Biopsy Detected Gleason Pattern 5 is Associated with Recurrence, Metastasis and Mortality in a Cohort of Men with High Risk Prostate Cancer

Sean P. Stroup, Daniel M. Moreira, Zinan Chen, Lauren Howard, Jonathan H. Berger, Martha K. Terris, William J. Aronson, Matthew R. Cooperberg, Christopher L. Amling, Christopher J. Kane, Stephen J. Freedland

To evaluate the relative risk of biochemical recurrence (BCR), metastasis, and death from prostate cancer contributed by biopsy Gleason pattern 5 among high-risk men with Gleason 8-10 disease in the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort. Men with biopsy Gleason sum 8-10 prostate cancer treated with radical prostatectomy were evaluated. The cohort was divided: Gleason 4+4 vs. those with any pattern 5 (i.e., Gleason 3+5, 5+3, 4+5, 5+4, and 5+5). Predictors of BCR, metastases, prostate cancer-specific survival, and overall survival were analyzed using Kaplan-Meier, log-rank test, and Cox proportional hazards models. We identified 634 high-risk men in the SEARCH database, of these, 394(62%) had Gleason 4+4, and 240(38%) had Gleason pattern 5 on biopsy. Baseline characteristics were not significantly different between groups. On multivariable analysis, relative to Gleason 4+4, high-risk men with Gleason pattern 5 had no differences in the risk of BCR (HR=1.26; 95%CI=0.99-1.61; P=0.065), but a significantly greater risk of metastasis (HR=2.55; 95%CI=1.50-4.35, p=0.001), prostate cancer-specific mortality (HR=2.67; 95%CI=0.1.26-5.66; P=0.010), and overall mortality (HR=1.60; 95%CI=1.09-2.34; P=0.016). Preoperative subclassification of high-risk prostate cancer by biopsy Gleason grading (4+4 vs. presence of any Gleason pattern 5) identified men at highest risk of progression. Presence of any Gleason 5 on biopsy is associated with a greater risk of metastasis, prostate cancer-specific mortality, and overall mortality. Grouping all Gleason 8-10 tumors together as "high-risk" may fail to fully stratify those at highest risk of poor outcomes.