Gleason Pattern 5 Prostate Cancer: Further Stratification of Patients With High-Risk Disease and Implications for Future Randomized Trials

Abstract

To compare prostate-specific antigen (PSA) outcomes in a cohort of men with high-risk prostate cancer based on the presence or absence of any Gleason Grade 5 component (primary, secondary, or tertiary). Our study cohort consisted of 312 men with T1c-T3N0M0 prostate cancer with Gleason Scores of 7 with tertiary Grade 5, 8, or 9-10 who underwent radical prostatectomy or external beam radiotherapy with or without androgen suppression therapy. Cox regression multivariable analysis was used to assess whether a difference existed in risk of PSA recurrence in men with Gleason Score of 9-10 compared with those with Gleason Score of 8 and 7 with tertiary Grade 5, adjusting for treatment, age, and known prostate cancer prognostic factors. After a median follow-up of 5.7 years, men with a Gleason Score of 8 had a lower risk of PSA recurrence than those with a Gleason Score of 9-10 (hazard ratio, 0.74; 95% confidence interval, 0.52-1.05; p = 0.09). Conversely, men with a Gleason Score of 7 with tertiary Grade 5 had a similar risk of PSA recurrence compared with men with a Gleason Score of 9-10 (hazard ratio, 1.08; 95% confidence interval, 0.60-1.94; p = 0.81). Median times to PSA failure for men with Gleason Scores of 9-10, 7 with tertiary Grade 5, and 8 were 4.5, 5.0, and 5.4 years, respectively. Our results highlight the importance of further substratification of the high-risk Gleason Score category of 8-10 into 8 vs. 9, 10, and 7 with tertiary Grade 5.