UROLOGICAL ONCOLOGY

Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials
Sylvester RJ, Van Der Meijden APM, Lamm DL
From the European Organization for Research and Treatment of Cancer Data Center, Brussels, Belgium, Jeroen Bosch Hospital’s-Hertogenbosch, The Netherlands, and the Mayo Clinic, Scottsdale, Arizona
J Urol. 2002; 168:1964-70

• 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.
  
  
• Editorial Comment
  The efficacy of BCG against recurrences of superficial bladder cancer is without question. However, it was widely disputed if BCG could act against the progression of superficial bladder cancers. Up to now, only one prospective trial could show clear results, whereas all others did not show any significant advantage. The reason was the few cases in each trial progressing to invasive or metastatic disease. This is where the power of a well performed metaanalysis comes into its role. Combined analysis of clinical trials comparing transurethral resection plus intravesical BCG to either resection alone or resection plus another treatment than BCG was performed and identified 25 trials with 4,863 patients. The combined analysis of this metaanalysis shows a clear advantage of BCG over other treatment, or over no treatment, on a high statistical level. Interestingly, this held true for the overall analysis as well as for the analysis by disease type (papillary, cis), and comparison to different treatment (Mitomycin C, other chemo, other immuno). The effect of BCG-maintenance was substantial. These results are highly important, and for the first time show very clearly and indisputable that BCG favorably alters the biologic course of superficial bladder cancer, even with regard to progression.

Dr. Andreas Böhle
Professor and Vice-Director of Urology
Medical University of Luebeck
Luebeck, Germany