Management of BCG Failures in Non-Muscle-Invasive Bladder Cancer

Abstract

Purpose: Bacillus Calmette-Guerin (BCG) intravesical therapy is the standard treatment in high-risk patients with non-muscle-invasive bladder cancer, but a significant number of patients experience recurrence after BCG therapy. Although several treatment options are available for recurrence after BCG therapy, the optimal treatment strategy is still controversial. We reviewed current and promising treatment options after BCG failure. Materials and Methods: A search of published literature using PubMed and meeting abstracts was performed. Results: BCG failures are further subdefined as BCG refractory, BCG resistant, BCG relapsing, and BCG intolerance. Several predictors for BCG response have been studied, but prediction or stratification before therapy seems to be difficult in clinical practice. Novel biomarkers associated with immunologic mechanisms appear to be promising to predict BCG failure. Radical cystectomy is the standard treatment for BCG-refractory disease, but the timing of cystectomy is controversial. BCG maintenance or combination with interferon- is a promising therapy for BCG resistance or relapse. Some salvage therapies or device-assisted instillations have been also promising, but the efficacy and safety of these novel therapies should be confirmed by large prospective studies before their clinical use in BCG failure. Conclusions: Patients with BCG failure are not a homogeneous group and need to be stratified. Radical cystectomy should be performed without delay in patients with BCG-refractory status, but salvage intravesical therapies may be an alternative in cases without true refractory status. Although BCG and interferon intravesical therapy is promising, more efficient salvage therapy after BCG failure is required.