The management of BCG failure in non-muscle-invasive bladder cancer: an update

Up to 40% of patients with non-muscle-invasive bladder cancer (NMIBC) will fail intravesical bacillus Calmette-Guérin (BCG) therapy. There is unfortunately no current gold standard for salvage intravesical therapy after appropriate BCG treatment. Indeed, outcomes are at best suboptimal. The vast majority of low-grade NMIBC are prone to recur but very rarely progress. Failure after intravesical BCG in these patients is usually superficial and low-grade. At the other end of the spectrum, failure to respond to BCG in high-risk T1 bladder cancer and/or carcinoma in situ (CIS or TIS) is more problematic, since those tumours often have the potential to progress to muscle invasion. In these cases, radical cystectomy remains the mainstay after BCG failure. With appropriate selection, certain patients who "fail" BCG (but with favourable risk factors) can be managed with intravesical regimens, including repeated BCG, BCG plus cytokines, intravesical chemotherapy, thermochemotherapy or new immunotherapeutic modalities. In this review, reasons explaining BCG failure, how to define BCG failure, optimal risk stratification and prediction of response and management of BCG failures are discussed.