Current status and future directions of the use of novel immunotherapeutic agents in bladder cancer

Purpose of review To report the available information on the current status and future direction of the use of checkpoint inhibitors as novel immunotherapeutic agents in bladder cancer. Recent findings In the past 3 years, five immunotherapies targeting programmed cell death 1 (Pembrolizumab and Durvalumab) or programmed cell death-ligand 1 (PD-L1) (Atezolizumab, nivolumab and Avelumab) pathways have been approved in second-line setting for patients who progressed during or after cisplatin-based chemotherapy. According to the most recent update, these patients should be PD-L1-positive to be eligible for immunotherapy. The use of novel checkpoint inhibitors was also very promising in other settings: Metastatic urothelial carcinoma without prior systemic treatment (IMvigor-130), as neoadjuvant treatment before radical cystectomy in patients with muscle invasive disease (PURE-01), and in Bacillus Calmette-Guerin (BCG) refractory nonmuscle invasive bladder cancer (KEYNOTE 057). Summary Ongoing trials on the role of checkpoint inhibitors in bladder cancer may change our approach to different stages of bladder cancer. For metastatic urothelial carcinoma, the role of combined immune and chemotherapy may improve survival. For localized bladder cancer, immunotherapy as neoadjuvant therapy may be associated with less toxicity and better tolerability. Finally, in the setting of a BCG-refractory or BCG-naive nonmuscle invasive disease checkpoint inhibitors may reduce/delay the risk of progression and subsequent cystectomy.