External validation of a prognostic Gleason grade classification system.

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123 Background: We aimed to evaluate a recently proposed prognostic Gleason grading system among two distinct cohorts of men receiving treatment for localized PCa with extended clinical follow. Methods: We identified patients receiving treatment with radical prostatectomy (RP) in two settings: an academic referral center and the multi-center Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) registry. We examined the independent prognostic ability of the proposed grade groups (3+3; 3+4; 4+3; 4+4; 9-10), adjusted for significant clinical and pathological characteristics, on disease recurrence, defined as two consecutive PSA values ≥ 0.2 ng/mL or receipt of salvage treatment, using Cox proportional hazards models. Adjusted pairwise comparisons were made between grade groups. Distant disease endpoints including metastatic progression and prostate cancer specific mortality (PCSM) were similarly evaluated within the CaPSURE cohort. Results: We identified 1,734 men receiving treatment at UCSF with immediate RP with pathologic assessment consistent with the 2005 ISUP modification, and 4,564 men within the CaPSURE database. Median follow up within the UCSF cohort was 33 months (interquartile range, IQR 16-58) and 91 months (IQR 50-135) within CaPSURE. Relative to Gleason grade 3+3, all prognostic Gleason grade groups were independently associated with risk of recurrence among the UCSF cohort (all p < 0.01). Adjusted pairwise comparisons of biopsy and pathologic Gleason groups, except 4+3 versus 4+4, also were statistically significant. Among the CaPSURE cohort, biopsy and pathologic prognostic Gleason grade groups were independently associated with risk of recurrence, metastatic progression and PCSM, though pairwise distinctions between Gleason 4+3 and 4+4 and Gleason 4+4 versus 9-10 were not significant. This study was limited by the comparatively smaller proportion of men receiving radical prostatectomy for higher Gleason grade ( > 4+4) disease. Conclusions: A proposed prognostic Gleason classification system stratifies men according to the risk of recurrence and downstream endpoints. However, the discrimination of outcomes among higher grade disease appeared less robust.