Abstract
BACKGROUND: High-risk non-muscle-invasive bladder cancer (NMIBC) is most commonly treated with Bacillus Calmette-Guérin (BCG) as first-line therapy. However, in light of the ongoing BCG shortage in the United States, a significant need exists for alternative treatment options, both in the upfront setting as well as for patients with BCG-refractory disease. While radical cystectomy remains the gold standard for patients with BCG-refractory disease, many patients are unfit or unwilling to undergo this procedure. Several new agents, many with novel mechanisms of action, have been approved or are actively being investigated in this setting. MATERIALS AND METHODS: Articles were chosen for review based on expert knowledge of the literature as well as on PubMed literature searches for the topics of focus. Appropriate articles were selected for inclusion by reviewing article titles, abstracts, and full texts. RESULTS: There is ample evidence for emerging therapies in BCG-refractory NMIBC including systemic immunotherapy and various intravesical options, such as chemotherapy, gene therapy, and novel drug delivery systems. Radical cystectomy, however, remains the gold standard. Response rates and duration of response vary across treatment modalities, with complete response rates at any time ranging from 41% to 82%. Radical cystectomy should still be recommended to patients with high-risk features given the risks of recurrence, progression, upstaging, and occult lymph node metastases. CONCLUSION: While radical cystectomy remains the standard of care for patients with BCG-refractory disease, many patients are unable or unwilling to undergo the procedure. Several novel therapies have been recently approved or are currently being investigated with overall promising early results.