Papel de PCA3 y SelectMDx en la optimización de la vigilancia activa en el cáncer de próstata / Role of PCA3 and SelectMDx in the optimization of active surveillance in prostate cancer

Introducción y objetivos: Un porcentaje no despreciable de pacientes incluidos en programas de vigilancia activa (VA) para el cáncer de próstata (CaP) de bajo y muy bajo riesgo son reclasificados en la biopsia confirmatoria o desarrollan progresión de la enfermedad durante el seguimiento. Nuestro objetivo es evaluar el papel del PCA3 y el SelectMDx, de manera individual y combinada, para predecir la progresión patológica (PP) en un programa habitual de VA.Materiales y métodosEstudio prospectivo y observacional que incluyó 86 pacientes inscritos en un protocolo de VA desde 2009 hasta 2019, con resultados de PCA3 y SelectMDx previos al diagnóstico de CaP o durante su periodo de confirmación. Se realizaron análisis univariantes y multivariantes para la correlación de las puntuaciones de PCA3 y SelectMDx, así como de las variables clinicopatológicas con la supervivencia libre de progresión patológica (SLPP). Se definieron los puntos de corte más fiables para ambos biomarcadores en el contexto de VA.ResultadosSelectMDx mostró diferencias estadísticamente significativas en relación con la SLPP (HR: 1,035; IC95%: 1,012-1,057) (p=0,002) con un índiceC de 0,670 (IC95%: 0,529-0,810) y un AUC de 0,714 (IC95%: 0,603-0,825) a 5años. En nuestra serie, el punto de corte más fiable para el SelectMDx fue 5, con una sensibilidad y una especificidad para la PP del 69,8 y del 67,4%, respectivamente. El punto de corte del test PCA3 fue de 65, con una sensibilidad y una especificidad para la PP del 51,16 y del 74,42%, respectivamente. La combinación de ambos biomarcadores no mejoró la predicción de la PP, con un índiceC de 0,630 (IC95%: 0,455-0,805).ConclusionesEn el contexto del CaP de bajo o muy bajo riesgo, SelectMDx >5 predijo una supervivencia libre de PP de 5años con una capacidad de discriminación moderada, superando al PCA3. La combinación de ambos no mejoró los resultados. (AU)

Introduction and objectives: A not negligible percentage of patients included in active surveillance (AS) for low and very low risk prostate cancer (PCa) are reclassified in the confirmatory biopsy or have disease progression during follow-up. Our aim is to evaluate the role of PCA3 and SelectMDx, in an individual and combined way, in the prediction of pathological progression (PP) in a standard AS program.Materials and methodsProspective and observational study comprised of 86 patients enrolled in an AS program from 2009 to 2019, with results for PCA3 and SelectMDx previous to PCa diagnosis or during their confirmatory period. Univariate and multivariate analysis were performed to correlate PCA3 and SelectMDx scores as well as clinical and pathological variables with PP-free survival (PPFS). The most reliable cut-offs for both biomarkers in the context of AS were defined.ResultsSelectMDx showed statistically significant differences related to PPFS (HR: 1.035; 95%CI: 1.012-1.057) (P=.002) with a C-index of 0.670 (95%CI: 0.529-0.810) and AUC of 0.714 (95%CI: 0.603-0.825) at 5years. In our series, the most reliable cut-off point for SelectMDx was 5, with a sensitivity and specificity for PP of 69.8% and 67.4%, respectively. Same figure for PCA3 was 65, with a sensitivity and specificity for PP of 51.16% and 74.42%, respectively. The combination of both biomarkers did not improve the prediction of PP, C-index 0.630 (95%CI: 0.455-0.805).ConclusionsIn the context of low or very low risk PCa, SelectMDx >5 predicted 5years PP free survival with a moderate discrimination ability outperforming PCA3. The combination of both tests did not improved outcomes. (AU)

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.

Role of PCA3 and SelectMDx in the optimization of active surveillance in prostate cancer.

INTRODUCTION & OBJECTIVES: A not negligible percentage of patients included in active surveillance (AS) for low and very low risk prostate cancer (PCa) are reclassified in the confirmatory biopsy or have disease progression during follow-up. Our aim is to evaluate the role of PCA3 and SelectMDx, in an individual and combined way, in the prediction of pathological progression (PP) in a standard AS program. MATERIALS & METHODS: Prospective and observational study comprised of 86 patients enrolled in an AS program from 2009 to 2019, with results for PCA3 and SelectMDx previous to PCa diagnosis or during their confirmatory period. Univariate and multivariate analysis were performed to correlate PCA3 and SelectMDx scores as well as clinical and pathological variables with PP-free survival (PPFS). The most reliable cut-offs for both biomarkers in the context of AS were defined. RESULTS: SelectMDx showed statistically significant differences related to PPFS (HR 1.035, 95%CI: 1.012-1.057) (p = 0.002) with a C-index of 0.670 (95%CI: 0.529-0.810) and AUC of 0.714 (95%CI: 0.603-0.825) at 5 years. In our series, the most reliable cut-off point for SelectMDx was 5, with a sensitivity and specificity for PP of 69.8% and 67.4%, respectively. Same figure for PCA3 was 65, with a sensitivity and specificity for PP of 51.16% and 74.42%, respectively. The combination of both biomarkers did not improve the prediction of PP, C-index 0.630 (95%CI: 0.455-0.805). CONCLUSIONS: In the context of low or very low risk PCa, SelectMDx > 5 predicted 5 years PP free survival with a moderate discrimination ability outperforming PCA3. The combination of both tests did not improved outcomes.

¿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)

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.

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.