Review of BCG immunotherapy for bladder cancer

SUMMARY For several decades, intravesical Bacillus Calmette–Guérin (iBCG) immunotherapy has been the gold standard adjuvant treatment for high-risk and selected intermediate-risk patients with non-muscle-invasive bladder cancer (NMIBC). In this review, the mechanisms of iBCG immune-mediated anti-cancer activity and resistance are presented. Furthermore, a literature review of short-term and systemic iBCG-related side effects was performed. A high incidence (75.5%) of iBCG-related short-term, self-limiting adverse events was observed, while more severe iBCG-related local/systemic complications (iBCG-rL/SCs) that required medical treatment or hospitalization occurred at a lower rate (2.35%). Disseminated was the most common form of iBCG-rSCs, while two-thirds of the cases were classified as infectious. The implementation of molecular-based techniques resulted in significantly higher diagnostic rates. Anti-tuberculous treatment (ATT) is the mainstay of treatment, while in patients with any iBCG-rL/SC form involving the vasculature, ATT should be combined with surgery. Local and osteoarticular forms have the lowest mortality, but their management necessitates severe and debilitating surgical procedures. The overall iBCG-attributed mortality in patients with iBCG-rL/SC was 7.4%, with disseminated, vascular, and lung involvements exhibiting the highest rates. Given the global shortage of BCG for the last two decades, as well as the paucity of effective options for iBCG-refractory or relapsing NMIBC patients, new therapeutic strategies are being tested with promising early results.