Perioperative immune-checkpoint inhibitors for muscle-invasive bladder cancer

Muscle-invasive bladder cancer (MIBC) has a high risk of recurrence following radical cystectomy. Neoadjuvant cisplatin-based chemotherapy has been used for decades to lower recurrence rates but a significant proportion of patients still have disease relapse. Recently, immune-checkpoint inhibitors (ICIs) have been evaluated for patients with MIBC, with some success. This has led to regulatory approval of adjuvant nivolumab, sandwich perioperative durvalumab and sandwich perioperative pembrolizumab with enfortumab vedotin. This review summarizes the history of practice-informing and practice-changing neoadjuvant, adjuvant and sandwich perioperative application of ICIs for MIBC, looks ahead to the promising developments in other ICI-based sandwich perioperative regimens, and highlights controversies surrounding overtreatment versus undertreatment and the need for predictive biomarkers.