BCG in perspective: advances in the treatment of superficial bladder cancer.

The management of superficial bladder cancer has advanced significantly in recent years. Controlled clinical trials suggest the benefits of cytotoxic chemotherapy apply primarily to well-differentiated tumours, are short-term and do not include a reduction in disease progression. In contrast, intravesical bacillus Calmette-Guérin (BCG) immunotherapy is effective in high-grade tumours, provides long-term protection from tumour recurrence and reduces disease progression. Controlled clinical trials have consistently demonstrated that BCG provides superior protection from tumour recurrence compared with thiotepa or doxorubicin. In comparisons with mitomycin C, only two of six studies found a significant advantage for BCG therapy; both studies evaluating high-risk patients showed a significant reduction in tumour recurrence with BCG compared with mitomycin C. Controlled trials have demonstrated that newer chemotherapies and more intensive regimens are not superior to standard thiotepa treatment. However, controlled comparisons of immunotherapy suggest that BCG is superior to both interferon and keyhole-limpet haemocyanin. Comparative studies showing BCG to be superior to chemotherapy and other immunotherapies have employed what we now know to be suboptimal BCG regimens. Using three additional weekly BCG (Connaught) treatments at 3 months, complete response in carcinoma in situ is increased from 73 to 87%. In patients who are disease free, maintenance BCG using three weekly treatments at 6-month intervals improves long-term disease-free status in stage Ta and T1 bladder cancer from 50 to 83%. Such maintenance therapy improves the excellent 86% survival obtained with a single 6-week course of BCG to 92% (p < 0.04).