Combined and individual effects of neoadjuvant chemotherapy and lymph node dissection on survival in non–muscle-invasive bladder cancer undergoing radical cystectomy

BACKGROUND: The roles of neoadjuvant chemotherapy (NAC) and lymph node dissection (LND), particularly their combined use, remain unclear in patients with non-muscle-invasive bladder cancer (NMIBC) undergoing radical cystectomy (RC). METHODS: Patients diagnosed with NMIBC and treated with RC were identified from the Surveillance, Epidemiology, and End Results database. Temporal trends in the utilization of NAC, LND, and their combination were analyzed. Kaplan-Meier and Cox proportional hazards models were used to compare overall survival (OS) across different treatment groups, including NAC, LND, and their combination, relative to no treatment. RESULTS: A total of 3,995 patients were included. The use of NAC and LND increased markedly over time. In the overall cohort, the combination of NAC and LND provided greater survival benefit (HR = 0.58, 95% CI 0.49-0.70, P < 0.001) than either treatment alone (HR = 0.73, 95% CI 0.66-0.81, P < 0.001). Subgroup analyses showed that the survival advantage of the combination compared with no treatment was not significant for nonurothelial or unspecified histology, low-grade disease, and Ta-Tis stage tumors. In patients with T1 high-grade urothelial carcinoma, NAC or LND alone improved OS (HR = 0.66, 95% CI 0.57-0.76, P < 0.001), and their combination yielded even greater benefit (HR = 0.52, 95% CI 0.42-0.65, P < 0.001), with significant advantages observed across nearly all subgroups. CONCLUSION: In NMIBC patients undergoing RP, LND represented the primary driver of survival benefit, whereas NAC alone was not independently associated with improved outcomes. The combination of NAC and LND conferred an additional, incremental advantage over either modality alone, with the magnitude of benefit varying across patient characteristics. In the T1 high-grade urothelial carcinoma subgroup, both NAC and LND were associated with improved survival, with LND providing the dominant effect and the combined strategy yielding the greatest benefit, with advantages over no treatment observed across nearly all subgroups.