BCG and the Treatment of Superficial Bladder Cancer

Abstract

In this report, we review the evolution of bacillus Calmette-Guérin (BCG) immunotherapy as a legitimate form of treatment in superficial, nonmuscle-invasive bladder cancer. In the US, an estimated 45 000 new cases of bladder cancer are diagnosed each year and the annual death rate approaches 11 000. Approximately 70 percent of these cancers are superficial at the time of initial presentation. The treatment of superficial bladder cancer has three objectives: (1) eradication of existing disease, (2) prophylaxis against tumor recurrence, and (3) prevention of tumor progression (either muscular invasion, metastatic spread, or both). Cystectomy generally is reserved for muscle-invasive disease. Transurethral resection of the bladder tumor is the preferred initial therapy. Intravesical instillations of various chemotherapeutic agents following transurethral resection have been extensively investigated. Some of the common agents used include thiotepa, mitomycin, and doxorubicin. Despite such treatment efforts, however, over 40 percent of patients with superficial bladder cancer experience a recurrence of their tumor within three years. Approximately half of these recurrences either present as less-well-differentiated tumors or have already penetrated into the bladder musculature, metastasized, or both. Since Morales et al. first introduced intravesical BCG vaccine for prophylaxis as well as for treatment of superficial bladder tumors in 1976, support has grown rapidly for its use as an alternative to chemotherapy. When used with prophylactic intent following transurethral resection, recurrence rates are lower than those achieved with other agents. In addition, BCG is emerging as the consensus drug of choice for treating carcinoma in situ of the bladder. The mechanisms by which BCG exerts its antitumor activity remain largely unknown. BCG is thought to stimulate a localized, nonspecific inflammatory response that leads to subsequent shedding of tumor cells. A large body of clinical and experimental data suggest an association between the development of an immunologic response to BCG and successful antitumor activity. No universally accepted therapeutic regimen has been agreed upon. One regimen commonly used consists of an ampul of BCG mixed with 50 mL of NaCl 0.9%, instilled once a week for six weeks and retained for two hours prior to voiding. Maintenance therapy generally consists of intravesical doses given at three-month cycles for at least two years of recurrence-free follow-up. Because BCG is a biologic agent, the commercially available products may differ in weight, colony-forming units per vial, and antigenicity. How these product characteristics affect clinical responsiveness to different strains of BCG remains unanswered.