Neoadjuvant immunotherapy-driven bladder preservation for muscle-invasive bladder cancer: A multicenter, propensity score-matched cohort study.

115 Background: Neoadjuvant immunotherapy-driven bladder preservation (Neoimmu-CMT), despite its prominence, is constrained in application due to the absence of robust clinical evidence. Currently, there is a lack of comparative studies on the efficacy of Neoimmu-CMT versus the traditional trimodal therapy (TMT) or neoadjuvant chemotherapy- driven bladder preservation (NAC-CMT). To address this gap, our study (ChiCTR2300069303) aims to assess Neoimmu-CMT's viability and identify suitable candidates through a multicenter, propensity score-matched analysis. Methods: The study included 163 patients from 14 hospitals, categorized into Neoimmu-CMT (n=97), TMT (n=30), and NAC-CMT (n=36) subgroups. PSM was utilized to mitigate baseline variability. Primary outcomes were disease-free survival (DFS), bladder-intact DFS (BI-DFS), and overall survival (OS). Univariate and multivariate Cox analyses were used to identify potential prognostic factors. Biomarker assessment comprised immunohistochemistry and single-cell RNA sequencing. Results: Post-PSM, Neoimmu-CMT significantly outperformed NAC-CMT in DFS (HR: 2.112, 95% CI: 1.247-3.576, P=0.005) and BI-DFS (HR: 2.329, 95% CI: 1.138-4.770, P=0.021), with a 2-year BI-DFS rate of 90.28% compared to NAC-CMT's 71.59%. However, Neoimmu-CMT and TMT showed no significant difference in DFS and BI-DFS, with Neoimmu-CMT marginally surpassing TMT in 2-year BI-DFS rates (86.42% vs. 80.89%). Clinical complete response to neoadjuvant treatment and lower clinical T stage were positive prognostic factors for Neoimmu-CMT. Biomarker analysis showed the tumor microenvironment immune phenotype closely relates to bladder preservation outcomes. Conclusions: Neoimmu-CMT is a promising bladder preservation strategy, comparable to TMT and superior to NAC-CMT. Its advancement could significantly broaden bladder preservation treatment options. [Table: see text]