Intravesical BCG: current results, natural history and implications for urothelial cancer prevention

Bacillus Calmette-Guerin (BCG) has been shown in randomized trials to be the most effective agent against superficial bladder tumors. BCG therapy prevents or reduces tumor recurrences, abrogates tumor progression and improves survival over surgery alone. The optimal BCG schedule varies among patients, reflecting a heterogeneous tumor population. Multifocality, high grade (G2,3) and T1 tumors are risk factors for tumor recurrence or invasion. Patients presenting with such features are most likely to benefit from BCG. An incomplete response to BCG portends a high risk of tumor progression. Non-responders have a 40-60% risk of developing muscle invasion or metastases within 10 years, compared with 10-15% for BCG responders. Further, 80% of non-responders progress in the bladder within 3-5 years. After 5 years, relapses are more common in the prostate (13-35%) and upper collecting system (15-33%); one-half of these are invasive tumors. This suggests that intense therapy directed at premalignant and early bladder lesions coupled with a chemoprevention strategy designed to protect the whole urothelium will be required to reverse a pan-urothelial tumor diathesis.