Emerging treatment options for bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer

Purpose of review The majority of new bladder cancer diagnoses are non-muscle invasive bladder cancer (NMIBC). For patients with intermediate-risk and high-risk NMIBC, the preferred treatment after transurethral tumor resection is bacillus Calmette-Guérin (BCG) intravesical therapy; however, some patients receiving BCG do not respond and are at risk for recurrence and progression to muscle invasive disease. Currently, there is a lack of bladder-sparing therapies for patients that do not respond to BCG therapy. This review highlights recent advances in bladder-sparing therapies for NMIBC that do not respond to BCG therapy. Recent findings Several clinical trials have emerged over the past several years using novel agents. Systemic immunotherapy with pembrolizumab has shown promising activity, and recently gained FDA approval for use in BCG-unresponsive NMIBC. Gene therapy using Nadofaragene firadenovec, a replication-deficient adenoviral vector delivering interferon (IFN) alfa, shows durable results and is pending regulatory approval. Several other agents are on the horizon and there will likely be an emergence of therapies over the next several years. Summary Patients with NMIBC that do not respond to BCG therapy are at high risk for progression to muscle invasive disease. Bladder-sparing therapeutic options for these patients are sparse but now include pembrolizumab and several other potential options are emerging. These bladder-sparing therapies will benefit patients unwilling or unable to undergo radical cystectomy.