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

e16598 Background: The rise of neoadjuvant immunotherapy has brought neoadjuvant immunotherapy-driven bladder preservation (Neoimmu-CMT) into the spotlight, yet its application is hampered by a scarcity of robust clinical evidence. There are no comparative studies on the effectiveness of Neoimmu-CMT versus 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 (PSM) 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. Interestingly, regardless of being combined with ADC (HR: 1.283, 95% CI: 0.224-7.359, P=0.780) or chemotherapy (HR: 0.769, 95% CI: 0.255-2.323, P=0.642), the DFS outcomes did not surpass those received with sole immunotherapy. Furthermore, conventional clinical parameters such as tumor-associated hydronephrosis, tumor number, and histology type did not emerge as significant predictors for bladder preservation outcomes. 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.