Intravesical and alternative bladder-preservation therapies in the management of non–muscle-invasive bladder cancer unresponsive to bacillus Calmette-Guérin

• Many salvage intravesical options exist for recurrent NMIBC.
• No guidelines exist regarding the optimal regimen or timing of salvage therapy.
• Current evidence is limited by small, single-arm trials with heterogeneous cohorts.
• Combination intravesical chemotherapy shows the best recurrence-free rate to date.
• The importance of counseling and shared decision-making cannot be understated.

Intravesical Bacillus Calmette-Guérin (BCG) remains the standard of care in the treatment of bladder carcinoma in situ and as adjuvant therapy after thorough transurethral resection of high-grade non–muscle-invasive bladder cancer. Despite BCG therapy, in up to 40% of patients it would recur and 60% to 70% of those would fail repeat BCG induction be deemed BCG unresponsive. For such patients, cystectomy remains the preferred treatment option per the American Urological Association and European Association of Urology, though some patients would be medically unfit or refuse radical surgery. Further intravesical therapy for bladder-preservation therapies may preserve quality of life in these patients and in some cases can be curative. There are numerous non-BCG intravesical salvage options available, including immunotherapy, single-agent chemotherapy, combination chemotherapy, and device-assisted chemotherapy. In addition, investigation of radiation-based treatment and other novel therapies including checkpoint inhibitors (programmed death-1/programmed death ligand-1), are currently underway. In this review, we examine the current status of alternatives to BCG in salvage therapy for bladder preservation.