Abstract
BACKGROUND: Although the latest Gleason grading system in 2014 has distinguished between Gleason 3 + 4 and 4 + 3, Gleason 8 and Gleason 9-10 are remained systemically classified. METHODS: A total of 261,125 patients diagnosed with prostate cancer (PCa) were selected between 2005 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. We used propensity score matching to balance clinical variables and then compared overall survival (OS) and cancer-specific survival (CSS) between Gleason score subgroups. We further establish a new Gleason survival grading system based on the hazard ratio (HR) values of each Gleason subgroup. Cox proportional hazards models and Kaplan-Meier curves were used to compare patient survival. RESULTS: Among PCa patients with Gleason score 8 disease, patients with Gleason 5 + 3 had significantly worse OS and CSS than those with Gleason 3 + 5 (OS: HR = 1.26, p = 0.042; CSS: HR = 1.42, p = 0.005) and 4 + 4 (HR = 1.50 for OS and HR = 1.69 for CSS, p < 0.001 for all). PCa patients with Gleason 5 + 3 and Gleason 4 + 5 may have the similar OS and CSS (reference Gleason score <=6, 5 + 3: OS HR = 2.44, CSS HR = 7.63; 4 + 5: OS HR = 2.40, CSS HR = 8.92; p < 0.001 for all). The new Gleason survival grading system reclassified the grades 4 and 5 of the 2014 updated Gleason grading system into three hierarchical grades, which makes the classification of grades more detailed and accurate. CONCLUSION: PCa patients with Gleason 8-10 may have three different survival subgroups, Gleason 3 + 5 and 4 + 4, Gleason 5 + 3 and 4 + 5, and Gleason 5 + 4 and 5 + 5. Our results maximize risk stratification for PCa patients, provide guidance for clinicians to assess their survival and clinical management, and make a recommendation for the next Gleason grading system update.