Differential Outcomes in Bladder Cancer After Neoadjuvant Chemotherapy: An International Multi-Institutional Study Comparing Isolated Nodal Disease vs Persistent Muscle-Invasive Disease

Abstract

Objective: To evaluate clinical outcomes based on patterns of residual disease in patients undergoing cystectomy after neoadjuvant chemotherapy (NAC), focusing on those with residual tumor only in lymph nodes. Methods: We retrospectively analyzed 174 patients who underwent post-NAC radical cystectomy between 2010 and 2023 at academic centers from the United States and Europe. Patients were stratified into two groups: those with isolated lymph node disease despite complete local response (n = 35) and those with persistent muscle-invasive or locally advanced disease without lymph node involvement (n = 139). Primary outcomes included recurrence, disease-specific mortality (DSM), and survival. Median follow-up was 27.0 months (interquartile range: 9.0-60.0). Results: Recurrence occurred in 33% of patients, with higher risk in patients with residual disease only in lymph nodes compared to those with persistent disease in the bladder and negative lymph nodes (adjusted OR: 0.43, 95% CI: 0.20-0.95, P = .036). DSM was 24%, with no significant difference between groups (adjusted OR: 0.70, 95% CI: 0.29-1.64, P = .407). Disease-related events occurred in 41% of patients, with lower risk in the group with residual disease in the bladder (adjusted OR: 0.46, 95% CI: 0.21-0.99, P = .048). Survival analyses showed no significant differences in DSM between groups (HR: 1.03, 95% CI: 0.48-2.20, P = 0.947). Variant histology (present in 36% of cases) did not influence outcomes. Conclusion: Patients with isolated lymph node disease, despite complete local response after NAC, demonstrate higher recurrence risk compared to those with persistent muscle-invasive disease, although this does not translate into survival differences. These findings suggest the need for risk-adapted surveillance strategies and consideration of additional therapeutic interventions in patients with isolated residual nodal disease.