¿3 + 4 = 6? Implicaciones de la estratificación del cáncer de próstata localizado Gleason 7 por número y porcentaje de cilindros positivos de biopsia en la selección de pacientes para vigilancia activa / 3+4 = 6? Implications of the stratification of localised Gleason 7 prostate cancer by number and percentage of positive biopsy cores in selecting patients for active surveillance

Objetivo: Investigar si el número y el porcentaje de cilindros positivos de la biopsia identifica un subgrupo de cáncer de próstata (CaP) Gleason 3 + 4 de comportamiento biológico similar a los Gleason 3 + 3. Material y método: Estudio observacional, tras prostatectomía radical, de una cohorte de 799 pacientes con CaP localizado de riesgo bajo (n = 582; Gleason 6; PSA < 10ng/ml y cT1c-2a) e intermedio favorable (n = 217; Gleason 3 + 4; PSA ≤ 10 ng/ml y pT2abc). Los tumores Gleason 3 + 4 se estratificaron por número (≤ 3 vs .> 3) y porcentaje de cilindros positivos (≤ 33% vs. > 33%). Se analizó su asociación con el riesgo de recidiva bioquímica (ReB) y mortalidad cáncer específica (MCE). Se realizaron diferentes modelos predictivos mediante regresión de Cox y se estimó (C-index) y comparó su capacidad predictiva. Resultados: Con una mediana de seguimiento de 71 meses, la probabilidad de ReB y de MCE en el grupo de pacientes con tumores Gleason 3+4 y número (≤3) o porcentaje bajo (≤33%) de cilindros positivos no fue significativamente diferente de las de los pacientes con tumores Gleason 6. A 5 y 10 años, no se observaron diferencias significativas en el número de ReB, en la probabilidad de permanecer libre de ReB, en el número de muertes por CaP ni en la probabilidad de muerte por CaP entre ambos grupos. Por el contrario, los pacientes con tumores Gleason 3+4 y >33% de cilindros positivos presentaron mayor número de muertes por CaP que los pacientes con tumores Gleason 6 y, a 10 años, la probabilidad de MCE fue significativamente mayor. Este subgrupo de tumores presentó un riesgo significativamente mayor de ReB (RR = 1,6; p = 0,02) respecto a los Gleason 6 y, sobre todo, de MCE (RR = 5,8; p = <0,01). El modelo con Gleason 3 + 4 estratificado por porcentaje de cilindros positivos mejoró significativamente la capacidad predictiva de ReB y MCE. Conclusiones: Un número<3 cilindros y un porcentaje < 33% de cilindros positivos identifica un subgrupo de tumores Gleason 3 + 4 con comportamiento biológico similar a los Gleason 6. A 10 años, no se observaron diferencias en el riesgo de ReB y MCE entre ambos grupos. Estos resultados aportan pruebas que apoyan a la vigilancia activa como alternativa para tumores Gleason 3 + 4 y baja extensión tumoral en biopsia

Objective: To determine whether the number and percentage of positive biopsy cores identify a Gleason 3 + 4 prostate cancer (PC) subgroup of similar biologic behaviour to Gleason 3 + 3. Material and method: An observational post-radical prostatectomy study was conducted of a cohort of 799 patients with localised low-risk (n = 582, Gleason 6, PSA < 10ng/ml and cT1c-2a) and favourable intermediate PC (n = 217, Gleason 3 + 4, PSA ≤ 10 ng/ml and pT2abc). The Gleason 3 + 4 tumours were stratified by number (≤ 3 vs.> 3) and by percentage of positive cores (≤ 33% vs. > 33%). We analysed the tumours’ association with the biochemical recurrence risk (BRR) and cancer-specific mortality (CSM). We conducted various predictive models using Cox regression and estimated (C-index) and compared their predictive capacity. Results: With a median follow-up of 71 months, the BRR and CSM of the patient group with Gleason 3 + 4 tumours and a low number (≤ 3) and percentage (≤ 33%) of positive cores were not significantly different from those of the patients with Gleason 6 tumours. At 5 and 10 years, there were no significant differences in the number of biochemical recurrences, the probability of remaining free of biochemical recurrences, the number of deaths by PC or the probability of death by PC between the 2 groups. In contrast, the patients with Gleason 3+4 tumours and more than 33% of positive cores presented more deaths by PC than the patients with Gleason 6 tumours. At 10 years, the probability of CSM was significantly greater. This subgroup of tumours showed a significantly greater BRR (RR, 1.6; P = .02) and CSM (RR, 5.8, P ≤ .01) compared with the Gleason 6 tumours. The model with Gleason 3 + 4 stratified by the percentage of positive cores significantly improved the predictive capacity of BRR and CSM. Conclusions: Fewer than 3 cores and a percentage < 33% of positive cores identifies a subgroup of Gleason 3 + 4 tumours with biological behaviour similar to Gleason 6 tumours. At 10 years, there were no differences in BRR and CSM between the 2 groups. These results provide evidence supporting active surveillance as an alternative for Gleason 3 + 4 tumours and low tumour extension in biopsy

3+4 = 6? Implications of the stratification of localised Gleason 7 prostate cancer by number and percentage of positive biopsy cores in selecting patients for active surveillance. / ¿3 + 4 = 6? Implicaciones de la estratificación del cáncer de próstata localizado Gleason 7 por número y porcentaje de cilindros positivos de biopsia en la selección de pacientes para vigilancia activa.

OBJECTIVE: To determine whether the number and percentage of positive biopsy cores identify a Gleason 3+4 prostate cancer (PC) subgroup of similar biologic behaviour to Gleason 3+3. MATERIAL AND METHOD: An observational post-radical prostatectomy study was conducted of a cohort of 799 patients with localised low-risk (n=582, Gleason 6, PSA <10ng/ml and cT1c-2a) and favourable intermediate PC (n=217, Gleason 3+4, PSA ≤10 ng/ml and pT2abc). The Gleason 3+4 tumours were stratified by number (≤3 vs.>3) and by percentage of positive cores (≤33% vs. >33%). We analysed the tumours' association with the biochemical recurrence risk (BRR) and cancer-specific mortality (CSM). We conducted various predictive models using Cox regression and estimated (C-index) and compared their predictive capacity. RESULTS: With a median follow-up of 71 months, the BRR and CSM of the patient group with Gleason 3+4 tumours and a low number (≤3) and percentage (≤33%) of positive cores were not significantly different from those of the patients with Gleason 6 tumours. At 5 and 10 years, there were no significant differences in the number of biochemical recurrences, the probability of remaining free of biochemical recurrences, the number of deaths by PC or the probability of death by PC between the 2 groups. In contrast, the patients with Gleason 3+4 tumours and more than 33% of positive cores presented more deaths by PC than the patients with Gleason 6 tumours. At 10 years, the probability of CSM was significantly greater. This subgroup of tumours showed a significantly greater BRR (RR, 1.6; P=.02) and CSM (RR, 5.8, P≤.01) compared with the Gleason 6 tumours. The model with Gleason 3+4 stratified by the percentage of positive cores significantly improved the predictive capacity of BRR and CSM. CONCLUSIONS: Fewer than 3 cores and a percentage <33% of positive cores identifies a subgroup of Gleason 3+4 tumours with biological behaviour similar to Gleason 6 tumours. At 10 years, there were no differences in BRR and CSM between the 2 groups. These results provide evidence supporting active surveillance as an alternative for Gleason 3+4 tumours and low tumour extension in biopsy.

Análisis de riesgos competitivos de mortalidad en cáncer de próstata tratado mediante prostatectomía radical / Competing risk analysis of mortality in prostate cancer treated with radical prostatectomy

Objetivo: Estimar el riesgo de muerte cáncer específica (MCE) frente al riesgo competitivo de mortalidad por otras causas (MOC) en pacientes con cáncer de próstata localizado (CaP-Lo) tratados mediante prostatectomía radical (PR). Material y método: Estudio observacional de una cohorte de 982 pacientes con CaP-Lo tratados mediante PR seleccionados de la base de datos del registro de CaP de nuestro servicio. Se ha realizado un análisis de riesgos competitivos calculando la probabilidad de MCE en presencia del riesgo competitivo por MOC. Se han construido curvas de incidencia acumulada y se han llevado a cabo estimaciones puntuales a 5, 10 y 15 años. El análisis se ha estratificado por edad (≤ 65 vs. > 65 años) y por grupos de riesgo: bajo (Gleason ≤ 6 y pT2abc); intermedio (Gleason = 7 y pT2abc) y elevado (Gleason 8-10 o pT3ab). Resultados: Con una mediana de seguimiento de 60 meses, la probabilidad global de fallecer por CaP fue del 3,5% y la de fallecer por otras causas del 9%. Se evidenció un efecto competitivo por MOC. El riesgo de MOC fue de casi 3 veces superior al de MCE. Este efecto se mantuvo para todos los grupos de riesgo, si bien su magnitud disminuyó progresivamente conforme aumentó el nivel del grupo de riesgo. A 10 años, la MCE fue únicamente de 0, 1 y 2% para los grupos de riesgo bajo, intermedio y elevado respectivamente, mientras que la probabilidad MOC fue de 4, 4 y 10%. El riesgo de fallecer se evidenció a partir de 10 años de seguimiento y fue más frecuente por otras causas no atribuibles al CaP y en pacientes de edad > 65 años. Conclusiones: El beneficio de la PR puede estar sobreestimado, ya que el riesgo de MOC es superior al de MCE independientemente del grupo de edad y grupo de riesgo, sobre todo a partir de los 10 años de seguimiento. Lo único que varía es la magnitud de la razón MCE/MOC. Esta información puede ayudar a decidir el tratamiento activo en pacientes con CaP-Lo y corta expectativa de vida

Objective: To determine the risk of cancer-specific mortality (CSM) versus the competing risk of mortality by other causes (MOC) in patients with localised prostate cancer (LPC) treated with radical prostatectomy (RP). Material and method: An observational cohort study of 982 patients with LPC treated with RP selected from our department’s PC registry database. A competing risk analysis was performed, calculating the probability of CSM in the presence of the competing risk of MOC. Cumulative incidence curves were constructed, and point estimates were performed at 5, 10 and 15 years. The analysis was stratified by age (≤ 65 vs. > 65 years) and risk group: low (Gleason score ≤ 6 and pT2abc); intermediate (Gleason score of 7 and pT2abc) and high (Gleason score of 8-10 or pT3ab). Results: With a median follow-up of 60 months, the overall probability of dying from PC was 3.5%, and the probability of dying from other causes was 9%. A competing effect for MOC was observed. The risk of MOC was almost 3 times greater than that of CSM. This effect remained for all risk groups, although its magnitude decreased progressively according to the risk group level. At 10 years, CSM was only 0%, 1% and 2% for the low, intermediate and high-risk groups, respectively, while the likelihood of MOC was 4%, 4% and 10%, respectively. The mortality risk was shown after 10 years of follow-up and was higher for other causes not attributable to PC and for patients older than 65 years. Conclusions: The benefit of RP might be overestimated, given that the risk of MOC is greater than that of CSM, regardless of the age group and risk group, especially after 10 years of followup. The only parameter that varied was the magnitude of the CSM/MOC ratio. This information could help in choosing the active treatment for patients with LPC and short life expectancies

Competing risk analysis of mortality in prostate cancer treated with radical prostatectomy. / Análisis de riesgos competitivos de mortalidad en cáncer de próstata tratado mediante prostatectomía radical.

OBJECTIVE: To determine the risk of cancer-specific mortality (CSM) versus the competing risk of mortality by other causes (MOC) in patients with localised prostate cancer (LPC) treated with radical prostatectomy (RP). MATERIAL AND METHOD: An observational cohort study of 982 patients with LPC treated with RP selected from our department's PC registry database. A competing risk analysis was performed, calculating the probability of CSM in the presence of the competing risk of MOC. Cumulative incidence curves were constructed, and point estimates were performed at 5, 10 and 15 years. The analysis was stratified by age (≤65 vs. >65 years) and risk group: low (Gleason score ≤6 and pT2abc); intermediate (Gleason score of 7 and pT2abc) and high (Gleason score of 8-10 or pT3ab). RESULTS: With a median follow-up of 60 months, the overall probability of dying from PC was 3.5%, and the probability of dying from other causes was 9%. A competing effect for MOC was observed. The risk of MOC was almost 3 times greater than that of CSM. This effect remained for all risk groups, although its magnitude decreased progressively according to the risk group level. At 10 years, CSM was only 0%, 1% and 2% for the low, intermediate and high-risk groups, respectively, while the likelihood of MOC was 4%, 4% and 10%, respectively. The mortality risk was shown after 10years of follow-up and was higher for other causes not attributable to PC and for patients older than 65years. CONCLUSIONS: The benefit of RP might be overestimated, given that the risk of MOC is greater than that of CSM, regardless of the age group and risk group, especially after 10years of follow-up. The only parameter that varied was the magnitude of the CSM/MOC ratio. This information could help in choosing the active treatment for patients with LPC and short life expectancies.