The limits of bacillus Calmette-Guerin for carcinoma in situ of the bladder

Purpose: Historically carcinoma in situ of the bladder has been treated with radical cystectomy based on the aggressive and potentially invasive nature of this disease. The introduction in the late 1970s of intravesical bacillus Calmette-Guerin (BCG) has made this therapy the gold standard in the management of carcinoma in situ. Cases that are refractory or resistant to BCG therapy are a management dilemma with various available treatment options. Materials and Methods: A comprehensive literature review of the current management of carcinoma in situ of the bladder was performed using MEDLINE, a review of current urology journals and abstracts from recent urology meetings. Data focused on BCG resistant carcinoma in situ of the bladder and current approaches in use for refractory disease. Results: Complete and durable response rates have been reported in more than 70% of patients with carcinoma in situ who are treated with intravesical BCG. To our knowledge the optimal therapeutic regimen has not been established, although extended periods of treatment beyond the originally described 6-week course have not been shown to improve complete response rates. Prolonged administration of BCG is associated with adverse side effects. Various prognostic indicators of recurrence and progression exist that may identify a subset of cases unlikely to respond favorably to a conservative approach, including carcinoma in situ with associated stage T1 bladder lesions, diffuse and multifocal carcinoma in situ, multiple recurrences with intravesical therapy and extravesical involvement. Current molecular markers may also predict the response of carcinoma in situ to therapy. Treatment options available for BCG refractory carcinoma in situ of the bladder include intravesical chemotherapy, combined immunochemotherapy and radical cystectomy. Intravesical valrubicin and oral bropirimine have been shown to induce a complete response rate of 21% to 50%, although data on long-term followup are forthcoming. Radical cystectomy remains effective therapy for aggressive carcinoma in situ of the bladder. Conclusions: The current management of carcinoma in situ of the bladder is ill defined due to the variable natural history and unpredictable response of this disease to therapy. Controversy exists as to the optimal treatment of carcinoma in situ of the bladder since different forms of carcinoma in situ may exist that complicate therapeutic decisions for appropriate therapy. Some tumor characteristics are associated with more aggressive behavior and may be predictive of treatment outcome.