Prediction of BCG responses in non-muscle-invasive bladder cancer in the era of novel immunotherapeutics

Abstract

Bacillus Calmette-Guerin (BCG) instillations are considered as a gold standard of therapy in high- and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Unfortunately, up to 40% of patients might experience treatment failure and even 15% of patients initially diagnosed with NMIBC will progress to muscle-invasive disease. Since patients, who fail to respond to BCG, are at particular risk of progression, immediate radical cystectomy (RC) is currently recommended to provide cancer control. However, immunotherapy in NMIBC management still evolves. Immune checkpoint inhibitors emerge as new immunotherapeutics, which in the future might be combined with BCG and may serve as an alternative to radical cystectomy in patients, who failed to respond to BCG alone or are at particular a priori risk of BCG failure, especially if RC is not a safe option. Therefore, there is an urgent need to identify NMIBC patients that will not benefit from BCG therapy and demand radical cystectomy. In the following review, we attempt to focus on several clinical and molecular factors and demonstrate the efforts directed to unravel their significance in BCG-failure risk assessment.

Keywords: BCG failure; BCG response; BCG-refractory bladder cancer; High-risk non-muscle-invasive bladder cancer.