Biopsy Gleason score 5 +  4 predicts worse outcomes than 4 + 5 after robot-assisted radical prostatectomy: a nationwide multicenter cohort study.

PURPOSE: Among Grade Group (GG) 5 prostate cancers (PCa), based on the Gleason grading system, those diagnosed preoperatively with Gleason score (GS) 5 + 4 have been reported to have poorer oncological prognoses compared to those with GS 4 + 5. However, the confounding effects of factors such as serum PSA level and clinical T stage remain unresolved. This study aimed to evaluate the impact of GS 5 + 4 versus 4 + 5 on postoperative prognosis, accounting for potential confounders. METHODS: This nationwide, multi-institutional retrospective cohort study included 827 patients who underwent robot-assisted radical prostatectomy (RARP) at 25 tertiary centers between 2011 and 2022. Patients were classified by preoperative biopsy as GS 4 + 5 (n = 671) or GS 5 + 4 (n = 156). Biochemical recurrence (BCR)-free survival was compared using inverse probability of treatment weighting (IPTW) and Cox regression, adjusting for age, BMI, PSA, clinical T stage, ASA physical status, and the use of extended lymph node dissection, nerve-sparing, and neoadjuvant hormone therapy. RESULTS: The median follow-up was 33.7 months. Adjusted 3- and 5-year BCR-free survival rates were 66.0% and 57.8% for GS 4 + 5, versus 54.8% and 44.6% for GS 5 + 4. GS 5 + 4 remained significantly associated with worse BCR-free survival compared to GS 4 + 5 (HR 1.41, 95% CI 1.04–1.89, p = 0.039). CONCLUSION: Among GG 5 PCa, GS 5 + 4 was associated with significantly poorer BCR-free survival compared to GS 4 + 5, even after adjustment for key confounders. These findings support considering further risk refinement within GG 5.