Treatment of Bacillus Calmette-Guerin refractory superficial bladder cancer: further intravesical therapy

We here report our clinical experience with salvage therapy for patients with bacillus Calmette-Guerin (BCG)-refractory superficial bladder cancer and discuss current approaches to the disease, especially focusing on bladder preservation. First, we evaluated the efficacy of an initial 6-week course of intravesical BCG in 93 patients with carcinoma in situ (CIS) of the bladder. Of these, 91% achieved a complete response (CR) at the evaluation at 3 months. The 2- and 5-year recurrence-free rates were 71 and 67%, respectively (mean follow-up 39 months). These results support the intravesical BCG as a first-line therapy for CIS. Next, we assessed the efficacy of a second course of intravesical BCG for 16 patients who failed the initial induction course for CIS. Of these, 94% achieved CR at the evaluation at 3-month, and the 2- and 5-year recurrence-free rates were 62 and 46%, respectively (mean follow-up 28 months). None of the patients who received a second course had disease progression. Thus, a second course of BCG therapy seems to be a reasonable option for CIS patients failing the initial course. We also report our initial experience with intravesical gemcitabine therapy for 3 patients with BCG-refractory CIS of the bladder and 1 patient with recurrent multiple tumors. Gemcitabine (1500 mg in 100 ml saline) was given in the bladder for 1 hour twice weekly for a total of 12 treatments. The treatment was associated with minimal bladder irritation and systemic absorption, and was well tolerated except in a 90-year-old man who discontinued therapy because of grade 2 toxicity. Two patients achieved CR and maintained a tumor-free status beyond 14 months, suggesting that the intravesical gemcitabine is a promising salvage therapy for BCG-refractory superficial bladder cancer.