Neoadjuvant immunotherapy for muscle-invasive bladder cancer: a 2025 update

Urothelial bladder cancer constitutes one of the most common malignancies of the urinary tract, comprising 90-95% of urothelial carcinomas. Only 25% of patients present with muscle-invasive bladder cancer (MIBC), a neoplasm associated with higher morbidity and mortality. Concerning localized MIBC, cisplatin-based chemotherapy remains the standard neoadjuvant treatment; however, its survival benefits are limited, and its use is restricted to patients with adequate performance status and renal function. Current clinical guidelines recommend neoadjuvant immunotherapy as a first- or second-line option, especially for cisplatin-ineligible patients. Neoadjuvant immunotherapy as monotherapy or in combination with chemotherapy or other immune checkpoint inhibitors is under active investigation. In the ABACUS trial, atezolizumab monotherapy achieved a 31% pathological complete response (pCR). The NCT03520491 trial showed a pCR rate of up to 46% with nivolumab and ipilimumab. The KCT0003804 trial, evaluating immunotherapy plus chemotherapy, reported a 59% pCR and 81.8% 1-year disease-free survival. This review provides an updated overview of clinical trials on neoadjuvant immunotherapy for MIBC, highlighting its therapeutic potential and safety.