Immune Mechanisms and Molecular Therapeutic Strategies to Enhance Immunotherapy in Non-Muscle Invasive Bladder Cancer - Beyond the Abstract

Recent advances in the bladder-sparing treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) have spurred investigation into the molecular mechanisms of tumor escape, revealing the close relationship between the tumor immune microenvironment (TME) and BCG response. In this review, Chu and Pietzak synthesize the current clinical and molecular landscape of BCG unresponsive bladder cancer (Figure 1).

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The challenge with NMIBC and bladder preservation is the need to provide therapies that are not only effective and durable, but also accompanied by favorable side effect profiles, patient acceptability, and ease of administration. Pembrolizumab remains the only FDA-approved therapy for BCG-unresponsive disease, but toxicity and durability of response are concerns. The authors summarize contemporary clinical trials currently testing novel bladder preservation therapies across clinical states of high risk NMIBC, with or without combination immunotherapy.

The need for stage-specific clinical trials to better delineate the risk-benefit ratio for the diverse array of bladder preserving treatments is necessary. While biomarker investigations are ongoing, the predictive value of biomarkers derived from correlative studies must ultimately be tested in a prospective fashion to stratify risk and guide treatment selection in clinical practice appropriately. As our understanding of the molecular landscape of NMIBC expands, we will be able to improve patient selection, tailor surveillance intensity, and expand bladder preservation strategies for high-risk NMIBC patients.

Written by: Carissa Chu, MD, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY

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