Neoadjuvant immunotherapy, chemotherapy, and combination therapy in muscle-invasive bladder cancer: A multi-center real-world retrospective study

To parallelly compare the efficacy of neoadjuvant immunotherapy (tislelizumab), neoadjuvant chemotherapy (gemcitabine and cisplatin), and neoadjuvant combination therapy (tislelizumab + GC) in patients with muscle-invasive bladder cancer (MIBC) and explore the efficacy predictors, we perform a multi-center, real-world cohort study that enrolls 253 patients treated with neoadjuvant treatments (combination therapy: 98, chemotherapy: 107, and immunotherapy: 48) from 15 tertiary hospitals. We demonstrate that neoadjuvant combination therapy achieves the highest complete response rate and pathological downstaging rate compared with neoadjuvant immunotherapy or chemotherapy. We develop and validate an efficacy prediction model consisting of pretreatment clinical characteristics, which can pinpoint candidates to receive neoadjuvant combination therapy. We also preliminarily reveal that patients who achieve pathological complete response after neoadjuvant treatments plus maximal transurethral resection of the bladder tumor may be safe to receive bladder preservation therapy. Overall, this study highlights the benefit of neoadjuvant combination therapy based on tislelizumab for MIBC. [Display omitted] •Neoadjuvant chemoimmunotherapy is safe and feasible for patients with bladder cancer•An efficacy prediction model for neoadjuvant chemoimmunotherapy is developed•Efficacy biomarkers are explored from bulk and single-cell RNA sequencing In a multi-center, real-world study, Hu et al. demonstrate that neoadjuvant chemoimmunotherapy achieves the highest response rate, compared with neoadjuvant immunotherapy or chemotherapy. Patients who achieve pathological complete response after neoadjuvant treatments plus maximal transurethral resection of the bladder tumor may be safe to receive bladder preservation therapy.