Impact of neoadjuvant chemotherapy on outcomes of bladder-preserving chemoradiotherapy in muscle-invasive bladder cancer.

Abstract

670 Background: NAC (neoadjuvant chemotherapy) has been established as the standard of care for patients with MIBC (muscle-invasive bladder cancer) undergoing radical cystectomy. However, its potential benefit prior to CCRT (concurrent chemoradiotherapy) remains largely unexplored. Methods: This retrospective analysis included 226 patients with clinical stage T2–4N0–1M0 MIBC treated at three university centers between January 2012 and December 2024. Among them, 170 received upfront CCRT, and 56 received NAC followed by CCRT. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), metastasis-free survival (MFS), and cystectomy-free survival (CFS). Results: Patients who received NAC were younger (mean age, 68 vs. 75 years; p < 0.001) and more likely to have N1 disease (16.1% vs. 4.1%; p = 0.005) compared with those treated with upfront CCRT. During a median follow-up of 83.7 months (95% confidence interval [CI], 66.0–101.4 months), 73 deaths were observed. CFS did not differ according to the receipt of NAC (p = 0.415). However, NAC was significantly associated with improved OS (hazard ratio [HR], 0.318; 95% CI, 0.163–0.620; p < 0.001), PFS (HR, 0.663; 95% CI, 0.442–0.994; p = 0.047), and MFS (HR, 0.444; 95% CI, 0.226–0.870; p = 0.018). After adjustment using inverse probability of treatment weighting (IPTW) including age, sex, ECOG performance status, histology, clinical T and N stage, tumor multiplicity, presence of carcinoma in situ, hydronephrosis, maximal transurethral resection of bladder tumor (TURBT) status, and radiation field, the survival benefit of NAC remained consistent for OS (HR, 0.272; 95% CI, 0.125–0.594; p = 0.001), PFS (HR, 0.543; 95% CI, 0.349–0.843; p = 0.007), and MFS (HR, 0.443; 95% CI, 0.224–0.877; p = 0.020). Conclusions: This multi-institutional study provides evidence that NAC before CCRT is associated with improved survival outcomes in patients with MIBC undergoing bladder-preserving treatment with curative intent.