Alternative Therapy to Intravesical Bacillus Calmette–Guerin in Nonmuscle Invasive Bladder Cancer

Abstract

Summary Intravesical Bacillus Calmette-Guerin (BCG) is recommended as an adjuvant therapy for intermediate and high-risk bladder cancers following complete resection. However, up to 45% of patients receiving BCG experience treatment failure. High failure rates along with increased toxicity and a global shortage of BCG availability have led to the search for alternative agents which can replace BCG. These agents can be used as second-line therapies after BCG failure before considering patients for radical cystectomy. Intravesical chemotherapeutic agents such as gemcitabine, docetaxel, valrubicin, sequential gemcitabine-docetaxel, and sequential valrubicin-docetaxel have been shown to yield comparable or better outcomes compared to BCG with low toxicity. Newer methods of drug delivery such as chemohyperthermia (CHT), electromotive drug administration (EMDA) and targeted releasing system 200 (TAR-200) have been reported to amplify drug delivery and enhance outcomes. The immune checkpoint inhibitor pembrolizumab has been used for BCG unresponsive disease with satisfactory response rates but with a higher risk of adverse events. A newer immunotherapeutic agent, ALT-803/N-803, which is an interleukin 15 superagonist, has shown promising short-term results. Novel oncolytic viral delivery systems such as nadofaragene-firadenovac, CG0070, CG0070-pembrolizumab have been shown to alter immune response and destroy malignant cells with good short-term outcomes. The number of BCG alternatives has surged in the recent past and newer agents continue to emerge. Expanding the study populations and long-term follow-up will enable affirming these alternatives as BCG equivalents in the future.