Emerging evidence of immunotherapy in BCG-unresponsive non-muscle invasive bladder cancer

BACKGROUND: BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) remains a therapeutic challenge due to its substantial risk of progression to muscle-invasive bladder cancer (MIBC) and require further management including radical cystectomy (RC). In this context, immunotherapy emerges as a promising alternative to delay or potentially avoid RC.METHODS: A collaborative review of the literature available on Medline was conducted to report the prospective and retrospective studies evaluating systemic and/or intravesical immunotherapy in BCG-unresponsive NMIBC patients. A total of 41 references published between 2003 and 2024 were included in this review.RESULTS: Checkpoint inhibitor emerges as a promising approach, with complete response rates ranging from 12% to 43% at 3 or 12 months for systemic immunotherapy, and from 48.4% to 87.5% at 3 or 12 months for the combination of systemic immunotherapy with intravesical instillation. Regarding adverse events, grade ≥3 events were observed in 7% to 41% of cases when the information was reported. Specifically, Keynote 057 demonstrated promising results with systemic pembrolizumab, leading to its FDA approval in January 2020, while SWOG S1605 showed similar outcomes with systemic atezolizumab. Regarding the combination of systemic immunotherapy and intravesical instillation, the SunRise 1 trial reports satisfactory results, particularly for the TAR-200 cohort alone and the TAR-200 combined with systemic Cetrelimab. Other trials involving systemic and/or intravesical immunotherapy are still ongoing, with results expected soon.CONCLUSIONS: In this setting, systemic and/or intravesical immunotherapy appears to be an increasingly well-supported therapeutic option, especially for patients with CIS, with acceptable major side effects.