Neoadjuvant Nivolumab–Ipilimumab versus Platinum-Based Chemotherapy in Muscle-Invasive Bladder Cancer: A Single-Institution, Propensity-Weighted Cohort Study

Introduction: Neoadjuvant chemotherapy (NAC) is standard for muscle-invasive bladder cancer (MIBC), yet many patients are platinum-ineligible. We compared outcomes of neoadjuvant nivolumab plus ipilimumab versus platinum-based NAC. Methods: This single-institution comparative cohort study compared a prospective immune checkpoint inhibitor (ICI) cohort (n=11) receiving nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) against a retrospective platinum-based NAC cohort (n=30). Propensity score-based overlap weighting was used to reduce measured confounding. Main outcomes included pathologic complete response (pCR), downstaging ( Results: Among surgically evaluable patients (ICI n=9; NAC n=30), pCR rates were 22.2% and 26.7%, respectively (p=1.00), and downstaging rates were 44.4% and 50.0% (p=1.00). Propensity-weighted analyses likewise showed no statistically significant differences in pathologic response. In the total ICI cohort (n=11), four patients (36.4%) did not complete all four planned cycles, including three because of grade 3 immune-related toxicity and one who died following an on-treatment acute myocardial infarction. At a median follow-up of 58.3 months in the ICI cohort, no recurrences were observed among the nine surgically treated patients during the available follow-up, compared with nine recurrences (30.0%) in the NAC cohort. Two-year OS was 100% in the ICI group and approximately 80% in the NAC group (log-rank p=0.18). Conclusion: Neoadjuvant dual ICI demonstrated pathologic activity, with response rates numerically within the range observed with standard NAC. Clinically meaningful immune-related adverse events were observed in the ICI cohort; however, no recurrences were observed among surgically treated ICI patients during the available follow-up. These findings support further investigation of dual ICI as a potential option when platinum-based NAC is not feasible or is declined. Keywords: muscle-invasive bladder cancer, MIBC, neoadjuvant chemotherapy, NAC, immune checkpoint inhibitor, ICI, nivolumab, ipilimumab, propensity score weighting