Immune checkpoint inhibition in muscle-invasive and locally advanced bladder cancer

Immune-checkpoint inhibitors (CPIs) have been implemented in the treatment algorithm of metastatic urothelial cancer as they have shown higher and more sustained responses compared with conventional second-line chemotherapy. Recently, several clinical trials have reported on CPIs in earlier disease stages such as muscle-invasive bladder cancer (MIBC). This review summarizes ongoing clinical trials and results from early phase clinical trials in muscle invasive and locally advanced bladder cancer.

In phase II clinical trials, neoadjuvant use of CPIs as mono and combination therapy, in patients with MIBC planned for radical cystectomy, has shown promising pathological complete response rates. Whether this will translate in survival benefit remains to be assessed. Combination of CPIs and conventional chemotherapy or other targeted agents promises to increase the efficacy of perioperative systemic therapy with potentially additive toxicities. Recently, preclinical models of combined trimodal therapy with CPIs delivered the proof of principle leading to several ongoing trials in this setting.

First results of clinical trials evaluating CPIs in MIBC demonstrate very promising results that warrant further investigation as they could revolutionize management of MIBC in the near future. The trend and hope are toward higher rates of safe and sustained bladder preservation.