define response criteria.Circulating cells of prostate cancerPCa cells can be detected in the circulation of patients with PCa by means of the determination of PSA mRNA by RT-PCR, and counted by CELLSEARCH® (Veridex, LLC). It has been reported that the number of circulating tumor cells may have prognostic significance in patients with CRPC being treated with chemotherapy, and it could be useful in assessing the response to the treatment.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> In one of the largest studies, the levels of circulating tumor cells were analyzed in 231 patients with CRPC before and after receiving chemotherapy.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> Those patients with 5 or more circulating tumor cells per 7.5ml before chemotherapy compared to those with less than 5 cells had a median survival significantly shorter, 10 versus 21 months (HR: 4.5; CI 95%: 3–6.7).Similarly, the changes in the number of circulating tumor cells (called conversion rate) during the treatment with chemotherapy are also correlated with the prognosis. The patients who maintained their cell levels below 5 per 7.5ml had a median survival of 26 months. By contrast, those who raised their levels above 5 only reached 9 months of survival, and those who did not have initially high levels and did not decrease them only survived 7 months. Given the large heterogeneity among patients with CRPC, their prognosis can vary significantly.First-line treatmentSince the 70s, the treatment with chemotherapy of the patients with PCa is being investigated. The reviews of the initial studies with chemotherapy described 8.7% of objective responses, but with no improvement in survival. In the 90s, the PSA was introduced as indirect assessment variable of response, which allowed for objective assessment. Another important step to estimate the effectiveness of the treatments was the introduction of parameters that made it possible to assess the palliation obtained by means of scales of quality of life, pain assessment, and analgesic consumption.In 1996, Tannock et al. published a study evaluating a treatment with mitoxantrone 12mg/m2 together with low-dose prednisone versus prednisone alone, with the main objective of estimating the palliation obtained by means of pain relief.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> In a parallel study conducted by the CALGB, a treatment with mitoxantrone 14mg/m2 with hydrocortisone was compared to hydrocortisone alone.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> Although modest, the positive results of these two studies stimulated research into the role of new drugs and chemotherapy in the treatment of PCa.The TAX 327 study was designed with the aim of assessing whether the low-dose treatment with docetaxel and corticosteroids could improve the survival obtained with mitoxantrone and prednisone.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> The SWOG 9916 study compared the treatment with docetaxel and estramustine versus mitoxantrone associated with prednisone.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> The results of two randomized studies indicate that treatment with docetaxel (either with low-dose prednisone or with estramustine) improve overall survival of these patients in a statistically significant way, although with a net profit of 2.5 and 2 months, respectively. Although the survival gain in absolute terms is modest, we must not forget what could be more important, as it is that a greater benefit in palliation of patients is observed: pain improvement, decreased consumption of analgesia, and improvement in parameters of quality of life, even when considering patients aged over 70.<a class="elsevierStyleCrossRef" href="#bib0135">27</a>Definition of progressionThe definition of progressive disease in patients with metastatic CRPC is still an unresolved issue. In 2008, a new consensus was reflected in a publication in order to assess the progression and assessment criteria of the disease in patients with CRPC by the Prostate-Specific Antigen Working Group (PCWG2) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The modification of the former criteria described by the PCWG1 with these new criteria should make it possible to select the patients for inclusion in clinical trials to the maximum, and so assess the effectiveness of new treatments.<a class="elsevierStyleCrossRef" href="#bib0140">28</a><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>One of the main concepts introduced by the PCWG2 is that it defines 5 patterns of spread of the disease with different evolution, and therefore with very different prognosis (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). These patients may have survival rates ranging from 9 months to 36 months, so it is very important to know what percentage of each is part of a clinical trial.<a class="elsevierStyleCrossRef" href="#bib0140">28</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Despite clarifying certain criteria, most studies on CRPC use the modified PCWG2 criteria. These modifications generally introduce the following changes:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.They use the RECIST 1.1 guidelines, and not those by the PCWG2, where it is advised that adenopathies should be bigger than 2cm.</li><li class="elsevierStyleListItem" id="lsti0010">2.They use the radiological progression criteria that are not covered by the PCWG2 and that were published by the group of the Memorial Sloan Kettering Cancer Center.<a class="elsevierStyleCrossRef" href="#bib0145">29</a></li></ul>Given that in the last year different drugs that have proven useful in the treatment of CRPC once they have progressed to docetaxel appeared, it is important to know which the prognostic factors to disease progression in this situation are. In this regard, Armstrong et al.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> have recently published a paper in which they analyzed the prognostic factors both before the start of chemotherapy with docetaxel and the progression to it, which were statistically significant (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). With the selected variables of this model we can generate a nomogram that estimates the survival after progression.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> In short, the definition of the different criteria for progression, as well as the knowledge of the prognostic factors when it occurs, are extremely important to indicate the start of new treatments or delay them in situations where they are not strictly necessary.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Second-line treatmentAs described above, the standard first-line treatment in PCa in progression with castration levels of testosterone is docetaxel. The experience in the treatment of patients to docetaxel failure is limited, until the arrival of cabazitaxel and abiraterone, which have shown increases in survival that will make it possible to find a standard second-line treatment. The treatments that have been used in clinical practice involve some cytostatics (mitoxantrone,<a class="elsevierStyleCrossRef" href="#bib0155">31</a> retreatment with docetaxel, cyclophosphamide,<a class="elsevierStyleCrossRef" href="#bib0160">32</a> carboplatin, satraplatin,<a class="elsevierStyleCrossRef" href="#bib0165">33</a> etc.), along with the maximum optimization of the sustaining treatment.The future of the second-line treatment of metastatic CRPC is encouraging, given the wide range of lines of research currently underway and the variety of treatment options expected to be available. In advanced stages, there are the studies with new cytostatics such as cabazitaxel, which are reviewed in more detail below; the epothilones, a new family of cytostatics which act stabilizing the polymerized microtubules disrupting the mitosis, in particular ixabepilone, patupilone, and a derivative of the halichondrin B, eribulin. Studies with new hormone therapies are also advanced such as abiraterone acetate, an inhibitor of the CYP17-α-hydroxylase and C17,20-lyase which will cause the inhibition of the CYP17 and, thus, the blocking of the extragonadal synthesis of androgens,<a class="elsevierStyleCrossRef" href="#bib0170">34</a> like the MDV3100 (Medivation®), which acts as an inhibitor of the androgen receptor blocking their passage to the core and their activation,<a class="elsevierStyleCrossRef" href="#bib0175">35</a> and like the SARDS, selective androgen receptor degraders. Sipuleucel-T (Provenge, Dendreon Corporation, Seattle, WA)<a class="elsevierStyleCrossRef" href="#bib0180">36</a> is the first immunotherapy available for the treatment of CRPC. To the classical radioisotopes like samarium and strontium, whose target is the bone, alpharadin (radium 233), an alpha-emitting radioactive isotope which has shown improved survival in patients treated and not treated with docetaxel, has recently been added. And other research lines with agents such as Custirsen (OGX-011) based on the induction of the apoptosis<a class="elsevierStyleCrossRef" href="#bib0185">37</a> or ProstVac-V (vaccine associated with poxvirus)<a class="elsevierStyleCrossRef" href="#bib0190">38</a> are also being tested.New cytostaticsCabazitaxelCabazitaxel (XRP6258; TXD 258; RPR116258A) is a new semisynthetic taxane that has demonstrated an antitumor activity as potent as docetaxel on cell lines.<a class="elsevierStyleCrossRef" href="#bib0195">39</a>In order to evaluate the efficacy and safety of cabazitaxel in patients with metastatic CRPC, an open and randomized phase III trial, called TROPIC, comparing cabazitaxel versus mitoxantrone has been developed. We recruited 755 patients who had progressed during (30%) or after (70%) treatment with docetaxel. The patients were stratified according to the ECOG and presence or absence of measurable disease and randomized to receive cabazitaxel (25mg/m2 IV) or mitoxantrone (12mg/m2 IV), both every three weeks and in combination with 10mg of daily oral prednisone.<a class="elsevierStyleCrossRef" href="#bib0200">40</a>With a primary objective of overall survival, cabazitaxel reached a median of 15.1 months (CI 95%: 14.1–16.3) versus 12.7 months (CI 95%: 11.6–13.7) of mitoxantrone, with statistical significance (p<0.0001) and a reduced risk of death by 30% (HR: 0.7; CI 95%: 0.59–0.83) in favor of cabazitaxel.An interesting fact is that in the subgroup analysis cabazitaxel demonstrated its benefit in survival in groups of patients with a very poor prognosis: in the patients who had progressed during the treatment with docetaxel and those who had progressed within three months after having completed treatment with docetaxel. This fact confirms the effectiveness of cabazitaxel regardless of the response to docetaxel, and it confirms the preclinical studies demonstrating its effectiveness in cell lines resistant to docetaxel.The secondary objectives of the study, progression-free survival (2.8 months, CI 95%: 2.4–3.0 versus 1.4 months; CI 95%: 1.4–1.7), (HR: 0.74; CI 95%: 0.64–0.86; p<0.0001), response rate (14.4 versus 4.4%; p=0.0005), and PSA response rate (39.2 versus 17.8%; p=0.0002) were also favorable to the cabazitaxel. Other secondary objectives like pain reduction were similar in both arms (9.2% for cabazitaxel versus 7.7% with mitoxantrone).In the future, the possibility to associate cabazitaxel with the new generation of hormone therapy such as abiraterone or MDV3100 remains open, as there may be a synergism.New hormone therapiesAbirateronePCa can maintain the signal activated mediated by the androgen receptor despite having suitable castration levels. One of the escapes is established by means of the overexpression of the cytochrome P-450c17 (CYP17), a key enzyme for the synthesis of extragonadal androgens, at the adrenal, prostate, and intratumoral level.The abiraterone acetate is an inhibitor of the CYP17-α-hydroxylase and the C17, 20-lyase that will cause the inhibition of CYP17 and, therefore, it is capable of blocking the extragonadal synthesis of androgens.The results of a phase III multicenter study that compared the efficacy of abiraterone and prednisone versus placebo and prednisone in patients with CRPC in progression after receiving docetaxel<a class="elsevierStyleCrossRef" href="#bib0170">34</a> have recently been published. The abiraterone was statistically superior in survival to placebo, 14.8 versus 10.9 (HR: 0.65; CI 95%: 0.54–0.77; p<0.001) months, which was associated with a 35% reduced risk of death.Furthermore, the abiraterone obtained an increase in the response rate and the progression-free survival according to the PSA and the radiological findings.The abiraterone was well tolerated. Some mineralocorticoid-related adverse events, including fluid retention, hypertension, and hypokalemia were more frequent in the abiraterone acetate and prednisone group versus the placebo and prednisone group.Consequently, the abiraterone was approved by the FDA in April 2011, and in September 2011 by the EMA, for PCa patients previously treated with docetaxel.MDV3100Other hormonal agents like MDV3100 (Medivation®) have a completely different action, acting as an androgen receptor inhibitor that blocks its passage to the core and its activation. After a phase I/II trial which obtained 56% of responses depending on PSA declines and 22% of radiological responses;<a class="elsevierStyleCrossRef" href="#bib0175">35</a> its effectiveness is being confirmed in two phase III studies, one of them to the progression of docetaxel (AFFIRM), which has been closed with the interim analysis when demonstrating a significant survival increase with MDV3100 and the other one prior to the administration of docetaxel in patients minimally symptomatic or asymptomatic (PREVAIL), which is underway.Treatment of skeletal-related events associated with bone metastasesSo far, we have used zoledronic acid (bisphosphonates) for the prevention of ERS,<a class="elsevierStyleCrossRef" href="#bib0205">41</a> but in July 2011, denosumab, with a novel mechanism of action, has been approved by the EMA. Denosumab is a human monoclonal antibody against RANKL that has shown better results than zoledronic acid in a phase III study in 1904 patients with CRPC for the prevention of ERS: the median time to onset of the first skeletal-related event was 20.7 months (CI 95%: 18.8–24.9) with denosumab compared with 17.1 months (15.0–19.4) with zoledronic acid.<a class="elsevierStyleCrossRef" href="#bib0210">42</a>ConclusionsThe CRPC treatment has rested on second hormone maneuvers, which have not shown increase in survival, and in the treatment with docetaxel, which prolongs survival modestly with a significant improvement of pain and quality of life. There were no contrasting treatments after failure to docetaxel. Fortunately, the PCa therapeutic horizon opens dramatically with the advent of new drugs such as cabazitaxel, abiraterone, sipuleucel T, alpharadin, MDV3100, etc., which will probably keep changing the course of this disease positively.<a class="elsevierStyleCrossRef" href="#bib0215">43</a> Cabazitaxel is presented as a reality, with FDA (June 2010) and EMA (March 2011) approval in the treatment of metastatic CRPC in progression to docetaxel, and it is considered the standard treatment of choice.<a class="elsevierStyleCrossRef" href="#bib0220">44</a> With some more delay, abiraterone, approved by the FDA (April 2011) and the EMA (September 2011), has the same indication. So far, cabazitaxel and in the near future abiraterone have proven effective drugs in the second-line treatment after progression to docetaxel, adding more than 2–4 months of survival and reducing the risk of death by 30–35%.Conflict of interestThe authors declare that they have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:2 [ "identificador" => "xres101693" "titulo" => array:6 [ 0 => "Abstract" 1 => "Context" 2 => "Objective" 3 => "Evidence acquisition" 4 => "Evidence synthesis" 5 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec88859" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres101692" "titulo" => array:6 [ 0 => "Resumen" 1 => "Contexto" 2 => "Objetivo" 3 => "Adquisición de la evidencia" 4 => "Síntesis de la evidencia" 5 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec88860" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Definition of the terms castration-resistant prostate cancer/hormone-refractory prostate cancer" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Hormone maneuvers prior to progression" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Prognostic factors" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Serum levels of prostate-specific antigen" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Circulating cells of prostate cancer" ] ] ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "First-line treatment" ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Definition of progression" ] 10 => array:3 [ "identificador" => "sec0045" "titulo" => "Second-line treatment" "secciones" => array:2 [ 0 => array:3 [ "identificador" => "sec0050" "titulo" => "New cytostatics" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Cabazitaxel" ] ] ] 1 => array:3 [ "identificador" => "sec0060" "titulo" => "New hormone therapies" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Abiraterone" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "MDV3100" ] ] ] ] ] 11 => array:2 [ "identificador" => "sec0075" "titulo" => "Treatment of skeletal-related events associated with bone metastases" ] 12 => array:2 [ "identificador" => "sec0080" "titulo" => "Conclusions" ] 13 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-10-03" "fechaAceptado" => "2011-10-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec88859" "palabras" => array:5 [ 0 => "Metastatic prostate cancer" 1 => "Castration-resistant prostate cancer" 2 => "Hormonal therapies" 3 => "Progression" 4 => "Cabazitaxel" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec88860" "palabras" => array:5 [ 0 => "Cáncer de próstata metastásico" 1 => "Cáncer de próstata resistente a castración" 2 => "Terapias hormonales" 3 => "Progresión" 4 => "Cabazitaxel" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "ContextHormonal therapy allows effective control of cancer-related symptoms in advanced stages. However, the disease will progress in almost all these metastatic prostate cancer patient until becoming resistant to androgen suppression. The emergence of new drugs will most probably have open up new expectations regarding the treatment of this cancer. ObjectiveThe aim of the present review has been to provide an overview of the current status of castration-resistant prostate cancer and to share the high expectations created with the new treatments. Evidence acquisitionEvidence was obtained from multidisciplinary meetings with the participation of urologists and oncologists, where they pooled the analysis of original articles in the literature and defined the content of the article. Evidence synthesisChemotherapy with docetaxel was a turning point in castration-resistant prostate cancer after the failure of hormonal therapy failure. For the first time, it achieved increased survival time in comparison with mitoxantrone and prednisone. Combination therapy with docetaxel and prednisone is the first-line choice treatment. Once the cancer has progressed, there is no clear alternative, although some novel agents have created expectations for the treatment of this type of cancer. ConclusionsThe range of therapeutic options for castration-resistant prostate cancer has increased dramatically with the arrival of new drugs. At present, cabazitaxel, and in the near future, abiraterone, have been found to be effective drugs in second-line treatment after progression to docetaxel, increasing survival by 2–4 months and reducing risk of death by 30–35%." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "ContextoEl tratamiento hormonal permite un control eficaz de los síntomas relacionados con el cáncer de próstata metastásico; sin embargo, la práctica totalidad de estos pacientes sufrirán progresión de su enfermedad cuando esta se hace resistente a la supresión androgénica. La aparición de nuevos fármacos permite abrir nuevas expectativas en el tratamiento de esta enfermedad. ObjetivoElaborar un documento de revisión sobre la situación actual del cáncer de próstata resistente a castración y compartir las grandes expectativas que se muestran con los nuevos tratamientos. Adquisición de la evidenciaReuniones multidisciplinares con la participación de urólogos y oncólogos, donde se pusieron en común el análisis bibliográfico de artículos originales y se definió el contenido del artículo. Síntesis de la evidenciaTras el fracaso de la hormonoterapia, la quimioterapia con docetaxel supuso un punto de inflexión en el cáncer de próstata resistente a castración, consiguiendo por primera vez beneficio en la supervivencia sobre mitoxantrone y prednisona. La combinación de docetaxel y prednisona es el tratamiento de elección en primera línea. Cuando progresa no hay alternativa clara, aunque nuevos agentes están generando expectativas en el tratamiento de esta enfermedad. ConclusionesEl horizonte terapéutico del cáncer de próstata resistente a la castración se abre de forma espectacular con la llegada de nuevos fármacos. Por el momento, cabazitaxel y en el futuro próximo abiraterona se han mostrado como fármacos eficaces en el tratamiento de segunda línea tras la progresión a docetaxel, añadiendo más de 2-4 meses de supervivencia y reduciendo un 30-35% el riesgo de muerte." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article: Alcaraz A, et al. Cáncer de próstata resistente a castración: ¿hacia dónde vamos? Actas Urol Esp. 2012;36:367–74." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "RECIST: Response Evaluation Criteria In Solid Tumors; PSA: prostate specific antigen." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Levels of testosterone considered of castration (testosterone <50ng/dl or <1.7nmol/l) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Three consecutive PSA elevations, separated by at least a week, resulting in two increases by 50% on the nadir with a PSA greater than 2ng/ml \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antiandrogen suppression of at least 4 weeks or a second hormone manipulation made, with PSA progression (despite consecutive hormone manipulations) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Progression of bone lesions, two or more in bone scans, or progression of the soft tissue lesions according to RECIST criteria \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab184244.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Criteria that define castration-resistant prostate cancer (CRPC)." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Park et al.<a class="elsevierStyleCrossRef" href="#bib0135">27</a>" "tabla" => array:2 [ "leyenda" => "HRPC: hormone-refractory prostate cancer; CRPC: castration-resistant prostate cancer; PCWG2: Prostate Cancer Clinical Trials Working Group 2; PET: positron emission tomography; PSA: prostate specific antigen; RECIST: Response Evaluation Criteria in Solid Tumors; MRI: magnetic resonance imaging; CT: computed tomography." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">PCWG2 criteria \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Assess PSA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Obtain the sequence of elevation of the values at least at weekly intervals. Minimum initial value 2.0ng/ml. Assess the pretreatment PSA doubling time if there are 3 or more values separated every 4 weeks or more \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Measurable disease or types of target, nodal, or visceral lesions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The presence of nodal or visceral lesions is enough to enter a study regardless of the PSA. No measurable lesions are required for inclusion. Use RECIST criteria to assess the soft tissue lesions (nodal or visceral) as target or non-target. Only ≥2cm diameter lymph nodes should be considered to assess their change in size. Record the presence of nodal and/or visceral disease separately \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Primary location of the tumor in the prostate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Register prior therapeutic treatment of the primary tumor. Perform pelvic imaging scans (CT, MRI, PET/CT, endorectal MRI, transrectal ultrasound) to document the presence or absence of disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Progression is considered when there are two or more new lesions. Confirm the ambiguous results with other imaging tests (CT or MRI) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other locations of the disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients with epidural lesions treated without epidural progression are eligible if another criteria for inclusion is met \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prior hormone maneuvers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The addition or deletion of hormone therapy with therapeutic intention due to existence of disease progression is considered maneuver or hormone intervention. Collect all the history of received hormone therapy, number, type, and duration of the same. Classify a PCa in progression with levels of testosterone in castration such as CRPC and not HRPC, because patients may respond to new hormone maneuvers \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serum levels of testosterone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">We consider patient in castration range with testosterone levels below 50ng/dl (>1.7nmol/l). There may be interlaboratory variability. The importance of maintaining testosterone levels in castration range in patients not undergoing orchiectomy is reaffirmed \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Response to antiandrogenic treatment suppression \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PCWG1 criterion is confirmed (because the antiandrogen withdrawal may produce response in patient with PCa in alleged progression it was recommended to wait for a period of 4–8 weeks before entering a clinical trial), but it is not recommended to wait such a long time for the suppression of the antiandrogen in patients who do not respond or who showed PSA decline of three months or less after the antiandrogen, whether administered as second-line therapy or as a late intervention \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previously administered nonhormone treatments \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Collect the local treatments, surgery or radiotherapy, or systemics administered, docetaxel or biological therapies, type, and duration thereof, including reasons for suppression, response presented, and interval without treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab184246.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Criteria for progression and assessment of the disease in CRPC (PCWG2)." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Park et al.<a class="elsevierStyleCrossRef" href="#bib0135">27</a>" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">a. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Local tumor progression without metastatic disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">b. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increased PSA in patient at testosterone suppression but without metastatic involvement \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">c. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nodal spread but without evidence of bone or visceral involvement \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">d. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bone involvement with or without lymph node involvement, but without visceral metastases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">e. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Visceral metastases \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab184245.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Patient groups according to prognosis and natural history of the CRPC (PCWG2)." ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Scher et al.<a class="elsevierStyleCrossRef" href="#bib0145">29</a>" "tabla" => array:2 [ "leyenda" => "CTX: chemotherapy; PSA: prostate specific antigen." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PreCTX variables \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pain \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Overall health (Karnofsky) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alkaline phosphatase level \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Number of metastatic sites \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Presence of metastatic sites \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hemoglobin values \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PSA value \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Period of time from to diagnosis (years) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PostCTX variables \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Progression in the first line of CTX \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Number of factors of progression (PSA, pain, radiological) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Number of three-week cycles of first line CTX \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab184247.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Prognostic factors of progression in CRPC." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:44 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global cancer statistics" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Jemal" 1 => "F. Bray" 2 => "M.M. Center" 3 => "J. Ferlay" 4 => "E. Ward" 5 => "D. Forman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3322/caac.20107" "Revista" => array:6 [ "tituloSerie" => "CA Cancer J Clin" "fecha" => "2011" "volumen" => "61" "paginaInicial" => "69" "paginaFinal" => "90" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21296855" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The changing face of prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.R. Cooperberg" 1 => "J.W. Moul" 2 => "P.R. Carroll" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2005.02.9751" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2005" "volumen" => "23" "paginaInicial" => "8146" "paginaFinal" => "8151" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16278465" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of biochemical recurrence in prostate cancer among US veterans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "E.M. Uchio" 1 => "M. Aslan" 2 => "C.K. Wells" 3 => "J. Calderone" 4 => "J. Concato" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archinternmed.2010.262" "Revista" => array:6 [ "tituloSerie" => "Arch Intern Med" "fecha" => "2010" "volumen" => "170" "paginaInicial" => "1390" "paginaFinal" => "1395" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20696967" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A re-evaluation of nonhormonal cytotoxic chemotherapy in the treatment of prostatic carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.A. Eisenberger" 1 => "R. Simon" 2 => "P.J. O’Dwyer" 3 => "H.A. Friedman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/jco.1985.3.6.827" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "1985" "volumen" => "3" "paginaInicial" => "827" "paginaFinal" => "841" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2409240" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cytotoxic chemotherapy for advanced hormone-resistant prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Yagoda" 1 => "D. Petrylak" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "1993" "volumen" => "71" "paginaInicial" => "1098" "paginaFinal" => "1109" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7679039" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "On behalf of the TAX 327 Investigators" "etal" => true "autores" => array:6 [ 0 => "I.F. Tannock" 1 => "R. de Wit" 2 => "W.R. Berry" 3 => "J. Horti" 4 => "A. Pluzanska" 5 => "K.N. Chi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa040720" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2004" "volumen" => "351" "paginaInicial" => "1502" "paginaFinal" => "1512" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15470213" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.P. Petrylak" 1 => "C.M. Tangen" 2 => "M.H. Hussain" 3 => "P.N. Lara" 4 => "J.A. Jones" 5 => "M.E. Taplin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa041318" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2004" "volumen" => "351" "paginaInicial" => "1513" "paginaFinal" => "1520" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15470214" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Quality of life and pain in advanced stage prostate cancer: results of a Southwest Oncology Group randomized trial comparing docetaxel and estramustine to mitoxantrone and prednisone" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.L. Berry" 1 => "C.M. Moinpour" 2 => "C.S. Jiang" 3 => "D.P. Ankerst" 4 => "D.P. Petrylak" 5 => "L.V. Vinson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2005.04.8207" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2006" "volumen" => "24" "paginaInicial" => "2828" "paginaFinal" => "2835" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16782921" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I.F. Tannock" 1 => "D. Osoba" 2 => "M.R. Stockler" 3 => "D.S. Ernst" 4 => "A.J. Neville" 5 => "M.J. Moore" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/jco.1996.14.6.1756" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "1996" "volumen" => "14" "paginaInicial" => "1756" "paginaFinal" => "1764" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8656243" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Novel secondary hormonal therapy in advanced prostate cancer: an update" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E.M. Van Allen" 1 => "C.J. Ryan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MOU.0b013e328329b73a" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Urol" "fecha" => "2009" "volumen" => "19" "paginaInicial" => "315" "paginaFinal" => "321" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19342958" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALBG 9583)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.J. Small" 1 => "S. Halabi" 2 => "N.A. Dawson" 3 => "W.M. Stadler" 4 => "B.I. Rini" 5 => "J. Picus" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2004.06.037" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2004" "volumen" => "22" "paginaInicial" => "1025" "paginaFinal" => "1033" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15020604" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antiandrogen withdrawal in castrate-refractory prostate cancer: a Southwest Oncology Group trial (SWOG 9426)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.O. Sartor" 1 => "C.M. Tangen" 2 => "M.H. Hussain" 3 => "M.A. Eisenberger" 4 => "M. Parab" 5 => "J.A. Fontana" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cncr.23473" "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "2008" "volumen" => "112" "paginaInicial" => "2393" "paginaFinal" => "2400" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18383517" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High dose bicalutamide for androgen-independent prostate cancer: effect of prior hormonal therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Joyce" 1 => "M.A. Fenton" 2 => "P. Rode" 3 => "M. Constantine" 4 => "L. Gaynes" 5 => "G. Kolvenbag" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Urol" "fecha" => "1998" "volumen" => "159" "paginaInicial" => "149" "paginaFinal" => "153" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9400459" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term outcome with androgen independent prostate cancer treated with ketoconazole and hidrocortisone" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Scholtz" 1 => "R. Jennrich" 2 => "S. Strum" 3 => "S. Brosman" 4 => "H. Johnson" 5 => "R. Lam" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.ju.0000158449.83022.40" "Revista" => array:6 [ "tituloSerie" => "J Urol" "fecha" => "2005" "volumen" => "173" "paginaInicial" => "1947" "paginaFinal" => "1952" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15879788" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of prednisone on prostate-specific antigen in patients with hormone-refractory prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "O. Sartor" 1 => "M. Weinberger" 2 => "A. Moore" 3 => "A. Li" 4 => "W.D. Figg" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Urology" "fecha" => "1998" "volumen" => "52" "paginaInicial" => "252" "paginaFinal" => "256" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9697790" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prospective, multicentre, randomized phase II trial of the herbal supplement PC-SPES and diethylbestrol in patients with androgen-independent prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W.K. Oh" 1 => "P.W. Kanthoff" 2 => "V. Weinberg" 3 => "G. Jones" 4 => "B.I. Rini" 5 => "M.K. Derynck" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Oncol" "fecha" => "2004" "volumen" => "22" "paginaInicial" => "3705" "paginaFinal" => "3712" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Low dose continuous oral fosfestrol is highly active in hormone refractory prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Orlando" 1 => "A. Chacon" 2 => "G. Salum" 3 => "D.R. Chacon" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Oncol" "fecha" => "2000" "volumen" => "11" "paginaInicial" => "177" "paginaFinal" => "181" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10761752" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current management of castrate-resistant prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.J. Hotte" 1 => "F. Saad" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Curr Oncol" "fecha" => "2001" "volumen" => "17" "numero" => "Suppl. 2" "paginaInicial" => "S72" "paginaFinal" => "S79" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20882137" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prostate specific-antigen and other prognostic factors in patients with hormone-resistant prostatic cancer undergoing experimental treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S.D. Fossa" 1 => "E. Paus" 2 => "M. Lindegaard" 3 => "D.W. Newling" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Br J Urol" "fecha" => "1992" "volumen" => "69" "paginaInicial" => "175" "paginaFinal" => "179" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1371425" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tumor marker doubling time in patients with prostate cancer: determination of prostate-specific antigen and prostatic acid phosphatase doubling time" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Akimoto" 1 => "M. Masai" 2 => "K. Akakura" 3 => "J. Shimazaki" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur Urol" "fecha" => "1995" "volumen" => "27" "paginaInicial" => "207" "paginaFinal" => "212" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7541360" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prostate-specific antigen progression predicts overall survival in patients with metastatic prostate cancer: data from Southwest Oncology Group Trials 9346 (Intergroup Study 0162) and 9916" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Hussain" 1 => "B. Goldman" 2 => "C. Tangen" 3 => "C.S. Higano" 4 => "D.P. Petrylak" 5 => "G. Wilding" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2008.19.9810" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2009" "volumen" => "27" "paginaInicial" => "2450" "paginaFinal" => "2456" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19380444" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Progression-free survival as a predictor of overall survival in men with castrate-resistant prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Halabi" 1 => "N.J. Vogelzang" 2 => "S.S. Ou" 3 => "K. Owzar" 4 => "L. Archer" 5 => "E.J. Small" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2008.18.9159" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2009" "volumen" => "27" "paginaInicial" => "2766" "paginaFinal" => "2771" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19380448" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PSA surge/flare-up in patients with castration-refractory prostate cancer during the initial phase of chemotherapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T. Nelius" 1 => "S. Filleur" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/pros.21024" "Revista" => array:6 [ "tituloSerie" => "Prostate" "fecha" => "2009" "volumen" => "69" "paginaInicial" => "1802" "paginaFinal" => "1807" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19676083" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.C. Danila" 1 => "G. Heller" 2 => "G.A. Gignac" 3 => "R. Gonzalez-Espinoza" 4 => "A. Anand" 5 => "E. Tanaka" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-07-1506" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2007" "volumen" => "13" "paginaInicial" => "7053" "paginaFinal" => "7058" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18056182" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Halabi" 1 => "E.J. Small" 2 => "P.W. Kantoff" 3 => "M.W. Kattan" 4 => "E.B. Kaplan" 5 => "N.A. Dawson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2003.06.100" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2003" "volumen" => "21" "paginaInicial" => "1232" "paginaFinal" => "1237" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12663709" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B9182 study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.W. Kantoff" 1 => "S. Halabi" 2 => "M. Conaway" 3 => "J. Picus" 4 => "J. Kirshner" 5 => "V. Hars" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/jco.1999.17.8.2506" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "1999" "volumen" => "17" "paginaInicial" => "2506" "paginaFinal" => "2513" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10561316" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Docetaxel-based systemic chemotherapy in elderly Korean men with castration-resistant prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.C. Park" 1 => "J.W. Lee" 2 => "J.S. Rim" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.acuro.2011.09.008" "Revista" => array:6 [ "tituloSerie" => "Actas Urol Esp" "fecha" => "2012" "volumen" => "36" "paginaInicial" => "425" "paginaFinal" => "430" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22386299" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "Prostate Cancer Clinical Trials Working Group" "etal" => true "autores" => array:6 [ 0 => "H.I. Scher" 1 => "S. Halabi" 2 => "I. Tannock" 3 => "M. Morris" 4 => "C.N. Sternberg" 5 => "M.A. Carducci" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2007.12.4487" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2008" "volumen" => "26" "paginaInicial" => "1148" "paginaFinal" => "1159" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18309951" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The association between measures of progression and survival in castrate metastatic prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H.I. Scher" 1 => "M. Warren" 2 => "G. Heller" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-06-1885" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2007" "volumen" => "13" "paginaInicial" => "1488" "paginaFinal" => "1492" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17332293" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prediction of survival following first line chemotherapy in men with castration resistant metastatic prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.J. Armstrong" 1 => "E. Garret-Mayer" 2 => "R. de Wit" 3 => "I. Tannock" 4 => "M. Eisenberger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-09-2514" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2010" "volumen" => "16" "paginaInicial" => "203" "paginaFinal" => "211" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20008841" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Survival and PSA response of patients in the TAX 327 study who crossed over to receive docetaxel after mitoxantrone or vice versa" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D.R. Berthold" 1 => "G.R. Pond" 2 => "R. de Wit" 3 => "M. Eisenberger" 4 => "I.F. Tannock" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/annonc/mdn288" "Revista" => array:6 [ "tituloSerie" => "Ann Oncol" "fecha" => "2008" "volumen" => "19" "paginaInicial" => "1749" "paginaFinal" => "1753" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18487550" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical and pharmacodynamic evaluation of metronomic cyclophosphamide, celecoxib and dexamethasone in advanced hormone-refractory prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Fontana" 1 => "L. Galli" 2 => "A. Fioravanti" 3 => "P. Orlandi" 4 => "C. Galli" 5 => "L. Landi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-08-3317" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2009" "volumen" => "15" "paginaInicial" => "4954" "paginaFinal" => "4962" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19622584" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Satraplatin demonstrates a significant clinical benefit in patients with HRPC: Results of a randomized phase III trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.N. Sternberg" 1 => "D. Petrylak" 2 => "F. Witjes" 3 => "J. Ferrero" 4 => "J. Eymard" 5 => "S. Falcon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2007.11.8711" "Revista" => array:6 [ "titulo" => "2007 ASCO Annual Meeting Proceedings Part I" "tituloSerie" => "J Clin Oncol" "fecha" => "2007" "volumen" => "25" "paginaInicial" => "5019" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17971602" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Abiraterone and increased survival in metastatic prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.S. de Bono" 1 => "C.J. Logothetis" 2 => "A. Molina" 3 => "K. Fizazi" 4 => "S. North" 5 => "L. Chu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1014618" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "2011" "volumen" => "364" "paginaInicial" => "1995" "paginaFinal" => "2005" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21612468" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1130862110002019" "estado" => "S300" "issn" => "11308621" ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.I. Scher" 1 => "T.M. Beer" 2 => "C.S. Higano" 3 => "A. Anand" 4 => "M.E. Taplin" 5 => "E. Efstathiou" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(10)60172-9" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2010" "volumen" => "375" "paginaInicial" => "1437" "paginaFinal" => "1446" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20398925" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sipuleucel-T immunotherapy for castration-resistant prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.W. Kantoff" 1 => "C.S. Higano" 2 => "N.D. Shore" 3 => "E.R. Berger" 4 => "E.J. Small" 5 => "D.F. Penson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1001294" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2010" "volumen" => "363" "paginaInicial" => "411" "paginaFinal" => "422" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20818862" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomized phase II study of docetaxel and prednisone with or without OGX-011 in patients with metastatic castration-resistant prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.N. Chi" 1 => "S.J. Hotte" 2 => "E.Y. Yu" 3 => "D. Tu" 4 => "B.J. Eigl" 5 => "I. Tannock" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2009.26.8771" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2010" "volumen" => "28" "paginaInicial" => "4247" "paginaFinal" => "4254" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20733135" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA targeted immunotherapy in metastatic castration-resistant prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.W. Kantoff" 1 => "T.J. Schuetz" 2 => "B.A. Blumenstein" 3 => "L.M. Glode" 4 => "D.L. Bilhartz" 5 => "M. Wyand" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2009.25.0597" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2010" "volumen" => "28" "paginaInicial" => "1099" "paginaFinal" => "1105" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20100959" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update on tubulin binding agents" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G. Attard" 1 => "A. Greystoke" 2 => "S. Kaye" 3 => "J. de Bono" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Pathol Biol (Paris)" "fecha" => "2006" "volumen" => "54" "paginaInicial" => "72" "paginaFinal" => "84" ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomized open-label trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.S. de Bono" 1 => "S. Oudard" 2 => "M. Ozguroglu" 3 => "S. Hansen" 4 => "J.P. Machiels" 5 => "I. Kocak" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(10)61389-X" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2010" "volumen" => "376" "paginaInicial" => "1147" "paginaFinal" => "1154" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20888992" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efectividad y tolerabilidad del ácido zoledrónico en el tratamiento del cáncer de próstata metastásico" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. Cózar-Olmo" 1 => "J. Carballido Rodriguez" 2 => "P. Luque Gálvez" 3 => "A.G. Tabernero Gómez" 4 => "A. Barreiro Mouro" 5 => "E. Sánchez Sánchez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Actas Urol Esp" "fecha" => "2008" "volumen" => "32" "paginaInicial" => "492" "paginaFinal" => "501" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18604999" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Fizazi" 1 => "M. Carducci" 2 => "M. Smith" 3 => "R. Damião" 4 => "J. Brown" 5 => "L. Karsh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(10)62344-6" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2011" "volumen" => "377" "paginaInicial" => "813" "paginaFinal" => "822" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21353695" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guía de la EAU sobre cáncer de próstata. Parte II: tratamiento del cáncer avanzado, recidivante y resistente a la castración" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Mottet" 1 => "J. Bellmunt" 2 => "M. Bolla" 3 => "S. Joniau" 4 => "M. Mason" 5 => "V. Matveev" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.acuro.2011.03.011" "Revista" => array:6 [ "tituloSerie" => "Actas Urol Esp" "fecha" => "2011" "volumen" => "35" "paginaInicial" => "565" "paginaFinal" => "579" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21757258" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Contemporary management of metastatic castration-resistant prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G. Sonpavde" 1 => "C.N. Sternberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MOU.0b013e3283449e19" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Urol" "fecha" => "2011" "volumen" => "21" "paginaInicial" => "241" "paginaFinal" => "247" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21455038" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735786/0000003600000006/v1_201304251924/S2173578612001394/v1_201304251924/en/main.assets" "Apartado" => array:4 [ "identificador" => "6275" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Review article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735786/0000003600000006/v1_201304251924/S2173578612001394/v1_201304251924/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578612001394?idApp=UINPBA00004N"]

Statistics

Review article

Castration-resistant prostate cancer: Where are we going?

Cáncer de próstata resistente a castración: ¿hacia dónde vamos?

A. Alcaraza,

Corresponding author

aalcaraz@clinic.ub.es

Corresponding author.

, R. Medinab, P. Marotoc, M.Á. Climentd, D. Castellanoe, J. Carlesf

a Servicio de Urología, IDIBAPS, Hospital Clínic de Barcelona, Barcelona, Spain

b Servicio de Urología, Hospital Universitario Virgen del Rocío, Sevilla, Spain

c Servicio de Oncología, Hospital de Sant Pau, Barcelona, Spain

d Servicio de Oncología, Instituto Valenciano de Oncología, Valencia, Spain

e Servicio de Oncología, Hospital Universitario 12 de Octubre, Madrid, Spain

f Servicio de Oncología, Instituto de Oncología de la Vall d’Hebron, Barcelona, Spain

Read

1062

Times
was read the article

209

Total PDF

853

Total HTML

Share statistics

 array:24 [
  "pii" => "S2173578612001394"
  "issn" => "21735786"
  "doi" => "10.1016/j.acuroe.2011.10.001"
  "estado" => "S300"
  "fechaPublicacion" => "2012-06-01"
  "aid" => "384"
  "copyright" => "AEU"
  "copyrightAnyo" => "2011"
  "documento" => "article"
  "crossmark" => 0
  "subdocumento" => "ssu"
  "cita" => "Actas Urol Esp. 2012;36:367-74"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:2 [
    "total" => 1071
    "formatos" => array:3 [
      "EPUB" => 11
      "HTML" => 852
      "PDF" => 208
    ]
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0210480611003883"
      "issn" => "02104806"
      "doi" => "10.1016/j.acuro.2011.10.010"
      "estado" => "S300"
      "fechaPublicacion" => "2012-06-01"
      "aid" => "384"
      "copyright" => "AEU"
      "documento" => "article"
      "crossmark" => 0
      "subdocumento" => "ssu"
      "cita" => "Actas Urol Esp. 2012;36:367-74"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:2 [
        "total" => 7624
        "formatos" => array:3 [
          "EPUB" => 18
          "HTML" => 6707
          "PDF" => 899
        ]
      ]
      "es" => array:12 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Art&#237;culo de revisi&#243;n</span>"
        "titulo" => "C&#225;ncer de pr&#243;stata resistente a castraci&#243;n&#58; &#191;hacia d&#243;nde vamos&#63;"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "367"
            "paginaFinal" => "374"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Castration-Resistant Prostate Cancer&#58; Where are We Going&#63;"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "A&#46; Alcaraz, R&#46; Medina, P&#46; Maroto, M&#46;&#193;&#46; Climent, D&#46; Castellano, J&#46; Carles"
            "autores" => array:6 [
              0 => array:2 [
                "nombre" => "A&#46;"
                "apellidos" => "Alcaraz"
              ]
              1 => array:2 [
                "nombre" => "R&#46;"
                "apellidos" => "Medina"
              ]
              2 => array:2 [
                "nombre" => "P&#46;"
                "apellidos" => "Maroto"
              ]
              3 => array:2 [
                "nombre" => "M&#46;&#193;&#46;"
                "apellidos" => "Climent"
              ]
              4 => array:2 [
                "nombre" => "D&#46;"
                "apellidos" => "Castellano"
              ]
              5 => array:2 [
                "nombre" => "J&#46;"
                "apellidos" => "Carles"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2173578612001394"
          "doi" => "10.1016/j.acuroe.2011.10.001"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578612001394?idApp=UINPBA00004N"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480611003883?idApp=UINPBA00004N"
      "url" => "/02104806/0000003600000006/v2_201304261440/S0210480611003883/v2_201304261440/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2173578612001400"
    "issn" => "21735786"
    "doi" => "10.1016/j.acuroe.2011.07.006"
    "estado" => "S300"
    "fechaPublicacion" => "2012-06-01"
    "aid" => "363"
    "copyright" => "AEU"
    "documento" => "article"
    "crossmark" => 0
    "subdocumento" => "sco"
    "cita" => "Actas Urol Esp. 2012;36:375-8"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 1229
      "formatos" => array:3 [
        "EPUB" => 9
        "HTML" => 967
        "PDF" => 253
      ]
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Casuistry</span>"
      "titulo" => "Is it necessary to place a surgical clamp early in the spermatic cord during testicular examination via inguinal approach&#63;"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "375"
          "paginaFinal" => "378"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "&#191;Resulta necesaria la colocaci&#243;n de una pinza quir&#250;rgica tempranamente en el cord&#243;n esperm&#225;tico durante la exploraci&#243;n testicular por v&#237;a inguinal&#63;"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "G&#46; Gueglio, M&#46; Bergero, S&#46; Treiyer, C&#46; Cristallo, M&#46; Isola, O&#46; Damia"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "G&#46;"
              "apellidos" => "Gueglio"
            ]
            1 => array:2 [
              "nombre" => "M&#46;"
              "apellidos" => "Bergero"
            ]
            2 => array:2 [
              "nombre" => "S&#46;"
              "apellidos" => "Treiyer"
            ]
            3 => array:2 [
              "nombre" => "C&#46;"
              "apellidos" => "Cristallo"
            ]
            4 => array:2 [
              "nombre" => "M&#46;"
              "apellidos" => "Isola"
            ]
            5 => array:2 [
              "nombre" => "O&#46;"
              "apellidos" => "Damia"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0210480611003342"
        "doi" => "10.1016/j.acuro.2011.07.018"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480611003342?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578612001400?idApp=UINPBA00004N"
    "url" => "/21735786/0000003600000006/v1_201304251924/S2173578612001400/v1_201304251924/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2173578612001382"
    "issn" => "21735786"
    "doi" => "10.1016/j.acuroe.2011.09.003"
    "estado" => "S300"
    "fechaPublicacion" => "2012-06-01"
    "aid" => "389"
    "copyright" => "AEU"
    "documento" => "article"
    "crossmark" => 0
    "subdocumento" => "fla"
    "cita" => "Actas Urol Esp. 2012;36:361-6"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 1003
      "formatos" => array:3 [
        "EPUB" => 11
        "HTML" => 820
        "PDF" => 172
      ]
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Major urologic surgical procedures in locally advanced colorectal cancers"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "361"
          "paginaFinal" => "366"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Procedimientos quir&#250;rgicos urol&#243;gicos mayores en el c&#225;ncer colorrectal localmente avanzado"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "C&#46; G&#246;kta&#351;&#46;, R&#46; Horuz, M&#46; Y&#305;ld&#305;r&#305;m, G&#46; Faydac&#305;, C&#46; &#350;ahin, S&#46; Albayrak"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "C&#46;"
              "apellidos" => "G&#246;kta&#351;&#46;"
            ]
            1 => array:2 [
              "nombre" => "R&#46;"
              "apellidos" => "Horuz"
            ]
            2 => array:2 [
              "nombre" => "M&#46;"
              "apellidos" => "Y&#305;ld&#305;r&#305;m"
            ]
            3 => array:2 [
              "nombre" => "G&#46;"
              "apellidos" => "Faydac&#305;"
            ]
            4 => array:2 [
              "nombre" => "C&#46;"
              "apellidos" => "&#350;ahin"
            ]
            5 => array:2 [
              "nombre" => "S&#46;"
              "apellidos" => "Albayrak"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0210480611003937"
        "doi" => "10.1016/j.acuro.2011.09.007"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480611003937?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578612001382?idApp=UINPBA00004N"
    "url" => "/21735786/0000003600000006/v1_201304251924/S2173578612001382/v1_201304251924/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>"
    "titulo" => "Castration-resistant prostate cancer&#58; Where are we going&#63;"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "367"
        "paginaFinal" => "374"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "A&#46; Alcaraz, R&#46; Medina, P&#46; Maroto, M&#46;&#193;&#46; Climent, D&#46; Castellano, J&#46; Carles"
        "autores" => array:6 [
          0 => array:4 [
            "nombre" => "A&#46;"
            "apellidos" => "Alcaraz"
            "email" => array:1 [
              0 => "aalcaraz&#64;clinic&#46;ub&#46;es"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">¿</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "R&#46;"
            "apellidos" => "Medina"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "P&#46;"
            "apellidos" => "Maroto"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "M&#46;&#193;&#46;"
            "apellidos" => "Climent"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "D&#46;"
            "apellidos" => "Castellano"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "J&#46;"
            "apellidos" => "Carles"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">f</span>"
                "identificador" => "aff0030"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:6 [
          0 => array:3 [
            "entidad" => "Servicio de Urolog&#237;a&#44; IDIBAPS&#44; Hospital Cl&#237;nic de Barcelona&#44; Barcelona&#44; Spain"
            "etiqueta" => "<span class="elsevierStyleSup">a</span>"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Servicio de Urolog&#237;a&#44; Hospital Universitario Virgen del Roc&#237;o&#44; Sevilla&#44; Spain"
            "etiqueta" => "<span class="elsevierStyleSup">b</span>"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Servicio de Oncolog&#237;a&#44; Hospital de Sant Pau&#44; Barcelona&#44; Spain"
            "etiqueta" => "<span class="elsevierStyleSup">c</span>"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Servicio de Oncolog&#237;a&#44; Instituto Valenciano de Oncolog&#237;a&#44; Valencia&#44; Spain"
            "etiqueta" => "<span class="elsevierStyleSup">d</span>"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Servicio de Oncolog&#237;a&#44; Hospital Universitario 12 de Octubre&#44; Madrid&#44; Spain"
            "etiqueta" => "<span class="elsevierStyleSup">e</span>"
            "identificador" => "aff0025"
          ]
          5 => array:3 [
            "entidad" => "Servicio de Oncolog&#237;a&#44; Instituto de Oncolog&#237;a de la Vall d&#8217;Hebron&#44; Barcelona&#44; Spain"
            "etiqueta" => "<span class="elsevierStyleSup">f</span>"
            "identificador" => "aff0030"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "C&#225;ncer de pr&#243;stata resistente a castraci&#243;n&#58; &#191;hacia d&#243;nde vamos&#63;"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Prostate cancer &#40;PCa&#41; is the most common tumor among the western male population if we exclude skin cancer&#46; Its incidence has been increasing&#44; reaching a peak in 1992&#44; decreasing until 1995&#44; and then increasing by 1&#37; annually&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Although the considerable increase in the use of the determination of the prostate specific antigen &#40;PSA&#41; may be one of the reasons for this growth&#44; there may also be genetic and environmental factors involved&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The incorporation of the PSA determination as an early diagnostic method makes it possible to detect many cases of PCa in localized stages&#44; where surgery or radiotherapy are potentially curative&#46; However&#44; between 20 and 40&#37; of the patients undergoing local treatment will have a biochemical relapse &#40;PSA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;2<span class="elsevierStyleHsp" style=""></span>ng&#47;ml after surgery&#41;&#44; and of those&#44; between 30 and 70&#37; will develop metastases 10 years after local treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> When the PCa progresses after local treatment or is diagnosed in advanced stages&#44; the possibility of healing becomes more complicated&#46; In fact&#44; PCa is the second leading cause of cancer death in the male population in North America and the western world&#44; and the third in developing countries&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Hormone treatment allows for lasting and effective control of disease-related symptoms in its advanced stage&#46; However&#44; virtually all the patients with metastatic PCa will suffer from progression of their disease when it becomes resistant to androgen suppression&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> This situation is called castration resistance&#46; The term hormone refractory is often used interchangeably&#44; but they represent different disease situations&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Traditionally&#44; chemotherapy showed modest efficacy in castration-resistant PCa &#40;CPRC&#41;&#44; with response rates of 10&#8211;20&#37;&#44; with no impact in increased survival&#44; which was estimated around the year&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The arrival of docetaxel was a turning point in the treatment of this disease&#46; Docetaxel achieved a higher response rate and improved biochemical control by reducing PSA levels&#44; and&#44; above all&#44; a benefit in metastatic PCa survival on mitoxantrone and prednisone&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;8</span></a> Therefore&#44; the combination of docetaxel and prednisone is the treatment of choice in first line in CRPC&#46; However&#44; there is no clear alternative when progression to docetaxel occurs&#46; Recently&#44; new agents such as cabazitaxel&#44; abiraterone&#44; and sipuleucel have proved able to improve the survival of our patients&#44; both before and after docetaxel&#44; which opens new prospects in the treatment of this disease&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">This review updates the treatment of metastatic PCa in progression with castration levels of testosterone&#44; how this clinical situation is defined&#44; its prognosis and first-line treatment&#44; and new options of second-line treatment&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Definition of the terms castration-resistant prostate cancer&#47;hormone-refractory prostate cancer</span><p id="par0030" class="elsevierStylePara elsevierViewall">Classically&#44; the term hormone-refractory PCa &#40;HRPC&#41; was used to define the PCa that experiences a progression in a patient undergoing gonadal androgen deprivation&#46; However&#44; within this concept of HRPC&#44; there is great heterogeneity with different types of patients according to their clinical situation&#44; the PSA elevation&#44; the possibility or not of new hormone treatments&#44; and the presence or absence of metastases&#46; The estimated mean survival ranges from 4 years for a patient with only PSA recurrence to 9&#8211;16 months for a symptomatic patient with extensive metastatic disease&#46; Contrary to what has traditionally been thought&#44; PCa progression after gonadal suppression does not necessarily mean that the disease is androgen-independent&#46; Therefore&#44; currently&#44; the term CRPC is more often used to differentiate it from HRPC&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> as the CRPC may still be sensitive to hormone manipulations&#44; while the true HRPC would not respond to any new hormone therapy&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The CRPC can respond to second hormone maneuvers such as suppression of antiandrogens&#44; use of corticosteroids or estrogens&#44; or above all&#44; to the incorporation of new drugs with mechanisms of different hormone action&#44; such as the new agents against the androgen receptor&#44; like the MDV3100&#44; or inhibitors of the androgen synthesis through the CYP17 inhibitor pathway&#44; such as abiraterone&#46; Therefore&#44; there would be a PCa independent to castration&#44; but sensitive to hormones&#44; the CRPC&#44; which can be treated with new hormone therapies&#44; different from a PCa totally refractory to hormone treatment&#44; the HRPC&#46; Therefore&#44; a CRPC is currently defined as one that meets the criteria listed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Hormone maneuvers prior to progression</span><p id="par0040" class="elsevierStylePara elsevierViewall">Hormone treatment of PCa is based on deprivation of testosterone&#44; which can be accomplished by means of a chemical or surgical castration and associated or not with antiandrogenic treatment&#46; Both hormone manipulations can be used separately or in combination with the so-called complete androgen blockade&#46; When a patient under hormone treatment experiences an elevation of the PSA&#44; the first step to be taken must be to confirm that testosterone levels are in castration range&#44; as testosterone levels higher than desired<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> have been described in up to 11&#37; of cases treated by orchiectomy&#44; with similar figures in those treated with LHRH agonists&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">After making sure that the patient is subjected to a proper castration&#44; before a PSA rise&#44; we have several options such as&#58; &#40;a&#41; withdrawal of antiandrogens&#59;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a> &#40;b&#41; addition or substitution of other antiandrogens&#59;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> &#40;c&#41; adrenal suppressive agents&#44; such as ketoconazole<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> and corticosteroids&#59;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> &#40;d&#41; estrogens like diethylstilbestrol<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and fosfestrol&#59;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> and &#40;e&#41; new lines of research&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> such as MDV3100 and abiraterone acetate&#44; which provide new therapeutic possibilities and confirm the idea that there is a big difference between the castration-resistant stage and the hormone-resistant stage&#44; opening a new door to research into hormone treatment&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Prognostic factors</span><p id="par0050" class="elsevierStylePara elsevierViewall">One of the main problems of the patients with CRPC is the difficulty to assess the response to a treatment and establish a proper prognosis&#46; We have to take into account that in the patients with HRPC&#44; there will be different groups with very different clinical situation and prognosis&#46; Therefore&#44; we must look for markers that may be useful and provide information on the evolution and prognosis of the disease and can assess the effectiveness of a treatment&#46; Within these indicators&#44; we can differentiate clinical parameters such as pain control&#44; analgesic consumption&#44; quality of life&#44; or overall condition&#46; On the other hand&#44; among analytical factors&#44; such as hemoglobin or LDH levels&#44; there is no doubt that the serum PSA levels are the most interesting tool&#46; In recent years&#44; as a result of constant research&#44; other approaches have been developed such as determination of the number of circulating tumor cells&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Serum levels of prostate-specific antigen</span><p id="par0055" class="elsevierStylePara elsevierViewall">PSA levels prior to treatment greater than 100 or 150<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;l have been associated with a lower survival&#44; especially when combined with the presence of anemia&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Other groups have reported that a PSA doubling time greater than 80 days is associated with better treatment outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In fact&#44; in large trials like the <span class="elsevierStyleItalic">South West Oncology Group</span> &#40;SWOG 9916&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> or those conducted by the <span class="elsevierStyleItalic">Cancer and Leukemia Group B</span> &#40;CALGB&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> increases in PSA were one of the criteria that made it possible to significantly differentiate the survival of patients&#46; Reciprocally&#44; PSA declines of at least 50&#37; are also used to define response criteria&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Circulating cells of prostate cancer</span><p id="par0060" class="elsevierStylePara elsevierViewall">PCa cells can be detected in the circulation of patients with PCa by means of the determination of PSA mRNA by RT-PCR&#44; and counted by CELLSEARCH<span class="elsevierStyleSup">&#174;</span> &#40;Veridex&#44; LLC&#41;&#46; It has been reported that the number of circulating tumor cells may have prognostic significance in patients with CRPC being treated with chemotherapy&#44; and it could be useful in assessing the response to the treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> In one of the largest studies&#44; the levels of circulating tumor cells were analyzed in 231 patients with CRPC before and after receiving chemotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Those patients with 5 or more circulating tumor cells per 7&#46;5<span class="elsevierStyleHsp" style=""></span>ml before chemotherapy compared to those with less than 5 cells had a median survival significantly shorter&#44; 10 versus 21 months &#40;HR&#58; 4&#46;5&#59; CI 95&#37;&#58; 3&#8211;6&#46;7&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Similarly&#44; the changes in the number of circulating tumor cells &#40;called conversion rate&#41; during the treatment with chemotherapy are also correlated with the prognosis&#46; The patients who maintained their cell levels below 5 per 7&#46;5<span class="elsevierStyleHsp" style=""></span>ml had a median survival of 26 months&#46; By contrast&#44; those who raised their levels above 5 only reached 9 months of survival&#44; and those who did not have initially high levels and did not decrease them only survived 7 months&#46; Given the large heterogeneity among patients with CRPC&#44; their prognosis can vary significantly&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">First-line treatment</span><p id="par0070" class="elsevierStylePara elsevierViewall">Since the 70s&#44; the treatment with chemotherapy of the patients with PCa is being investigated&#46; The reviews of the initial studies with chemotherapy described 8&#46;7&#37; of objective responses&#44; but with no improvement in survival&#46; In the 90s&#44; the PSA was introduced as indirect assessment variable of response&#44; which allowed for objective assessment&#46; Another important step to estimate the effectiveness of the treatments was the introduction of parameters that made it possible to assess the palliation obtained by means of scales of quality of life&#44; pain assessment&#44; and analgesic consumption&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In 1996&#44; Tannock et al&#46; published a study evaluating a treatment with mitoxantrone 12<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> together with low-dose prednisone versus prednisone alone&#44; with the main objective of estimating the palliation obtained by means of pain relief&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> In a parallel study conducted by the CALGB&#44; a treatment with mitoxantrone 14<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> with hydrocortisone was compared to hydrocortisone alone&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Although modest&#44; the positive results of these two studies stimulated research into the role of new drugs and chemotherapy in the treatment of PCa&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The TAX 327 study was designed with the aim of assessing whether the low-dose treatment with docetaxel and corticosteroids could improve the survival obtained with mitoxantrone and prednisone&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The SWOG 9916 study compared the treatment with docetaxel and estramustine versus mitoxantrone associated with prednisone&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The results of two randomized studies indicate that treatment with docetaxel &#40;either with low-dose prednisone or with estramustine&#41; improve overall survival of these patients in a statistically significant way&#44; although with a net profit of 2&#46;5 and 2 months&#44; respectively&#46; Although the survival gain in absolute terms is modest&#44; we must not forget what could be more important&#44; as it is that a greater benefit in palliation of patients is observed&#58; pain improvement&#44; decreased consumption of analgesia&#44; and improvement in parameters of quality of life&#44; even when considering patients aged over 70&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Definition of progression</span><p id="par0085" class="elsevierStylePara elsevierViewall">The definition of progressive disease in patients with metastatic CRPC is still an unresolved issue&#46; In 2008&#44; a new consensus was reflected in a publication in order to assess the progression and assessment criteria of the disease in patients with CRPC by the <span class="elsevierStyleItalic">Prostate-Specific Antigen Working Group</span> &#40;PCWG2&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The modification of the former criteria described by the PCWG1 with these new criteria should make it possible to select the patients for inclusion in clinical trials to the maximum&#44; and so assess the effectiveness of new treatments&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">One of the main concepts introduced by the PCWG2 is that it defines 5 patterns of spread of the disease with different evolution&#44; and therefore with very different prognosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; These patients may have survival rates ranging from 9 months to 36 months&#44; so it is very important to know what percentage of each is part of a clinical trial&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Despite clarifying certain criteria&#44; most studies on CRPC use the modified PCWG2 criteria&#46; These modifications generally introduce the following changes&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0100" class="elsevierStylePara elsevierViewall">They use the RECIST 1&#46;1 guidelines&#44; and not those by the PCWG2&#44; where it is advised that adenopathies should be bigger than 2<span class="elsevierStyleHsp" style=""></span>cm&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0105" class="elsevierStylePara elsevierViewall">They use the radiological progression criteria that are not covered by the PCWG2 and that were published by the group of the <span class="elsevierStyleItalic">Memorial Sloan Kettering Cancer Center</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p></li></ul></p><p id="par0110" class="elsevierStylePara elsevierViewall">Given that in the last year different drugs that have proven useful in the treatment of CRPC once they have progressed to docetaxel appeared&#44; it is important to know which the prognostic factors to disease progression in this situation are&#46; In this regard&#44; Armstrong et al&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> have recently published a paper in which they analyzed the prognostic factors both before the start of chemotherapy with docetaxel and the progression to it&#44; which were statistically significant &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; With the selected variables of this model we can generate a nomogram that estimates the survival after progression&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> In short&#44; the definition of the different criteria for progression&#44; as well as the knowledge of the prognostic factors when it occurs&#44; are extremely important to indicate the start of new treatments or delay them in situations where they are not strictly necessary&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Second-line treatment</span><p id="par0115" class="elsevierStylePara elsevierViewall">As described above&#44; the standard first-line treatment in PCa in progression with castration levels of testosterone is docetaxel&#46; The experience in the treatment of patients to docetaxel failure is limited&#44; until the arrival of cabazitaxel and abiraterone&#44; which have shown increases in survival that will make it possible to find a standard second-line treatment&#46; The treatments that have been used in clinical practice involve some cytostatics &#40;mitoxantrone&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> retreatment with docetaxel&#44; cyclophosphamide&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> carboplatin&#44; satraplatin&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> etc&#46;&#41;&#44; along with the maximum optimization of the sustaining treatment&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The future of the second-line treatment of metastatic CRPC is encouraging&#44; given the wide range of lines of research currently underway and the variety of treatment options expected to be available&#46; In advanced stages&#44; there are the studies with new cytostatics such as cabazitaxel&#44; which are reviewed in more detail below&#59; the epothilones&#44; a new family of cytostatics which act stabilizing the polymerized microtubules disrupting the mitosis&#44; in particular ixabepilone&#44; patupilone&#44; and a derivative of the halichondrin B&#44; eribulin&#46; Studies with new hormone therapies are also advanced such as abiraterone acetate&#44; an inhibitor of the CYP17-&#945;-hydroxylase and C17&#44;20-lyase which will cause the inhibition of the CYP17 and&#44; thus&#44; the blocking of the extragonadal synthesis of androgens&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> like the MDV3100 &#40;Medivation<span class="elsevierStyleSup">&#174;</span>&#41;&#44; which acts as an inhibitor of the androgen receptor blocking their passage to the core and their activation&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> and like the SARDS&#44; selective androgen receptor degraders&#46; Sipuleucel-T &#40;Provenge&#44; Dendreon Corporation&#44; Seattle&#44; WA&#41;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> is the first immunotherapy available for the treatment of CRPC&#46; To the classical radioisotopes like samarium and strontium&#44; whose target is the bone&#44; alpharadin &#40;radium 233&#41;&#44; an alpha-emitting radioactive isotope which has shown improved survival in patients treated and not treated with docetaxel&#44; has recently been added&#46; And other research lines with agents such as Custirsen &#40;OGX-011&#41; based on the induction of the apoptosis<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> or ProstVac-V &#40;vaccine associated with poxvirus&#41;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> are also being tested&#46;</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">New cytostatics</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Cabazitaxel</span><p id="par0125" class="elsevierStylePara elsevierViewall">Cabazitaxel &#40;XRP6258&#59; TXD 258&#59; RPR116258A&#41; is a new semisynthetic taxane that has demonstrated an antitumor activity as potent as docetaxel on cell lines&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">In order to evaluate the efficacy and safety of cabazitaxel in patients with metastatic CRPC&#44; an open and randomized phase III trial&#44; called TROPIC&#44; comparing cabazitaxel versus mitoxantrone has been developed&#46; We recruited 755 patients who had progressed during &#40;30&#37;&#41; or after &#40;70&#37;&#41; treatment with docetaxel&#46; The patients were stratified according to the ECOG and presence or absence of measurable disease and randomized to receive cabazitaxel &#40;25<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> IV&#41; or mitoxantrone &#40;12<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> IV&#41;&#44; both every three weeks and in combination with 10<span class="elsevierStyleHsp" style=""></span>mg of daily oral prednisone&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">With a primary objective of overall survival&#44; cabazitaxel reached a median of 15&#46;1 months &#40;CI 95&#37;&#58; 14&#46;1&#8211;16&#46;3&#41; versus 12&#46;7 months &#40;CI 95&#37;&#58; 11&#46;6&#8211;13&#46;7&#41; of mitoxantrone&#44; with statistical significance &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; and a reduced risk of death by 30&#37; &#40;HR&#58; 0&#46;7&#59; CI 95&#37;&#58; 0&#46;59&#8211;0&#46;83&#41; in favor of cabazitaxel&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">An interesting fact is that in the subgroup analysis cabazitaxel demonstrated its benefit in survival in groups of patients with a very poor prognosis&#58; in the patients who had progressed during the treatment with docetaxel and those who had progressed within three months after having completed treatment with docetaxel&#46; This fact confirms the effectiveness of cabazitaxel regardless of the response to docetaxel&#44; and it confirms the preclinical studies demonstrating its effectiveness in cell lines resistant to docetaxel&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The secondary objectives of the study&#44; progression-free survival &#40;2&#46;8 months&#44; CI 95&#37;&#58; 2&#46;4&#8211;3&#46;0 versus 1&#46;4 months&#59; CI 95&#37;&#58; 1&#46;4&#8211;1&#46;7&#41;&#44; &#40;HR&#58; 0&#46;74&#59; CI 95&#37;&#58; 0&#46;64&#8211;0&#46;86&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#44; response rate &#40;14&#46;4 versus 4&#46;4&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0005&#41;&#44; and PSA response rate &#40;39&#46;2 versus 17&#46;8&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0002&#41; were also favorable to the cabazitaxel&#46; Other secondary objectives like pain reduction were similar in both arms &#40;9&#46;2&#37; for cabazitaxel versus 7&#46;7&#37; with mitoxantrone&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">In the future&#44; the possibility to associate cabazitaxel with the new generation of hormone therapy such as abiraterone or MDV3100 remains open&#44; as there may be a synergism&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">New hormone therapies</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Abiraterone</span><p id="par0155" class="elsevierStylePara elsevierViewall">PCa can maintain the signal activated mediated by the androgen receptor despite having suitable castration levels&#46; One of the escapes is established by means of the overexpression of the cytochrome P-450c17 &#40;CYP17&#41;&#44; a key enzyme for the synthesis of extragonadal androgens&#44; at the adrenal&#44; prostate&#44; and intratumoral level&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The abiraterone acetate is an inhibitor of the CYP17-&#945;-hydroxylase and the C17&#44; 20-lyase that will cause the inhibition of CYP17 and&#44; therefore&#44; it is capable of blocking the extragonadal synthesis of androgens&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The results of a phase III multicenter study that compared the efficacy of abiraterone and prednisone versus placebo and prednisone in patients with CRPC in progression after receiving docetaxel<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> have recently been published&#46; The abiraterone was statistically superior in survival to placebo&#44; 14&#46;8 versus 10&#46;9 &#40;HR&#58; 0&#46;65&#59; CI 95&#37;&#58; 0&#46;54&#8211;0&#46;77&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; months&#44; which was associated with a 35&#37; reduced risk of death&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Furthermore&#44; the abiraterone obtained an increase in the response rate and the progression-free survival according to the PSA and the radiological findings&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The abiraterone was well tolerated&#46; Some mineralocorticoid-related adverse events&#44; including fluid retention&#44; hypertension&#44; and hypokalemia were more frequent in the abiraterone acetate and prednisone group versus the placebo and prednisone group&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Consequently&#44; the abiraterone was approved by the FDA in April 2011&#44; and in September 2011 by the EMA&#44; for PCa patients previously treated with docetaxel&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">MDV3100</span><p id="par0185" class="elsevierStylePara elsevierViewall">Other hormonal agents like MDV3100 &#40;Medivation<span class="elsevierStyleSup">&#174;</span>&#41; have a completely different action&#44; acting as an androgen receptor inhibitor that blocks its passage to the core and its activation&#46; After a phase I&#47;II trial which obtained 56&#37; of responses depending on PSA declines and 22&#37; of radiological responses&#59;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> its effectiveness is being confirmed in two phase III studies&#44; one of them to the progression of docetaxel &#40;AFFIRM&#41;&#44; which has been closed with the interim analysis when demonstrating a significant survival increase with MDV3100 and the other one prior to the administration of docetaxel in patients minimally symptomatic or asymptomatic &#40;PREVAIL&#41;&#44; which is underway&#46;</p></span></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Treatment of skeletal-related events associated with bone metastases</span><p id="par0190" class="elsevierStylePara elsevierViewall">So far&#44; we have used zoledronic acid &#40;bisphosphonates&#41; for the prevention of ERS&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> but in July 2011&#44; denosumab&#44; with a novel mechanism of action&#44; has been approved by the EMA&#46; Denosumab is a human monoclonal antibody against RANKL that has shown better results than zoledronic acid in a phase III study in 1904 patients with CRPC for the prevention of ERS&#58; the median time to onset of the first skeletal-related event was 20&#46;7 months &#40;CI 95&#37;&#58; 18&#46;8&#8211;24&#46;9&#41; with denosumab compared with 17&#46;1 months &#40;15&#46;0&#8211;19&#46;4&#41; with zoledronic acid&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusions</span><p id="par0195" class="elsevierStylePara elsevierViewall">The CRPC treatment has rested on second hormone maneuvers&#44; which have not shown increase in survival&#44; and in the treatment with docetaxel&#44; which prolongs survival modestly with a significant improvement of pain and quality of life&#46; There were no contrasting treatments after failure to docetaxel&#46; Fortunately&#44; the PCa therapeutic horizon opens dramatically with the advent of new drugs such as cabazitaxel&#44; abiraterone&#44; sipuleucel T&#44; alpharadin&#44; MDV3100&#44; etc&#46;&#44; which will probably keep changing the course of this disease positively&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> Cabazitaxel is presented as a reality&#44; with FDA &#40;June 2010&#41; and EMA &#40;March 2011&#41; approval in the treatment of metastatic CRPC in progression to docetaxel&#44; and it is considered the standard treatment of choice&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> With some more delay&#44; abiraterone&#44; approved by the FDA &#40;April 2011&#41; and the EMA &#40;September 2011&#41;&#44; has the same indication&#46; So far&#44; cabazitaxel and in the near future abiraterone have proven effective drugs in the second-line treatment after progression to docetaxel&#44; adding more than 2&#8211;4 months of survival and reducing the risk of death by 30&#8211;35&#37;&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0200" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:15 [
        0 => array:2 [
          "identificador" => "xres101693"
          "titulo" => array:6 [
            0 => "Abstract"
            1 => "Context"
            2 => "Objective"
            3 => "Evidence acquisition"
            4 => "Evidence synthesis"
            5 => "Conclusions"
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec88859"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "xres101692"
          "titulo" => array:6 [
            0 => "Resumen"
            1 => "Contexto"
            2 => "Objetivo"
            3 => "Adquisici&#243;n de la evidencia"
            4 => "S&#237;ntesis de la evidencia"
            5 => "Conclusiones"
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec88860"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Definition of the terms castration-resistant prostate cancer&#47;hormone-refractory prostate cancer"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Hormone maneuvers prior to progression"
        ]
        7 => array:3 [
          "identificador" => "sec0020"
          "titulo" => "Prognostic factors"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Serum levels of prostate-specific antigen"
            ]
            1 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Circulating cells of prostate cancer"
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "First-line treatment"
        ]
        9 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Definition of progression"
        ]
        10 => array:3 [
          "identificador" => "sec0045"
          "titulo" => "Second-line treatment"
          "secciones" => array:2 [
            0 => array:3 [
              "identificador" => "sec0050"
              "titulo" => "New cytostatics"
              "secciones" => array:1 [
                0 => array:2 [
                  "identificador" => "sec0055"
                  "titulo" => "Cabazitaxel"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "sec0060"
              "titulo" => "New hormone therapies"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0065"
                  "titulo" => "Abiraterone"
                ]
                1 => array:2 [
                  "identificador" => "sec0070"
                  "titulo" => "MDV3100"
                ]
              ]
            ]
          ]
        ]
        11 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Treatment of skeletal-related events associated with bone metastases"
        ]
        12 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Conclusions"
        ]
        13 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conflict of interest"
        ]
        14 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2011-10-03"
    "fechaAceptado" => "2011-10-17"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec88859"
          "palabras" => array:5 [
            0 => "Metastatic prostate cancer"
            1 => "Castration-resistant prostate cancer"
            2 => "Hormonal therapies"
            3 => "Progression"
            4 => "Cabazitaxel"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec88860"
          "palabras" => array:5 [
            0 => "C&#225;ncer de pr&#243;stata metast&#225;sico"
            1 => "C&#225;ncer de pr&#243;stata resistente a castraci&#243;n"
            2 => "Terapias hormonales"
            3 => "Progresi&#243;n"
            4 => "Cabazitaxel"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Context</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hormonal therapy allows effective control of cancer-related symptoms in advanced stages&#46; However&#44; the disease will progress in almost all these metastatic prostate cancer patient until becoming resistant to androgen suppression&#46; The emergence of new drugs will most probably have open up new expectations regarding the treatment of this cancer&#46;</p> <span class="elsevierStyleSectionTitle">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The aim of the present review has been to provide an overview of the current status of castration-resistant prostate cancer and to share the high expectations created with the new treatments&#46;</p> <span class="elsevierStyleSectionTitle">Evidence acquisition</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Evidence was obtained from multidisciplinary meetings with the participation of urologists and oncologists&#44; where they pooled the analysis of original articles in the literature and defined the content of the article&#46;</p> <span class="elsevierStyleSectionTitle">Evidence synthesis</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Chemotherapy with docetaxel was a turning point in castration-resistant prostate cancer after the failure of hormonal therapy failure&#46; For the first time&#44; it achieved increased survival time in comparison with mitoxantrone and prednisone&#46; Combination therapy with docetaxel and prednisone is the first-line choice treatment&#46; Once the cancer has progressed&#44; there is no clear alternative&#44; although some novel agents have created expectations for the treatment of this type of cancer&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The range of therapeutic options for castration-resistant prostate cancer has increased dramatically with the arrival of new drugs&#46; At present&#44; cabazitaxel&#44; and in the near future&#44; abiraterone&#44; have been found to be effective drugs in second-line treatment after progression to docetaxel&#44; increasing survival by 2&#8211;4 months and reducing risk of death by 30&#8211;35&#37;&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Contexto</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El tratamiento hormonal permite un control eficaz de los s&#237;ntomas relacionados con el c&#225;ncer de pr&#243;stata metast&#225;sico&#59; sin embargo&#44; la pr&#225;ctica totalidad de estos pacientes sufrir&#225;n progresi&#243;n de su enfermedad cuando esta se hace resistente a la supresi&#243;n androg&#233;nica&#46; La aparici&#243;n de nuevos f&#225;rmacos permite abrir nuevas expectativas en el tratamiento de esta enfermedad&#46;</p> <span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Elaborar un documento de revisi&#243;n sobre la situaci&#243;n actual del c&#225;ncer de pr&#243;stata resistente a castraci&#243;n y compartir las grandes expectativas que se muestran con los nuevos tratamientos&#46;</p> <span class="elsevierStyleSectionTitle">Adquisici&#243;n de la evidencia</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Reuniones multidisciplinares con la participaci&#243;n de ur&#243;logos y onc&#243;logos&#44; donde se pusieron en com&#250;n el an&#225;lisis bibliogr&#225;fico de art&#237;culos originales y se defini&#243; el contenido del art&#237;culo&#46;</p> <span class="elsevierStyleSectionTitle">S&#237;ntesis de la evidencia</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Tras el fracaso de la hormonoterapia&#44; la quimioterapia con docetaxel supuso un punto de inflexi&#243;n en el c&#225;ncer de pr&#243;stata resistente a castraci&#243;n&#44; consiguiendo por primera vez beneficio en la supervivencia sobre mitoxantrone y prednisona&#46; La combinaci&#243;n de docetaxel y prednisona es el tratamiento de elecci&#243;n en primera l&#237;nea&#46; Cuando progresa no hay alternativa clara&#44; aunque nuevos agentes est&#225;n generando expectativas en el tratamiento de esta enfermedad&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">El horizonte terap&#233;utico del c&#225;ncer de pr&#243;stata resistente a la castraci&#243;n se abre de forma espectacular con la llegada de nuevos f&#225;rmacos&#46; Por el momento&#44; cabazitaxel y en el futuro pr&#243;ximo abiraterona se han mostrado como f&#225;rmacos eficaces en el tratamiento de segunda l&#237;nea tras la progresi&#243;n a docetaxel&#44; a&#241;adiendo m&#225;s de 2-4 meses de supervivencia y reduciendo un 30-35&#37; el riesgo de muerte&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara">Please cite this article&#58; Alcaraz A&#44; et al&#46; C&#225;ncer de pr&#243;stata resistente a castraci&#243;n&#58; &#191;hacia d&#243;nde vamos&#63; Actas Urol Esp&#46; 2012&#59;36&#58;367&#8211;74&#46;</p>"
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">RECIST&#58; Response Evaluation Criteria In Solid Tumors&#59; PSA&#58; prostate specific antigen&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Levels of testosterone considered of castration &#40;testosterone &#60;50<span class="elsevierStyleHsp" style=""></span>ng&#47;dl or &#60;1&#46;7<span class="elsevierStyleHsp" style=""></span>nmol&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Three consecutive PSA elevations&#44; separated by at least a week&#44; resulting in two increases by 50&#37; on the nadir with a PSA greater than 2<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antiandrogen suppression of at least 4 weeks or a second hormone manipulation made&#44; with PSA progression &#40;despite consecutive hormone manipulations&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Progression of bone lesions&#44; two or more in bone scans&#44; or progression of the soft tissue lesions according to RECIST criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab184244.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Criteria that define castration-resistant prostate cancer &#40;CRPC&#41;&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "Source&#58; Park et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>"
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">HRPC&#58; hormone-refractory prostate cancer&#59; CRPC&#58; castration-resistant prostate cancer&#59; PCWG2&#58; Prostate Cancer Clinical Trials Working Group 2&#59; PET&#58; positron emission tomography&#59; PSA&#58; prostate specific antigen&#59; RECIST&#58; Response Evaluation Criteria in Solid Tumors&#59; MRI&#58; magnetic resonance imaging&#59; CT&#58; computed tomography&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">PCWG2 criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Assess PSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Obtain the sequence of elevation of the values at least at weekly intervals&#46; Minimum initial value 2&#46;0<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; Assess the pretreatment PSA doubling time if there are 3 or more values separated every 4 weeks or more&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Measurable disease or types of target&#44; nodal&#44; or visceral lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The presence of nodal or visceral lesions is enough to enter a study regardless of the PSA&#46; No measurable lesions are required for inclusion&#46; Use RECIST criteria to assess the soft tissue lesions &#40;nodal or visceral&#41; as target or non-target&#46; Only &#8805;2<span class="elsevierStyleHsp" style=""></span>cm diameter lymph nodes should be considered to assess their change in size&#46; Record the presence of nodal and&#47;or visceral disease separately&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary location of the tumor in the prostate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Register prior therapeutic treatment of the primary tumor&#46; Perform pelvic imaging scans &#40;CT&#44; MRI&#44; PET&#47;CT&#44; endorectal MRI&#44; transrectal ultrasound&#41; to document the presence or absence of disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Progression is considered when there are two or more new lesions&#46; Confirm the ambiguous results with other imaging tests &#40;CT or MRI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Other locations of the disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with epidural lesions treated without epidural progression are eligible if another criteria for inclusion is met&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prior hormone maneuvers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The addition or deletion of hormone therapy with therapeutic intention due to existence of disease progression is considered maneuver or hormone intervention&#46; Collect all the history of received hormone therapy&#44; number&#44; type&#44; and duration of the same&#46; Classify a PCa in progression with levels of testosterone in castration such as CRPC and not HRPC&#44; because patients may respond to new hormone maneuvers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serum levels of testosterone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">We consider patient in castration range with testosterone levels below 50<span class="elsevierStyleHsp" style=""></span>ng&#47;dl &#40;&#62;1&#46;7<span class="elsevierStyleHsp" style=""></span>nmol&#47;l&#41;&#46; There may be interlaboratory variability&#46; The importance of maintaining testosterone levels in castration range in patients not undergoing orchiectomy is reaffirmed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Response to antiandrogenic treatment suppression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PCWG1 criterion is confirmed &#40;because the antiandrogen withdrawal may produce response in patient with PCa in alleged progression it was recommended to wait for a period of 4&#8211;8 weeks before entering a clinical trial&#41;&#44; but it is not recommended to wait such a long time for the suppression of the antiandrogen in patients who do not respond or who showed PSA decline of three months or less after the antiandrogen&#44; whether administered as second-line therapy or as a late intervention&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Previously administered nonhormone treatments&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Collect the local treatments&#44; surgery or radiotherapy&#44; or systemics administered&#44; docetaxel or biological therapies&#44; type&#44; and duration thereof&#44; including reasons for suppression&#44; response presented&#44; and interval without treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab184246.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Criteria for progression and assessment of the disease in CRPC &#40;PCWG2&#41;&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "Source&#58; Park et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>"
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">a&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Local tumor progression without metastatic disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">b&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased PSA in patient at testosterone suppression but without metastatic involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">c&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nodal spread but without evidence of bone or visceral involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">d&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bone involvement with or without lymph node involvement&#44; but without visceral metastases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">e&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Visceral metastases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab184245.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Patient groups according to prognosis and natural history of the CRPC &#40;PCWG2&#41;&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "Source&#58; Scher et al&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>"
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">CTX&#58; chemotherapy&#59; PSA&#58; prostate specific antigen&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">PreCTX variables</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Overall health &#40;Karnofsky&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Alkaline phosphatase level&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Number of metastatic sites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Presence of metastatic sites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hemoglobin values&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>PSA value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Period of time from to diagnosis &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">PostCTX variables</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Progression in the first line of CTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Number of factors of progression &#40;PSA&#44; pain&#44; radiological&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Number of three-week cycles of first line CTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab184247.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Prognostic factors of progression in CRPC&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:44 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global cancer statistics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Jemal"
                            1 => "F&#46; Bray"
                            2 => "M&#46;M&#46; Center"
                            3 => "J&#46; Ferlay"
                            4 => "E&#46; Ward"
                            5 => "D&#46; Forman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3322/caac.20107"
                      "Revista" => array:6 [
                        "tituloSerie" => "CA Cancer J Clin"
                        "fecha" => "2011"
                        "volumen" => "61"
                        "paginaInicial" => "69"
                        "paginaFinal" => "90"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21296855"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The changing face of prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;R&#46; Cooperberg"
                            1 => "J&#46;W&#46; Moul"
                            2 => "P&#46;R&#46; Carroll"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2005.02.9751"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2005"
                        "volumen" => "23"
                        "paginaInicial" => "8146"
                        "paginaFinal" => "8151"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16278465"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of biochemical recurrence in prostate cancer among US veterans"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46;M&#46; Uchio"
                            1 => "M&#46; Aslan"
                            2 => "C&#46;K&#46; Wells"
                            3 => "J&#46; Calderone"
                            4 => "J&#46; Concato"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/archinternmed.2010.262"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Intern Med"
                        "fecha" => "2010"
                        "volumen" => "170"
                        "paginaInicial" => "1390"
                        "paginaFinal" => "1395"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20696967"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A re-evaluation of nonhormonal cytotoxic chemotherapy in the treatment of prostatic carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46;A&#46; Eisenberger"
                            1 => "R&#46; Simon"
                            2 => "P&#46;J&#46; O&#8217;Dwyer"
                            3 => "H&#46;A&#46; Friedman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/jco.1985.3.6.827"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "1985"
                        "volumen" => "3"
                        "paginaInicial" => "827"
                        "paginaFinal" => "841"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2409240"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cytotoxic chemotherapy for advanced hormone-resistant prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Yagoda"
                            1 => "D&#46; Petrylak"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "1993"
                        "volumen" => "71"
                        "paginaInicial" => "1098"
                        "paginaFinal" => "1109"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7679039"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "On behalf of the TAX 327 Investigators"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46;F&#46; Tannock"
                            1 => "R&#46; de Wit"
                            2 => "W&#46;R&#46; Berry"
                            3 => "J&#46; Horti"
                            4 => "A&#46; Pluzanska"
                            5 => "K&#46;N&#46; Chi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa040720"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2004"
                        "volumen" => "351"
                        "paginaInicial" => "1502"
                        "paginaFinal" => "1512"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15470213"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;P&#46; Petrylak"
                            1 => "C&#46;M&#46; Tangen"
                            2 => "M&#46;H&#46; Hussain"
                            3 => "P&#46;N&#46; Lara"
                            4 => "J&#46;A&#46; Jones"
                            5 => "M&#46;E&#46; Taplin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa041318"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2004"
                        "volumen" => "351"
                        "paginaInicial" => "1513"
                        "paginaFinal" => "1520"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15470214"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Quality of life and pain in advanced stage prostate cancer&#58; results of a Southwest Oncology Group randomized trial comparing docetaxel and estramustine to mitoxantrone and prednisone"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;L&#46; Berry"
                            1 => "C&#46;M&#46; Moinpour"
                            2 => "C&#46;S&#46; Jiang"
                            3 => "D&#46;P&#46; Ankerst"
                            4 => "D&#46;P&#46; Petrylak"
                            5 => "L&#46;V&#46; Vinson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2005.04.8207"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2006"
                        "volumen" => "24"
                        "paginaInicial" => "2828"
                        "paginaFinal" => "2835"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16782921"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer&#58; a Canadian randomized trial with palliative end points"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46;F&#46; Tannock"
                            1 => "D&#46; Osoba"
                            2 => "M&#46;R&#46; Stockler"
                            3 => "D&#46;S&#46; Ernst"
                            4 => "A&#46;J&#46; Neville"
                            5 => "M&#46;J&#46; Moore"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/jco.1996.14.6.1756"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "1996"
                        "volumen" => "14"
                        "paginaInicial" => "1756"
                        "paginaFinal" => "1764"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8656243"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Novel secondary hormonal therapy in advanced prostate cancer&#58; an update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46;M&#46; Van Allen"
                            1 => "C&#46;J&#46; Ryan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MOU.0b013e328329b73a"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Urol"
                        "fecha" => "2009"
                        "volumen" => "19"
                        "paginaInicial" => "315"
                        "paginaFinal" => "321"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19342958"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients&#58; a phase III trial &#40;CALBG 9583&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;J&#46; Small"
                            1 => "S&#46; Halabi"
                            2 => "N&#46;A&#46; Dawson"
                            3 => "W&#46;M&#46; Stadler"
                            4 => "B&#46;I&#46; Rini"
                            5 => "J&#46; Picus"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2004.06.037"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2004"
                        "volumen" => "22"
                        "paginaInicial" => "1025"
                        "paginaFinal" => "1033"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15020604"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antiandrogen withdrawal in castrate-refractory prostate cancer&#58; a Southwest Oncology Group trial &#40;SWOG 9426&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;O&#46; Sartor"
                            1 => "C&#46;M&#46; Tangen"
                            2 => "M&#46;H&#46; Hussain"
                            3 => "M&#46;A&#46; Eisenberger"
                            4 => "M&#46; Parab"
                            5 => "J&#46;A&#46; Fontana"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cncr.23473"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "2008"
                        "volumen" => "112"
                        "paginaInicial" => "2393"
                        "paginaFinal" => "2400"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18383517"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High dose bicalutamide for androgen-independent prostate cancer&#58; effect of prior hormonal therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Joyce"
                            1 => "M&#46;A&#46; Fenton"
                            2 => "P&#46; Rode"
                            3 => "M&#46; Constantine"
                            4 => "L&#46; Gaynes"
                            5 => "G&#46; Kolvenbag"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Urol"
                        "fecha" => "1998"
                        "volumen" => "159"
                        "paginaInicial" => "149"
                        "paginaFinal" => "153"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9400459"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term outcome with androgen independent prostate cancer treated with ketoconazole and hidrocortisone"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Scholtz"
                            1 => "R&#46; Jennrich"
                            2 => "S&#46; Strum"
                            3 => "S&#46; Brosman"
                            4 => "H&#46; Johnson"
                            5 => "R&#46; Lam"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.ju.0000158449.83022.40"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Urol"
                        "fecha" => "2005"
                        "volumen" => "173"
                        "paginaInicial" => "1947"
                        "paginaFinal" => "1952"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15879788"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of prednisone on prostate-specific antigen in patients with hormone-refractory prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "O&#46; Sartor"
                            1 => "M&#46; Weinberger"
                            2 => "A&#46; Moore"
                            3 => "A&#46; Li"
                            4 => "W&#46;D&#46; Figg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Urology"
                        "fecha" => "1998"
                        "volumen" => "52"
                        "paginaInicial" => "252"
                        "paginaFinal" => "256"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9697790"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prospective&#44; multicentre&#44; randomized phase II trial of the herbal supplement PC-SPES and diethylbestrol in patients with androgen-independent prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;K&#46; Oh"
                            1 => "P&#46;W&#46; Kanthoff"
                            2 => "V&#46; Weinberg"
                            3 => "G&#46; Jones"
                            4 => "B&#46;I&#46; Rini"
                            5 => "M&#46;K&#46; Derynck"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Oncol"
                        "fecha" => "2004"
                        "volumen" => "22"
                        "paginaInicial" => "3705"
                        "paginaFinal" => "3712"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low dose continuous oral fosfestrol is highly active in hormone refractory prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Orlando"
                            1 => "A&#46; Chacon"
                            2 => "G&#46; Salum"
                            3 => "D&#46;R&#46; Chacon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2000"
                        "volumen" => "11"
                        "paginaInicial" => "177"
                        "paginaFinal" => "181"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10761752"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current management of castrate-resistant prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46;J&#46; Hotte"
                            1 => "F&#46; Saad"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Curr Oncol"
                        "fecha" => "2001"
                        "volumen" => "17"
                        "numero" => "Suppl&#46; 2"
                        "paginaInicial" => "S72"
                        "paginaFinal" => "S79"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20882137"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prostate specific-antigen and other prognostic factors in patients with hormone-resistant prostatic cancer undergoing experimental treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46;D&#46; Fossa"
                            1 => "E&#46; Paus"
                            2 => "M&#46; Lindegaard"
                            3 => "D&#46;W&#46; Newling"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Urol"
                        "fecha" => "1992"
                        "volumen" => "69"
                        "paginaInicial" => "175"
                        "paginaFinal" => "179"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1371425"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tumor marker doubling time in patients with prostate cancer&#58; determination of prostate-specific antigen and prostatic acid phosphatase doubling time"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46; Akimoto"
                            1 => "M&#46; Masai"
                            2 => "K&#46; Akakura"
                            3 => "J&#46; Shimazaki"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Urol"
                        "fecha" => "1995"
                        "volumen" => "27"
                        "paginaInicial" => "207"
                        "paginaFinal" => "212"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7541360"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prostate-specific antigen progression predicts overall survival in patients with metastatic prostate cancer&#58; data from Southwest Oncology Group Trials 9346 &#40;Intergroup Study 0162&#41; and 9916"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Hussain"
                            1 => "B&#46; Goldman"
                            2 => "C&#46; Tangen"
                            3 => "C&#46;S&#46; Higano"
                            4 => "D&#46;P&#46; Petrylak"
                            5 => "G&#46; Wilding"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2008.19.9810"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2009"
                        "volumen" => "27"
                        "paginaInicial" => "2450"
                        "paginaFinal" => "2456"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19380444"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Progression-free survival as a predictor of overall survival in men with castrate-resistant prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; Halabi"
                            1 => "N&#46;J&#46; Vogelzang"
                            2 => "S&#46;S&#46; Ou"
                            3 => "K&#46; Owzar"
                            4 => "L&#46; Archer"
                            5 => "E&#46;J&#46; Small"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2008.18.9159"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2009"
                        "volumen" => "27"
                        "paginaInicial" => "2766"
                        "paginaFinal" => "2771"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19380448"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "PSA surge&#47;flare-up in patients with castration-refractory prostate cancer during the initial phase of chemotherapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "T&#46; Nelius"
                            1 => "S&#46; Filleur"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/pros.21024"
                      "Revista" => array:6 [
                        "tituloSerie" => "Prostate"
                        "fecha" => "2009"
                        "volumen" => "69"
                        "paginaInicial" => "1802"
                        "paginaFinal" => "1807"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19676083"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;C&#46; Danila"
                            1 => "G&#46; Heller"
                            2 => "G&#46;A&#46; Gignac"
                            3 => "R&#46; Gonzalez-Espinoza"
                            4 => "A&#46; Anand"
                            5 => "E&#46; Tanaka"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1158/1078-0432.CCR-07-1506"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Cancer Res"
                        "fecha" => "2007"
                        "volumen" => "13"
                        "paginaInicial" => "7053"
                        "paginaFinal" => "7058"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18056182"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Halabi"
                            1 => "E&#46;J&#46; Small"
                            2 => "P&#46;W&#46; Kantoff"
                            3 => "M&#46;W&#46; Kattan"
                            4 => "E&#46;B&#46; Kaplan"
                            5 => "N&#46;A&#46; Dawson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2003.06.100"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2003"
                        "volumen" => "21"
                        "paginaInicial" => "1232"
                        "paginaFinal" => "1237"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12663709"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer&#58; results of the cancer and leukemia group B9182 study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;W&#46; Kantoff"
                            1 => "S&#46; Halabi"
                            2 => "M&#46; Conaway"
                            3 => "J&#46; Picus"
                            4 => "J&#46; Kirshner"
                            5 => "V&#46; Hars"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/jco.1999.17.8.2506"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "1999"
                        "volumen" => "17"
                        "paginaInicial" => "2506"
                        "paginaFinal" => "2513"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10561316"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Docetaxel-based systemic chemotherapy in elderly Korean men with castration-resistant prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46;C&#46; Park"
                            1 => "J&#46;W&#46; Lee"
                            2 => "J&#46;S&#46; Rim"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.acuro.2011.09.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "Actas Urol Esp"
                        "fecha" => "2012"
                        "volumen" => "36"
                        "paginaInicial" => "425"
                        "paginaFinal" => "430"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22386299"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone&#58; recommendations of the Prostate Cancer Clinical Trials Working Group"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "Prostate Cancer Clinical Trials Working Group"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46;I&#46; Scher"
                            1 => "S&#46; Halabi"
                            2 => "I&#46; Tannock"
                            3 => "M&#46; Morris"
                            4 => "C&#46;N&#46; Sternberg"
                            5 => "M&#46;A&#46; Carducci"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2007.12.4487"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2008"
                        "volumen" => "26"
                        "paginaInicial" => "1148"
                        "paginaFinal" => "1159"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18309951"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The association between measures of progression and survival in castrate metastatic prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "H&#46;I&#46; Scher"
                            1 => "M&#46; Warren"
                            2 => "G&#46; Heller"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1158/1078-0432.CCR-06-1885"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Cancer Res"
                        "fecha" => "2007"
                        "volumen" => "13"
                        "paginaInicial" => "1488"
                        "paginaFinal" => "1492"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17332293"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prediction of survival following first line chemotherapy in men with castration resistant metastatic prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;J&#46; Armstrong"
                            1 => "E&#46; Garret-Mayer"
                            2 => "R&#46; de Wit"
                            3 => "I&#46; Tannock"
                            4 => "M&#46; Eisenberger"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1158/1078-0432.CCR-09-2514"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Cancer Res"
                        "fecha" => "2010"
                        "volumen" => "16"
                        "paginaInicial" => "203"
                        "paginaFinal" => "211"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20008841"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Survival and PSA response of patients in the TAX 327 study who crossed over to receive docetaxel after mitoxantrone or vice versa"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46;R&#46; Berthold"
                            1 => "G&#46;R&#46; Pond"
                            2 => "R&#46; de Wit"
                            3 => "M&#46; Eisenberger"
                            4 => "I&#46;F&#46; Tannock"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/annonc/mdn288"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2008"
                        "volumen" => "19"
                        "paginaInicial" => "1749"
                        "paginaFinal" => "1753"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18487550"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and pharmacodynamic evaluation of metronomic cyclophosphamide&#44; celecoxib and dexamethasone in advanced hormone-refractory prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Fontana"
                            1 => "L&#46; Galli"
                            2 => "A&#46; Fioravanti"
                            3 => "P&#46; Orlandi"
                            4 => "C&#46; Galli"
                            5 => "L&#46; Landi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1158/1078-0432.CCR-08-3317"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Cancer Res"
                        "fecha" => "2009"
                        "volumen" => "15"
                        "paginaInicial" => "4954"
                        "paginaFinal" => "4962"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19622584"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Satraplatin demonstrates a significant clinical benefit in patients with HRPC&#58; Results of a randomized phase III trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;N&#46; Sternberg"
                            1 => "D&#46; Petrylak"
                            2 => "F&#46; Witjes"
                            3 => "J&#46; Ferrero"
                            4 => "J&#46; Eymard"
                            5 => "S&#46; Falcon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2007.11.8711"
                      "Revista" => array:6 [
                        "titulo" => "2007 ASCO Annual Meeting Proceedings Part I"
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2007"
                        "volumen" => "25"
                        "paginaInicial" => "5019"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17971602"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Abiraterone and increased survival in metastatic prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;S&#46; de Bono"
                            1 => "C&#46;J&#46; Logothetis"
                            2 => "A&#46; Molina"
                            3 => "K&#46; Fizazi"
                            4 => "S&#46; North"
                            5 => "L&#46; Chu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1014618"
                      "Revista" => array:7 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2011"
                        "volumen" => "364"
                        "paginaInicial" => "1995"
                        "paginaFinal" => "2005"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21612468"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1130862110002019"
                          "estado" => "S300"
                          "issn" => "11308621"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antitumour activity of MDV3100 in castration-resistant prostate cancer&#58; a phase 1&#8211;2 study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46;I&#46; Scher"
                            1 => "T&#46;M&#46; Beer"
                            2 => "C&#46;S&#46; Higano"
                            3 => "A&#46; Anand"
                            4 => "M&#46;E&#46; Taplin"
                            5 => "E&#46; Efstathiou"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(10)60172-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2010"
                        "volumen" => "375"
                        "paginaInicial" => "1437"
                        "paginaFinal" => "1446"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20398925"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sipuleucel-T immunotherapy for castration-resistant prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;W&#46; Kantoff"
                            1 => "C&#46;S&#46; Higano"
                            2 => "N&#46;D&#46; Shore"
                            3 => "E&#46;R&#46; Berger"
                            4 => "E&#46;J&#46; Small"
                            5 => "D&#46;F&#46; Penson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1001294"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2010"
                        "volumen" => "363"
                        "paginaInicial" => "411"
                        "paginaFinal" => "422"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20818862"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Randomized phase II study of docetaxel and prednisone with or without OGX-011 in patients with metastatic castration-resistant prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;N&#46; Chi"
                            1 => "S&#46;J&#46; Hotte"
                            2 => "E&#46;Y&#46; Yu"
                            3 => "D&#46; Tu"
                            4 => "B&#46;J&#46; Eigl"
                            5 => "I&#46; Tannock"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2009.26.8771"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2010"
                        "volumen" => "28"
                        "paginaInicial" => "4247"
                        "paginaFinal" => "4254"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20733135"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA targeted immunotherapy in metastatic castration-resistant prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;W&#46; Kantoff"
                            1 => "T&#46;J&#46; Schuetz"
                            2 => "B&#46;A&#46; Blumenstein"
                            3 => "L&#46;M&#46; Glode"
                            4 => "D&#46;L&#46; Bilhartz"
                            5 => "M&#46; Wyand"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2009.25.0597"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2010"
                        "volumen" => "28"
                        "paginaInicial" => "1099"
                        "paginaFinal" => "1105"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20100959"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Update on tubulin binding agents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "G&#46; Attard"
                            1 => "A&#46; Greystoke"
                            2 => "S&#46; Kaye"
                            3 => "J&#46; de Bono"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Pathol Biol &#40;Paris&#41;"
                        "fecha" => "2006"
                        "volumen" => "54"
                        "paginaInicial" => "72"
                        "paginaFinal" => "84"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment&#58; a randomized open-label trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;S&#46; de Bono"
                            1 => "S&#46; Oudard"
                            2 => "M&#46; Ozguroglu"
                            3 => "S&#46; Hansen"
                            4 => "J&#46;P&#46; Machiels"
                            5 => "I&#46; Kocak"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(10)61389-X"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2010"
                        "volumen" => "376"
                        "paginaInicial" => "1147"
                        "paginaFinal" => "1154"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20888992"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efectividad y tolerabilidad del &#225;cido zoledr&#243;nico en el tratamiento del c&#225;ncer de pr&#243;stata metast&#225;sico"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;M&#46; C&#243;zar-Olmo"
                            1 => "J&#46; Carballido Rodriguez"
                            2 => "P&#46; Luque G&#225;lvez"
                            3 => "A&#46;G&#46; Tabernero G&#243;mez"
                            4 => "A&#46; Barreiro Mouro"
                            5 => "E&#46; S&#225;nchez S&#225;nchez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Actas Urol Esp"
                        "fecha" => "2008"
                        "volumen" => "32"
                        "paginaInicial" => "492"
                        "paginaFinal" => "501"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18604999"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer&#58; a randomised&#44; double-blind study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Fizazi"
                            1 => "M&#46; Carducci"
                            2 => "M&#46; Smith"
                            3 => "R&#46; Dami&#227;o"
                            4 => "J&#46; Brown"
                            5 => "L&#46; Karsh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(10)62344-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2011"
                        "volumen" => "377"
                        "paginaInicial" => "813"
                        "paginaFinal" => "822"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21353695"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gu&#237;a de la EAU sobre c&#225;ncer de pr&#243;stata&#46; Parte II&#58; tratamiento del c&#225;ncer avanzado&#44; recidivante y resistente a la castraci&#243;n"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Mottet"
                            1 => "J&#46; Bellmunt"
                            2 => "M&#46; Bolla"
                            3 => "S&#46; Joniau"
                            4 => "M&#46; Mason"
                            5 => "V&#46; Matveev"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.acuro.2011.03.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "Actas Urol Esp"
                        "fecha" => "2011"
                        "volumen" => "35"
                        "paginaInicial" => "565"
                        "paginaFinal" => "579"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21757258"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Contemporary management of metastatic castration-resistant prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46; Sonpavde"
                            1 => "C&#46;N&#46; Sternberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MOU.0b013e3283449e19"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Urol"
                        "fecha" => "2011"
                        "volumen" => "21"
                        "paginaInicial" => "241"
                        "paginaFinal" => "247"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21455038"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/21735786/0000003600000006/v1_201304251924/S2173578612001394/v1_201304251924/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "6275"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Review article"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/21735786/0000003600000006/v1_201304251924/S2173578612001394/v1_201304251924/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578612001394?idApp=UINPBA00004N"
]

Article information

ISSN: 21735786
Original language: English

DOI:10.1016/j.acuroe.2011.10.001

The statistics are updated each day

Year/Month	Html	Pdf	Total

2023 March	1	1	2
2018 March	1	0	1
2018 February	6	8	14
2018 January	11	1	12
2017 December	15	0	15
2017 November	26	2	28
2017 October	22	3	25
2017 September	8	2	10
2017 August	18	4	22
2017 July	21	2	23
2017 June	29	1	30
2017 May	23	2	25
2017 April	21	2	23
2017 March	22	1	23
2017 February	14	0	14
2017 January	23	1	24
2016 December	17	3	20
2016 November	21	1	22
2016 October	30	9	39
2016 September	28	2	30
2016 August	17	4	21
2016 July	11	1	12
2016 June	16	5	21
2016 May	17	7	24
2016 April	16	10	26
2016 March	14	8	22
2016 February	11	10	21
2016 January	14	10	24
2015 December	10	6	16
2015 November	11	6	17
2015 October	12	10	22
2015 September	9	3	12
2015 August	10	3	13
2015 July	6	6	12
2015 June	10	1	11
2015 May	11	4	15
2015 April	13	13	26
2015 March	15	6	21
2015 February	11	2	13
2015 January	23	1	24
2014 December	30	9	39
2014 November	13	2	15
2014 October	25	8	33
2014 September	32	6	38
2014 August	30	3	33
2014 July	31	4	35
2014 June	20	4	24
2014 May	10	1	11
2014 April	1	0	1
2014 January	2	0	2
2013 December	13	1	14
2013 November	10	3	13
2013 October	14	4	18
2013 September	8	2	10
2013 July	0	1	1

Show all

Indexed in:

Follow us:

Subscribe:

Statistics

Indexed in:

Follow us:

Subscribe:

Statistics

Subscribe to our newsletter