Salvage therapeutic strategies for bacillus Calmette-Guerin failure

To give an overview of current options for conservative treatment of patients failing intravesical bacillus Calmette-Guerin (BCG) and to discuss emerging approaches with potential future clinical applications.

Radical cystectomy is the standard-of-care for patients failing BCG therapy. In patients unfit or unwilling to undergo surgery, salvage therapy options could be proposed with the aim to offer local cancer control and prevent progression to muscle-invasive disease. Salvage treatments have been conducted using intravesical chemotherapy regimens, chemoradiation or chemohyperthermia. Intravesical agents such as valrubicin, gemcitabine or docetaxel showed response rates varying between 16 and 40%, whereas combination treatments of gemcitabine with docetaxel or mitomycin reported response rates in up to 50% of all patients with durable responses in about one out of three patients. For chemohyperthermia, 2-year recurrence rates between 41 and 56% have been reported. Ongoing clinical trials are evaluating chemoradiation as well as novel approaches such as systemic immunotherapy, viral gene therapy, targeted therapy or vaccination strategies with promising preliminary outcomes.

Salvage therapeutic bladder-sparing strategies for BCG failure such as intravesical chemotherapy or chemoradiation should currently only be considered in patients unfit for or refusing surgery. Innovative concepts such as chemohyperthermia, checkpoint inhibitors, targeted therapy or viral gene therapy could lead to major changes in clinical management of BCG failures in the future.