Background: Bladder-sparing trimodality therapy (TMT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC), and biomarkers to inform therapy selection are needed. Objective: To evaluate immune and stromal signatures in MIBC treated with TMT. Overall design: Gene expression profiling was used to study molecular sub typing and the tumor microenvironment in the setting of bladder preservation therapy for muscle-invasive bladder cancer.