A single-center comparison of our initial experiences in treating penile and urethral cancer with video-endoscopic inguinal lymphadenectomy (VEIL) and later experiences in melanoma cases.

Background: Video-endoscopic inguinal lymphadenectomy (VEIL) is a minimally invasive approach that is increasingly indicated in oncological settings, with mounting evidence for its long-term oncological safety. Objectives: To present our single-center experience of treating penile and urethral cancer with VEIL, as well as its more recent application in melanoma patients. Methods: We prospectively recorded our experiences with VEIL from September 2010 to July 2018, registering the patient primary indication, surgical details, complications, and follow-up. Results: Twenty-nine patients were operated in one (24) or both (5) groins; 18 had penile cancer, 1 had urethral cancer, and 10 had melanoma. A mean 8.62 ± 4.45 lymph nodes were removed using VEIL and of these, an average of 1.00 ± 2.87 were metastatic; 16 patients developed lymphocele and 10 presented some degree of lymphedema; there were no skin or other major complications. The median follow-up was 19.35 months; there were 3 penile cancer patient recurrences in the VEIL-operated side. None of the melanoma patients presented a lymphatic inguinal recurrence. Conclusions: VEIL is a minimally invasive technique which appears to be oncologically safe showing fewer complications than open surgery. However, complications such as lymphorrhea, lymphocele, or lymphedema were not diminished by using VEIL.

Does active surveillance avoid overtreatment in prostate cancer? Lessons learned from salvage radical prostatectomies.

OBJECTIVE: Determine whether our institution´s active surveillance (AS) protocol is a suitable strategy to minimise prostate cancer overtreatment. MATERIAL AND METHODS: Retrospective analysis of 516 patients on AS after prostate cancer diagnosis. Population divided into "per-protocol" vs "induced" AS depending on fulfilment of protocol´s inclusion criteria. Radical prostatectomies after AS were selected and stratified based on: reclassification, progression or patient anxiety. Clinicopathological features and biochemical relapse-free survival were studied. Primary endpoint was overtreatment ratio based on the presence of insignificant prostate cancer and adverse pathological features in the surgical specimen. Kaplan-Meier curves were used to estimate the biochemical relapse-free survival and compared with log-rank test. RESULTS: 304 patients fulfilled inclusion criteria; 100 proceeded to radical prostatectomy (31% "induced", 69% "per-protocol" AS). Surgery indications were reclassification, progression and anxiety in 66%, 18% and 16% of patients respectively. Rate of positive lymph nodes was higher in the progression group (11%) compared to reclassification and anxiety (5% and 0% respectively, P = .002). Positive surgical margins were more frequently reported in the progression cohort compared to reclassification (28% vs 20%). Median follow-up from diagnosis until last radical prostatectomy was 48.3 months (32.4-70). 3 year biochemical relapse-free survival in the salvage radical prostatectomy was 85.4% (95 CI 78.3-93.2). Insignificant cancer was noticed in 7% of patients (Epstein´s vs 24% Wolters´ criteria). Rate of patients with adverse pathological features was 36%. CONCLUSIONS: The majority of patients who underwent salvage surgery after AS were not overtreated. Radical prostatectomy should be considered a safe rescue treatment.

¿La vigilancia activa evita el sobretratamiento en el cáncer de próstata? Lecciones aprendidas de prostatectomías radicales de rescate / Does active surveillance avoid overtreatment in prostate cancer? Lessons learned from salvage radical prostatectomies

Objetivo: Determinar si el protocolo de vigilancia activa (VA) de nuestra institución es una estrategia adecuada para minimizar el sobretratamiento del cáncer de próstata.Material y métodosAnálisis retrospectivo de 516 pacientes en VA tras el diagnóstico de cáncer de próstata. La población se dividió en «VA por protocolo» vs. «VA inducida», dependiendo del cumplimiento de los criterios de inclusión del protocolo. Las prostatectomías radicales después de la VA fueron seleccionadas y estratificadas en base a reclasificación, progresión o ansiedad del paciente. Se estudiaron las características clinicopatológicas y la supervivencia libre de recidiva bioquímica. La variable principal del estudio fue el porcentaje de sobretratamiento con relación a la presencia de un cáncer de próstata insignificante y de características patológicas adversas en la pieza quirúrgica. Se utilizaron las curvas de Kaplan-Meier para estimar la supervivencia libre de recidiva bioquímica y se compararon con la prueba log-rank.ResultadosUn total de 304 pacientes cumplieron los criterios de inclusión; 100 procedieron a una prostatectomía radical (31% «VA inducida», 69% «VA por protocolo»). Las indicaciones para la cirugía fueron la reclasificación, la progresión y la ansiedad de los pacientes (66, 18 y 16%, respectivamente). (AU)

Objective: Determine whether our institution's active surveillance (AS) protocol is a suitable strategy to minimise prostate cancer overtreatment.Material and methodsRetrospective analysis of 516 patients on AS after prostate cancer diagnosis. Population divided into «per-protocol» vs «induced» AS depending on fulfilment of protocol's inclusion criteria. Radical prostatectomies after AS were selected and stratified based on reclassification, progression or patient anxiety. Clinicopathological features and biochemical relapse-free survival were studied. Primary endpoint was overtreatment ratio based on the presence of insignificant prostate cancer and adverse pathological features in the surgical specimen. Kaplan-Meier curves were used to estimate the biochemical relapse-free survival and compared with log-rank test.Results304 patients fulfilled inclusion criteria; 100 proceeded to radical prostatectomy (31% «induced», 69% «per-protocol» AS). Surgery indications were reclassification, progression and anxiety in 66%, 18% and 16% of patients, respectively. Rate of positive lymph nodes was higher in the progression group (11%) compared to reclassification and anxiety (5% and 0%, respectively; P=.002). Positive surgical margins were more frequently reported in the progression cohort compared to reclassification (28% vs 20%). Median follow-up from diagnosis until last radical prostatectomy was 48.3months (32.4-70). Three year biochemical relapse-free survival in the salvage radical prostatectomy was 85.4% (95%CI: 78.3-93.2). Insignificant cancer was noticed in 7% of patients (Epstein's vs 24% Wolters’ criteria). Rate of patients with adverse pathological features was 36%. (AU)

Frecuencia de PSA indetectable en pacientes con cáncer de próstata N+ baja carga tras prostatectomía radical y linfadenectomía ampliada / Undetectable PSA after radical prostatectomy is more likely in low burden N+ prostate cancer patients when an extended lymph node dissection is performed

Objetivos: Analizar la probabilidad de PSA indetectable (< 0,01 ng/ml) tras disección ampliada de los ganglios linfáticos pélvicos (DGLP-ampliada) versus disección estándar de los ganglios linfáticos (GL) pélvicos (DGLP-estándar) en pacientes pN+. Materiales y métodos: Se realizó una investigación en la base de datos institucional de cáncer de próstata para obtener información sobre pacientes que se sometieron a prostatectomía radical (PR) con DGLP, con hallazgos de 3 o menos metástasis ganglionares entre 2007 y 2017. La DGLP ampliada se definió de acuerdo con el número de GL. Los pacientes con un percentil 75 o superior de ganglios linfáticos extraídos conformaron el grupo DGLPa; los pacientes con un percentil 25 o inferior se adjudicaron al grupo DGLPe (DGLP estándar). Se compararon las variables clínicas y patológicas entre ambos grupos. Se utilizaron la prueba de la t de Student para comparar las variables continuas y la prueba de la chi al cuadrado para las variables categóricas. La regresión logística multivariable evaluó la probabilidad de PSA indetectable al tercer mes desde la operación. El método de Kaplan-Meier estimó la probabilidad de recurrencia bioquímica. Las diferencias entre los grupos se compararon mediante la prueba de log-rank. Resultados: De 1.478 pacientes tratados en el periodo considerado, se seleccionó a 95 con 3 o menos metástasis en los ganglios linfáticos. Tras aplicar los criterios de inclusión, 23 pacientes con una mediana de 11 GL extraídos se incluyeron en el grupo PGLPe (percentil 25) y 23 pacientes con > 27 GL se incluyeron en el grupo PGLPa (percentil 75). El tiempo quirúrgico fue más largo para el grupo de DGLPa. Dieciséis pacientes (69,6%) tratados con DGLPa presentaron PSA indetectable tras la operación. En el análisis multivariable, la probabilidad de PSA indetectable a los 3 meses fue mayor en los pacientes tratados con DGLPa (HR = 5,18; IC del 95%, 1,16-23,11; p = 0,03). Conclusiones: Independientemente de las características de la enfermedad, la DGLPa tiene más probabilidades de predecir un PSA indetectable al tercer mes tras la PR

Objectives: To analyze the likelihood of undetectable PSA (< 0.01 ng/mL) after extended (ePLND) versus standard pelvic lymph-nodes dissection (sPLND) in pN+ patients. Materials and methods: The institutional prospectively maintained Prostate Cancer Database was queried for patients who underwent radical prostatectomy with PLND and were found with 3or less lymph-nodal metastases between 2007 and 2017. The extension of the PLND was defined according to the number of lymph-nodes (LN) removed. Patients in the 75th or higher percentile of lymph-nodes removed were considered as the ePLND group; patients in the 25th or lower percentile in the sPLND group. Groups were compared in clinical and pathological variables. Student T-test was used for comparing continuous variables; chi-square test was used for categorical variables. Multivariable logistic regression assessed the probability of undetectable PSA at 3rd month postoperatively. Kaplan-Meier method estimated the probability of biochemical recurrence. Differences between the groups were compared by Log-rank test. Results: 1478 patients were treated within the time span considered. 95 with 1 to 3 lymph-nodal metastases were extracted. After accounting for inclusion criteria, 23 patients with a median of 11 LN removed were included in the sPLND group (25th percentile); 23 patients with > 27 LN were included in ePLND group (75th percentile). Surgical time was longer for ePLND. Sixteen patients (69.6%) who underwent ePLND had undetectable PSA postoperatively. At multivariable analysis, the probability of undetectable PSA at 3rd month was higher in patients who received an ePLND (HR = 5.18; IC 95% = 1.16-23.11; P = .03). Conclusions: ePLND is more likely to predict undetectable PSA at third month after radical prostatectomy, irrespective of disease characteristics

Undetectable PSA after radical prostatectomy is more likely in low burden N+ prostate cancer patients when an extended lymph node dissection is performed. / Frecuencia de PSA indetectable en pacientes con cáncer de próstata N+ baja carga tras prostatectomía radical y linfadenectomía ampliada.

OBJECTIVES: To analyze the likelihood of undetectable PSA (< 0.01 ng/mL) after extended (ePLND) versus standard pelvic lymph-nodes dissection (sPLND) in pN+ patients. MATERIALS AND METHODS: The institutional prospectively maintained Prostate Cancer Database was queried for patients who underwent radical prostatectomy with PLND and were found with 3or less lymph-nodal metastases between 2007 and 2017. The extension of the PLND was defined according to the number of lymph-nodes (LN) removed. Patients in the 75th or higher percentile of lymph-nodes removed were considered as the ePLND group; patients in the 25th or lower percentile in the sPLND group. Groups were compared in clinical and pathological variables. Student T-test was used for comparing continuous variables; chi-square test was used for categorical variables. Multivariable logistic regression assessed the probability of undetectable PSA at 3rd month postoperatively. Kaplan-Meier method estimated the probability of biochemical recurrence. Differences between the groups were compared by Log-rank test. RESULTS: 1478 patients were treated within the time span considered. 95 with 1 to 3 lymph-nodal metastases were extracted. After accounting for inclusion criteria, 23 patients with a median of 11 LN removed were included in the sPLND group (25th percentile); 23 patients with > 27 LN were included in ePLND group (75th percentile). Surgical time was longer for ePLND. Sixteen patients (69.6%) who underwent ePLND had undetectable PSA postoperatively. At multivariable analysis, the probability of undetectable PSA at 3rd month was higher in patients who received an ePLND (HR=5.18; IC 95%=1.16-23.11; P=.03). CONCLUSIONS: ePLND is more likely to predict undetectable PSA at third month after radical prostatectomy, irrespective of disease characteristics.

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.

PCA3 como biomarcador de segunda línea en un programa de screening oportunista prospectivo, aleatorizado y controlado / PCA3 as a second-line biomarker in a prospective controlled randomized opportunistic prostate cancer screening programme

Objetivos: Determinar el comportamiento del PCA3 como un marcador de segunda línea en un programa de cribado oportunista de cáncer de próstata (CaP) y su comparación con la calculadora de riesgo 3 del cribado aleatorizado europeo en cáncer de próstata (ERSPC RC-3). Material y métodos: En total de 5.199 hombres de 40-75 años se hicieron la prueba del antígeno prostático específico (PSA) y un tacto rectal (TR). Aquellos con TR normal y PSA ≥ 3ng/ml se realizaron un PCA3. Todos los hombres con PCA3 ≥ 35 se hicieron biopsia inicial (BxI) -12 cilindros-. Aquellos con PCA3 < 35 se aleatorizaron 1:1 a BxI u observación. Los resultados se comparan con los obtenidos con la aplicación de la calculadora ERSPC RC-3. Resultados: PCA3 se testó en 838 hombres (16,1%). En los grupos PCA3(+) y PCA3(-), las tasas de detección global de CaP fueron del 40,9 y del 14,7% a una mediana de seguimiento de 21,7 meses (p < 0,001. En el grupo PCA3(+) (n = 301, 35,9%), se identificó CaP en 115 hombres en BxI (38,2%). En el brazo aleatorizado, 256 se hicieron BxI y se objetivó CaP en 46 (18,0%) (p < 0,001). La potencial tasa de ahorro de biopsias siguiendo el corte PCA3 = 35 hubiera sido de 64,1% frente a la de 76,6% si hubiéramos usado ERSPC RC-3. Sin embargo, la tasa estimada de falsos negativos de CaP de alto grado (CaPAG = Gleason ≥ 7) se hubiera reducido un 37,1% (de 89 a 56 pacientes) al usar el PCA3. Si hubiéramos usado el corte 35 de PCA3 para no realizar BxI, hubiésemos dejado de diagnosticar un 14,7% de CaP y un 9,1% de CaP clínicamente significativo, a un seguimiento medio aproximado de 2 años. Conclusiones: Cuando se usa PCA3-35 como biomarcador de segunda línea en hombres con PSA ≥ 3ng/ml y TR normal, se puede obviar la BxI un 12,5% menos que usando la ERSPC RC-3, pero reduciendo los falsos negativos un 36,2%. A un seguimiento de 21,7 meses, este protocolo dual no hubiera detectado un 9,1% de CaP clínicamente significativo, por lo que el seguimiento con estrictos criterios de biopsia basados en PSA y TR es obligatorio en casos con PCA3 < 35

Objectives: PCA3 performance as a single second line biomarker is compared to the European Randomised Study of Screening for Prostate Cancer risk calculator model 3 (ERSPC RC-3) in an opportunistic screening in prostate cancer (PCa). Material and methods: 5,199 men, aged 40-75y, underwent prostate-specific antigen (PSA) screening and digital rectal examination (DRE). Men with a normal DRE and PSA ≥3ng/ml had a PCA3 test done. 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. We compared them to those obtained with ERSPC RC-3. Results: PCA3 test was performed on 838 men (16.1%). In PCA3(+) and PCA3(-) groups, global PCa detection rates were 40.9% and 14.7% with a median follow-up (FU) of 21.7 months (P <.001). In the PCA3(+) arm (n = 301, 35.9%), PCa was identified in 115 men at IBx (38.2%). In the randomized arm, 256 underwent IBx and PCa was found in 46 (18.0%) (P < .001). The biopsy-sparing potential would have been 64.1% as opposed to 76.6% if we had used ERSPC RC-3. However, the estimated false negative cases for HGPCa would have been reduced by 37.1% (89 to 56 patients). Moreover, if we had applied PCA3-35 to avoid IBx, 14.7% PCa and 9.1% of clinical significant PCa patients would not have been diagnosed during this FU. Conclusions: When PCA3-35 is used as a second-line biomarker when PSA ≥ 3ng/ml and DRE is normal, IBx could be avoided in 12.5% less than if ERSPC RC-3 is used and would reduce the false negative cases by 36.2%. At a FU of 21.7 months, this dual protocol would miss 9.1% of clinically significant PCa, so strict FU is mandatory with established biopsy criteria based on PSA and DRE in cases with PCA3 < 35

PCA3 as a second-line biomarker in a prospective controlled randomized opportunistic prostate cancer screening programme. / PCA3 como biomarcador de segunda línea en un programa de screening oportunista prospectivo, aleatorizado y controlado.

OBJECTIVES: PCA3 performance as a single second line biomarker is compared to the European Randomised Study of Screening for Prostate Cancer risk calculator model 3 (ERSPC RC-3) in an opportunistic screening in prostate cancer (PCa). MATERIAL AND METHODS: 5,199 men, aged 40-75y, underwent prostate-specific antigen (PSA) screening and digital rectal examination (DRE). Men with a normal DRE and PSA ≥3ng/ml had a PCA3 test done. 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. We compared them to those obtained with ERSPC RC-3. RESULTS: PCA3 test was performed on 838 men (16.1%). In PCA3(+) and PCA3(-) groups, global PCa detection rates were 40.9% and 14.7% with a median follow-up (FU) of 21.7 months (P<.001). In the PCA3(+) arm (n=301, 35.9%), PCa was identified in 115 men at IBx (38.2%). In the randomized arm, 256 underwent IBx and PCa was found in 46 (18.0%) (P<.001). The biopsy-sparing potential would have been 64.1% as opposed to 76.6% if we had used ERSPC RC-3. However, the estimated false negative cases for HGPCa would have been reduced by 37.1% (89 to 56 patients). Moreover, if we had applied PCA3-35 to avoid IBx, 14.7% PCa and 9.1% of clinical significant PCa patients would not have been diagnosed during this FU. CONCLUSIONS: When PCA3-35 is used as a second-line biomarker when PSA ≥3ng/ml and DRE is normal, IBx could be avoided in 12.5% less than if ERSPC RC-3 is used and would reduce the false negative cases by 36.2%. At a FU of 21.7 months, this dual protocol would miss 9.1% of clinically significant PCa, so strict FU is mandatory with established biopsy criteria based on PSA and DRE in cases with PCA3 <35.

Asociación del síndrome de hipogonadismo tardío y síndrome metabólico con el cáncer de próstata y su agresividad / Association between late-onset hypogonadism syndrome plus metabolic syndrome and prostate cancer and its aggressiveness

Objetivo: Evaluar la relación entre el cáncer de próstata (CaP) y la presencia de síndrome metabólico (SM) y síndrome de hipogonadismo tardío (SHT). Material y método: Estudio retrospectivo de 686 pacientes sometidos a biopsia prostática. Analizamos: variables demográficas, datos clínicos y resultados de la biopsia. Para diagnosticar el SM se utilizaron los criterios de la American Heart Association. Para el diagnóstico de SHT se utilizó el cuestionario ADAM y los niveles de testosterona (TT). Evaluamos la relación de la testosterona libre (TL) y testosterona biodisponible (TB) con el CaP y su agresividad y la utilidad de la ratio TT/PSA en el diagnóstico de CaP. Resultados: Mediana de edad 65 años. El SM no se asoció al CaP (39,4% vs 35% p = 0,1) pero sí a un CaP Gleason > 7 (50,4% vs 29,44% p = 0,002). El SHT, TL baja y TB baja se asociaron a una mayor presencia de CaP (51% vs 35% p = 0,02; 44,86% vs 33,33%, p = 0,03; 46,46% vs 33,08%, p = 0,01 respectivamente) y a mayor probabilidad de CaP Gleason >7 (61,54% vs 37,5% p = 0,02; 54,17% vs 34,12%, p = 0,02; 54,35% vs 34,48% p = 0,02 respectivamente). Además, la mediana de la ratio de TT/PSA fue significativamente menor en los pacientes con BxP positiva (p = 0.022). Conclusiones: el SM no se asoció con la probabilidad de tener CaP, pero sí con el CaP Gleason > 7. Por otro lado, el SHT presentó un mayor porcentaje de CaP y una mayor presencia de CaP Gleason > 7, al igual que los niveles bajos de TL y los niveles bajos de TB

Objective: To assess the relationship between prostate cancer (PC) and the presence of metabolic syndrome and late-onset hypogonadism (LOH) syndrome. Material and method: A retrospective study was conducted on 686 patients who underwent prostate biopsy. We analysed the demographic variables, clinical data and biopsy results. To diagnose metabolic syndrome, we employed the criteria of the American Heart Association. For the diagnosis of LOH syndrome, we employed the Androgen Deficiency in the Aging Male questionnaire and testosterone levels (TT). We evaluated the relationship between free testosterone (FT) and bioavailable testosterone (BT) on one hand and PC and its aggressiveness on the other, as well as the usefulness of the TT to prostate specific antigen (TT/PSA) ratio in the PC diagnosis. :Results The patient's median age was 65 years. Metabolic syndrome is not associated with PC (39.4% vs. 35%; P = .1) but is associated with a PC Gleason score > 7 (50.4% vs. 29.44%; P = .002). LOH, low FT and low BT are associated with an increased presence of PC (51% vs. 35%, P = .02; 44.86% vs. 33.33%, P = .03; and 46.46% vs. 33.08%, P = .01, respectively) and with an increased probability of a PC Gleason score > 7 (61.54% vs. 37.5%, P = .02; 54.17% vs. 34.12%, P = .02; 54.35% vs. 34.48%, P = .02, respectively). Additionally, the median TT/PSA ratio was significantly lower in patients with positive biopsies (P = .022). Conclusions: Metabolic syndrome was not associated with the probability of having PC but was associated with a PC Gleason score > 7. Moreover, LOH syndrome had a higher percentage of PC and a greater presence of PC Gleason scores > 7, as did low levels of FT and low levels of BT

Association between late-onset hypogonadism syndrome plus metabolic syndrome and prostate cancer and its aggressiveness. / Asociación del síndrome de hipogonadismo tardío y síndrome metabólico con el cáncer de próstata y su agresividad.

OBJECTIVE: To assess the relationship between prostate cancer (PC) and the presence of metabolic syndrome and late-onset hypogonadism (LOH) syndrome. MATERIAL AND METHOD: A retrospective study was conducted on 686 patients who underwent prostate biopsy. We analysed the demographic variables, clinical data and biopsy results. To diagnose metabolic syndrome, we employed the criteria of the American Heart Association. For the diagnosis of LOH syndrome, we employed the Androgen Deficiency in the Aging Male questionnaire and testosterone levels (TT). We evaluated the relationship between free testosterone (FT) and bioavailable testosterone (BT) on one hand and PC and its aggressiveness on the other, as well as the usefulness of the TT to prostate specific antigen (TT/PSA) ratio in the PC diagnosis. RESULTS: The patient's median age was 65 years. Metabolic syndrome is not associated with PC (39.4% vs. 35%; P=.1) but is associated with a PC Gleason score >7 (50.4% vs. 29.44%; P=.002). LOH, low FT and low BT are associated with an increased presence of PC (51% vs. 35%, P=.02; 44.86% vs. 33.33%, P=.03; and 46.46% vs. 33.08%, P=.01, respectively) and with an increased probability of a PC Gleason score >7 (61.54% vs. 37.5%, P=.02; 54.17% vs. 34.12%, P=.02; 54.35% vs. 34.48%, P=.02, respectively). Additionally, the median TT/PSA ratio was significantly lower in patients with positive biopsies (P=.022). CONCLUSIONS: Metabolic syndrome was not associated with the probability of having PC but was associated with a PC Gleason score >7. Moreover, LOH syndrome had a higher percentage of PC and a greater presence of PC Gleason scores >7, as did low levels of FT and low levels of BT.

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

Síntomas del tracto urinario inferior y función eréctil en pacientes con sospecha de cáncer de próstata / Urinary tract symptoms and erectile function in patients at risk of prostate cancer

Introducción y objetivo: Estimamos que en España se llevan a acabo alrededor de 63.000 biopsias de próstata. No hay datos al respecto del estado funcional de los pacientes que acuden a realizarse dicha prueba, ni de si el resultado de la biopsia responde a un patrón funcional concreto. Planteamos un estudio que resuelva el anterior planteamiento. Material y método: Se incluyeron 1.128 biopsias. Los pacientes cumplimentaban, antes de la biopsia, los cuestionarios: IPSS, IIEF-5 y ICIQ-SF. Se recopilaron de forma prospectiva las variables clínicas, patológicas y los resultados de los cuestionarios. Se procedió a un análisis descriptivo de la muestra a estudio, incluyendo el resultado de los cuestionarios. Se comparó el resultado medio de los cuestionarios en función de la presencia de cáncer en la biopsia. Los síntomas del tracto urinario inferior (STUI) y de disfunción eréctil se categorizaron en grados de severidad, y se calculó la distribución de los mismos en función del resultado de la biopsia y, cuando la biopsia era positiva, del grupo de riesgo clínico. Resultados: La edad media de los pacientes era de 65 años. La tasa de biopsias positivas fue del 32,71%. El 52,2% refirió padecer síntomas del tracto urinario inferior (STUI) moderados y el 13,4% severos. En cuanto a la influencia de los STUI en la CV de los pacientes solo un 12,6% refería que su vida no estaba influenciada por los STUI. El 50,76% padecía algún grado de disfunción eréctil. Según los resultados del ICIQ-SF un 24% de la muestra refería padecer algún tipo de incontinencia urinaria, si bien es cierto que la mayor parte de ellos lo etiquetaba como escapes de escasa cuantía. Los pacientes con cáncer de próstata tenían un IPSS y un IIEF-5 medio menor. No se encontraron diferencias de la tasa diagnóstica de cáncer en función de la seriedad de los síntomas del tracto urinario. Conclusiones: Los pacientes a quienes indicamos una biopsia de próstata padecen con una alta probabilidad STUI, aproximadamente un 50% tiene cierto grado de disfunción eréctil y un 24% problemas de escapes urinarios

Introduction and objective: We estimate that more tan 63000 prostate biopsies are performed in our country each year. There are no functional status data of those patients and if there is a relationship between biopsy result and functional status. In order to solve that question we have performed this study. Material and method: 1,128 prostate biopsies were included. Patients fill in the IPSS, IIEF-5 and ICIQ-SF questionnaires before the prostate biopsy was performed. A prospective data collection of clinical, pathological and questionnaires results was done. A descriptive analysis was carried out. IPSS and IIEF-5 results were categorized. Results were compared depending on the biopsy result. In the subgroup of patients with prostate cancer, questionnaires results were stratify according to the clinical risk group. Results: The mean age of the sample was 65. Prostate cancer detection rate was 32,71%, 52,2% of the sample had mild lower urinary tract symptoms (LUTS) and 13,4% had severe LUTS at the time of the biopsy. Regarding the impact of LUTS on quality of life (QOL), only 12,6% showed a perfect QOL. More than 50 percent of patients suffered from some degree of erectile dysfunction at the time of the biopsy. According to ICIQ-SF, 24% of the sample experienced some kind of urinary incontinence, although it is true that most of them classified it as small amount. Patients with a positive biopsy had a lower IPSS and IIEF-5 average score. There were no differences in the prostate cancer detection rate stratified by the severity of LUTS. Conclusions: Patients undergoing prostate biopsy have, with a high probability, LUTS. Approximately 50% suffer from some degree of erectile dysfunction and 24% had some kind of urinary leakage

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.

Urinary tract symptoms and erectile function in patients at risk of prostate cancer.

INTRODUCTION AND OBJECTIVE: We estimate that more tan 63000 prostate biopsies are performed in our country each year. There are no functional status data of those patients and if there is a relationship between biopsy result and functional status. In order to solve that question we have performed this study. MATERIAL AND METHOD: 1,128 prostate biopsies were included. Patients fill in the IPSS, IIEF-5 and ICIQ-SF questionnaires before the prostate biopsy was performed. A prospective data collection of clinical, pathological and questionnaires results was done. A descriptive analysis was carried out. IPSS and IIEF-5 results were categorized. Results were compared depending on the biopsy result. In the subgroup of patients with prostate cancer, questionnaires results were stratify according to the clinical risk group. RESULTS: The mean age of the sample was 65. Prostate cancer detection rate was 32,71%, 52,2% of the sample had mild lower urinary tract symptoms (LUTS) and 13,4% had severe LUTS at the time of the biopsy. Regarding the impact of LUTS on quality of life (QOL), only 12,6% showed a perfect QOL. More than 50 percent of patients suffered from some degree of erectile dysfunction at the time of the biopsy. According to ICIQ-SF, 24% of the sample experienced some kind of urinary incontinence, although it is true that most of them classified it as small amount. Patients with a positive biopsy had a lower IPSS and IIEF-5 average score. There were no differences in the prostate cancer detection rate stratified by the severity of LUTS. CONCLUSIONS: Patients undergoing prostate biopsy have, with a high probability, LUTS. Approximately 50% suffer from some degree of erectile dysfunction and 24% had some kind of urinary leakage.

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.