Improving Anti-PD-1/PD-L1 Therapy for Localized Bladder Cancer

In high-risk non-muscle invasive bladder cancer (HR-NMIBC), patient outcome is negatively affected by lack of response to Bacillus-Calmette Guérin (BCG) treatment. Lack of response to cisplatin-based neoadjuvant chemotherapy and cisplatin ineligibility reduces successful treatment outcomes in muscle-invasive bladder cancer (MIBC) patients. The effectiveness of PD-1/PD-L1 immune checkpoint inhibitors (ICI) in metastatic disease has stimulated its evaluation as a treatment option in HR-NMIBC and MIBC patients. However, the observed responses, immune-related adverse events and high costs associated with ICI have provided impetus for the development of methods to improve patient stratification, enhance anti-tumorigenic effects and reduce toxicity. Here, we review the challenges and opportunities offered by PD-1/PD-L1 inhibition in HR-NMIBC and MIBC. We highlight the gaps in the field that need to be addressed to improve patient outcome including biomarkers for response stratification and potentially synergistic combination therapy regimens with PD-1/PD-L1 blockade.