Neoadjuvant therapy for muscle-invasive bladder cancer.

INTRODUCTION: Muscle-invasive bladder cancer (MIBC) is generally a highly aggressive malignancy with early and mostly distant recurrences. Cisplatin-based combinations have been established as neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) providing overall survival as well as disease-free survival benefit. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic urothelial carcinoma and are being tested in the neoadjuvant setting as well. AREAS COVERED: This review covers the existing guidelines for the management of MIBC. It summarizes the use of different NAC regimens. It also discusses the published literature of ICIs in this setting and explores future perspectives. EXPERT OPINION: Cisplatin-based NAC is the standard of care in MIBC prior to RC. Cisplatin-ineligible MIBC patients have not demonstrated to clearly benefit from a chemotherapy regimen and proceed directly to RC, although novel agents have been evaluated in this setting. Pembrolizumab and atezolizumab as monotherapy have shown feasibility and promising pathologic response rates. The combination of cisplatin-based chemotherapy with ICIs and chemotherapy-free ICI alone approaches are being investigated in randomized trials. Molecular subclassification and development of predictive biomarkers in MIBC will further help to identify optimal treatment strategies in these patients.