Real-world Outcomes of Adjuvant Nivolumab in High-risk Bladder and Upper Tract Urothelial Carcinoma after Radical Surgery

Adjuvant nivolumab after radical surgery for patients with high-risk urothelial carcinoma was associated with improved disease-free survival and overall survival in a large multicenter real-world cohort. These findings are consistent with clinical trial results and contribute real-world evidence regarding postoperative treatment strategies. Adjuvant nivolumab has shown efficacy in randomized trials for high-risk urothelial carcinoma after radical surgery, but its real-world outcomes remain unclear. To evaluate the association between adjuvant nivolumab and oncological outcomes in real-world practice. This retrospective, multicenter study analyzed 366 patients with high-risk bladder cancer or upper tract urothelial carcinoma who underwent radical surgery between 2016 and 2025 at 18 institutions in the Japanese AGEHA database. Patients were classified into an adjuvant nivolumab group ( n = 126) and a composite control group ( n = 240), consisting of adjuvant chemotherapy ( n = 59) or observation alone ( n = 181). The primary analysis compared adjuvant nivolumab with observation alone using propensity score matching (PSM). Secondary analyses included PSM comparisons between adjuvant nivolumab, adjuvant chemotherapy, and exploratory subgroup analyses. In the primary PSM cohort (97 matched pairs), adjuvant nivolumab was associated with improved disease-free survival (DFS; hazard ratio HR = 0.56, 95% confidence interval CI = 0.35–0.88) and overall survival (OS; HR = 0.40, 95% CI = 0.19–0.81) compared with observation alone. In secondary analyses, DFS and OS appeared similar between adjuvant nivolumab and adjuvant chemotherapy. Site-specific analyses demonstrated consistent benefits in patients with muscle-invasive bladder cancer, whereas adequate covariate balance could not be achieved for patients with upper tract urothelial carcinoma. In this multicenter real-world cohort, adjuvant nivolumab was associated with improved DFS and OS compared with observation after radical surgery; however, these findings require confirmation in future studies designed to minimize residual confounding.