Prognostic Value of Gleason Score for Overall Survival in Prostate Cancer: A Population-Based SEER Cohort Study

Background/Objectives: Prostate cancer is biologically heterogeneous, and prognostic stratification informs the choice between definitive treatment and conservative management. Most evidence on the Gleason score addresses prostate cancer-specific mortality rather than survival from any cause. We assessed the association between Gleason score category and overall survival in a contemporary population-based cohort. Methods: Using Surveillance, Epidemiology, and End Results (SEER) Research Data from 17 registries (November 2024 submission), we included men aged 40 years and older with a first primary malignant prostate cancer and a recorded Gleason Score Clinical Recode (2010+). Because this recode is undefined before 2010, the analytic period was 2010–2019. Gleason score was categorized as ≤6, 7, and ≥8. Overall survival was estimated by Kaplan–Meier methods and compared by log-rank test; multivariable Cox regression adjusted for age, race and ethnicity, marital status, summary stage, surgery at the primary site, radiation therapy, and chemotherapy, with localized disease as the stage reference. Results: Among 374,763 men, 145,668 (38.9%) had Gleason ≤ 6, 148,773 (39.7%) Gleason 7, and 80,322 (21.4%) Gleason ≥ 8, with mortality during follow-up of 11.3%, 14.6% and 36.6% respectively (log-rank p < 0.0001). Adjusted hazards of death were higher for Gleason 7 (HR 1.53, 95% CI 1.50–1.57) and Gleason ≥ 8 (HR 2.89, 95% CI 2.82–2.95) relative to Gleason ≤ 6. Advancing age, regional disease (HR 1.47, 95% CI 1.43–1.51) and distant disease (HR 3.74, 95% CI 3.65–3.84) were also associated with increased mortality. The grade association attenuated over follow-up, the hazard ratio for Gleason ≥ 8 falling from 4.12 within two years to 2.17 beyond five years. Conclusions: Gleason score category is independently associated with overall survival and retains prognostic value on the all-cause mortality scale, with greatest discrimination in the years immediately following diagnosis.