Novel Therapeutic Strategies for BCG-unresponsive Non-muscle Invasive Bladder Cancer

Development of therapeutic strategies for non-muscle-invasive bladder cancer (NMIBC) that failed intravesical Bacillus Calmette - Guerin (BCG) therapy remains an urgent priority for clinicians. Currently, radical cystectomy is the recommended standard of care treatment options for these patients. Intravesical chemotherapy using gemcitabine and docetaxel are regarded as the most effective treatment options for unresponsive NMIBC, however, these options are ineffective in the control of bladder cancer. In this review, we present the definition of BCG unresponsive NMIBC and discuss about the recent management options that include immunotherapy, intravesical chemotherapy, gene therapy, and targeted individualized therapy. Notably, immunotherapy is the most recent strategy utilizing the PD-1/PD-L1 and other immune checkpoint inhibitors (ICIs). Pembrolizumab (KEYNOTE-057), Atezolizumab (SWOG S1605) and Nivolumab were developed and are efficacious in BCG –unresponsive NMIBC. In summary, ICIs are considered as the most promising agent for BCG unresponsive NMIBC in the future.