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

Purpose: Historically carcinoma in situ of the bladder has been treated wit h radical cystectomy based on the aggressive and potentially invasive natur e of this disease. The introduction in the late 1970s of intravesical bacil lus Calmette-Guerin (BCG) has made this therapy the gold standard in the ma nagement of carcinoma in situ. Cases that are refractory or resistant to BC G therapy are a management dilemma with various available treatment options . Materials and Methods: A comprehensive literature review of the current man agement of carcinoma in situ of the bladder was performed using MEDLINE, a review of current urology journals and abstracts from recent urology meetin gs. Data focused on BCG resistant carcinoma in situ of the bladder and curr ent approaches in use for refractory disease. Results: Complete and durable response rates have been reported in more tha n 70% of patients with carcinoma in situ who are treated with intravesical BCG. To our knowledge the optimal therapeutic regimen has not been establis hed, although extended periods of treatment beyond the originally described 6-week course have not been shown to improve complete response rates. Prol onged administration of BCG is associated with adverse side effects. Variou s prognostic indicators of recurrence and progression exist that may identi fy a subset of cases unlikely to respond favorably to a conservative approa ch, including carcinoma in situ with associated stage T1 bladder lesions, d iffuse and multifocal carcinoma in situ, multiple recurrences with intraves ical therapy and extravesical involvement. Current molecular markers may al so predict the response of carcinoma in situ to therapy. Treatment options available for BCG refractory carcinoma in situ of the bladder include intra vesical chemotherapy, combined immunochemotherapy and radical cystectomy. I ntravesical valrubicin and oral bropirimine have been shown to induce a com plete response rate of 21% to 50%, although data on long-term followup are forthcoming. Radical cystectomy remains effective therapy for aggressive ca rcinoma 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 s itu may exist that complicate therapeutic decisions for appropriate therapy . Some tumor characteristics are associated with more aggressive behavior a nd may be predictive of treatment outcome.