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) i nduces various immunological reactions and decreases the recurrence ra te of superficial bladder tumors. To determine whether additional immu ne stimulation with concomitant intradermal BCG applications could fur ther 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 com bined with intradermal application. Materials and Methods: A total of 76 patients received intravesical and intradermal BCG, while 78 receiv ed intravesical BCG only. Median followup was 41 months (range 2 to 89 ) and 36 months (range 2 to 86), respectively. Both treatment groups w ere comparable regarding patient age and number of previous transureth ral bladder tumor resections, as well as tumor recurrence rate, stage and grade before BCG therapy. Results: A highly significant decrease i n the monthly tumor recurrence rate was observed in both arms after BC G compared to the pretreatment recurrence rates (p <0.0001). Recurrenc e 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 unab le to find any difference between the 2 groups regarding interval to i nitial recurrence or recurrence rates after BCG treatment. Changes in the purified protein derivative skin test performed before and after B CG 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 prognos tic factor. Patients with increased body temperature greater than 37.5 C had a significantly lower recurrence rate than those without fever ( 37.5C or less) after BCG instillation (p = 0.009). Moreover, fever aft er BCG instillation was observed significantly more frequently in pati ents with a positive purified protein derivative skin test before trea tment (p = 0.021).Conclusions: The therapeutic benefit from intravesic al BCG apparently was not substantially improved by simultaneous intra dermal BCG vaccination. Fever following intravesical BCG; instillation is an important prognostic factor regarding superficial bladder tumor recurrence. Fever occurs predominantly in patients who were previousl y sensitized to mycobacteria (by BCG vaccination or infection) as show n by a positive pretreatment purified protein derivative skin test. Th is finding suggests that previously sensitized patients respond signif icantly better to a single course of intravesical BCG.