Failure of Bacillus Calmette-Guérin therapy in non-muscle-invasive bladder cancer: Definition and treatment options.

UNLABELLED: Adjuvant intravesical bacillus Calmette- Guérin (BCG) therapy is the standard conservative adjuvant treatment and the most effective regimen for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). The term "BCG failure" is generally used to refer to recurrence or progression following BCG therapy, as experienced by many patients. However, the term has been defined inconsistently, and several studies have indicated that patients with a particular pattern of BCG failure have a worse prognosis. There are many different treatment options for patients who experience BCG failure.

OBJECTIVE: To summarize the different current definitions of BCG failure and the present treatment options available for patients with high-risk NMIBC who experience BCG failure.

EVIDENCE SYNTHESIS: Overall, the failure rate in response to BCG is about 40-50%. Most guidelines recommend that patients failing BCG should be offered radical cystectomy (RC). The significant potential for progression specific to high-risk NMIBC leads some clinicians to argue that immediate RC should be considered the preferred first-line treatment in high-risk patients, bearing in mind that it achieves a long-term survival rate in excess of 90% with ongoing improvements in morbidity. While other salvage intravesical treatments have to be considered oncologically inferior to RC, several therapies are now available if the patient is unfit to undergo RC or if bladder preservation is the objective, and some agents have shown promise in the context of BCG failure.

CONCLUSIONS: The definition, prediction, and treatment of BCG failure remain topics of debate. Patients with BCG failure need carefully selected, individualized therapy in experienced hands. Stratification of patients with BCG failure into groups can identify those with a better or worse prognosis. RC should be the selected option if a patient experiences BCG failure, but several promising intravesical salvage options are available for those cases in which the patient is unfit for surgery or bladder preservation is preferred. Currently data are still inadequate to allow formulation of definitive recommendations, and larger and higher quality studies of salvage intravesical therapies are urgently required.