Perioperative immunotherapy in muscle-invasive bladder cancer: a narrative review of neoadjuvant, adjuvant, and antibody-drug conjugate-based strategies

BACKGROUND: Muscle-invasive bladder cancer (MIBC) remains a lethal disease even after radical cystectomy, and roughly half of patients eventually relapse, which has pushed clinical research toward intensifying systemic treatment around the time of surgery. INTRODUCTION: Immune checkpoint inhibitors (ICIs), first validated in metastatic urothelial carcinoma, have now been tested across the full perioperative spectrum, from neoadjuvant monotherapy and to adjuvant checkpoint blockade and, more recently, antibody-drug conjugate combinations, raising the question of how each strategy contributes to curative-intent care. METHODS: This narrative review summarizes the available clinical evidence on perioperative immunotherapy for MIBC, drawing on phase 1 to phase 3 trials identified through a structured, non-systematic search of PubMed/MEDLINE and ClinicalTrials.gov, up to 2026. RESULTS: Perioperative immunotherapy has demonstrated meaningful improvements in pathological response and survival outcomes in MIBC. NIAGARA established the clinical benefit of adding durvalumab to cisplatin-based neoadjuvant chemotherapy, while the phase III EV-303 and EV-304 trials demonstrated substantial pathological response and survival benefits with perioperative enfortumab vedotin plus pembrolizumab in cisplatin-ineligible and cisplatin-eligible populations, respectively. In the adjuvant setting, CheckMate 274 supported nivolumab, whereas IMvigor011 demonstrated improvements in disease-free and overall survival with ctDNA-guided atezolizumab. Despite these advances, optimal patient selection, treatment sequencing, and the potential for bladder preservation remain unresolved. CONCLUSION: Perioperative immunotherapy, increasingly paired with novel agents and guided by pathological response, perioperative safety, and emerging biomarkers, is reshaping curative-intent treatment of MIBC.