Update on intravesical agents for non-muscle-invasive bladder cancer.

Major controversies still exist with regard to the indication, type and regimen of intravesical therapy for non-muscle-invasive bladder cancer. Other areas of controversy are the criteria for response/failure of treatment and for decisions regarding secondary intravesical therapy versus radical cystectomy. In this article, we analyze the different intravesical therapeutic strategies and compare their safety and efficacy. Well-designed clinical trials have found that the addition of bacillus Calmette-Guerin (BCG) to transurethral resection (TUR) decreases the risk for both disease recurrence and progression. These encouraging results are sustained even in patients with recurrent or aggressive disease, including patients whose prior intravesical chemotherapy has failed. Most investigators believe that the efficacy of BCG therapy can be maximized with maintenance therapy. Mitomycin C (MMC), the most commonly used intravesical chemotherapy to date, decreases the risk of disease recurrence but not disease progression when used after TUR compared with TUR alone. The oncologic efficacy of intravesical MMC can be optimized by increasing its concentration in addition to alkalinizing and reducing urine production. For patients at high risk of disease progression, BCG with maintenance therapy should be the preferred primary intravesical therapeutic strategy. However, MMC can be considered as a viable alternative for patients with papillary tumors (no carcinoma in situ) that are at low or intermediate risk of disease progression. Combination intravesical therapy may be more successful than single-agent strategies. Intravesical therapy failures indicate the need to include radical cystectomy as an option in the management decision.