Resultados oncológicos a largo plazo del tratamiento cáncer de próstata de alto riesgo mediante prostatectomía radical en un hospital oncológico / Long-term oncological results of treatment for high-risk prostate cancer using radical prostatectomy in a cancer hospital

Objetivos: Analizar los resultados oncológicos más relevantes en el tratamiento mediante prostatectomía radical (PR) en el cáncer de próstata de alto riesgo (CPAR) en un hospital oncológico. Material y métodos: Estudio retrospectivo descriptivo de las PR realizadas en nuestro centro desde 1986 a 2017 en CPAR para conocer como objetivo primario las supervivencia global (SG) y cáncer específica (SCE), y como objetivos secundarios las supervivencias libre de progresión bioquímica (SLPB), libre de progresión metastática (SLPM), la necesidad de tratamiento de rescate (SLTR), la necesidad de hormonoterapia (SLHT) y finalmente el desarrollo de cáncer de próstata resistente a la castración. Se realizan análisis de regresión de Cox para establecer modelos predictivos y conocer el peso de cada variable definitoria de alto riesgo. Resultados: Se realizaron 2.093 PR de las cuales 480 (22,9%) fueron en CPAR. La mediana de seguimiento de la serie global fue 79,57 meses (P25-75 37,92-135,16). No se realizó linfadenectomía (LDN) en el 6,5% de los casos, mientras que fue LDN obturatriz en 51,2% y extensa en 42,3%. La SG a 5, 10 y 15 años fue de 89,8% (IC 95%: 86,7-92,9%), 73,3% (IC 95%: 68-78,6%) y 51,4% (IC 95%: 43,8-59%). La SCE a 5, 10 y 15 años fue de 94,8% (IC 95%: 92,4-97,2%), 84,0% (IC 95%: 79,3-88,7%) y 75,5% (IC 95%: 68,8-82,2%) La SLPM a 5, 10 y 15 años fue de 87,4% (IC 95%: 84,1-90,7%), 72,2% (IC 95%: 66,7-77,7%) y 61,7% (IC 95%: 54,3-69,1%) respectivamente. Se requirió radioterapia de rescate en 120 pacientes de 477 analizados (25,1%) y 293/477 nunca han requerido hormonoterapia (61,4%). En relación con el uso de HT en los 93 pacientes pN1, 33 (35,5%) no la han necesitado. El tiempo desde la PR a la progresión bioquímica es la variable de mayor peso pronóstico para la SLPM, la SCE y la SG. Conclusiones: La PR más LDN extensa debería ser la primera maniobra terapéutica cuando es factible dentro de una estrategia multimodal. Es necesario un seguimiento mayor de la serie para validar la hipótesis de unos mejores resultados oncológicos basándose en una aplicación más precoz de la RT de rescate, una LDN extensa y los fármacos prolongadores de supervivencia en la fase de CPRC

Objectives: To analyse the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital. Material and methods: A descriptive retrospective study of RP was conducted at our centre from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk. Results: A total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (P25-75 37.92-135.16). Lymphadenectomy was not performed in 6.5% of the cases. The lymphadenectomy was of the obturator type in 51.2% of the cases and extended in 42.3%. Overall survival at 5, 10 and 15 years was 89.8% (95% CI 86.7-92.9%), 73.3% (95% CI 68-78.6%) and 51.4% (95% CI 43.8-59%), respectively. CSS at 5, 10 and 15 years was 94.8% (95% CI 92.4-97.2%), 84.0% (95% CI 79.3-88.7%) and 75.5% (95% CI 68.8-82.2%), respectively. MFS at 5, 10 and 15 years was 87.4% (95% CI 84.1-90.7%), 72.2% (95% CI 66.7-77.7%) and 61.7% (95% CI 54.3-69.1%), respectively. A total of 120 patients of 477 analysed (25.1%) required rescue radiation therapy, and 293/477 never required hormone therapy (61.4%). Of the 93 pN1 patients, 33 (35.5%) did not require hormone therapy. The time from RP to biochemical progression was the variable with the greatest prognostic weight for MFS, CSS and overall survival. Conclusions: RP plus extended lymphadenectomy should be the first therapeutic manoeuvre when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase

Long-term oncological results of treatment for high-risk prostate cancer using radical prostatectomy in a cancer hospital. / Resultados oncológicos a largo plazo del tratamiento cáncer de próstata de alto riesgo mediante prostatectomía radical en un hospital oncológico.

OBJECTIVES: To analyse the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital. MATERIAL AND METHODS: A descriptive retrospective study of RP was conducted at our centre from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk. RESULTS: A total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (P25-75 37.92-135.16). Lymphadenectomy was not performed in 6.5% of the cases. The lymphadenectomy was of the obturator type in 51.2% of the cases and extended in 42.3%. Overall survival at 5, 10 and 15 years was 89.8% (95% CI 86.7-92.9%), 73.3% (95% CI 68-78.6%) and 51.4% (95% CI 43.8-59%), respectively. CSS at 5, 10 and 15 years was 94.8% (95% CI 92.4-97.2%), 84.0% (95% CI 79.3-88.7%) and 75.5% (95% CI 68.8-82.2%), respectively. MFS at 5, 10 and 15 years was 87.4% (95% CI 84.1-90.7%), 72.2% (95% CI 66.7-77.7%) and 61.7% (95% CI 54.3-69.1%), respectively. A total of 120 patients of 477 analysed (25.1%) required rescue radiation therapy, and 293/477 never required hormone therapy (61.4%). Of the 93 pN1 patients, 33 (35.5%) did not require hormone therapy. The time from RP to biochemical progression was the variable with the greatest prognostic weight for MFS, CSS and overall survival. CONCLUSIONS: RP plus extended lymphadenectomy should be the first therapeutic manoeuvre when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase.

Programa de monitorización de la vigilancia activa en cáncer de próstata en España de la Sociedad Española de Urología; resultados preliminares / Preliminary results of the Spanish Association of Urology National Registry in Active Surveillance for prostate cancer

Objetivos: Presentar un registro nacional de pacientes con cáncer de próstata seguidos mediante vigilancia activa, con la intención de testar la hipótesis de que la mortalidad cáncer específica en pacientes de muy bajo riesgo y riesgo bajo es menor del 5% a 15 años. Material y métodos: Estudio multicéntrico observacional (AEU-PIEM/2014/0001) promovido por la Asociación Española de Urología mediante su plataforma para estudios multicéntricos, en donde los criterios de inclusión clínico-patológicos son: cT1a-cT3a, PSA ≤ 20 ng/ml, biopsia (Bx) inicial mínima de 10 cilindros, número de cilindros afectos ≤ 3, Gleason 1.° = 3 y Gleason 2.° ≤ 4, y volumen prostático conocido (en cc). No se establece un seguimiento unificado para todos los centros reclutadores, y sí una encuesta en la que se reflejen las características del seguimiento en función de unos parámetros tangibles que permitan su comparabilidad. Con la misma filosofía de flexibilidad no se considera obligada la utilización de determinados biomarcadores o de RMN mutiparamétrica para su inclusión. Resultados: Se presentan las características y posibilidades del registro a modo descriptivo y los resultados preliminares de 324 pacientes incluidos en sus primeros 5 meses de funcionamiento por 15 centros reclutadores. De la misma forma se describen las variables clínico-patológicas, biomarcadores, técnicas de radiodiagnóstico y cuestionarios de calidad de vida contemplados por la base de datos, así como las posibilidades de seguimiento indefinido y abierto a cualquier tratamiento activo reconocido en guías clínicas. Conclusiones: La AEU-PIEM/2014/0001 constituye una herramienta extremadamente útil a todos los urólogos españoles para la investigación clínica multicéntrica, y sin duda permitirá la difusión de la vigilancia activa entre nuestros pacientes de una forma más coordinada, permitiendo mantener las ventajas del screeningoportunista optimizado en cáncer de próstata sin incurrir en el sobretratamiento

Objectives: To present a National Registry of patients with prostate cancer as monitored through active surveillance, with the intention of testing the hypothesis that cancer-specific mortality in very low-risk and low-risk patients is less than 5% at 15 years. Material and methods: A multicentre observational study (AEU-PIEM/2014/0001) sponsored by the Spanish Association of Urology was conducted using their platform for multicentre studies. The clinical-pathological inclusion criteria were as follows: cT1a-cT3a, PSA ≤ 20 ng/ml, initial minimum biopsy of 10 cores, number of affected cores ≤ 3, 1st Gleason score of 3 and 2nd Gleason score ≤ 4 and a known prostate volume (in cc). A unified follow-up was not established for all recruiting centres; however, a survey was conducted that reflects the follow-up characteristics based on a number of tangible parameters that allow for their comparison. With the same philosophy of flexibility, the use of certain biomarkers and multiparametric MRI was not considered necessary for inclusion. Results: We describe the Registry's characteristics and possibilities, as well as the preliminary results from the 324 patients included in its first 5 months of operation in the 15 recruiting centres. We also report the clinical-pathological variables, biomarkers, radiodiagnosis technique and quality-of-life questionnaires considered for the database, as well as the possibilities for indefinite follow-up, remaining open to any active treatment recognized in clinical guidelines. Conclusions: The AEU-PIEM/2014/0001 represents an extremely useful tool for all Spanish urologists for multicentre clinical research. The registry will undoubtedly enable the dissemination of active surveillance of our patients in a more coordinated manner, thus maintaining the advantages of optimised opportunistic screening for prostate cancer without resulting in overtreatment

Preliminary results of the Spanish Association of Urology National Registry in Active Surveillance for prostate cancer.

OBJECTIVES: To present a National Registry of patients with prostate cancer as monitored through active surveillance, with the intention of testing the hypothesis that cancer-specific mortality in very low-risk and low-risk patients is less than 5% at 15 years. MATERIAL AND METHODS: A multicentre observational study (AEU-PIEM/2014/0001) sponsored by the Spanish Association of Urology was conducted using their platform for multicentre studies. The clinical-pathological inclusion criteria were as follows: cT1a-cT3a, PSA ≤ 20 ng/ml, initial minimum biopsy of 10 cores, number of affected cores ≤ 3, 1st Gleason score of 3 and 2nd Gleason score ≤ 4 and a known prostate volume (in cc). A unified follow-up was not established for all recruiting centres; however, a survey was conducted that reflects the follow-up characteristics based on a number of tangible parameters that allow for their comparison. With the same philosophy of flexibility, the use of certain biomarkers and multiparametric MRI was not considered necessary for inclusion. RESULTS: We describe the Registry's characteristics and possibilities, as well as the preliminary results from the 324 patients included in its first 5 months of operation in the 15 recruiting centres. We also report the clinical-pathological variables, biomarkers, radiodiagnosis technique and quality-of-life questionnaires considered for the database, as well as the possibilities for indefinite follow-up, remaining open to any active treatment recognized in clinical guidelines. CONCLUSIONS: The AEU-PIEM/2014/0001 represents an extremely useful tool for all Spanish urologists for multicentre clinical research. The registry will undoubtedly enable the dissemination of active surveillance of our patients in a more coordinated manner, thus maintaining the advantages of optimised opportunistic screening for prostate cancer without resulting in overtreatment.

Evaluación del dolor y factores asociados en pacientes sometidos a biopsia de próstata / Assessment and clinical factors associated with pain in patients undergoing transrectal prostate biopsy

Objetivos: Cuantificar el grado de dolor que sufren los pacientes sometidos a biopsia transrectal de próstata ecodirigida en la práctica clínica habitual, y evaluar qué factores clínicos se encuentran asociados a un mayor dolor. Material y métodos: Análisis de una serie multicéntrica de pacientes con biopsia de próstata según la práctica clínica habitual. La biopsia se realizó vía transrectal con un protocolo de anestesia local sobre el paquete nervioso posterolateral. Se evaluó el dolor a los 20 min del procedimiento a través de la escala visual analógica (0-10). Se analiza el grado de dolor soportado y se estudia la asociación de forma uni/multivariante de variables clínicas seleccionadas y el grado de dolor. Resultados: Se analizaron un total de 1.188 pacientes de 64 años de mediana de edad. Un 30% de las biopsias fueron diagnósticas de tumor. La mediana de dolor fue de 2, con un 65% de pacientes con dolor ≤ 2. El análisis multivariante muestra que el volumen prostático (RR: 1,34, IC 95%: 1,01-1,77; p = 0,04), el hecho de tener una biopsia previa (RR: 2,25, IC 95%: 1,44-3,52; p < 0,01), la edad (RR:0,63, IC 95%: 0,47-0,85; p < 0,01) y un tacto doloroso (RR: 1,95, IC 95%: 1,28-2,96; p < 0,01), son factores asociados de forma independiente con mayor dolor durante el procedimiento. Conclusiones: La biopsia transrectal con anestesia local es una técnica poco dolorosa. Factores como la edad, una biopsia previa, un tacto doloroso y el volumen prostático se asocian con la presencia de un mayor dolor durante el procedimiento

Objectives: To quantify the degree of pain experienced by patients who undergo ultrasound-guided transrectal prostate biopsy in standard clinical practice and assess the clinical factors associated with increased pain. Material and methods: Analysis of a multicenter series of patients with prostate biopsy according to standard clinical practice. The biopsy was performed transrectally with a protocol of local anesthesia on the posterolateral nerve bundle. The pain was assessed at 20 minutes into the procedure using the visual analog scale (0-10). The degree of pain was analyzed, and the association was studied using a univariate/multivariate analysis of selected clinical variables and the degree of pain. Results: A total of 1188 patients with a median age of 64 years were analyzed. Thirty percent of the biopsies were diagnosed with a tumor. The median pain score was 2, with 65% of the patients reporting a pain score ≤ 2. The multivariate analysis showed that the prostate volume (RR, 1.34; 95% CI 1.01-1.77; P = .04), having a previous biopsy (RR, 2.25; 95% CI 1.44-3.52; P < .01), age (RR, .63; 95% CI .47-.85; P < .01) and feel palpation (RR, 1.95; 95% CI 1.28-2.96; P < .01) were factors independently associated with greater pain during the procedure. Conclusions: Transrectal biopsy with local anesthesia is a relatively painless technique. Factors such as age, a previous biopsy, pain on being touched and prostate volume were associated with the presence of greater pain during the procedure

Assessment and clinical factors associated with pain in patients undergoing transrectal prostate biopsy.

OBJECTIVES: To quantify the degree of pain experienced by patients who undergo ultrasound-guided transrectal prostate biopsy in standard clinical practice and assess the clinical factors associated with increased pain. MATERIAL AND METHODS: Analysis of a multicenter series of patients with prostate biopsy according to standard clinical practice. The biopsy was performed transrectally with a protocol of local anesthesia on the posterolateral nerve bundle. The pain was assessed at 20minutes into the procedure using the visual analog scale (0-10). The degree of pain was analyzed, and the association was studied using a univariate/multivariate analysis of selected clinical variables and the degree of pain. RESULTS: A total of 1188 patients with a median age of 64 years were analyzed. Thirty percent of the biopsies were diagnosed with a tumor. The median pain score was 2, with 65% of the patients reporting a pain score ≤2. The multivariate analysis showed that the prostate volume (RR, 1.34; 95% CI 1.01-1.77; P=.04), having a previous biopsy (RR, 2.25; 95% CI 1.44-3.52; P<.01), age (RR, .63; 95% CI .47-.85; P<.01) and feel palpation (RR, 1.95; 95% CI 1.28-2.96; P<.01) were factors independently associated with greater pain during the procedure. CONCLUSIONS: Transrectal biopsy with local anesthesia is a relatively painless technique. Factors such as age, a previous biopsy, pain on being touched and prostate volume were associated with the presence of greater pain during the procedure.

Fístula rectovaginal y enterocutánea espontáneas: potenciales complicaciones durante la terapia con fármacos antiangiogénicos en cáncer renal / Spontaneous enterocutaneous and rectovaginal fistula: potential complications during therapy with anti-angiogenic drugs in renal cancer

Se presentan dos casos de fístula, enterovaginal y enterocutánea asociadas a tratamiento con pazopanib, un inhibidor de la angiogénesis para el tratamiento de cáncer renal metastásico. El tiempo entre el inicio del fármaco y la aparición de la fístula fue de 6 y 16 meses, respectivamente; en ninguno de los casos hubo antecedentes de radioterapia o cirugía previa en la zona donde surgió la complicación. Según lo reportado en la literatura, alrededor de un 70% de pacientes se benefician de un tratamiento conservador. Las fístulas enterovaginales y enterocutáneas, suponen menos del 1% de las complicaciones publicadas por el uso de fármacos antiangiogénicos; a pesar de eso, es una complicación que deberíamos tener presente, pues se reporta una mortalidad cercana al 30%. A través de este artículo, queremos trasmitir nuestra experiencia en este tipo de complicación, ya por su baja incidencia, es indudable, que esta por vía de información, nos podemos apoyar los diferentes especialistas que tratan a estos pacientes; tomando las precauciones necesarias y decidiendo un manejo adecuado

We present two cases of enterovaginal and enterocutaneous fistulae associated to treatment with pazopanib, which is an angiogenesis inhibitor for the treatment of metastatic renal cancer. The times from drug administration and the first appearance of a fistula were 6 and 16 months, respectively. None of the cases had a history of surgery or radiotherapy in the area where the complication was observed. Enterovaginal and enterocutaneous fistula represent less than 1% of all published complications caused by the use of antiangiogenic drugs. However, they must be taken into account as the reported mortality rate is close to 30%. Given its low incidence, we believe that sharing this data is a great way to help specialists who have to treat these patients to take the necessary precautions and decide on an adequate approach

Información obligatoria que debe conocer un paciente con cáncer de próstata candidato a vigilancia activa / Obligatory Information that a Patient Diagnosed of Prostate Cancer and Candidate for an Active Surveillance Protocol must know

Objetivos: Conocer la información necesaria para reproducir los resultados de la literatura en vigilancia activa (VA) en cáncer de próstata (CaP) en nuestro propio centro, de tal forma que dicha información sea objetiva y se le pueda dar al paciente de forma fehaciente. Contemplamos estudiar el porcentaje de pacientes candidatos a VA y que la escogen en nuestro ambiente, los datos de infraestadificación, infragradación y predicción de CaP insignificante, depurar el poder predictivo de distintas variables clínicas para mejorar nuestros criterios de selección y analizar los resultados de nuestros pacientes en VA. Material y métodos: Revisión retro y prospectiva de nuestras bases de datos. Se analiza un periodo de un año natural seleccionando posibles candidatos a VA. Análisis de nuestras prostatectomías radicales para conocer las tasas de infraestadificación, infragradación y tasa de CaP insignificante (criterios de Epstein). Análisis uni/multivariado de variables clínicas en pacientes con tumor insignificante en pieza de prostatectomía radical. Valoración prospectiva de supervivencia global y libre de tratamiento activo (SLTA) en pacientes en VA. Resultados: Entre octubre de 2010 y octubre de 2011, un 44,7% de los CaP cumplían criterios para ser incluidos en VA, y un 11,2% la escogieron. Nuestros porcentajes de infraestadificación, infragradación y tasa de CaP insignificante fueron 14%; 31,4%; y 55,7% respectivamente, pero solo 6 pacientes (6,97%) tuvieron CaP ≥ pT3a + Gleason ≥ 7 + volumen > 0,5 cc. En el estudio multivariado para predicción de tumor insignificante, la densidad de PSA y el número de cilindros afectos son factores independientes. Con un seguimiento medio de 36 ± 39 meses, de 232 incluidos en VA, 63 pacientes pasaron a tratamiento activo (27,1%), solo 13 por ansiedad sin progresión patológica. La mediana del tiempo de SLTA es de 72,7 meses (IC 95%: 30,9-114,4). La SLTA a los 24 meses es del 76,4% (69,7-83,1%) y a 48 meses es del 58,1% (48,8-67,4%). Solo 10 pacientes (4,3%) fallecieron, 9 por causa diferente al CaP. La supervivencia global estimada a 5 años es del 92,8% (IC 95%: 86,7-98,9%). Conclusiones: El conocimiento exacto de la casuística de cada centro debería ser obligatorio para informar a los pacientes verazmente de la rentabilidad de la biopsia y de si los porcentajes de infragradación, infraestadificación y de CaP insignificante se adecuan a los de la literatura. A 3 años reproducimos los resultados de las series más longevas de VA, por lo que el programa de VA puede seguir implementándose e incluyendo cada vez a más pacientes

Objectives To know the necessary information to reproduce the results found in the literature on active surveillance (AS) in prostate cancer (PCa) in our own center so that the information would be objective and correctly given to the patients. We have aimed to study the percentage of candidates for AS chosen in our setting, and the data on infrastaging, subgrading and prediction of insignificant PCa, debugging the predictive value of clinical variables to improve our selection criteria and finally to analyze the results of our patients enrolled in AS. Materials and methods: A retro- and prospective review of our data bases was performed. A one-year period was analyzed to know AS candidates. Analysis of our radical prostatectomy specimens for infrastaging, subgrading and prediction of insignificant PCa (Epstein's criteria) was made as well as a uni/multivariate analysis of clinical variables in patients with insignificant PCa in the specimen. A prospective validation was performed with overall survival and survival free of active treatment (SFAT) as endpoints in patients enrolled in AS. Results: Between October-2010/October-2011, 44.7% of our PCa were candidates for AS, but only 11.2% choose it. The percentages found for infrastaging, subgrading and prediction of insignificant PCa were 14%, 31.4% and 55.7%, respectively. However, only just 6 patients (6.97%) had ≥ pT3a + Gleason ≥7 + volume > 0.5 cc PCa. The multivariate analysis showed that PSA density and number of affected cores were independent predictors of insignificant PCa. With a mean follow-up of 36 ± 39 months, 63 out of 232 patients enrolled in AS went on to active treatment (27.1%), with only 13 due to anxiety without pathologic progression. Median time of SFAT was 72.7 months (CI 95% 30.9-114.4). SFAT at 24 months was 76.4% (69.7-83.1%) and at 48 months 58.1% (48.8-67.4%). Only 10 patients died (4.3%), 9 due to causes different of PCa. Estimated overall survival at 5 years was 92.8% (CI 95% 86.7-98.9%). Conclusions: It should be mandatory to have the exact knowledge of the local data of each Center in order to objectively inform patients about prostate biopsy efficiency, and if percentages of infrastaging, subgrading and prediction of insignificant PCa are in accordance with the literature. At 3 years, we reproduced the results of the longest series of AS, so we have ascertained that our AS protocol can be implemented with increasingly more patients

Prostatectomy pathology findings in an active surveillance population.

OBJECTIVES: The difficulty in predicting indolent prostate cancer leads to the use of different inclusion criteria in an active surveillance (AS) program. This chapter presents the pathology findings of radical prostatectomy (RP) in patients whose disease meet criteria for AS, as well as of those who are operated during AS. METHODS: Two independent Medline searches were conducted, both of them with a double objective: pathological findingsin radical prostatectomy specimens of patients who could have been included in AS and pathological features of patients operated after an AS period. The following terms were used for the research: "prostaticneoplasm", "radical prostatectomy" and "active surveillance": "radical prostatectomy", "after", "following" and "active surveillance". Pathological findings in radical prostatectomy specimens, down staging and downgrading rates were recorded. Active surveillance length and reason for surgery was included when it was available. RESULTS: Depending on different AS inclusion criteria, clinical downgrading rate (pathological Gleason > 6) varied between 12.1 and 61% and clinical downstaging between 0-26%. Pathological Gleason score =8 was reported in 0-7.8% and there were anecdotal findings of seminal vesicle invasion or positive nodes. Overall, unfavorable pathology (Gleason ≥ 7 or stage ≥ pT3)was detected in 13.1-42.4%, based on different definitions. The criteria at John Hopkins were the strictest and had the lowest clinical downgrading and downstaging. On the other hand, the Memorial Sloan Kettering Cancer Center(MSKCC) criteria had the highest risk of unfavorable pathology but had the highest recruitment capacity. Indolent tumor was observed in 70-82.2% according to the current definition. The average duration in AS prior to surgery was 15-37 months. pT3 stage was seen in 7.7-36.7%, Gleason score 3+4 in 18.6-42.9%, Gleason score 4+3 in 1.4-31.8%, Gleason score >7 in 0-10.3%, positive margins in 3-40.9%. Seminal vesicle invasion rate was extremely low (0-2.9%) as well as positive nodes (0-4.5%). CONCLUSIONS: Although there is a low risk of clinical downstaging and downgrading between patients who have being included in AS, it remains feasible. The probability of predicting an indolent tumor depends greatly on the quality of the prostate biopsy and/or the confirmatory biopsy. On the other hand, most patients who progress in an AS program can have a high probability of cure. We are still in the early stages of AS management in order to be able to predict the biological behavior and the cure rate of radical prostatectomy in patients after a long AS period.

Resultados anatomopatológicos en candidatos a vigilancia activa en cáncer de próstata / Pathologic findings in patients with prostate cancer candidates for active surveillance

OBJETIVO: La existencia de diferentes criterios de inclusión en programas de vigilancia activa (VA) refleja la dificultad de predecir la presencia de un tumor insignificante. Nuestro objetivo en este capítulo es analizar los resultados anatomopatológicos de prostatectomías realizadas (PR) tanto en pacientes que presentaban criterios de inclusión en VA y se operaron como los de aquellos que se operaron tras estar en VA. MÉTODOS: Se realizaron dos búsquedas bibliográficas independientes a través de Medline, ambas con doble finalidad: artículos que estudian resultados patológicos en pacientes con diferentes criterios de inclusión en VA introduciendo los siguientes términos: "prostatic neoplasms", "radical prostatectomy" y "active surveillance", y artículos que estudian resultados en prostatectomías tras un periodo inicial de inclusión en VA con los siguientes términos: "radical prostatectomy", "after", "following" y "active surveillance". Se analizan los hallazgos en piezas de PR y tasas de infragradación e infraestadiaje. En el análisis de la segunda búsqueda se incluye, cuando está disponible, el tiempo de permanencia en VA y el motivo de tratamiento. RESULTADOS: La tasa de infragradación (Gleason>6) oscila entre 12,1 y 61%, la tasa de infraestadiaje oscila entre 0 y 26%, dependiendo de los diferentes criterios de inclusión analizados y las series de diferentes centros. Índices de Gleason ≥8 se encuentran en 0-7,8% y la presencia de invasión de vesículas seminales y adenopatías es anecdótica. De manera conjunta, patología desfavorable (Gleason ≥7 o estadio ≥pT3) se halla entre 13,1 y el 42,4% según las series. Los criterios de inclusión más estrictos pero con menor índice de infragradación e infraestadiaje corresponden a los del John Hopkins y los más laxos con mayor riesgo de patología desfavorable son los del grupo del Memorial Sloan Kettering Cancer Center (MSKCC). Con la definición actual de cáncer insignificante, éste está presente en el 70 a 82,2% de las prostatectomías realizadas en pacientes con los principales criterios de inclusión en programas de VA. El tiempo medio de permanencia en un programa de VA previo a la realización de PR oscila de 15 a 37 meses. En las PR realizadas después de un tiempo variable bajo VA encontramos: estadio pT3a = 7,7 a 36,7%, Gleason 3+4 = 18,6 a 42,9%, Gleason 4+3 = 1,4 a 31,8%, Gleason >7 = 0 a 10,3%, márgenes positivos = 3-40,9%. La presencia de invasión de vesículas seminales es anecdótica (0-2,9%) al igual que la de ganglios positivos (0-4,5%). CONCLUSIONES: El riesgo de infragradación e infraestadiaje, aunque bajo, es real, independientemente de los criterios utilizados para incluir a un paciente en VA pero se reduce conforme se hagan más restrictivos. La precisión para definir un tumor clínicamente insignificante depende en gran medida de la calidad de la biopsia y/o de la rebiopsia de confirmación. Por otra parte, pacientes que progresan bajo VA pueden ser rescatados con alta probabilidad de curación, aunque aún es pronto para conocer el comportamiento biológico y la respuesta terapéutica a largo plazo de pacientes bajo VA

OBJECTIVES: The difficulty in predicting indolent prostate cancer leads to the use of different inclusion criteria in an active surveillance (AS) program. This chapter presents the pathology findings of radical prostatectomy (RP) in patients whose disease meet criteria for AS, as well as of those who are operated during AS.METHODS: Two independent Medline searches were conducted, both of them with a double objective: pathological findingsin radical prostatectomy specimens of patients who could have been included in AS and pathological features of patients operated after an AS period. The following terms were used for the research: "prostaticneoplasm", "radical prostatectomy" and "active surveillance";: "radical prostatectomy", "after", "following" and "active surveillance". Pathological findings in radical prostatectomy specimens, down staging and downgrading rates were recorded. Active surveillance length and reason for surgery was included when it was available. RESULTS: Depending on different AS inclusion criteria, clinical downgrading rate (pathological Gleason>6) varied between 12.1 and 61% and clinical downstaging between 0-26%. Pathological Gleason score ≥8 was reported in 0-7.8% and there were anecdotal findings of seminal vesicle invasion or positive nodes. Overall, unfavorable pathology (Gleason ≥7 or stage ≥pT3) was detected in 13.1 -42.4%, based on different definitions. The criteria at John Hopkins were the strictest and had the lowest clinical downgrading and downstaging. On the other hand, the Memorial Sloan Kettering Cancer Center (MSKCC) criteria had the highest risk of unfavorable pathology but had the highest recruitment capacity. Indolent tumor was observed in 70-82.2% according to the current definition. The average duration in AS prior to surgery was 15-37 months. pT3 stage was seen in 7.7-36.7%, Gleason score 3+4 in 18.6-42.9%, Gleason score 4+3 in 1.4-31.8%, Gleason score >7 in 0-10.3%, positive margins in 3-40.9%. Seminal vesicle invasion rate was extremely low (0-2.9%) as well as positive nodes (0-4.5%). CONCLUSIONS: Although there is a low risk of clinical downstaging and downgrading between patients who have being included in AS, it remains feasible. The probability of predicting an indolent tumor depends greatly on the quality of the prostate biopsy and/or the confirmatory biopsy. On the other hand, most patients who progress in an AS program can have a high probability of cure. We are still in the early stages of AS management in order to be able to predict the biological behavior and the cure rate of radical prostatectomy in patients after a long AS period

Optimización de un programa de cribado oportunista de cáncer de próstata; ensayo aleatorizado prospectivo del papel del PSA y del PCA3 en uso secuencial / Optimizing prostate cancer screening; prospective randomized controlled study of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening program

Objetivos: Reducir el número de biopsias (Bx) innecesarias en un programa de cribado oportunista en cáncer de próstata (CaP). Material y métodos: Estudio prospectivo y aleatorizado evaluando el PCA3 como biomarcador de segunda línea. De septiembre de 2010 a septiembre de 2012 2.366 hombres con edad en rango 40-74 años, y más de 10 años de expectativa de vida, fueron estudiados mediante PSA y tacto rectal (TR), excluyendo los biopsiados previamente o con infección urinaria reciente. Ante un TR sospechoso y/o PSA > 3 ng/ml se les realizó un PCA3. A todos aquellos con PCA3 ≥ 35 se les realizó una Bx inicial (IBx) -12 cilindros-. Con PCA3 < 35 fueron aleatorizados 1:1 a IBx u observación. Los criterios de rebiopsia (16-18 cilindros) durante el seguimiento fueron un incremento de PSA > 0,5 ng/ml a 6 meses o PSAv > 0,75 ng/ml/año. Resultados: Con un seguimiento medio de 10,1 meses se testó el PCA3 en 321/2.366 hombres (13,57%), 289 en la primera visita y 32 durante el seguimiento. Entre los 110 hombres con PCA3+ (34,3%) se identificó CaP en 43 en IBx (39,1%). En el brazo aleatorizado 110 se observaron y 101 se biopsiaron, encontrando 12 CaP (11,9%), mostrando un reducción en la detección de CaP estadísticamente significativa en esta cohorte (p < 0,001). Las tasas de detección global de CaP fueron de 40,9 y 9,5% para las ramas PCA3+ y PCA3- respectivamente (p < 0,001). AUC para PSA y PCA3 fueron 0,601 y 0,74. Este es un protocolo abierto en este momento, limitado por su seguimiento insuficiente. Conclusiones: El PCA3 como biomarcador de segunda línea en un programa de cribado oportunista podría potencialmente evitar un 65,7% de IBx y 50,1% a 10 meses de seguimiento, dejando de diagnosticar 3,2% de CaP de alto grado

Objectives: To reduce unnecessary biopsies (Bx) in an opportunistic screening programme of prostate cancer. Material and methods: We perform a prospective evaluation of PCA3 as a second line biomarker in an opportunistic screening for prostate cancer (PCa). From September-2010 until September-2012, 2,366 men, aged 40-74 years and with > 10 years life expectancy, were initially screened with PSA/digital rectal examination (DRE). Men with previous Bx or with recent urine infections were excluded. Men with abnormal DRE and/or PSA > 3 ng/ml were submitted for PCA3. All men with PCA3 ≥ 35 underwent an initial biopsy (IBx) -12 cores-. Men with PCA3 < 35 were randomized 1:1 to either IBx or observation. Re-biopsy (16-18 cores) criteria were PSA increase > 0.5 ng/ml at 4-6months or PSAv > 0.75 ng/ml/year. Results: With median follow-up (FU) of 10.1 months, PCA3 was performed in 321/2366 men (13.57%), 289 at first visit and 32 during FU. All 110 PCA3+ men (34.3%) were biopsied and PCa was identified in 43 men in IBx (39.1%). In the randomized arm, 110 were observed and 101 underwent biopsy, finding 12 PCa (11.9%), showing a statistically significant reduction of PCa detection rate in this cohort (P < 0.001). Global PCa detection rates were 40.9% and 9.5% for the PCA3+ and PCA3- branches, respectively (P < 0.001). Area under the curve for PSA and PCA3 were 0.601 and 0.74, respectively. This is an ongoing prospective study limited by its short follow-up period and still limited enrolment. Conclusions: PCA3 as a second line biomarker within an opportunistic dual screening protocol, can potentially avoid 65.7% and 50.1% biopsies at first round and at median FU of 10.1 months, respectively, just missing around 3.2% of high grade PCa

Obligatory information that a patient diagnosed of prostate cancer and candidate for an active surveillance protocol must know.

OBJECTIVES: To know the necessary information to reproduce the results found in the literature on active surveillance (AS) in prostate cancer (PCa) in our own center so that the information would be objective and correctly given to the patients. We have aimed to study the percentage of candidates for AS chosen in our setting, and the data on infrastaging, subgrading and prediction of insignificant PCa, debugging the predictive value of clinical variables to improve our selection criteria and finally to analyze the results of our patients enrolled in AS. MATERIALS AND METHODS: A retro- and prospective review of our data bases was performed. A one-year period was analyzed to know AS candidates. Analysis of our radical prostatectomy specimens for infrastaging, subgrading and prediction of insignificant PCa (Epstein's criteria) was made as well as a uni/multivariate analysis of clinical variables in patients with insignificant PCa in the specimen. A prospective validation was performed with overall survival and survival free of active treatment (SFAT) as endpoints in patients enrolled in AS. RESULTS: Between October-2010/October-2011, 44.7% of our PCa were candidates for AS, but only 11.2% choose it. The percentages found for infrastaging, subgrading and prediction of insignificant PCa were 14%, 31.4% and 55.7%, respectively. However, only just 6 patients (6.97%) had≥pT3a+Gleason≥7+volume>0.5cc PCa. The multivariate analysis showed that PSA density and number of affected cores were independent predictors of insignificant PCa. With a mean follow-up of 36±39months, 63 out of 232 patients enrolled in AS went on to active treatment (27.1%), with only 13 due to anxiety without pathologic progression. Median time of SFAT was 72.7 months (CI 95% 30.9-114.4). SFAT at 24 months was 76.4% (69.7-83.1%) and at 48 months 58.1% (48.8-67.4%). Only 10 patients died (4.3%), 9 due to causes different of PCa. Estimated overall survival at 5 years was 92.8% (CI 95% 86.7-98.9%). CONCLUSIONS: It should be mandatory to have the exact knowledge of the local data of each Center in order to objectively inform patients about prostate biopsy efficiency, and if percentages of infrastaging, subgrading and prediction of insignificant PCa are in accordance with the literature. At 3 years, we reproduced the results of the longest series of AS, so we have ascertained that our AS protocol can be implemented with increasingly more patients.

La prostatectomía radical es un tratamiento razonable para los pacientes mayores de 70 años / Radical Prostatectomy is a Reasonable Treatment for Patients Over 70 Years of Age

Objetivo: Comparar la naturaleza tumoral y la evolución oncológica de los pacientes intervenidos mediante prostatectomía radical en 3 grupos de edad. Material y método: De la base de datos de cumplimentación prospectiva de nuestro Servicio, analizamos 1.012 pacientes intervenidos entre los años 1986 y diciembre de 2009. Se excluyeron los pacientes con tratamiento neo o adyuvante y aquellos con PSA preoperatorio mayor de 50. Se dividió la muestra en 3 grupos: menores de 60, de 61 a 69 y los de 70 y mayores. Se analizaron las variables clínicas, patológicas, la evolución bioquímica y la necesidad de rescate. Consideramos recidiva bioquímica cuando los valores de PSA alcanzan cifras mayores de 0,4 en 2 mediciones consecutivas. Se definió rescate como la necesidad de tratamiento hormonal o de la administración de radioterapia. Procedimos a un estudio comparativo, un análisis de supervivencia univariante mediante curvas de Kaplan y Meyer y multivariante mediante regresión de Cox. Resultados: La mediana de seguimiento fue de 55,1 meses. De los 1.012 pacientes incluidos en el estudio 317 pacientes (31,3%) experimentaron progresión bioquímica y 259 (25,6%) necesitaron rescate. Observamos que los grupos de mayor edad tenían un PSA significativamente más alto y mayores estadios que el resto. No se objetivaron diferencias en el Gleason de la pieza quirúrgica ni en el estado de los márgenes quirúrgicos. La supervivencia libre de recidiva bioquímica a los 5 años fue del 72,3% (IC 95%: 66,4-78,2) en los pacientes menores de 60 años, del 65,3% (IC 95%: 60,6-70,0) para los pacientes menores de 70 y del 62,2% (IC 95%: 53,2-71,1) para los pacientes con 70 o más años; p < 0,05. En el estudio univariante la edad fue un factor que se asoció significativamente a la recidiva bioquímica; sin embargo, en el estudio multivariante pierde su interés y lo cobrabá el PSA, el estado patológico y el Gleason. La supervivencia libre de rescate no difería por grupos de edad. Conclusiones: En el presente estudio se objetivó una peor evolución bioquímica de los pacientes mayores de 70 años, sin embargo esta peor evolución bioquímica estuvo condicionada por tumores clínicamente más agresivos, lo que a nuestro juicio justifica la decisión tomada en cuanto a la actitud quirúrgica para con estos pacientes

Objective: To compare the tumor nature and oncological course of patients operated on by radical prostatectomy in three age groups. Materials and methods: From the prospective completion of the data base of our department, we analyzed 1012 patients operated on between 1986 and December 2009. Patients with neo- or adjuvant treatment and those with pre-operative PSA over 50 were excluded. The sample was divided into three groups: younger than 60, 60-69 and over 70. The clinical, pathological variables, biochemical course and need for rescue treatment were analyzed. We consider biochemical relapse as when the PSA values reached values greater than 0.4 in two consecutive measurements. Rescue was defined as the need for hormone treatment or radiotherapy. We then made a comparative study, a univariate survival analysis by Kaplan and Meyer Curves and multivariate by Cox's regression. Results: The median follow-up was 55.1 months. Of the 1012 patients included in the study, 317 patients (31.3%) had biochemical progression and 259 (25.6%) required rescue treatment. We observed that the groups with the older age had a significantly higher PSA and higher stages than the rest. No differences were observed in the Gleason score of the surgical specimen or in the state of the surgical margins. Biochemical relapse free survival at 5 years was 72.3% (CI 66.4-78.2) in patients under 60 years, 65.3% (CI 60.6-70.0) for patients under 70 and 62.2% (CI 53.2-71.1) for patients of 70 years or older; P < 0.05. In the univariate study, age was a factor that was significantly associated to biochemical relapse. However, it loses interest in the multivariate study and PSA, pathological state and Gleason score regain interest. Rescue treatment free survival did not differ by age groups. Conclusions: In the current study, worse biochemical evolution of patients over 70 was observed. However, this worse biochemical course was conditioned by clinically more aggressive tumors that, in our opinion, justifies the decision made in regards to the surgical approach taken with these patients

Radical prostatectomy is a reasonable treatment for patients over 70 years of age.

OBJECTIVE: To compare the tumor nature and oncological course of patients operated on by radical prostatectomy in three age groups. MATERIAL AND METHOD: From the prospective completion of the data base of our department, we analyzed 1012 patients operated on between 1986 and December 2009. Patients with neo- or adjuvant treatment and those with pre-operative PSA over 50 were excluded. The sample was divided into three groups: younger than 60, 60 to 69 and over 70. The clinical, pathological variables, biochemical course and need for rescue treatment were analyzed. We consider biochemical relapse as when the PSA values reached values greater than 0.4 in two consecutive measurements. Rescue was defined as the need for hormone treatment or radiotherapy. We then made a comparative study, a univariate survival analysis by Kaplan and Meyer Curves and multivariate by Cox's regression. RESULTS: The median follow-up was 55.1 months. Of the 1012 patients included in the study, 317 patients (31.3%) had biochemical progression and 259 (25.6%) required rescue treatment. We observed that the groups with the older age had a significantly higher PSA and higher stages than the rest. No differences were observed in the Gleason score of the surgical specimen or in the state of the surgical margins. Biochemical relapse free survival at 5 years was 72.3% (CI 66.4-78.2) in patients under 60 years, 65.3% (CI 60.6-70.0) for patients under 70 and 62.2% (CI 53.2-71.1) for patients of 70 years or older; P<.05. In the univariate study, age was a factor that was significantly associated to biochemical relapse. However, it loses interest in the multivariate study and PSA, pathological state and Gleason score regain interest. Rescue treatment free survival did not differ by age groups. CONCLUSIONS: In the current study, worse biochemical evolution of patients over 70 was observed. However, this worse biochemical course was conditioned by clinically more aggressive tumors that, in our opinion, justifies the decision made in regards to the surgical approach taken with these patients.

Optimizing prostate cancer screening; prospective randomized controlled study of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening program.

OBJECTIVES: To reduce unnecessary biopsies (Bx) in an opportunistic screening programme of prostate cancer. MATERIAL AND METHODS: We perform a prospective evaluation of PCA3 as a second line biomarker in an opportunistic screening for prostate cancer (PCa). From September-2010 until September-2012, 2,366 men, aged 40-74 years and with >10 years life expectancy, were initially screened with PSA/digital rectal examination (DRE). Men with previous Bx or with recent urine infections were excluded. Men with abnormal DRE and/or PSA >3 ng/ml were submitted for PCA3. All men with PCA3 ≥ 35 underwent an initial biopsy (IBx) -12cores-. Men with PCA3 < 35 were randomized 1:1 to either IBx or observation. Re-biopsy(16-18 cores) criteria were PSA increase >.5 ng/ml at 4-6 months or PSAv > .75 ng/ml/year. RESULTS: With median follow-up (FU) of 10.1 months, PCA3 was performed in 321/2366 men (13.57%), 289 at first visit and 32 during FU. All 110 PCA3+ men (34.3%) were biopsied and PCa was identified in 43 men in IBx (39.1%). In the randomized arm, 110 were observed and 101 underwent biopsy, finding 12 PCa (11.9%), showing a statistically significant reduction of PCa detection rate in this cohort (P<.001). Global PCa detection rates were 40.9% and 9.5% for the PCA3+ and PCA3- branches, respectively (P<.001). Area under the curve for PSA and PCA3 were .601 and .74, respectively. This is an ongoing prospective study limited by its short follow-up period and still limited enrolment. CONCLUSIONS: PCA3 as a second line biomarker within an opportunistic dual screening protocol, can potentially avoid 65.7% and 50.1% biopsies at first round and at median FU of 10.1 months, respectively, just missing around 3.2% of high grade PCa.

El margen quirúrgico es el factor pronóstico de mayor relevancia en los pacientes con cáncer de próstata que infiltra las vesículas seminales / Margin Status is a very Important Prognostic Factor for Patients with pT3b Prostate Cancer

Objetivo: Pese al diagnóstico precoz del cáncer de próstata, la invasión de las vesículas seminales por este tumor es un escenario patológico, todavía presente en nuestra práctica clínica. El objetivo del presente trabajo es evaluar los factores pronósticos clínicos y patológicos en la evolución de este subgrupo de pacientes. Material y método: Previa autorización por el comité de investigación clínica de nuestro centro, procedimos a la selección en nuestra base de datos de los pacientes con estadio pT3b intervenidos durante el periodo comprendido entre los años 1987-2010. Excluimos los pacientes con tratamientos neoadyuvantes. Mediante el método de Kaplan-Meier se evaluó el periodo libre de recidiva bioquímica (SLRB) y el periodo libre de necesidad de tratamientos complementarios (SLTC) (adyuvante o rescate). El modelo de regresión de Cox se utilizó para determinar las variables clínicas y patológicas que se asociaban a las anteriores circunstancias. Resultados: De 1.470 procedimientos 101 pacientes fueron incluidos en el estudio. Con una mediana de seguimiento de 4 años y 4 meses, 28 pacientes (27,7%) fallecieron, 18 por el tumor y 74 (73,3%) presentaron progresión bioquímica. La SLRB a los 5 años fue del 30,2% (IC 95%: 20,2-40,1) mientras que la SLTC fue del 16,9% (IC 95%: 8,1-25,8%).En el estudio multivariante el estado de los márgenes quirúrgicos (R1) fue la variable que se asoció de manera independiente y significativa a la recidiva bioquímica y a la necesidad de rescate. El PSA preoperatorio se asoció a la recidiva bioquímica, y la presencia de adenopatías patológicas a la necesidad de tratamiento. El número de ganglios extraídos y la puntuación Gleason no alcanzaron la significación estadística. Conclusión: En el grupo de pacientes con infiltración de las vesículas seminales R1 es un factor de mal pronóstico común, tanto para la recidiva bioquímica como para la necesidad de rescate (AU)

Objective: Despite early diagnosis of prostate cancer, seminal vesicle invasion is still a common clinical scenario nowadays. The objective of this study is to evaluate clinical and pathological prognostic factors in that subgroup of patients. Material and methods: After approval of our Ethical Committee, we selected all pT3b prostate cancer patients operated between 1987 and 2010. Neoadjuvant treatment patients were excluded. The biochemical free survival periods BFS and the period free of complementary treatment were calculated with the Kaplan Meier method. Cox regression model was used to select those variables associated with biochemical failure and the need for complementary treatment. We considered complementary treatment when radiotherapy or hormone therapy in an adjuvant or salvage scheme was required. Results: 101 patients were selected from 1470 procedures. Among these, 28 patients died (27,7%), 18 due to tumor, and 74 showed biochemical relapse (73,3%). The median follow up was of 4 years and 4 months. The five years BFS was 30.2% (IC 95%: 20.2-40.1), whereas the 5 year period free of complementary treatment was 16.9% (IC 95%: 8.1-25.8%).In the multivariate analysis, margin status (R) was independently and significantly associated with biochemical relapse and the need for complementary treatment. Likewise, the preoperative PSA was associated to biochemical relapse and N1 tumours were clearly associated to complementary treatment. Conclusion: pT3b prostate cancer patients with R1 disease have a worse biochemical prognosis and higher probability of complementary treatment (AU)

Margin status is a very important prognostic factor for patients with pT3b prostate cancer.

OBJECTIVE: Despite early diagnosis of prostate cancer, seminal vesicle invasion is still a common clinical scenario nowadays. The objective of this study is to evaluate clinical and pathological prognostic factors in that subgroup of patients. MATERIAL AND METHODS: After approval of our Ethical Committee, we selected all pT3b prostate cancer patients operated between 1987 and 2010. Neoadjuvant treatment patients were excluded. The biochemical free survival periods BFS and the period free of complementary treatment were calculated with the Kaplan Meier method. Cox regression model was used to select those variables associated with biochemical failure and the need for complementary treatment. We considered complementary treatment when radiotherapy or hormone therapy in an adjuvant or salvage scheme was required. RESULTS: 101 patients were selected from 1470 procedures. Among these, 28 patients died (27,7%), 18 due to tumor, and 74 showed biochemical relapse (73,3%). The median follow up was of 4 years and 4 months. The five years BFS was 30.2% (IC 95%: 20.2-40.1), whereas the 5 year period free of complementary treatment was 16.9% (IC 95%: 8.1-25.8%). In the multivariate analysis, margin status (R) was independently and significantly associated with biochemical relapse and the need for complementary treatment. Likewise, the preoperative PSA was associated to biochemical relapse and N1 tumours were clearly associated to complementary treatment. CONCLUSION: pT3b prostate cancer patients with R1 disease have a worse biochemical prognosis and higher probability of complementary treatment.

Resultados del uso expandido del PCA3 score en una población española con sospecha de cáncer de próstata / Outcomes of Expanded Use of PCA3 Testing in a Spanish Population with Clinical Suspicion of Prostate Cancer

Objetivos: La expresión del gen DD3PCA3 (PCA3) es específica del cáncer de próstata. El porcentaje de biopsias que se pueden ahorrar con este biomarcador es de 35-67%. Nuestro objetivo es analizar los resultados en uso rutinario y establecer en qué subgrupo de pacientes es más rentable según el número de biopsias previas. Material y métodos: Analizamos a 474 pacientes, biopsiados previamente (grupo A, n=337) o no (grupo B, n=134) en los que se solicitó el PCA3. Subdividimos el grupo A en A1 (una biopsia previa, n=182) y A2 (>1 biopsia previa, n=155). La recomendación de biopsiar o no se tomó de forma independiente por cada uno de los urólogos del Servicio junto con el antígeno prostático específico (PSA) y tacto rectal. Resultados: La mediana de edad fue 65 años (rango 38-84). La tasa informativa del PCA3 score fue del 99,6% y su mediana 29 (rango 1-3245). El porcentaje de ahorro de biopsias fue 49%. Las áreas bajo la curva ROC para PSA y PCA3 fueron de 0,532(p=0,417) y 0,672(p<0,0001). La sensibilidad de PSA≥4 y PCA3≥35 fueron 87 y 85%, la especificidad 12 y 33%, el valor predictivo positivo (VPP) 34 y 39% y el valor predictivo negativo (VPN) 63 y 81%. Tomado el valor de PCA3 como variable contínua, a mayor PCA3 obtenemos mayor porcentaje de biopsias positivas (p<0,0001). Conclusiones: El uso rutinario del PCA3 ahorra la mitad de las biopsias, basándose sobre todo en su alto VPN. La mayor rentabilidad diagnóstica del PCA3 la obtenemos en pacientes sin biopsia. Entre los pacientes ya biopsiados, los resultados son ligeramente mejores en aquellos con solo una (AU)

Objectives: DD3PCA3 (PCA3) gene expression is prostate cancer-specific. Routine use of this biomarker has resulted in a 35-67% reduction in the number of required biopsies. The aim of this study is to evaluate our outcomes in its routine use and to establish in which group of patients this is the most efficient, depending on the number of previous PCA3 biopsies. Material and methods: A total of 474 consecutive patients who had previously undergone a biopsy (group A, n=337) or not (group B, n=134) for whom a PCA3 was requested were analyzed. We subdivided group A into A1 (a previous biopsy, n=182) and A2 (<1 previous biopsy, n=155). The recommendation of whether to perform a biopsy or not was made independently by each of the 11 clinicians and guided by prostatic specific antigen (PSA) levels and digital rectal examination. Results: Median age was 65 years (range 38 to 84). PCA3 score had an informative ratio of 99.6%, with a median of 29 (range 1-3245). The percentage of biopsy sparing was 49% of the cases. ROC analysis demonstrated an AUC for PSA and PCA3 of 0.532 (P=.417) and 0.672 (P<.0001), respectively. Sensitivities of PSA≥ 4 and PCA3≥ 35 were 87% vs. 85%, with specificities of 12% vs. 33%, PPV 34% vs. 39% and NPV 63% vs. 81%, respectively. The PCA3 score showed direct correlation with the percentage of positive biopsies (P<.0001). Conclusions: Routine use of PCA3, due to its high NPV, results in a significant reduction in the number of biopsies. PCA3 appears to be more efficient in biopsy-naive patients. Among patients already biopsied, the results are superior in those biopsied only once (AU)

Diagnóstico fotodinámico con hexaminolevulinato en el cáncer vesical no músculo invasivo: experiencia del grupo BLUE / Hexaminolevulinate photodynamic diagnosis in non-muscle invasive bladder cancer: experience of the BLUE group

Objetivos: El diagnóstico fotodinámico (DFD) con hexaminolevulinato se ha empezado a utilizar recientemente para mejorar la detección del cáncer vesical no músculo invasivo. Nuestro objetivo principal fue comparar el rendimiento diagnóstico de DFD frente a endoscopia con luz blanca convencional (LB) en nuestro medio. Material y métodos: Se realizó cistoscopia fluorescente con hexaminolevulinato en el momento de la RTU a 305 pacientes de 7 hospitales españoles. Todas las lesiones detectadas con LB y DFD fueron enumeradas y registradas en una base de datos online. Se analizó histopatológicamente cada lesión por separado. En 148 pacientes se tomaron además biopsias múltiples aleatorias (BMA). Resultados: Se biopsiaron un total de 1.659 lesiones: 522 identificadas con DFD y LB, 237 sólo con DFD, 19 sólo con LB y 881 BMA. De 600 neoplasias diagnosticadas DFD detectó 563, LB 441 y BMA 29 (20 CIS). La tasa media de sobredetección de DFD sobre LB fue del 31,9% globalmente, pero en el caso del CIS fue del 209%. La sensibilidad de DFD fue 93,8% y la de LB 78,2%. La especificidad de DFD fue 81,5% y la de LB 90,5%. En el 23% de los pacientes se detectó al menos una lesión neoplásica más con DFD que con LB. Conclusión: La RTU con hexaminolevulinato mejora el rendimiento diagnóstico y la calidad de la resección del cáncer vesical superficial, especialmente del CIS. La mayor sensibilidad de DFD es a costa de una menor especificidad. En nuestro estudio BMA rescató algunos falsos negativos de DFD para detectar CIS (AU)

Objectives: Photodynamic diagnosis (PDD) with hexaminolevulinate has been recently used to improve detection of non-muscle invasive bladder cancer. Our main purpose was to quantify the benefit of PDD vs. conventional white light cystoscopy (WL) in our area. Material and methods: Fluorescence-guided cystoscopy using hexaminolevulinate was performed at the time of the transurethral resection (TUR) in 305 patients from 7 Spanish hospitals. All lesions found with WL and PDD were numbered and recorded in an online database. Each lesion was sent separately for pathology analysis. Random biopsies were also obtained in 148 patients. Results: A total of 1659 lesions were biopsied: 522 were identified with PDD and WL, 237 only with PDD, 19 only with WL and 881 random biopsies. Of the 600 tumors, PDD detected 563, WL 441 and random biopsies 29 (20 CIS). The mean overdetection rate for PDD over WL was 31.9% for all types of lesions, but it was 209% for carcinoma in situ (CIS). Sensitivity was 93.8% for PDD and 78.2% for WL. Specificity was 81.5% for PDD and 90.5% for WL. In 23% of patients, PDD detected at least one additional neoplastic lesion compared to WL. Conclusions: Hexaminolevulinate fluorescence cystoscopy improves detection and resection of non-muscle invasive bladder cancer, especially of CIS. Sensitivity of PDD is higher than WL, but specificity is lower. In our study, random biopsies were able to detect some CIS not visible under PDD (AU)

[Outcomes of expanded use of PCA3 testing in a Spanish population with clinical suspicion of prostate cancer]. / Resultados del uso expandido del PCA3 score en una población española con sospecha de cáncer de próstata.

OBJECTIVES: DD3(PCA3) (PCA3) gene expression is prostate cancer-specific. Routine use of this biomarker has resulted in a 35-67% reduction in the number of required biopsies. The aim of this study is to evaluate our outcomes in its routine use and to establish in which group of patients this is the most efficient, depending on the number of previous PCA3 biopsies. MATERIAL AND METHODS: A total of 474 consecutive patients who had previously undergone a biopsy (group A, n=337) or not (group B, n=134) for whom a PCA3 was requested were analyzed. We subdivided group A into A(1) (a previous biopsy, n=182) and A(2) (<1 previous biopsy, n=155). The recommendation of whether to perform a biopsy or not was made independently by each of the 11 clinicians and guided by prostatic specific antigen (PSA) levels and digital rectal examination. RESULTS: Median age was 65 years (range 38 to 84). PCA3 score had an informative ratio of 99.6%, with a median of 29 (range 1-3245). The percentage of biopsy sparing was 49% of the cases. ROC analysis demonstrated an AUC for PSA and PCA3 of 0.532 (P=.417) and 0.672 (P<.0001), respectively. Sensitivities of PSA≥ 4 and PCA3≥ 35 were 87% vs. 85%, with specificities of 12% vs. 33%, PPV 34% vs. 39% and NPV 63% vs. 81%, respectively. The PCA3 score showed direct correlation with the percentage of positive biopsies (P<.0001). CONCLUSIONS: Routine use of PCA3, due to its high NPV, results in a significant reduction in the number of biopsies. PCA3 appears to be more efficient in biopsy-naive patients. Among patients already biopsied, the results are superior in those biopsied only once.