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array:23 [ "pii" => "S2173578620300196" "issn" => "21735786" "doi" => "10.1016/j.acuroe.2019.09.001" "estado" => "S300" "fechaPublicacion" => "2020-04-01" "aid" => "1208" "copyright" => "AEU" "copyrightAnyo" => "2019" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "edi" "cita" => "Actas Urol Esp. 2020;44:125-30" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0210480619301731" "issn" => "02104806" "doi" => "10.1016/j.acuro.2019.09.001" "estado" => "S300" "fechaPublicacion" => "2020-04-01" "aid" => "1208" "copyright" => "AEU" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "edi" "cita" => "Actas Urol Esp. 2020;44:125-30" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Actualización del protocolo de manejo del cáncer de próstata resistente a la castración metastásico de la Asociación Andaluza de Urología" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "125" "paginaFinal" => "130" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Update of the Andalusian Association of Urology protocol for the management of metastatic castration-resistant prostate cancer" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2128 "Ancho" => 2225 "Tamanyo" => 246956 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Algoritmo de tratamiento de pacientes con CPRCm subtipos óseo y ganglionar. Grupo metástasis óseas: con afectación ósea con o sin afectación ganglionar y sin evidencia de afectación visceral; Grupo metástasis ganglionares: con afectación ganglionar (pélvica o extrapélvica) sin evidencia de afectación ósea o visceral<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">2,4</span></a>. La presencia de síntomas se basa en las escalas Brief Pain Inventory Short Form (BPI-SF) o Escala analgésica de la Organización Mundial de la Salud (OMS). * Los criterios de inelegibilidad a terapias sistémicas incluyen: a) la fragilidad del paciente, b) la existencia de múltiples comorbilidades por posible aumento del riesgo de efectos adversos<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">10</span></a>, c) la negativa del paciente/familiares a recibir este tratamiento, d) que condicione la eficacia o seguridad de las siguientes líneas de tratamiento<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">11</span></a>. Es importante tener en cuenta la decisión clínica del médico a la hora de decidir el esquema de tratamiento más adecuado para el paciente. <span class="elsevierStyleSup">†</span> Radio-223 ha de usarse antes del desarrollo de metástasis viscerales. El retraso en la administración de radio-223 puede afectar a que el paciente pueda obtener el beneficio proveído por el tratamiento completo (6 inyecciones).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.L. Álvarez-Ossorio, J.M. Cozar-Olmo, Á. Juárez-Soto, R. Medina-López, J. Moreno-Jiménez, M.J. Requena-Tapia" "autores" => array:6 [ 0 => array:2 [ "nombre" => "J.L." "apellidos" => "Álvarez-Ossorio" ] 1 => array:2 [ "nombre" => "J.M." "apellidos" => "Cozar-Olmo" ] 2 => array:2 [ "nombre" => "Á." "apellidos" => "Juárez-Soto" ] 3 => array:2 [ "nombre" => "R." "apellidos" => "Medina-López" ] 4 => array:2 [ "nombre" => "J." "apellidos" => "Moreno-Jiménez" ] 5 => array:2 [ "nombre" => "M.J." "apellidos" => "Requena-Tapia" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173578620300196" "doi" => "10.1016/j.acuroe.2019.09.001" "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/S2173578620300196?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480619301731?idApp=UINPBA00004N" "url" => "/02104806/0000004400000003/v2_202006090719/S0210480619301731/v2_202006090719/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173578620300184" "issn" => "21735786" "doi" => "10.1016/j.acuroe.2019.10.003" "estado" => "S300" "fechaPublicacion" => "2020-04-01" "aid" => "1224" "copyright" => "AEU" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Actas Urol Esp. 2020;44:131-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "The relationship between inguinal hernia and minimally-invasive surgery for prostate cancer: A systematic review of the literature" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "131" "paginaFinal" => "138" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La relación entre hernia inguinal y cirugía mínimamente invasiva para el cáncer de próstata: revisión sistemática de la literatura" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 376 "Ancho" => 1250 "Tamanyo" => 74333 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A) Persistence of the vaginal peritoneal duct and indirect right vesico-inguinal hernia objectified during a laparoscopic radical prostatectomy with transperitoneal access. B) Bilateral direct subclinical inguinal hernia.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "R. Bertolo, M.C. Mir Maresma, P. Bove, J. Rubio-Briones, M. Ramírez-Backhaus" "autores" => array:5 [ 0 => array:2 [ "nombre" => "R." "apellidos" => "Bertolo" ] 1 => array:2 [ "nombre" => "M.C." "apellidos" => "Mir Maresma" ] 2 => array:2 [ "nombre" => "P." "apellidos" => "Bove" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Rubio-Briones" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Ramírez-Backhaus" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210480619302165" "doi" => "10.1016/j.acuro.2019.10.005" "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/S0210480619302165?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578620300184?idApp=UINPBA00004N" "url" => "/21735786/0000004400000003/v1_202004300403/S2173578620300184/v1_202004300403/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Update of the Andalusian Association of Urology protocol for the management of metastatic castration-resistant prostate cancer" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "125" "paginaFinal" => "130" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "J.L. Álvarez-Ossorio, J.M. Cozar-Olmo, Á. Juárez-Soto, R. Medina-López, J. Moreno-Jiménez, M.J. Requena-Tapia" "autores" => array:6 [ 0 => array:3 [ "nombre" => "J.L." "apellidos" => "Álvarez-Ossorio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "J.M." "apellidos" => "Cozar-Olmo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Á." "apellidos" => "Juárez-Soto" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "R." "apellidos" => "Medina-López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "J." "apellidos" => "Moreno-Jiménez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 5 => array:4 [ "nombre" => "M.J." "apellidos" => "Requena-Tapia" "email" => array:1 [ 0 => "tapia3434@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Servicio de Urología, Hospital Puerta del Mar, Cádiz, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Urología, Hospital Virgen de las Nieves, Granada, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Urología, Hospital de Jerez, Cádiz, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Urología, Hospital Virgen del Rocío, Sevilla, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Urología, Complejo Hospitalario de Jaén, Jaén, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Urología, Hospital Reina Sofía, Córdoba, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Actualización del protocolo de manejo del cáncer de próstata resistente a la castración metastásico de la Asociación Andaluza de Urología" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3348 "Ancho" => 3167 "Tamanyo" => 469026 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Algorithm for monitoring mCRPC patients treated with radium-223 or abiraterone/enzalutamide. *Disregard PSA rise before 12 weeks (flare) which can be due to a transient effect on its production.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> PSA is not a reliable biomarker for radium-223 treatment. <span class="elsevierStyleSup">†</span>Symptoms, especially pain, may increase (flare) during first treatment cycle. **In the ALSYMCA study, the reduction of these two biomarkers was related to increased survival rates.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Although the value of these biomarkers has not been validated, monitoring is recommended in the absence of other validated biomarkers. <span class="elsevierStyleSup">#</span>Imaging tests should be performed in the face of progression suspicion by clinical or biochemical evaluation during this period.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Castration-resistant prostate cancer (CRPC) is a progressive disease with a high risk for developing metastasis (mCRPC), most likely spread to the bone.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The management of mCRPC remains a challenge today as it is a heterogeneous disease for which there are various therapeutic alternatives with different mechanisms of action, forms of administration and toxicity profiles. Prospective, comparative studies of these treatments as scarce, as well as information about the optimal sequencing to achieve maximum clinical benefit. This therapeutic scenario requires adequate baseline assessment and monitoring of the patient.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="par0010" class="elsevierStylePara elsevierViewall">To develop a treatment protocol for the management of mCRPC based on the most recent evidence and clinical experience, including the essential aspects of the patients’ baseline assessment, the choice and sequence of treatments and monitoring.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Baseline assessment</span><p id="par0015" class="elsevierStylePara elsevierViewall">Baseline evaluation of the patient with mCRPC should include clinical, biochemical and imaging determinations (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Clinical assessment</span><p id="par0020" class="elsevierStylePara elsevierViewall">Based on medical history, anamnesis and patient-reported outcomes. The instruments and scales used for patients' assessment are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Pain is the symptom with highest impact on quality of life in these cases. Other evaluations include symptom interference in daily life, health-related quality of life (HRQOL), the presence of comorbidities and analgesic use. The Comprehensive Geriatric Assessment (CGA) of the older patient with cancer G8 questionnaire<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> is applied for the evaluation of men older than 70 years. In case of recurrence, the patient would be submitted to a new assessment, which would also include information on the sequence of previous treatments, the type of progression and adverse effects. These assessment instruments are included in the national<span class="elsevierStyleSup">4</span> and European<span class="elsevierStyleSup">1</span> guidelines of mCRPC.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Imaging</span><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">99m</span>Tc Bone scan and abdominopelvic computed tomography (CT) are the standard imaging tests for baseline evaluation.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Based on the extent of metastasis,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> clinical subtypes with heterogenous prognosis and management are identified (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Laboratory tests</span><p id="par0030" class="elsevierStylePara elsevierViewall">The parameters to be included in this assessment are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Treatment</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Treatment for bone disease</span><p id="par0035" class="elsevierStylePara elsevierViewall">The algorithm presented in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a> refers to ECOG 0-1 patients and includes the latest modifications performed in the updated version of the European guidelines.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Initial treatment is based on patients' symptoms (pain). The use of the different agents in painless or mildly symptomatic patients is based on the evidence provided by the COU-AA-302<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> (abiraterone) and PREVAIL<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> (enzalutamide) studies, and for those with moderate-severe pain, therapy is based on the TAX 327<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> (docetaxel) and ALSYMPCA<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> (radium-223) studies (in case of ineligibility for treatment with docetaxel).</p><p id="par0045" class="elsevierStylePara elsevierViewall">Although abiraterone and enzalutamide are the most commonly used as 1st line treatment, patients will eventually present recurrence.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Several studies suggest the existence of cross-resistance between abiraterone and enzalutamide, which discourages sequencing.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The use of drugs with different mechanisms of action to progression allows a more complete approach to the disease.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Second and 3rd line recommendations are based on the evidence provided by the COU-AA-301<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> (abiraterone), AFFIRM<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> (enzalutamide) and ALSYMPCA<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> (radio-223) studies.</p><p id="par0050" class="elsevierStylePara elsevierViewall">This treatment scenario convolutes as the patient's therapeutic approach evolves, especially with regard to the use of abiraterone and docetaxel in hormone-sensitive PC or the use of enzalutamide, apalutamide and darolutamide in non-metastatic CRPC,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> which could result in a 2nd line treatment administration for the management of mCRPC in the future.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The use of bone protective agents (denosumab, zoledronic acid) together with calcium and vitamin D is recommended for the prevention of skeletal-related events, with the corresponding toxicity assessment.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Recently, the Spanish Agency of Medicine and Medical Devices has warned about the increased risk of vertebral fractures after discontinuation of denosumab.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Treatment for nodal disease</span><p id="par0060" class="elsevierStylePara elsevierViewall">Specific scientific evidence is scarce. Treatment options are shown in <a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Monitoring</span><p id="par0065" class="elsevierStylePara elsevierViewall">It is based on the follow-up of parameters analyzed at baseline, taking into account the specific toxicity indicators for each treatment (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). An indicative monitoring algorithm is proposed in <a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">On-treatment progression can be defined as “a convincing and consistent increase in prostate specific antigen (PSA), evidence of radiographic progression or the presence of clinical symptoms while the patient is being treated”.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The decision to discontinue therapy must be based on at least two of these 3 criteria.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The “no longer clinically benefiting” (NLCB) reporting metric highlights the distinction between the first evidence of progression and the clinical need to discontinue/change treatment.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The decision on whether or not to continue treatment depends on the pursued therapeutic objective.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Clinical monitoring</span><p id="par0080" class="elsevierStylePara elsevierViewall">It is recommended to ignore changes in pain or HRQL occurred during <12 weeks after treatment initiation in the absence of convincing evidence of progression.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Increased pain related to mCRPC is considered a progression criterion (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>).</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Imaging monitoring</span><p id="par0085" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a> shows the recommended frequency for imaging monitoring according to treatment response.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Bone progression is not considered unless at least 2 new lesions were seen on the first on-treatment scan, followed by 2 or more additional lesions on the second post-treatment scan (rule 2 + 2).<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4</span></a> Ambiguous lesions can be confirmed by CT or MRI. In the absence of new lesions, it is recommended to continue treatment if there are no other signs of progression. Soft tissue progression would be assessed according to RECIST 1.1 criteria. Treatment should be discontinued in the event of unequivocal progression of visceral disease without PSA or clinical progression.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Biochemical monitoring</span><p id="par0095" class="elsevierStylePara elsevierViewall">PSA cannot be considered an absolute marker of disease activity; it must be completed with clinical and imaging tests, if necessary (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>). The efficacy of radium-223 is not demonstrated by immediate PSA decline. However, androgen axis inhibitors or chemotherapy produce wide fluctuations.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,15</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Recent studies suggest that markers of total bone alkaline phosphatase (tALP) and lactate dehydrogenase (LDH) may be good candidates for biochemical monitoring.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Clinical trials define PSA response as ≥50% PSA decline confirmed by a second evaluation at least 3 weeks after treatment initiation. This threshold is used to classify patients treated with abiraterone or enzalutamide as "good responders" (PSA decline of ≥50%) or "partial responders" (PSA decline of <50%). PSA would not act as a marker of efficacy in patients treated with radium-223.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,15</span></a> Regular evaluation of tALP and LDH is recommended for the interpretation of discordant results (e.g., elevated PSA and clinical improvement).<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conclusions</span><p id="par0110" class="elsevierStylePara elsevierViewall">The analysis of the most recent evidence together with clinical experience, allow the elaboration of protocols like the present one, conveniently improving the management of the patient with mCRPC, consolidating aspects regarding baseline assessment, appropriate treatment selection and patient monitoring.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflicts of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">Bayer Hispania sponsored the creation and writing of this work. However, the company has not been involved in the contents of the study.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Objective" ] 2 => array:3 [ "identificador" => "sec0015" "titulo" => "Baseline assessment" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Clinical assessment" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Imaging" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Laboratory tests" ] ] ] 3 => array:3 [ "identificador" => "sec0035" "titulo" => "Treatment" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Treatment for bone disease" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Treatment for nodal disease" ] ] ] 4 => array:3 [ "identificador" => "sec0050" "titulo" => "Monitoring" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Clinical monitoring" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Imaging monitoring" ] ] ] 5 => array:2 [ "identificador" => "sec0065" "titulo" => "Biochemical monitoring" ] 6 => array:2 [ "identificador" => "sec0070" "titulo" => "Conclusions" ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Conflicts of interest" ] 8 => array:2 [ "identificador" => "xack459581" "titulo" => "Acknowledgements" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-08-28" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Álvarez-Ossorio JL, et al. Actualización del protocolo de manejo del cáncer de próstata resistente a la castración metastásico de la Asociación Andaluza de Urología. Actas Urol Esp. 2020;44:125–130.</p>" ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2128 "Ancho" => 2345 "Tamanyo" => 295936 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Algorithm of treatment for patients with bone and lymph node mCRPC. Bone metastasis group: bone -with or without nodal- involvement and no evidence of visceral disease; Nodal metastasis group: (pelvic or extrapelvic) nodal involvement with no evidence of bone or visceral affectation.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4</span></a> The presence of symptoms is based on the Brief Pain Inventory Short Form (BPI-SF) or the World Health Organization (WHO) analgesic ladder. *The ineligibility criteria for systemic therapies include (a) frail patients, (b) the existence of multiple comorbidities which could increase the risk of adverse effects,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> (c) patient or family refusal, d) when efficacy or safety of the subsequent lines of treatment is conditioned.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The provider’s clinical opinion must be taken into account when choosing the most appropriate treatment scheme for the patient. <span class="elsevierStyleSup">†</span>Radium-223 must be used before the development of visceral metastases. Delayed administration of radium-223 may affect the patient's benefit provided by the whole treatment (6 injections).</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3348 "Ancho" => 3167 "Tamanyo" => 469026 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Algorithm for monitoring mCRPC patients treated with radium-223 or abiraterone/enzalutamide. *Disregard PSA rise before 12 weeks (flare) which can be due to a transient effect on its production.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> PSA is not a reliable biomarker for radium-223 treatment. <span class="elsevierStyleSup">†</span>Symptoms, especially pain, may increase (flare) during first treatment cycle. **In the ALSYMCA study, the reduction of these two biomarkers was related to increased survival rates.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Although the value of these biomarkers has not been validated, monitoring is recommended in the absence of other validated biomarkers. <span class="elsevierStyleSup">#</span>Imaging tests should be performed in the face of progression suspicion by clinical or biochemical evaluation during this period.</p>" ] ] 2 => array:9 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Adapted from Scher et al.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>" "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">BPI-SF: Brief Pain Inventory Short Form; ECOG: Eastern Cooperative Oncology Group; EQ-5D: EuroQoL-5D (5 dimensions); VAS: visual analog scale; FACT-P: Functional Assessment of Cancer Therapy-Prostate; BS: bone scan; BMI: body mass index; LDH: lactate dehydrogenase; WHO: World Health Organization; PSADT: PSA doubling time; GOT: glutamic-oxalacetic transaminase; GPT: glutamic-pyruvic transaminase; MRI: magnetic resonance imaging; tALP: total alkaline phosphatase; CT: computed tomography.</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"><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">Assessment \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">Variable \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 " rowspan="8" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical</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">Age \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 (question 3 of the BPI-SF, WHO analgesic ladder, VAS) \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">Performance status (ECOG) \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">Health-related quality of life (EQ-5D, FACT-P)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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">Signs and symptoms related to bone 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">Comorbidities \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">Analgesic use<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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 systemic treatments/adverse effects \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 " rowspan="9" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Imaging</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: <span class="elsevierStyleSup">99m</span>Tc bone scan \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">Use the first post-treatment scan as baseline. \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">Nodal: contrast CT \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">In cases of intolerance to contrast: abdominopelvic MRI and CT without contrast \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">Pathologic and measurable lesions: ≥1.5 cm in short axis \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">Pathologic lesions according to clinical discretion: 1–1.5 cm \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">Visceral: contrast CT \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">In cases of intolerance to contrast: abdominopelvic MRI and CT without contrast \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">Pathologic, measurable lesions: ≥1 cm in long axis \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 " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Laboratory tests (blood and urine)</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">Complete blood count \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">Testosterone \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">Tumor markers (PSA, PSADT) \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 activity markers: tALP, LDH \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">Evaluation of liver function (Child-Pugh, GOT, GPT) \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">Assessment of kidney function (glomerular filtration and electrolytes) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2280550.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Regarding patients >70 years, these aspects are included in the G8 questionnaire, which also contains nutritional status, weight loss, BMI, motor skills and psychological status.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Baseline assessment of the patient with mCRPC.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "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=""><thead title="thead"><tr title="table-row"><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">Subtype \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">Characteristics \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">Bone 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">Bone -with or without nodal- involvement and no evidence of visceral disease \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">Nodal 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">Lymph node involvement (pelvic, with lymph nodes > 1 cm, or extrapelvic) 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-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">Visceral 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">Visceral involvement with or without bone or nodal disease. Includes lung, liver, adrenal or central nervous system \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2280551.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Clinical subtypes of the mCRPC according to the extent of metastases.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4</span></a></p>" ] ] 4 => array:9 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Taken from Scher et al.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>, Loizaga-Iriarte et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>, Crawford et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and Gillessen et al.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>" "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">BPI-SF: Brief Pain Inventory Short Form; VAS: visual analog scale; LDH: lactate dehydrogenase; WHO: World Health Organization; PSA: prostate specific antigen; tALP: total alkaline phosphatase.</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"><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">Androgen axis inhibitors (abiraterone/enzalutamide) \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">Targeted alpha therapy (radium-223) \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 " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Monitoring protocol</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">[0.2–3] <span class="elsevierStyleItalic">Clinical</span>: new signs, symptoms and changes since the last review (related to the disease as well potentially associated with the administered treatment (toxicity)<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Progression criterion: increased pain related to mCRPC (>3 points in the BPI-SF questionnaire, ≥1 step rise in the WHO analgesic ladder or increased VAS)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Toxicity must be classified according to the Common Terminology Criteria for Adverse Events system</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 " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\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"><span class="elsevierStyleItalic">Biochemical</span>: \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"><span class="elsevierStyleItalic">Biochemical</span>: \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 assessment: reduction ≥50% considered “good responder”, “partial responder” if <50%. Progression: increase ≥25% and ≥2 ng/ml vs. baseline value after 12 weeks of starting treatment in patients without an initial rise in PSA, or with respect to nadir and confirmed in a second determination ≥ 3 weeks in patients with an initial rise in PSA<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></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">PSA changes do not correspond to treatment response. \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">Transient PSA and tALP rises have been described up to 3 months after treatment initiation with abiraterone. Wait 3 months before making therapeutic decisions \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">LDH and especially tALP could be response markers<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> \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 " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\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"><span class="elsevierStyleItalic">Imaging:</span> \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"><span class="elsevierStyleItalic">Imaging:</span> \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">Partially responding patients: suspicion of progression in monthly or every three months routine reviews \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">Suspicion of progression in monthly visits during treatment or quarterly at post-treatment follow-up \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">Responding patients: suspicion of progression every 3 or 6 months in visits on a routine basis \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">Routinely, at 6 months after the end of treatment \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">Possible radiographic <span class="elsevierStyleItalic">flare</span> \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"> \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">When to stop/change treatment \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 decision to abandon treatment must be based on at least two of the three progression criteria \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">Complete treatment includes 6 cycles. All 6 must be completed in order to obtain the maximum benefit \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"> \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 absence of PSA (stable or <30% decrease) or radiological response 3 months after treatment initiation may be indicative of resistance<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></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">To radiographic and clinical progression \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2280552.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">It should not be evaluated based only on PSA.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Monitoring and therapeutic change criteria.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Mottet N, van den Bergh RCN, Briers E, Cornford P, de Santis M, Fanti S, et al. 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