Stage-dependent survival in patients treated with neoadjuvant chemotherapy and radical cystectomy

BACKGROUND: The aim of this study is to investigate the differential stage-dependent outcomes of patients undergoing radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). METHODS: We performed a retrospective analysis of 1422 patients with cT2-4N0 MIBC treated with RC, with/without cisplatin-based NAC, from our multicenter cooperation program (treated period: 1992-2021). Patients were stratified according to their pathologic stage at RC. Cancer-specific survival (CSS) and overall survival (OS) were calculated using mixed-effects Cox analysis. RESULTS: Analysis was conducted on 761 patients treated with NAC followed by RC and 661 treated with RC only (median follow-up 19 months). Of 337 (24%) patients who died, 259 (18%) died of bladder cancer. On univariable analyses, increased pathologic stage was significantly associated with worse CSS (HR=1.59, 95% CI 1.46-1.73; P<0.01) and OS (HR=1.58, 95% CI 1.47-1.71; P<0.001). On multivariable mixed-effects model, patients after RC only had significantly worse CSS with stage pT≥3/N1-3 and OS with stage pT≥2/N0-3 compared to those with stage pT≤1N0. Patients after RC and NAC had significantly worse CSS and OS already at stage ypT≥2/N0-3 compared to those with ypT≤1N0. On subgroup analyses, CSS (HR=4.26; 95% CI 2.03-8.95; P<0.001) but not OS (HR=1.1; 95% CI 0.5-2.4; P=0.81) was worse for pT2N0 patients after NAC versus no-NAC. This difference was not maintained on multivariable analysis. CONCLUSIONS: NAC improves pathologic stage at the time of RC. Patients with residual MIBC after NAC have worse survival outcomes compared to those with the same pathologic stage who did not receive NAC, suggesting a need for better adjuvant therapy in these patients.