Bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer: Its definition and future therapeutic strategies

Bacillus Calmette-Guérin induction with or without maintenance is the gold standard therapy for intermediate-/high-risk non-muscle-invasive bladder cancer; however, one-third of patients treated with adequate bacillus Calmette-Guérin therapy do not achieve sufficient responses, and this is referred to as "bacillus Calmette-Guérin failure." The term, bacillus Calmette-Guérin failure, is ambiguous and includes a very heterogeneous population of patients. By strictly focusing on patients who are unlikely to benefit from additional bacillus Calmette-Guérin therapy and who need to be treated with radical cystectomy, the new concept of "bacillus Calmette-Guérin unresponsive" was recently proposed, and might accelerate the development of novel therapeutic options for bacillus Calmette-Guérin-unresponsive disease. A promising therapeutic strategy for bacillus Calmette-Guérin-unresponsive disease is the blockade of the programmed cell death-1/programmed cell death-ligand 1 pathway, which is considered to be activated by bacillus Calmette-Guérin therapy. Several large clinical trials have been carried out to assess the potential of programmed cell death-1/programmed cell death-ligand 1 blockade in bacillus Calmette-Guérin-naïve high-risk non-muscle-invasive bladder cancer and bacillus Calmette-Guérin-unresponsive disease. Furthermore, clinical trials that are targeting bacillus Calmette-Guérin-unresponsive disease with other strategies, such as vaccines, gene therapy, and targeted and cytotoxic therapies, are ongoing. The findings of these trials are awaited in order to establish appropriate bladder-sparing approaches for patients with bacillus Calmette-Guérin-unresponsive disease.