Neoadjuvant immunotherapy driven bladder preservation for muscle invasive bladder cancer

The study included 163 patients with muscle-invasive bladder cancer (MIBC) from 14 hospitals, categorized into the neoadjuvant immunotherapy-combined-modality therapy (Neoimmu-CMT), trimodal therapy (TMT), and neoadjuvant chemotherapy-combined-modality therapy (NAC-CMT) subgroups. Propensity score matching (PSM) was utilized to mitigate baseline variability. Univariate and multivariate Cox analyses were used to identify potential prognostic factors. Biomarker assessment comprised immunohistochemistry and single-cell RNA sequencing. After PSM, Neoimmu-CMT demonstrated superior efficacy over NAC-CMT and comparability to TMT. A clinical complete response to neoadjuvant treatment and lower clinical T stage were positive prognostic factors for Neoimmu-CMT. Biomarker analysis showed that the immune phenotype of the tumor microenvironment (TME) was closely associated with bladder preservation outcomes. We assessed the potential relationship between various cell types in the TME and bladder preservation outcomes using single-cell RNA sequencing. The results showed that the dynamic distribution of fibroblast and NK/T cell subclusters was associated with bladder preservation outcomes. In the future, the development of Neoimmu-CMT will substantially expand its application in bladder preservation therapies.