Preventing Progression and Improving Survival with BCG Maintenance

Abstract

BCG immunotherapy provides a superior reduction in tumour recurrence compared with chemotherapy. Unlike chemotherapy, however, it also appears to reduce disease progression. The benefit of BCG is long-term, but protection from disease progression without maintenance therapy is lost when comparisons are made after 15 years. Data suggest that optimal maintenance therapy with BCG provides even better protection from tumour recurrence, reduces disease progression and improves survival. Maintenance BCG schedules using single instillations at 1–3 month intervals have not been proved to be better than induction alone. However, a Southwest Oncology Group (SWOG) study using three, weekly instillations of Connaught BCG, found this regimen to be markedly superior. Before the introduction of BCG, carcinoma in situ (CIS) would progress to muscle invasion in 52% of patients. In the SWOG study, the additional instillations increased the complete response rate in CIS from the expected 68% to 84%. With maintenance BCG, long-term (7 years) tumour recurrence in high-risk patients reduced from the expected 52% with a single 6-week course to only 25% (p < 0.000001). Worsening-free survival, defined as the absence of evidence of disease progression, including pathologic stage T2 or greater disease, or the need for systemic chemotherapy, radiation therapy or cystectomy, significantly increased (p < 0.049, log rank test). In 391 randomized patients, the already excellent 86% survival at 4 years observed with induction therapy improved to 92% in patients receiving maintenance BCG (p < 0.04). There is thus increasingly good evidence that BCG maintenance therapy, at the optimal treatment schedule, provides superior protection from tumour progression and recurrence, and improves long-term survival.