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.

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.

Value of the identification of microsatellite instability in colorectal cancer

OBJECTIVE: Recent studies defend a possible prognostic and therapeutic value of the identification of microsatellite instability (MSI) in colorectal cancer. This work tries to assess the impact that the identification of MSI tumours can have in clinical practice. MATERIAL AND METHODS: We recovered tumour samples from 92 of the 143 patients operated on for colorectal cancer in our institution between 1995 and 2000. Five MSI markers (BAT 25, BAT 26, D2S123, D5S346 and D17S250) were studied on them. The rate and clinicopathologic characteristics of MSI tumours were investigated along with their impact on the global and disease-free survival as compared with microsatellite stable (MSS) tumours. RESULTS: All 5 microsatellite markers' status were established in 73 patients (79.3% of the samples). Among them, 7 tumours showed instability in just one marker (low microsatellite instability [MSI-L]) whereas 5 tumours had mutations in 2 or more markers (high microsatellite instability [MSI-H]), for a total 15.4% rate of MSI tumours. All MSI-H tumours were located in the right colon. We could not fi nd any impact from MSI detection on global or disease-free survival. CONCLUSIONS: MSI determination did not identify groups of patients with a different prognosis. Moreover, with such low incidence its determination can only be justified in those cases that fulfill Bethesda's criteria to identify families with Lynch's syndrome (AU)