Mechanisms of action of intravesical BCG for bladder cancer.

Though superficial bladder cancer patients have been treated with intravesical BCG since 1976 the mechanisms of action remain unknown. Evidence points towards an immune mechanism of BCG induced antitumor activity. Although specific antitumor immunity may play a role in BCG immunotherapy, additional work is needed to more clearly define this possibility. Several investigators have noted a clinical association between favorable response to BCG therapy and a systemic response delayed type hypersensitivity (DTH) to BCG antigen indicated by conversion to a positive purified protein derivative (PPD) skin test. Additional animal studies have in turn documented evidence of specific binding between BCG and fibronectin (FN) found in the urothelial basement membrane which appears necessary for the development of both the DTH response and antitumor activity. Other studies have suggested which cellular components of the immune system and lymphokines may be involved in the antitumor response. Further work will be needed to better understand BCG mechanisms as these findings may be important to other forms of cancer therapy. Questions of immune suppression, genetic influence on the immune response and immunocompetence at the time of surgery may assume increasing importance. A strong effort will therefore be needed to better understand these mechanisms so that patients may be selected, treated and followed in a more effective manner.