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

Abstract

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 lowgrade. 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.

Current intravesical therapy for non-muscle invasive bladder cancer

“…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, thermo-chemotherapy or new immunotherapeutic modalities [108]. The challenge remains who to select for conservative treatment versus radical cystectomy, since the outcome after progression is far worse.…”

Association between Metabolic Syndrome and Recurrence of Nonmuscle Invasive Bladder Cancer following bacillus Calmette-Guérin Treatment

“…1,2 Prognosis from this form of the disease is generally excellent. 3 This is in part due to the use of intravesical bacillus Calmette-Guérin (BCG), which has been shown to be effective in eradicating carcinoma in situ (CIS), as well as preventing recurrence and progression of disease following surgical resection of papillary tumors.…”

“…Regrettably, BCG fails in up to 40% of patients. 2 The etiology of BCG failure is not well understood, and is the subject of continual investigation, as the ability to identify patients in whom BCG will fail would allow for pursuit of an alternative treatment approach. This could minimize potential risks associated with BCG use, prevent delays in utilization of more effective alternative treatments, and help preserve BCG for those who are likely to benefit, particularly important in the setting of worldwide BCG shortages.…”

Novel Therapeutic Approaches for Recurrent Nonmuscle Invasive Bladder Cancer

“…Despite the success of BCG therapy, however, recurrence rates remain high, and progression is still possible. 2 Patients who fail BCG therapy have limited options, and most will succumb to bladder removal. Thus, there is strong impetus to find alternative treatment options in NMIBC.…”