The Emerging Treatment of BCG (Bacillus Calmette-Guérin)-Unresponsive Non–Muscle-Invasive Bladder Cancer

Abstract

Bacillus Calmette-Guérin (BCG) remains the cornerstone in the treatment of high-risk non-muscle-invasive bladder cancer (NMIBC), effectively preventing recurrence and progression. Unfortunately, a significant proportion of patients are classified as BCG-unresponsive, and there have been no definite alternative treatments for these disease group except for radical cystectomy, which is still challenging and sometimes not applicable. Therefore, there has been a need for alternative bladder-preserving treatments for patients who desire a bladder-sparing approach or are too frail for major surgery. Intravesical therapies, such as gemcitabine, mitomycin C and docetaxel, are mostly studied approaches, showing some promising results. However, no definitive conclusion has be drawn because of the heterogeneity of the studies and protocols and the limited number of patients enrolled in most of these studies. Immunotherapy and anti-inflammatory agents, though promising, require further validation through ongoing clinical trials to ensure their safety and efficacy. Gene therapy is also being explored, though it is in its early stages, with challenges in gene delivery and immune regulation still to be addressed. Photodynamic therapy and hyperthermia, particularly in combination with other treatments like intravesical chemotherapy, have shown potential in improving outcomes for BCG-unresponsive patients, though they are not yet considered first-line treatments. While these novel approaches hold promise, more robust data and clinical trial results are necessary to guide treatment protocols. In conclusion, ongoing research and clinical trials will continue to shape the future of NMIBC management, with the aim of providing more effective and bladder-preserving options for patients.

Keywords

• non–muscle-invasive bladder cancer
• bcg vaccine
• genetic therapy
• immunotherapy
• photochemotherapy