Intravesical versus intravesical plus intradermal bacillus Calmette-Guerin: a prospective randomized study in patients with recurrent superficial bladder tumors.

PURPOSE: Intravesical instillation of bacillus Calmette-Guerin (BCG) induces various immunological reactions and decreases the recurrence rate of superficial bladder tumors. To determine whether additional immune stimulation with concomitant intradermal BCG applications could further lower the recurrence rate, 154 patients with superficial bladder tumors at high risk for recurrence were randomized to receive either 6 intravesical instillations of 120 mg. Pasteur strain BCG alone or combined with intradermal application.
MATERIALS AND METHODS: A total of 76 patients received intravesical and intradermal BCG, while 78 received intravesical BCG only. Median followup was 41 months (range 2 to 89) and 36 months (range 2 to 86), respectively. Both treatment groups were comparable regarding patient age and number of previous transurethral bladder tumor resections, as well as tumor recurrence rate, stage and grade before BCG therapy.
RESULTS: A highly significant decrease in the monthly tumor recurrence rate was observed in both arms after BCG compared to the pretreatment recurrence rates (p < 0.0001). Recurrence rate decreased from 0.73 +/- 1.07 (standard deviation) to 0.06 +/- 0.13 in the combined treatment group and from 0.71 +/- 0.90 to 0.074 +/- 0.17 in the intravesical treatment only group. However, we were unable to find any difference between the 2 groups regarding interval to initial recurrence or recurrence rates after BCG treatment. Changes in the purified protein derivative skin test performed before and after BCG therapy were not useful to predict response to treatment because 44% of our patients already had a positive test before treatment. Also, interpretation of the skin test was difficult and not always reliable. In the multivariate analysis, however, fever was an important prognostic factor. Patients with increased body temperature greater than 37.5C had a significantly lower recurrence rate than those without fever (37.5C or less) after BCG instillation (p = 0.009). Moreover, fever after BCG instillation was observed significantly more frequently in patients with a positive purified protein derivative skin test before treatment (p = 0.021).
CONCLUSIONS: The therapeutic benefit from intravesical BCG apparently was not substantially improved by simultaneous intradermal BCG vaccination. Fever following intravesical BCG instillation is an important prognostic factor regarding superficial bladder tumor recurrence. Fever occurs predominantly in patients who were previously sensitized to mycobacteria (by BCG vaccination or infection) as shown by a positive pretreatment purified protein derivative skin test. This finding suggests that previously sensitized patients respond significantly better to a single course of intravesical BCG.

RCT Entities:   Population Interventions Outcomes