Androgen deprivation therapy in patients with localized disease: Comparison with curative intent treatments and time to castration resistance. Results of the Spanish Prostate Cancer Registry | Actas Urológicas Españolas (English Edition)

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Results of the Spanish Prostate Cancer Registry" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "156" "paginaFinal" => "163" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "J. Garcia-Rodriguez, J.M. Fernandez-Gomez, J.M. Cozar, B. Miñana, F. Gomez-Veiga, A. Rodriguez-Antolin" "autores" => array:8 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "Garcia-Rodriguez" "email" => array:1 [ 0 => "jgrmed@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0125" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J.M." "apellidos" => "Fernandez-Gomez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0125" ] ] ] 2 => array:3 [ "nombre" => "J.M." "apellidos" => "Cozar" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0130" ] ] ] 3 => array:3 [ "nombre" => "B." 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"apellidos" => "Rodriguez-Antolin" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0145" ] ] ] 6 => array:2 [ "colaborador" => "On behalf of Grupo Español de Cáncer de Próstata (GESCAP)" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "◊" "identificador" => "fn0005" ] ] ] 7 => array:1 [ "colaborador" => "On behalf of Grupo Español de Cáncer de Próstata (GESCAP)" ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Departamento de Urología, Hospital Universitario Central de Asturias, Oviedo, Spain" "etiqueta" => "a" "identificador" => "aff0125" ] 1 => array:3 [ "entidad" => "Departamento de Urología, Hospital Virgen de las Nieves, Granada, Spain" "etiqueta" => "b" "identificador" => "aff0130" ] 2 => array:3 [ "entidad" => "Departamento de Urología, Hospital Morales Meseguer, Murcia, Spain" "etiqueta" => "c" "identificador" => "aff0135" ] 3 => array:3 [ "entidad" => "Departamento de Urología, Hospital Clínico, Salamanca, Spain" "etiqueta" => "d" "identificador" => "aff0140" ] 4 => array:3 [ "entidad" => "Departamento de Urología, Hospital Universitario 12 de Octubre, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0145" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Terapia de privación de andrógenos en pacientes con enfermedad localizada: comparación de las opciones de tratamiento y tiempo hasta la resistencia a la castración. Resultados del Registro Español de Cáncer de Próstata" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 4253 "Ancho" => 1315 "Tamanyo" => 332717 ] ] "descripcion" => array:1 [ "en" => "(a) Overall survival according to group (Group 1: with patients with low and intermediate risk clinically localized tumors; Group 2: high risk and locally advanced (T3-4) tumors. Group 3: patients with metastatic tumors). (b) Cancer-specific survival according to group (Group 1: with patients with low and intermediate risk clinically localized tumors; Group 2: high risk and locally advanced (T3-4) tumors. Group 3: patients with metastatic tumors)." ] ] ] "textoCompleto" => "IntroductionAndrogen deprivation therapy (ADT) is indicated in metastatic prostate cancer and may be also an option in locally advanced tumors unsuitable for surgery or Radiotherapy.<a class="elsevierStyleCrossRef" href="#bib0145">1</a> Although ADT is not a therapeutic option in localized tumors,<a class="elsevierStyleCrossRefs" href="#bib0150">2,3</a> it is frequently used in daily practice.<a class="elsevierStyleCrossRef" href="#bib0160">4</a> In this way, ADT was applied in a substantial number of patients with localized prostate cancer in the Spanish Prostate Cancer Registry series on prostate cancer<a class="elsevierStyleCrossRef" href="#bib0165">5</a> and in other international series of localized prostate cancer.<a class="elsevierStyleCrossRefs" href="#bib0150">2,6,7</a>Some reports have demonstrated an overall survival benefit in patients with localized or locally advanced prostate cancer who undergo ADT, especially in elderly patients with associated morbidities.<a class="elsevierStyleCrossRef" href="#bib0160">4</a> Frequently, high mortality from non-cancer-specific causes occurs in these patients. Age at the onset of ADT, PSA and tumor stage are important factors of overall and cancer-specific survival, being castration resistance the most significant determinant of cancer-specific survival.<a class="elsevierStyleCrossRef" href="#bib0180">8</a>Nevertheless, up to now the effect of primary ADT in patients with localized disease has not been well documented.<a class="elsevierStyleCrossRef" href="#bib0160">4</a> Outcomes of non-metastatic tumors may be different that those of metastatic tumors in patients with prostate cancer treated with ADT.<a class="elsevierStyleCrossRef" href="#bib0180">8</a> Thus, in the present paper the evolution of tumors treated with ADT as primary therapy in the Spanish Prostate Cancer Registry has been analyzed, comparing the progression of metastatic tumors with those of localized and locally advanced prostate tumors.Material and methodsIn our series, 719 patients treated with ADT as primary treatment (19.4% of the overall Spanish Prostate Cancer Registry) were analyzed. The study protocol was reviewed and approved by the Ethics Committee of the Hospital Virgen de las Nieves (Granada). Thus, the study was conducted in accordance with the ethical principles of human research of the Declaration of Helsinki and specific informed consent was obtained from each participant.To simplify, the series was distributed in balanced groups, including clinically localized tumors and metastatic tumors. For localized tumors the D’Amico classification was taken into account (low risk: cT1-cT2a and Gleason <7 and PSA ≤10ng/ml, intermediate risk: cT2b or Gleason=7 or PSA >10 and ≤20ng/ml; and high risk: cT2c or PSA >20ng/ml or Gleason >7). Thus, the overall cohort was classified in three groups, as follows: group 1, with patients with low and intermediate risk clinically localized tumors; group 2, with high risk and locally advanced (T3-4) tumors and, finally, group 3, including patients with metastatic tumors (nodal or bone metastases). (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>In almost all cases, continuous androgen deprivation (ADT) was used (only 6% of patients received intermittent ADT), and only 4 patients underwent subalbugineal orchiectomy. The clinical-pathological characteristics (age, T stage, N, M, PSA at diagnosis, and D’Amico risk group) were studied in non-metastatic tumors treated with ADT, as well as the time from diagnosis to treatment, comparing these parameters with the characteristics of patients with metastatic tumors treated with ADT.Subsequently, the time to castration resistance (defined as three consecutive PSA elevations separated by at least one week, with two 50% increments over the nadir with PSA greater than 2ng/ml, testosterone levels of less than 50ng/dl or 1.7nmol/l, progression of bone lesions ≥2 in bone scintigraphy or progression of soft tissue lesions according to RECIST criteria) and overall cancer-specific survival, both in patients with metastatic and non-metastatic tumors undergoing ADT was analyzed. In addition, in non-metastatic tumors, survival in patients treated with ADT was compared with data taken from patients who underwent local treatments (radical prostatectomy, external beam radiotherapy and brachytherapy, excluding cryotherapy, active surveillance and observation) in the series of the Spanish Prostate Cancer Registry.The quantitative variables were described by means of the mean and standard deviation, or by the median and interquartile range (iqr) in case of a non-normal distribution. In the first case (normal distribution) the groups were compared by means of an analysis of the variance, and in the second by the nonparametric Kruskall-Wallis test. For the qualitative variables, the groups were compared using the Ji2 test from the contingency tables. The Kaplan–Meier method was used to calculate the survival and the probability of castration resistance. The probability curves for the development of castration resistance and survival were compared by the logrank test. Cox proportional hazard models were used to calculate the hazard ratio associated to each factor.ResultsFinally, 703 cases were analyzed (in 16 patients data were incomplete). The mean age was 74.4 years. The characteristics of the complete series have been previously published.<a class="elsevierStyleCrossRef" href="#bib0165">5</a> Of the patients treated with ADT, 231 had clinically localized tumors of low- or intermediate-risk of the D’Amico classification (group 1), 301 had high-risk or locally advanced tumors (group 2) and 171 metastatic tumors (group 3), either by nodal or bone involvement. There were no differences in age between groups, although logically there were significant differences in mean PSA at diagnosis (p<0.0001), which was very high in the group of metastatic tumors (group 3, mean PSA: 389ng/dl) compared to the other groups (group 1: 10.2ng/dl, group 2: 60.9ng/dl). Likewise, both the Gleason score distribution of biopsy as and the clinical local stage were related to the corresponding D’Amico risk group. The use of complete androgen blockade (LHRH agonist with antiandrogens) was significantly higher (p=0.0007) in patients with metastatic tumors (57.6%) than in group 2 (49.8%) or group 1 (38.8%). Time to initiation of ADT in group 3 (metastatic) was significantly lower (10 days; p<0.00001) than in group 2 (month and a half) or in group 1 (2 months).With a median follow-up of 35.8 months (iqr: 18.5m) and a maximum of 39 months, 18.8% of patients (n=132) became castration-resistant: 67% of metastatic tumors, 29.5% in group 2 and only 3% in group 1. Thus, at 3 years after the onset of ADT, only 1.5% of patients in group 1 were castration-resistant compared to 14.9% in group 2 or 55.5% in group 3. The median time until – castration resistance was 26 months in group 3 (HR: 42.76, 95%CI: 15.69–116.52). There were significant differences (p<0.001) in the time to castration resistance, which was significantly lower in group 3 (metastatic). Like this, the time to castration resistance was significantly lower in group 3 than in group 2 (HR: 7.6, 95%CI: 2.73–21.5), which also was significantly lower than in group 1 (in groups 1 and 2 medians of time to castration resistance were not reached) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In the multivariate analysis no independent factors of castration resistance were detected.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>During follow-up, there were 179 deaths (25.5%) of which 89 (12.6%) were due to prostate cancer. With a maximum of 39 months of follow-up, the overall mortality was 48.5%. The cancer-specific mortality was 29.5% in the group of metastatic tumors, being higher than in group 2 (overall mortality of 18.9% and cancer-specific mortality of 7.1%) or in group 1 (overall mortality of 16.8% and cancer-specific mortality of 1.3%) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>a and b). Thus, after 3 years of ADT, only 14.6% of patients in group 1 had died (1% due to prostate cancer), compared to 20.5% in group 2 or 46.8% in group 3 (9.2% and 31.3% due to prostate cancer, respectively). The median overall survival in metastatic tumors undergoing ADT was 38 months (median not reached in the other groups). There were significant differences in the overall survival time between the group of metastatic tumors (p<0.001) and the other 2 groups (HR: 2.99; 95%CI, 2.03–4.04), although there were not statistical differences between group 1 and group 2. Cancer-specific mortality was significantly higher in the group of metastatic tumors (group 3) (p<0.0001), which was statistically higher than in group 2 (high-risk and locally advanced tumors) (p=0.01) and than in group 1 (low- or intermediate-risk localized tumors).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Lastly, overall and cancer-specific survival in groups 1 (low- and intermediate-risk tumors) and 2 (high-risk and locally advanced tumors) treated with ADT were compared with those in patients who underwent local treatment (radical prostatectomy or radiotherapy -external beam radiotherapy and brachytherapy-) in the Spanish Prostate Cancer Registry. In both, group 1 and group 2, overall survival was worse in patients undergoing ADT (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Regarding cancer-specific survival, in group 1 was significantly worse using ADT (p<0.05) than radical prostatectomy or radiotherapy, whose curves practically overlapped (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). In high-risk and locally advanced tumors (group 2), ADT also had a lower cancer-specific survival (p<0.001) than the local treatments (HR: 0.1; 90%CI: 0.025–0.45 respect to radical prostatectomy and HR: 0.16; 90%CI: 0.072–0.39 respect to radiotherapy) (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia>DiscussionAlthough ADT is indicated for the treatment of advanced disease,<a class="elsevierStyleCrossRef" href="#bib0185">9</a> some authors have confirmed that in clinical practice a significant proportion of patients receives ADT as primary treatment for localized disease.<a class="elsevierStyleCrossRefs" href="#bib0160">4,5,10,11</a> Watchful waiting is considered an acceptable approach for many patients with localized well- or moderately differentiated disease, particularly among those with significant comorbidities or those who are hesitant to proceed with radical therapy due to potential side effects. In fact, for many patients expectant management can cause significant anxiety,<a class="elsevierStyleCrossRef" href="#bib0170">6</a> which is associated with a greater probability of receiving active treatment.<a class="elsevierStyleCrossRef" href="#bib0200">12</a> Since ADT is known to provide a decline of prostate-specific antigen (PSA) in about 90% of patients with hormone-naïve prostate cancer, patients and physicians may perceive ADT as an effective treatment and less invasive than radiation therapy or surgery. Although the time to initiate castration in our series was significantly longer in patients with clinically localized tumors than with metastatic tumors, the onset of ADT was deferred only about 2 months after the diagnosis of localized prostate cancer.ADT is the standard of care for patients with biochemical recurrence after definitive primary therapy, locally advanced disease or metastatic disease, but the majority of patients will progress to castration resistant disease (CRPC) within 2–3 years.<a class="elsevierStyleCrossRef" href="#bib0205">13</a> Different characteristics of PSA variation after starting ADT such as pretreatment PSA level, nadir, time to nadir, and doubling time have clinical significances as prognostic factors to predict CRPC.<a class="elsevierStyleCrossRefs" href="#bib0210">14–19</a> However, the accuracy of these patterns as predictors is still unclear and most of them, as PSA nadir or doubling time, may be in fact surrogate markers of cancer behavior. To our knowledge, this is the first study that compare the evolution to CRPC according to different stages of the tumor. In our series, the median of time to castration resistance in metastatic tumors was of 26 months, much lower than in localized or locally advanced tumors. Interestingly, after 3 years of ADT, significant differences in time to castration resistance were found between groups in our series. In this way, only 1.5% of patients with low and intermediate risk localized tumors were resistant to castration compared to 14.9% in the group of high risk localized tumors and locally advanced tumors or 55.5% in the metastatic tumors. During the last decade, numerous studies have shown that despite systemic androgen depletion, AR signaling remains active and supports the survival and growth of cancer cells.<a class="elsevierStyleCrossRef" href="#bib0240">20</a> The progression of CRPC is now known to be due to the onset of a number of resistance mechanisms induced by the selective pressure of endocrine therapy.<a class="elsevierStyleCrossRef" href="#bib0245">21</a> Castration is able to induce clonal selection and subsequent growth of androgen-independent cellular clones.<a class="elsevierStyleCrossRef" href="#bib0250">22</a> However, in spite of current clinical staging limitations, our results suggest that several unknown mechanisms could be present in prostate tumors before castration, even in previous periods of undetectable metastatic disease, which could determine a differential response to ADT and evolution to castration resistance. Therefore, this could be the reason why some patients with hormone-sensitive disease might benefit from chemotherapy in association with endocrine therapy.<a class="elsevierStyleCrossRef" href="#bib0250">22</a>Moreover, ADT can have substantial long-term adverse consequences on the quality and quantity of life.<a class="elsevierStyleCrossRef" href="#bib0255">23</a> These adverse effects include impaired cognitive function, loss of muscle strength, anemia, bone loss or fractures, coronary heart disease, insulin sensitivity and diabetes mellitus.<a class="elsevierStyleCrossRef" href="#bib0260">24</a> Recently, Wong et al. have demonstrated no benefit to primary androgen deprivation therapy and possibly greater mortality, presenting a strong argument against its use as primary therapy in these patients,<a class="elsevierStyleCrossRef" href="#bib0170">6</a> which has been reflected in different guidelines.<a class="elsevierStyleCrossRefs" href="#bib0265">25,26</a> In the present series, a high mortality rate (greater than 25%) was observed in patients treated with ADT, although more than half of deaths were caused by factors not related to the tumor. Unfortunately, the cause of mortality in patients who did not die from prostate cancer was not registered and therefore, a potential relationship with ADT toxicity could not be established. In addition, probably an important bias in the selection of cases for ADT occurred, including a higher proportion of patients unfit for local treatment in spite of a localized disease.In the present study, the mortality from prostate cancer in metastatic tumors was around 30% (the cause of the death in the remaining patients was not analyzed), being only of 1% in patients with low- and intermediate-risk localized tumors, similar results to those published for watchful waiting.<a class="elsevierStyleCrossRefs" href="#bib0275">27,28</a> However, in the group 2 (localized high risk tumors and locally advanced tumors) the cancer-specific mortality was 7.1%. Compared to the results obtained in patients undergoing local treatments included in the Spanish Registry of Prostate Cancer, significant lower cancer-specific survival was demonstrated in relation to ADT in both groups, i.e., in low- and intermediate-risk tumors (group 1) and in high-risk and locally advanced tumors (group 2). These results seems to indicate that ADT is not a sufficient therapy for localized disease, mainly for high risk and locally advanced tumors in which local treatment is required to improve survival.<a class="elsevierStyleCrossRef" href="#bib0210">14</a>There are several limitations in our study. Because of the retrospective nature of data collection, the limited information about the cause of death in patients who died of non-tumor related causes and a short follow-up period, the statistical results should be interpreted cautiously. However, some clearly significant results were obtained which were provided from a large multicenter series. Therefore, despite these limitations, this series does add important information about the evolution of patients with non-metastatic prostate tumors treated with ADT in the real clinical world.In conclusion, a longer time until the castration resistance was observed in patients treated with ADT with well- and intermediate-risk localized tumors than in high risk and locally advanced tumors. Moreover, patients with metastatic tumors shown the shortest time to castration resistance. Consequently, new research is necessary to achieve a better knowledge of the natural history of prostate cancer and to detect aggressive features which probably are already present even in early phases. On the other hand, in patients with non-metastatic tumors, cancer-specific survival was shorter using ADT as primary treatment, especially in the group of high-risk and locally advanced tumors, where local treatment was significantly more effective.FundingAstellas Pharma, Inc. is the legal promoter of this study." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1330674" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1226039" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1330673" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:1 [ "identificador" => "abst0025" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1226038" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "xack459582" "titulo" => "Acknowledgements" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-10-21" "fechaAceptado" => "2019-06-09" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1226039" "palabras" => array:3 [ 0 => "Androgen deprivation therapy" 1 => "Localized prostate cancer" 2 => "Castration resistance" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1226038" "palabras" => array:3 [ 0 => "Terapia de privación androgénica" 1 => "Cáncer de próstata localizado" 2 => "Resistencia a castración" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundThe effect of primary androgen deprivation therapy (ADT) in patients with localized prostate cancer (PCa) has not been well documented. The objective of the present study was to analyze the outcome of tumors treated with ADT as primary therapy in the Spanish Prostate Cancer Registry (19.4% of the series). Patients and methodsPatients were classified in three groups: (1) with low/intermediate risk clinically localized tumors; (2) with high risk and locally advanced (T3-4) tumors; (3) with metastatic tumors. Time to castration resistance and overall cancer-specific survival were analyzed. In non-metastatic tumors, survivals in patients treated with ADT were compared with data from patients who underwent local treatments from the Spanish Prostate Cancer Registry. Results703 cases were analyzed. There were significant differences in the time to castration resistance, which was lower in the group of metastatic tumors. During follow-up, there were 179 deaths (25.5%) of which 89 (12.6%) were due to PCa. After 3 years of ADT, only 14.6% of patients in group 1 had died (1% due to PCa), 20.5% in group 2 and 46.8% in group 3 (9.2% and 31.3% due to PCa, respectively). Cancer-specific survival was significantly worse in group 1 using ADT than radical prostatectomy or radiotherapy. In high-risk and locally advanced tumors, ADT also had a lower cancer-specific survival than local treatments. ConclusionA longer time until the castration resistance was observed in patients with well- and intermediate-risk localized tumors treated with ADT. Patients with metastatic tumors showed the shortest time to castration resistance." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "Antecedentes El efecto del tratamiento primario de privación androgénica (TPA) en pacientes con cáncer de próstata (CP) localizado no está bien documentado. El objetivo del presente estudio fue analizar el resultado de los tumores tratados con TPA como terapia primaria en el Registro Español de Cáncer de Próstata (19,4% de la serie). Pacientes y métodosLos pacientes se clasificaron en tres grupos: 1) con tumores clínicamente localizados de riesgo bajo/intermedio; 2) con tumores de alto riesgo y localmente avanzados (T3-4); 3) con tumores metastásicos. Se analizó el tiempo hasta la resistencia a la castración y la supervivencia general específica del cáncer. En tumores no metastásicos, las supervivencias en pacientes tratados con TPA se compararon con los datos de pacientes que recibieron tratamientos locales del Registro Español de Cáncer de Próstata. ResultadosSe analizaron 703 casos. Hubo diferencias significativas en el tiempo de resistencia a la castración, que fue menor en el grupo de tumores metastásicos. Durante el seguimiento hubo 179 muertes (25,5%), de las cuales 89 (12,6%) se debieron a CP. Después de 3 años de TPA, solo el 14,6% de los pacientes en el grupo 1 fallecieron (1% debido a CP), el 20,5% en el grupo 2 y el 46,8% en el grupo 3 (9,2% y 31,3% debido a CP, respectivamente). La supervivencia específica del cáncer fue significativamente peor en el grupo 1 tratado con TPA que en el que recibió prostatectomía radical o radioterapia. En los tumores de alto riesgo y localmente avanzados, la TPA también tuvo una menor supervivencia específica al cáncer que los tratamientos locales. ConclusiónSe observó un tiempo más largo hasta la resistencia a la castración en pacientes con tumores localizados de riesgo intermedio y bien tratados con TPA. Los pacientes con tumores metastásicos mostraron el menor tiempo hasta la resistencia a la castración." "secciones" => array:4 [ 0 => array:1 [ "identificador" => "abst0025" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Garcia-Rodriguez J, Fernandez-Gomez JM, Cozar JM, Miñana B, Gomez-Veiga F, Rodriguez-Antolin A, et al. Terapia de privación de andrógenos en pacientes con enfermedad localizada: comparación de las opciones de tratamiento y tiempo hasta la resistencia a la castración. Resultados del Registro Español de Cáncer de Próstata. Actas Urol Esp. 2020;44:156–163." ] 1 => array:3 [ "etiqueta" => "◊" "nota" => "The researchers participating in the Grupo Español de Cáncer de Próstata (GESCAP) are listed in <a class="elsevierStyleCrossRef" href="#sec0030">Appendix A</a>." "identificador" => "fn0005" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "CHUAC (Paula Pórtela, Eva Blanco, Juan Andrés González), Hospital Regional Universitario Carlos Haya (Víctor Baena, Pedro Morales), Fundación Puigvert (Humberto Villavicencio, Joan Palou), H. de Basurto (Ana Loizaga), H. Clínic i Provincial de Barcelona (Alex Ciudin, Diaconau Mihai), H. Clínico Universitario de Valencia (José María Martínez Jabaloyas, Ana Castelló, Nelson Díez), H. Clínico Universitario Lozano Blesa (Francisco Javier Romero, Jorge Subirá, Ana Isabel Chávez, Victoria Capapé, María Mata, Javier Elizalde), H. General Universitario de Alicante (Juan José Lobato, Jesús Jiménez, Luís Pérez Llorca, Juan Antonio Tenza), H. General Universitario Gregorio Marañón (Felipe Herranz, Adrián Husillos, Esther López, Daniel Ramírez, Igor Blaha), H. General Universitario Morales Meseguer (Emilio Izquierdo, Leandro Reina), H. U. 12 de Octubre (Juan Passas, Laura Díez), H. U. Central de Asturias (Miguel A. Hevia), H. U. de Bellvitge (Manel Castells), H. U. de Canarias (Tomás Concepción Masip, Ana Cristina Plata), H. U. Infanta Cristina (Simón Asuar Aydillo, Juan Alonso, Jesús Mateos), H. U. Puerta de Hierro-Majadahonda (Joaquín Carballido, Claudio Martínez, Jennifer Areche), H. U. Ramón y Cajal (Rafael Rodríguez, Vital Hevia, Sara Álvarez), H. U. Reina Sofía (María José Requena, Rafael Prieto, José Luís Carazo, Javier Márquez, Enrique Gómez, José Horacio García), H. U. Río Hortega (José Amón, Marcos Cepeda, Luis Álvarez, Verónica Rodríguez, Beatriz de la Cruz, Alberto Rivero, Juan Francisco Sánchez, Juan Antonio Mainez), H. U. Virgen del Rocío (Rafael Medina, Manuel Conde), H. U. Virgen Macarena (Jesús Castiñeiras, Antonio Carlos González Baena, Ernesto Sánchez, Rubén Campanario, Rocío Saiz, Edwin Romero), H. U. Vall d’Hebron (Juan Morote, Carles Xavier Raventós, Ana Celma), H. Virgen de las Nieves (Fernando Vázquez), H. Virgen de la Salud (Antonio Gómez, Elena Buendía, Natanael García)." "etiqueta" => "Appendix A" "titulo" => "Grupo Español de Cáncer de Próstata" "identificador" => "sec0030" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2634 "Ancho" => 1591 "Tamanyo" => 210863 ] ] "descripcion" => array:1 [ "en" => "Probability of castration resistance according to group (Group 1: with patients with low and intermediate risk clinically localized tumors; Group 2: high risk and locally advanced (T3-4) tumors. Group 3: patients with metastatic tumors)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 4253 "Ancho" => 1315 "Tamanyo" => 332717 ] ] "descripcion" => array:1 [ "en" => "(a) Overall survival according to group (Group 1: with patients with low and intermediate risk clinically localized tumors; Group 2: high risk and locally advanced (T3-4) tumors. Group 3: patients with metastatic tumors). (b) Cancer-specific survival according to group (Group 1: with patients with low and intermediate risk clinically localized tumors; Group 2: high risk and locally advanced (T3-4) tumors. Group 3: patients with metastatic tumors)." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 4285 "Ancho" => 1479 "Tamanyo" => 301540 ] ] "descripcion" => array:1 [ "en" => "(a) Overall survival in group 1 (low- and intermediate- localized risk tumors) according to treatment including patients from the Spanish Prostate Cancer Registry. (b) Overall survival in group 2 (high risk localized and locally advanced tumors) according to treatment including patients from the Spanish Prostate Cancer Registry." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 2430 "Ancho" => 1511 "Tamanyo" => 174499 ] ] "descripcion" => array:1 [ "en" => "Cancer-specific survival in group 1 (low- and intermediate- localized risk tumors) according to treatment including patients from the Spanish Prostate Cancer Registry." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 2403 "Ancho" => 1519 "Tamanyo" => 179837 ] ] "descripcion" => array:1 [ "en" => "Cancer-specific survival in group 2 (high risk localized and locally advanced tumors) according to treatment including patients from the Spanish Prostate Cancer Registry. ADT: Androgen Deprivation Therapy; EBR and/or BT: External beam radiation and/or brachytherapy; RP: radical Prostatectomy." ] ] 5 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Group 1: with patients with low and intermediate risk clinically localized tumors; Group 2: high risk and locally advanced (T3-4) tumors. Group 3: patients with metastatic tumors (nodal or bone metastases)." "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"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Median age \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">PSA at diagnosis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">PSA at start of treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Gleason ≤6 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Gleason >6 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">N° positive cores \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">% T≤T1c/≥T2a \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 1 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">231 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">146 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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">75.3/24.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 2 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">301 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42.8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25.5 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">252 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \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">30.5/69.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 3 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">171 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.3 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">101.6 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">155 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \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">9.7/90.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2280557.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of the series according to D’Amico classification and presence of metastases." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:28 [ 0 => array:3 [ "identificador" => "bib0145" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EAU guidelines on prostate cancer Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. 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Original article

Androgen deprivation therapy in patients with localized disease: Comparison with curative intent treatments and time to castration resistance. Results of the Spanish Prostate Cancer Registry

Terapia de privación de andrógenos en pacientes con enfermedad localizada: comparación de las opciones de tratamiento y tiempo hasta la resistencia a la castración. Resultados del Registro Español de Cáncer de Próstata

J. Garcia-Rodrigueza,

Corresponding author

jgrmed@hotmail.com

Corresponding author.

, J.M. Fernandez-Gomeza, J.M. Cozarb, B. Miñanac, F. Gomez-Veigad, A. Rodriguez-Antoline, On behalf of Grupo Español de Cáncer de Próstata (GESCAP) ◊, On behalf of Grupo Español de Cáncer de Próstata (GESCAP)

a Departamento de Urología, Hospital Universitario Central de Asturias, Oviedo, Spain

b Departamento de Urología, Hospital Virgen de las Nieves, Granada, Spain

c Departamento de Urología, Hospital Morales Meseguer, Murcia, Spain

d Departamento de Urología, Hospital Clínico, Salamanca, Spain

e Departamento de Urología, Hospital Universitario 12 de Octubre, Madrid, Spain

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especially in elderly patients with associated morbidities&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">4</span></a> Frequently&#44; high mortality from non-cancer-specific causes occurs in these patients&#46; Age at the onset of ADT&#44; PSA and tumor stage are important factors of overall and cancer-specific survival&#44; being castration resistance the most significant determinant of cancer-specific survival&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Nevertheless&#44; up to now the effect of primary ADT in patients with localized disease has not been well documented&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">4</span></a> Outcomes of non-metastatic tumors may be different that those of metastatic tumors in patients with prostate cancer treated with ADT&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">8</span></a> Thus&#44; in the present paper the evolution of tumors treated with ADT as primary therapy in the Spanish Prostate Cancer Registry has been analyzed&#44; comparing the progression of metastatic tumors with those of localized and locally advanced prostate tumors&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Material and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">In our series&#44; 719 patients treated with ADT as primary treatment &#40;19&#46;4&#37; of the overall Spanish Prostate Cancer Registry&#41; were analyzed&#46; The study protocol was reviewed and approved by the Ethics Committee of the Hospital Virgen de las Nieves &#40;Granada&#41;&#46; Thus&#44; the study was conducted in accordance with the ethical principles of human research of the Declaration of Helsinki and specific informed consent was obtained from each participant&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">To simplify&#44; the series was distributed in balanced groups&#44; including clinically localized tumors and metastatic tumors&#46; For localized tumors the D&#8217;Amico classification was taken into account &#40;low risk&#58; cT1-cT2a and Gleason &#60;7 and PSA &#8804;10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; intermediate risk&#58; cT2b or Gleason<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7 or PSA &#62;10 and &#8804;20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#59; and high risk&#58; cT2c or PSA &#62;20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml or Gleason &#62;7&#41;&#46; Thus&#44; the overall cohort was classified in three groups&#44; as follows&#58; group 1&#44; with patients with low and intermediate risk clinically localized tumors&#59; group 2&#44; with high risk and locally advanced &#40;T3-4&#41; tumors and&#44; finally&#44; group 3&#44; including patients with metastatic tumors &#40;nodal or bone metastases&#41;&#46; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In almost all cases&#44; continuous androgen deprivation &#40;ADT&#41; was used &#40;only 6&#37; of patients received intermittent ADT&#41;&#44; and only 4 patients underwent subalbugineal orchiectomy&#46; The clinical-pathological characteristics &#40;age&#44; T stage&#44; N&#44; M&#44; PSA at diagnosis&#44; and D&#8217;Amico risk group&#41; were studied in non-metastatic tumors treated with ADT&#44; as well as the time from diagnosis to treatment&#44; comparing these parameters with the characteristics of patients with metastatic tumors treated with ADT&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Subsequently&#44; the time to castration resistance &#40;defined as three consecutive PSA elevations separated by at least one week&#44; with two 50&#37; increments over the nadir with PSA greater than 2<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; testosterone levels of less than 50<span class="elsevierStyleHsp" style=""></span>ng&#47;dl or 1&#46;7<span class="elsevierStyleHsp" style=""></span>nmol&#47;l&#44; progression of bone lesions &#8805;2 in bone scintigraphy or progression of soft tissue lesions according to RECIST criteria&#41; and overall cancer-specific survival&#44; both in patients with metastatic and non-metastatic tumors undergoing ADT was analyzed&#46; In addition&#44; in non-metastatic tumors&#44; survival in patients treated with ADT was compared with data taken from patients who underwent local treatments &#40;radical prostatectomy&#44; external beam radiotherapy and brachytherapy&#44; excluding cryotherapy&#44; active surveillance and observation&#41; in the series of the Spanish Prostate Cancer Registry&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The quantitative variables were described by means of the mean and standard deviation&#44; or by the median and interquartile range &#40;iqr&#41; in case of a non-normal distribution&#46; In the first case &#40;normal distribution&#41; the groups were compared by means of an analysis of the variance&#44; and in the second by the nonparametric Kruskall-Wallis test&#46; For the qualitative variables&#44; the groups were compared using the Ji<span class="elsevierStyleSup">2</span> test from the contingency tables&#46; The Kaplan&#8211;Meier method was used to calculate the survival and the probability of castration resistance&#46; The probability curves for the development of castration resistance and survival were compared by the logrank test&#46; Cox proportional hazard models were used to calculate the hazard ratio associated to each factor&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">Finally&#44; 703 cases were analyzed &#40;in 16 patients data were incomplete&#41;&#46; The mean age was 74&#46;4 years&#46; The characteristics of the complete series have been previously published&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">5</span></a> Of the patients treated with ADT&#44; 231 had clinically localized tumors of low- or intermediate-risk of the D&#8217;Amico classification &#40;group 1&#41;&#44; 301 had high-risk or locally advanced tumors &#40;group 2&#41; and 171 metastatic tumors &#40;group 3&#41;&#44; either by nodal or bone involvement&#46; There were no differences in age between groups&#44; although logically there were significant differences in mean PSA at diagnosis &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#44; which was very high in the group of metastatic tumors &#40;group 3&#44; mean PSA&#58; 389<span class="elsevierStyleHsp" style=""></span>ng&#47;dl&#41; compared to the other groups &#40;group 1&#58; 10&#46;2<span class="elsevierStyleHsp" style=""></span>ng&#47;dl&#44; group 2&#58; 60&#46;9<span class="elsevierStyleHsp" style=""></span>ng&#47;dl&#41;&#46; Likewise&#44; both the Gleason score distribution of biopsy as and the clinical local stage were related to the corresponding D&#8217;Amico risk group&#46; The use of complete androgen blockade &#40;LHRH agonist with antiandrogens&#41; was significantly higher &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0007&#41; in patients with metastatic tumors &#40;57&#46;6&#37;&#41; than in group 2 &#40;49&#46;8&#37;&#41; or group 1 &#40;38&#46;8&#37;&#41;&#46; Time to initiation of ADT in group 3 &#40;metastatic&#41; was significantly lower &#40;10 days&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;00001&#41; than in group 2 &#40;month and a half&#41; or in group 1 &#40;2 months&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">With a median follow-up of 35&#46;8 months &#40;iqr&#58; 18&#46;5<span class="elsevierStyleHsp" style=""></span>m&#41; and a maximum of 39 months&#44; 18&#46;8&#37; of patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>132&#41; became castration-resistant&#58; 67&#37; of metastatic tumors&#44; 29&#46;5&#37; in group 2 and only 3&#37; in group 1&#46; Thus&#44; at 3 years after the onset of ADT&#44; only 1&#46;5&#37; of patients in group 1 were castration-resistant compared to 14&#46;9&#37; in group 2 or 55&#46;5&#37; in group 3&#46; The median time until &#8211; castration resistance was 26 months in group 3 &#40;HR&#58; 42&#46;76&#44; 95&#37;CI&#58; 15&#46;69&#8211;116&#46;52&#41;&#46; There were significant differences &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; in the time to castration resistance&#44; which was significantly lower in group 3 &#40;metastatic&#41;&#46; Like this&#44; the time to castration resistance was significantly lower in group 3 than in group 2 &#40;HR&#58; 7&#46;6&#44; 95&#37;CI&#58; 2&#46;73&#8211;21&#46;5&#41;&#44; which also was significantly lower than in group 1 &#40;in groups 1 and 2 medians of time to castration resistance were not reached&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; In the multivariate analysis no independent factors of castration resistance were detected&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">During follow-up&#44; there were 179 deaths &#40;25&#46;5&#37;&#41; of which 89 &#40;12&#46;6&#37;&#41; were due to prostate cancer&#46; With a maximum of 39 months of follow-up&#44; the overall mortality was 48&#46;5&#37;&#46; The cancer-specific mortality was 29&#46;5&#37; in the group of metastatic tumors&#44; being higher than in group 2 &#40;overall mortality of 18&#46;9&#37; and cancer-specific mortality of 7&#46;1&#37;&#41; or in group 1 &#40;overall mortality of 16&#46;8&#37; and cancer-specific mortality of 1&#46;3&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>a and b&#41;&#46; Thus&#44; after 3 years of ADT&#44; only 14&#46;6&#37; of patients in group 1 had died &#40;1&#37; due to prostate cancer&#41;&#44; compared to 20&#46;5&#37; in group 2 or 46&#46;8&#37; in group 3 &#40;9&#46;2&#37; and 31&#46;3&#37; due to prostate cancer&#44; respectively&#41;&#46; The median overall survival in metastatic tumors undergoing ADT was 38 months &#40;median not reached in the other groups&#41;&#46; There were significant differences in the overall survival time between the group of metastatic tumors &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and the other 2 groups &#40;HR&#58; 2&#46;99&#59; 95&#37;CI&#44; 2&#46;03&#8211;4&#46;04&#41;&#44; although there were not statistical differences between group 1 and group 2&#46; Cancer-specific mortality was significantly higher in the group of metastatic tumors &#40;group 3&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#44; which was statistically higher than in group 2 &#40;high-risk and locally advanced tumors&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; and than in group 1 &#40;low- or intermediate-risk localized tumors&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Lastly&#44; overall and cancer-specific survival in groups 1 &#40;low- and intermediate-risk tumors&#41; and 2 &#40;high-risk and locally advanced tumors&#41; treated with ADT were compared with those in patients who underwent local treatment &#40;radical prostatectomy or radiotherapy -external beam radiotherapy and brachytherapy-&#41; in the Spanish Prostate Cancer Registry&#46; In both&#44; group 1 and group 2&#44; overall survival was worse in patients undergoing ADT &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Regarding cancer-specific survival&#44; in group 1 was significantly worse using ADT &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; than radical prostatectomy or radiotherapy&#44; whose curves practically overlapped &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; In high-risk and locally advanced tumors &#40;group 2&#41;&#44; ADT also had a lower cancer-specific survival &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; than the local treatments &#40;HR&#58; 0&#46;1&#59; 90&#37;CI&#58; 0&#46;025&#8211;0&#46;45 respect to radical prostatectomy and HR&#58; 0&#46;16&#59; 90&#37;CI&#58; 0&#46;072&#8211;0&#46;39 respect to radiotherapy&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">Although ADT is indicated for the treatment of advanced disease&#44;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">9</span></a> some authors have confirmed that in clinical practice a significant proportion of patients receives ADT as primary treatment for localized disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">4&#44;5&#44;10&#44;11</span></a> Watchful waiting is considered an acceptable approach for many patients with localized well- or moderately differentiated disease&#44; particularly among those with significant comorbidities or those who are hesitant to proceed with radical therapy due to potential side effects&#46; In fact&#44; for many patients expectant management can cause significant anxiety&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a> which is associated with a greater probability of receiving active treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">12</span></a> Since ADT is known to provide a decline of prostate-specific antigen &#40;PSA&#41; in about 90&#37; of patients with hormone-na&#239;ve prostate cancer&#44; patients and physicians may perceive ADT as an effective treatment and less invasive than radiation therapy or surgery&#46; Although the time to initiate castration in our series was significantly longer in patients with clinically localized tumors than with metastatic tumors&#44; the onset of ADT was deferred only about 2 months after the diagnosis of localized prostate cancer&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">ADT is the standard of care for patients with biochemical recurrence after definitive primary therapy&#44; locally advanced disease or metastatic disease&#44; but the majority of patients will progress to castration resistant disease &#40;CRPC&#41; within 2&#8211;3 years&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">13</span></a> Different characteristics of PSA variation after starting ADT such as pretreatment PSA level&#44; nadir&#44; time to nadir&#44; and doubling time have clinical significances as prognostic factors to predict CRPC&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">14&#8211;19</span></a> However&#44; the accuracy of these patterns as predictors is still unclear and most of them&#44; as PSA nadir or doubling time&#44; may be in fact surrogate markers of cancer behavior&#46; To our knowledge&#44; this is the first study that compare the evolution to CRPC according to different stages of the tumor&#46; In our series&#44; the median of time to castration resistance in metastatic tumors was of 26 months&#44; much lower than in localized or locally advanced tumors&#46; Interestingly&#44; after 3 years of ADT&#44; significant differences in time to castration resistance were found between groups in our series&#46; In this way&#44; only 1&#46;5&#37; of patients with low and intermediate risk localized tumors were resistant to castration compared to 14&#46;9&#37; in the group of high risk localized tumors and locally advanced tumors or 55&#46;5&#37; in the metastatic tumors&#46; During the last decade&#44; numerous studies have shown that despite systemic androgen depletion&#44; AR signaling remains active and supports the survival and growth of cancer cells&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">20</span></a> The progression of CRPC is now known to be due to the onset of a number of resistance mechanisms induced by the selective pressure of endocrine therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">21</span></a> Castration is able to induce clonal selection and subsequent growth of androgen-independent cellular clones&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">22</span></a> However&#44; in spite of current clinical staging limitations&#44; our results suggest that several unknown mechanisms could be present in prostate tumors before castration&#44; even in previous periods of undetectable metastatic disease&#44; which could determine a differential response to ADT and evolution to castration resistance&#46; Therefore&#44; this could be the reason why some patients with hormone-sensitive disease might benefit from chemotherapy in association with endocrine therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">22</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Moreover&#44; ADT can have substantial long-term adverse consequences on the quality and quantity of life&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">23</span></a> These adverse effects include impaired cognitive function&#44; loss of muscle strength&#44; anemia&#44; bone loss or fractures&#44; coronary heart disease&#44; insulin sensitivity and diabetes mellitus&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">24</span></a> Recently&#44; Wong et al&#46; have demonstrated no benefit to primary androgen deprivation therapy and possibly greater mortality&#44; presenting a strong argument against its use as primary therapy in these patients&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a> which has been reflected in different guidelines&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">25&#44;26</span></a> In the present series&#44; a high mortality rate &#40;greater than 25&#37;&#41; was observed in patients treated with ADT&#44; although more than half of deaths were caused by factors not related to the tumor&#46; Unfortunately&#44; the cause of mortality in patients who did not die from prostate cancer was not registered and therefore&#44; a potential relationship with ADT toxicity could not be established&#46; In addition&#44; probably an important bias in the selection of cases for ADT occurred&#44; including a higher proportion of patients unfit for local treatment in spite of a localized disease&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In the present study&#44; the mortality from prostate cancer in metastatic tumors was around 30&#37; &#40;the cause of the death in the remaining patients was not analyzed&#41;&#44; being only of 1&#37; in patients with low- and intermediate-risk localized tumors&#44; similar results to those published for watchful waiting&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">27&#44;28</span></a> However&#44; in the group 2 &#40;localized high risk tumors and locally advanced tumors&#41; the cancer-specific mortality was 7&#46;1&#37;&#46; Compared to the results obtained in patients undergoing local treatments included in the Spanish Registry of Prostate Cancer&#44; significant lower cancer-specific survival was demonstrated in relation to ADT in both groups&#44; i&#46;e&#46;&#44; in low- and intermediate-risk tumors &#40;group 1&#41; and in high-risk and locally advanced tumors &#40;group 2&#41;&#46; These results seems to indicate that ADT is not a sufficient therapy for localized disease&#44; mainly for high risk and locally advanced tumors in which local treatment is required to improve survival&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">There are several limitations in our study&#46; Because of the retrospective nature of data collection&#44; the limited information about the cause of death in patients who died of non-tumor related causes and a short follow-up period&#44; the statistical results should be interpreted cautiously&#46; However&#44; some clearly significant results were obtained which were provided from a large multicenter series&#46; Therefore&#44; despite these limitations&#44; this series does add important information about the evolution of patients with non-metastatic prostate tumors treated with ADT in the real clinical world&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In conclusion&#44; a longer time until the castration resistance was observed in patients treated with ADT with well- and intermediate-risk localized tumors than in high risk and locally advanced tumors&#46; Moreover&#44; patients with metastatic tumors shown the shortest time to castration resistance&#46; Consequently&#44; new research is necessary to achieve a better knowledge of the natural history of prostate cancer and to detect aggressive features which probably are already present even in early phases&#46; On the other hand&#44; in patients with non-metastatic tumors&#44; cancer-specific survival was shorter using ADT as primary treatment&#44; especially in the group of high-risk and locally advanced tumors&#44; where local treatment was significantly more effective&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Funding</span><p id="par0095" class="elsevierStylePara elsevierViewall">Astellas Pharma&#44; Inc&#46; is the legal promoter of this study&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The effect of primary androgen deprivation therapy &#40;ADT&#41; in patients with localized prostate cancer &#40;PCa&#41; has not been well documented&#46; The objective of the present study was to analyze the outcome of tumors treated with ADT as primary therapy in the Spanish Prostate Cancer Registry &#40;19&#46;4&#37; of the series&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Patients were classified in three groups&#58; &#40;1&#41; with low&#47;intermediate risk clinically localized tumors&#59; &#40;2&#41; with high risk and locally advanced &#40;T3-4&#41; tumors&#59; &#40;3&#41; with metastatic tumors&#46; Time to castration resistance and overall cancer-specific survival were analyzed&#46; In non-metastatic tumors&#44; survivals in patients treated with ADT were compared with data from patients who underwent local treatments from the Spanish Prostate Cancer Registry&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">703 cases were analyzed&#46; There were significant differences in the time to castration resistance&#44; which was lower in the group of metastatic tumors&#46; During follow-up&#44; there were 179 deaths &#40;25&#46;5&#37;&#41; of which 89 &#40;12&#46;6&#37;&#41; were due to PCa&#46; After 3 years of ADT&#44; only 14&#46;6&#37; of patients in group 1 had died &#40;1&#37; due to PCa&#41;&#44; 20&#46;5&#37; in group 2 and 46&#46;8&#37; in group 3 &#40;9&#46;2&#37; and 31&#46;3&#37; due to PCa&#44; respectively&#41;&#46; Cancer-specific survival was significantly worse in group 1 using ADT than radical prostatectomy or radiotherapy&#46; In high-risk and locally advanced tumors&#44; ADT also had a lower cancer-specific survival than local treatments&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A longer time until the castration resistance was observed in patients with well- and intermediate-risk localized tumors treated with ADT&#46; Patients with metastatic tumors showed the shortest time to castration resistance&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Antecedentes El efecto del tratamiento primario de privaci&#243;n androg&#233;nica &#40;TPA&#41; en pacientes con c&#225;ncer de pr&#243;stata &#40;CP&#41; localizado no est&#225; bien documentado&#46; El objetivo del presente estudio fue analizar el resultado de los tumores tratados con TPA como terapia primaria en el Registro Espa&#241;ol de C&#225;ncer de Pr&#243;stata &#40;19&#44;4&#37; de la serie&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Los pacientes se clasificaron en tres grupos&#58; 1&#41; con tumores cl&#237;nicamente localizados de riesgo bajo&#47;intermedio&#59; 2&#41; con tumores de alto riesgo y localmente avanzados &#40;T3-4&#41;&#59; 3&#41; con tumores metast&#225;sicos&#46; Se analiz&#243; el tiempo hasta la resistencia a la castraci&#243;n y la supervivencia general espec&#237;fica del c&#225;ncer&#46; En tumores no metast&#225;sicos&#44; las supervivencias en pacientes tratados con TPA se compararon con los datos de pacientes que recibieron tratamientos locales del Registro Espa&#241;ol de C&#225;ncer de Pr&#243;stata&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se analizaron 703 casos&#46; Hubo diferencias significativas en el tiempo de resistencia a la castraci&#243;n&#44; que fue menor en el grupo de tumores metast&#225;sicos&#46; Durante el seguimiento hubo 179 muertes &#40;25&#44;5&#37;&#41;&#44; de las cuales 89 &#40;12&#44;6&#37;&#41; se debieron a CP&#46; Despu&#233;s de 3 a&#241;os de TPA&#44; solo el 14&#44;6&#37; de los pacientes en el grupo 1 fallecieron &#40;1&#37; debido a CP&#41;&#44; el 20&#44;5&#37; en el grupo 2 y el 46&#44;8&#37; en el grupo 3 &#40;9&#44;2&#37; y 31&#44;3&#37; debido a CP&#44; respectivamente&#41;&#46; La supervivencia espec&#237;fica del c&#225;ncer fue significativamente peor en el grupo 1 tratado con TPA que en el que recibi&#243; prostatectom&#237;a radical o radioterapia&#46; En los tumores de alto riesgo y localmente avanzados&#44; la TPA tambi&#233;n tuvo una menor supervivencia espec&#237;fica al c&#225;ncer que los tratamientos locales&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se observ&#243; un tiempo m&#225;s largo hasta la resistencia a la castraci&#243;n en pacientes con tumores localizados de riesgo intermedio y bien tratados con TPA&#46; Los pacientes con tumores metast&#225;sicos mostraron el menor tiempo hasta la resistencia a la castraci&#243;n&#46;</p></span>"
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          0 => array:1 [
            "identificador" => "abst0025"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Pacientes y m&#233;todos"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&#243;n"
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    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Garcia-Rodriguez J&#44; Fernandez-Gomez JM&#44; Cozar JM&#44; Mi&#241;ana B&#44; Gomez-Veiga F&#44; Rodriguez-Antolin A&#44; et al&#46; Terapia de privaci&#243;n de andr&#243;genos en pacientes con enfermedad localizada&#58; comparaci&#243;n de las opciones de tratamiento y tiempo hasta la resistencia a la castraci&#243;n&#46; Resultados del Registro Espa&#241;ol de C&#225;ncer de Pr&#243;stata&#46; Actas Urol Esp&#46; 2020&#59;44&#58;156&#8211;163&#46;</p>"
      ]
      1 => array:3 [
        "etiqueta" => "&#9674;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">The researchers participating in the Grupo Espa&#241;ol de C&#225;ncer de Pr&#243;stata &#40;GESCAP&#41; are listed in <a class="elsevierStyleCrossRef" href="#sec0030">Appendix A</a>&#46;</p>"
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      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0105" class="elsevierStylePara elsevierViewall">CHUAC &#40;Paula P&#243;rtela&#44; Eva Blanco&#44; Juan Andr&#233;s Gonz&#225;lez&#41;&#44; Hospital Regional Universitario Carlos Haya &#40;V&#237;ctor Baena&#44; Pedro Morales&#41;&#44; Fundaci&#243;n Puigvert &#40;Humberto Villavicencio&#44; Joan Palou&#41;&#44; H&#46; de Basurto &#40;Ana Loizaga&#41;&#44; H&#46; Cl&#237;nic i Provincial de Barcelona &#40;Alex Ciudin&#44; Diaconau Mihai&#41;&#44; H&#46; Cl&#237;nico Universitario de Valencia &#40;Jos&#233; Mar&#237;a Mart&#237;nez Jabaloyas&#44; Ana Castell&#243;&#44; Nelson D&#237;ez&#41;&#44; H&#46; Cl&#237;nico Universitario Lozano Blesa &#40;Francisco Javier Romero&#44; Jorge Subir&#225;&#44; Ana Isabel Ch&#225;vez&#44; Victoria Capap&#233;&#44; Mar&#237;a Mata&#44; Javier Elizalde&#41;&#44; H&#46; General Universitario de Alicante &#40;Juan Jos&#233; Lobato&#44; Jes&#250;s Jim&#233;nez&#44; Lu&#237;s P&#233;rez Llorca&#44; Juan Antonio Tenza&#41;&#44; H&#46; General Universitario Gregorio Mara&#241;&#243;n &#40;Felipe Herranz&#44; Adri&#225;n Husillos&#44; Esther L&#243;pez&#44; Daniel Ram&#237;rez&#44; Igor Blaha&#41;&#44; H&#46; General Universitario Morales Meseguer &#40;Emilio Izquierdo&#44; Leandro Reina&#41;&#44; H&#46; U&#46; 12 de Octubre &#40;Juan Passas&#44; Laura D&#237;ez&#41;&#44; H&#46; U&#46; Central de Asturias &#40;Miguel A&#46; Hevia&#41;&#44; H&#46; U&#46; de Bellvitge &#40;Manel Castells&#41;&#44; H&#46; U&#46; de Canarias &#40;Tom&#225;s Concepci&#243;n Masip&#44; Ana Cristina Plata&#41;&#44; H&#46; U&#46; Infanta Cristina &#40;Sim&#243;n Asuar Aydillo&#44; Juan Alonso&#44; Jes&#250;s Mateos&#41;&#44; H&#46; U&#46; Puerta de Hierro-Majadahonda &#40;Joaqu&#237;n Carballido&#44; Claudio Mart&#237;nez&#44; Jennifer Areche&#41;&#44; H&#46; U&#46; Ram&#243;n y Cajal &#40;Rafael Rodr&#237;guez&#44; Vital Hevia&#44; Sara &#193;lvarez&#41;&#44; H&#46; U&#46; Reina Sof&#237;a &#40;Mar&#237;a Jos&#233; Requena&#44; Rafael Prieto&#44; Jos&#233; Lu&#237;s Carazo&#44; Javier M&#225;rquez&#44; Enrique G&#243;mez&#44; Jos&#233; Horacio Garc&#237;a&#41;&#44; H&#46; U&#46; R&#237;o Hortega &#40;Jos&#233; Am&#243;n&#44; Marcos Cepeda&#44; Luis &#193;lvarez&#44; Ver&#243;nica Rodr&#237;guez&#44; Beatriz de la Cruz&#44; Alberto Rivero&#44; Juan Francisco S&#225;nchez&#44; Juan Antonio Mainez&#41;&#44; H&#46; U&#46; Virgen del Roc&#237;o &#40;Rafael Medina&#44; Manuel Conde&#41;&#44; H&#46; U&#46; Virgen Macarena &#40;Jes&#250;s Casti&#241;eiras&#44; Antonio Carlos Gonz&#225;lez Baena&#44; Ernesto S&#225;nchez&#44; Rub&#233;n Campanario&#44; Roc&#237;o Saiz&#44; Edwin Romero&#41;&#44; H&#46; U&#46; Vall d&#8217;Hebron &#40;Juan Morote&#44; Carles Xavier Ravent&#243;s&#44; Ana Celma&#41;&#44; H&#46; Virgen de las Nieves &#40;Fernando V&#225;zquez&#41;&#44; H&#46; Virgen de la Salud &#40;Antonio G&#243;mez&#44; Elena Buend&#237;a&#44; Natanael Garc&#237;a&#41;&#46;</p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Grupo Espa&#241;ol de C&#225;ncer de Pr&#243;stata"
            "identificador" => "sec0030"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Cancer-specific survival in group 2 &#40;high risk localized and locally advanced tumors&#41; according to treatment including patients from the Spanish Prostate Cancer Registry&#46;</p> <p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">ADT&#58; Androgen Deprivation Therapy&#59; EBR and&#47;or BT&#58; External beam radiation and&#47;or brachytherapy&#59; RP&#58; radical Prostatectomy&#46;</p>"
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