It is nearly 40 years since Bacillus Calmette–Guérin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment.
The immune response to BCG can be summarized as follows: infection of urothelial and bladder tumor cells by BCG results in internalization of BCG, which increases the expression of antigen -presenting molecules. This induces an immune response via cytokine release. Th1 cytokines (IL-2, tumor necrosis factor, IL-12, and IFN-γ) and Th2 cytokines (IL-4, IL-5, IL-6, and IL-10) along with IL-8 and IL-17 are all implicated. This complex immune cascade induces antitumor activity mediated by cytotoxic T lymphocytes, natural killer cells, neutrophils, and macrophages.
There is now a large body of evidence demonstrating the superior efficacy of BCG in the treatment of bladder cancer when compared with TUR alone or TUR and chemotherapy. The European Association of Urology (EAU) guidelines on non-muscle invasive bladder cancer in 2013 report a total of five meta-analyses to substantiate this claim. In addition, there have been individual randomized controlled trials comparing BCG with epirubicin and IFN, mitomycin C, and epirubicin alone, all of which showed BCG to be the best agent with respect to preventing recurrence.
More immunotherapy treatments are under research now, which may show advantages over BCG, or supplement the limitations of BCG.
Fuge O et al. Immunotherapy for bladder cancer. Research and Reports in Urology. 2015;7:65-79.
Morales A et al. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol. 1976;116(2):180–183.