Impact of intravesical chemotherapy versus BCG immunotherapy on recurrence of superficial transitional cell carcinoma of the bladder: metaanalytic reevaluation.

Bacille Calmette-Guérin (BCG) immunotherapy is currently considered the most effective agent in the management of superficial bladder cancer. Prior work suggests that the efficacy of intravesical chemotherapy in preventing tumor recurrence may be greater than previously suggested. This latter finding, therefore, brings into question the currently perceived superiority of BCG treatment for this disease. A metaanalysis was performed to rigorously examine existing data relevant to this relationship and to quantify the relative efficacy of both treatment modalities on tumor recurrence. A prospective protocol outlining the above-noted metaanalysis was initially developed followed by a thorough search of the existing published literature using strict eligibility criteria. Nine randomized trials were found that met protocol specifications. These reports contained data on 2,261 patients that were statistically combined using a fixed effects model (Peto). The outcome of interest was the proportion of patients with recurrence at 1, 2, and 3 years following intravesical therapy (i.e., a summary odds ratio, ORp). Combining all nine trials using 1-year recurrence as the endpoint demonstrated significant statistical heterogeneity, although the ORp favored BCG over intravesical chemotherapy (0.89 [0.74-1.07]). This precluded statistical pooling of the data and sensitivity analyses were performed to determine the source of heterogeneity. These tests showed that the prior chemotherapy treatment in a large number of the randomized trials biased study results in favor of the BCG arms. Once the data were stratified on presence or absence of prior drug treatment, intravesical chemotherapy reduced 1-, 2-, and 3-year recurrence by 21% to 82% versus BCG, depending on the endpoint of interest. The available data suggest that clinical trials directly comparing intravesical BCG to intravesical chemotherapy must stratify on the presence or absence of prior chemotherapy. Recurrences following prior intravesical chemotherapy appear less responsive to drug therapy than those in chemotherapy-naive patients. The currently perceived superiority of BCG therapy may therefore be an artifact of this phenomenon, since most randomized trials include chemotherapy failures in their chemotherapy treatment arms.