Objective: Currently, the true impact of intravesical chemotherapy or immunotherapy (bacilli Calmette-Guerin [BCG]) on the rate of progression of superficial transitional cell carcinoma of the bladder to muscle invasive disease is unclear. A metaanalysis was performed to statistically compare the efficacy of these treatments in preventing tumor progression in this disease setting.
Methods: A prospective protocol outlining the metaanalysis noted here was developed followed by a thorough search of the existing published literature using strict eligibility criteria. Eight randomized, controlled trials were found that met protocol specifications. These reports contained data on 2427 patients who were statistically pooled using a fixed-effects model (Peto). The outcome of interest was the proportion of patients progressing to muscle invasive or metastatic disease expressed as a summary odds ratio (ORp). An ORp greater than unity favored BCG versus chemotherapy.
Results: Initial pooling of these 8 trials gave a nonstatistically significant summary odds ratio of 1.24 (0.95-1.61) without evidence of statistical heterogeneity. Analysis by drug type showed significant attenuation of the ORp when the effects of mitomycin C were compared with BCG, ie, 1.04 (0.76-1.42) suggesting that: 1) mitomycin is probably more active than the other chemotherapeutics used in the available trials and 2) BCG is not clearly superior to mitomycin C. Sensitivity analyses also demonstrated that failure to control for prior intravesical drug treatment in all but 2 of the analyzed studies produces a spurious result favoring BCG over intravesical chemotherapy.
Conclusion: The available data fail to support a clear superiority of intravesical BCG over intravesical chemotherapy in preventing progression of superficial transitional cell carcinoma of the bladder. Mitomycin C appears more effective than the other commonly used drugs, and failure to control for prior intravesical chemotherapy in most of available studies results in a spurious finding of greater clinic effect of BCG over chemotherapy.