Adrian P.M. van der Meijden

PURPOSE: We determine if intravesical bacillus Calmette-Guerin (BCG) reduces the risk of progression after transurethral resection to stage T2 disease or higher in patients with superficial (stage Ta, T1 or carcinoma in situ) bladder cancer. MATERIALS AND METHODS: A meta-analysis was performed of the published results of randomized clinical trials comparing transurethral resection plus intravesical BCG to either resection alone or resection plus another treatment other than BCG. RESULTS: We identified 24 trials with progression information on 4,863 patients. Based on a median followup of 2.5 years and a maximum of 15 years, 260 of 2,658 patients on BCG (9.8%) had progression compared to 304 of 2,205 patients in the control groups (13.8%), a reduction of 27% in the odds of progression on BCG (OR 0.73, p = 0.001). The percent of patients with progression was low (6.4% of 2,880 patients with papillary tumors and 13.9% of 403 patients with carcinoma in situ, reflecting the short followup and relatively low risk patients entered in many of the trials. The size of the treatment effect was similar in patients with papillary tumors and in those with carcinoma in situ. However, only patients receiving maintenance BCG benefited. There was no statistically significant difference in treatment effect for either overall survival or death due to bladder cancer. CONCLUSIONS: Intravesical BCG significantly reduces the risk of progression after transurethral resection in patients with superficial bladder cancer who receive maintenance treatment. Thus, it is the agent of choice for patients with intermediate and high risk papillary tumors and those with carcinoma in situ.

PURPOSE: We determined if 1 immediate instillation of chemotherapy after transurethral resection (TUR) decreases the risk of recurrence in patients with stage Ta T1 single and multiple bladder cancer overall and separately. MATERIALS AND METHODS: A meta-analysis was performed of the published results of randomized clinical trials comparing TUR alone to TUR plus 1 immediate instillation of chemotherapy. RESULTS: Our study included 7 randomized trials with recurrence information on 1476 patients. Based on a median followup of 3.4 years and a maximum of 14.5 years, 267 of 728 patients (36.7%) receiving 1 postoperative instillation of epirubicin, mitomycin C, thiotepa or (2'R)-4'-O-tetrahydropyranyl-doxorubicin (pirarubicin) had recurrence compared to 362 of 748 patients (48.4%) with TUR alone, a decrease of 39% in the odds of recurrence with chemotherapy (OR 0.61, p <0.0001). Patients with a single tumor (OR 0.61) and those with multiple tumors (OR 0.44) benefited. However, after 1 instillation 65.2% of patients with multiple tumors had recurrence compared to 35.8% of patients with single tumors, showing that 1 instillation alone is insufficient treatment for patients with multiple tumors. CONCLUSIONS: One immediate intravesical instillation of chemotherapy significantly decreases the risk of recurrence after TUR in patients with stage Ta T1 single and multiple bladder cancer. It is the treatment of choice in patients with a single, low risk papillary tumor and is recommended as the initial treatment after TUR in patients with higher risk tumors.

PURPOSE: We determined the short-term and long-term efficacy of bacillus Calmette-Guerin (BCG) and chemotherapy in the treatment of patients with carcinoma in situ (CIS). MATERIALS AND METHODS: A meta-analysis was performed on published results of randomized clinical trials comparing intravesical BCG to intravesical chemotherapy. RESULTS: Nine randomized trials including 700 patients with CIS compared BCG to either mitomycin C (MMC), epirubicin, adriamycin, or sequential MMC/adriamycin. Of 298 patients on BCG 203 (68.1%) had a complete response compared with 158 of 307 patients on chemotherapy (51.5%), a reduction of 47% in the odds of nonresponse on BCG (OR 0.53, p =0.0002). Based on a median followup of 3.6 years, 161 of 345 patients on BCG (46.7%) had no evidence of disease compared with 93 of 355 patients on chemotherapy (26.2%), a reduction of 59% in the odds of treatment failure on BCG (OR 0.41, p <0.0001). Although the long-term benefit of BCG was smaller in trials with MMC, BCG was superior to MMC in trials with maintenance BCG (OR 0.57, p =0.04). The reduction of 26% in the risk of progression on BCG (p =0.20) is consistent with the reduction of 27% (p =0.001) previously reported in a larger superficial bladder cancer meta-analysis. CONCLUSIONS: Intravesical BCG significantly reduces the risk of short and long-term treatment failure compared with intravesical chemotherapy. Therefore, it is considered to be the intravesical agent of choice in the treatment of CIS.