Efficacy of neoadjuvant/induction (NAC) chemotherapy in nonmetastatic muscle-invasive bladder cancer treated with chemoradiotherapy (CRT): A systematic review and meta-analysis.

Abstract

814 Background: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the established standard for nonmetastatic muscle-invasive bladder cancer (MIBC). However, bladder-sparing approaches using chemoradiotherapy (CRT) offer comparable outcomes. While NAC has proven beneficial before RC, its value prior to CRT remains uncertain. This systematic review and meta-analysis aimed to evaluate the impact of NAC on outcomes in patients undergoing CRT for bladder preservation. Methods: A comprehensive search of PubMed, Embase, and Cochrane databases was conducted to identify studies comparing NAC plus CRT versus CRT alone in MIBC. Both randomized controlled trials (RCTs) and observational studies were eligible. Studies with overlapping populations or non-English publications were excluded. Heterogeneity was assessed with I² statistics, and all analyses were performed using random-effects models in Review Manager 5.4.1. The study was registered in PROSPERO (CRD42024590258). Results: Four observational studies, encompassing 3,354 patients, were included as no RCTs met the inclusion criteria. NAC was administered to 656 patients (19.5%). Median follow-up ranged from 15.9 to 74.4 months. All patients in the NAC group received platinum-based chemotherapy (MVAC, ddMVAC, GC, or CMV). Concurrent CRT regimens included cisplatin, gemcitabine, or mitomycin with radiotherapy. No significant difference in overall survival was observed between NAC + CRT and CRT alone (HR = 0.99, 95% CI 0.87–1.13, p = 0.89, I² = 0%). Disease-free survival data were available from two studies, showing no significant difference (HR = 1.07, 95% CI 0.57–2.01, p = 0.82, I² = 39%). All included studies had a serious risk of bias, mainly due to confounding and selection bias, as assessed by the ROBINS-I tool. The overall certainty of the evidence was rated as very low using the GRADE framework. Conclusions: Our analysis found no survival benefit from adding NAC to CRT in patients with MIBC. However, the quality of the evidence is very low, largely due to the retrospective nature of the data. Further randomized clinical trials are needed to clarify the role of NAC in bladder preservation strategies.