Has a 3-fold decreased dose of bacillus Calmette-Guerin the same efficacy against recurrences and progression of T1G3 and Tis bladder tumors than the standard dose? Results of a prospective randomized trial.

Purpose: We determined if a third of the dose of intravesical bacillus Calmette-Guerin (BCG) has the same efficacy than a standard dose for decreasing the risk of recurrence and progression after transurethral resection in patients with superficial high risk (stages T1G3 and carcinoma in situ) bladder cancer. Also, we evaluated toxic side effects.
Material and Methods: A total of 155 patients with a mean age +/- SD of 67 +/- 10.1 years with superficial bladder cancer, including stages T1G3 in 90, a Tis primary tumor in 23 and associated Tis disease in 42, were enrolled and randomly assigned to be treated after transurethral resection of all visible lesions with intravesical BCG, Connaught strain (weekly x 6 and fortnightly x 6 thereafter) with the standard dose of 81 mg or with the decreased dose of 27 mg.
Results: Median followup was 61 months (range 3 to 102). Disease recurred in 32 patients (39%) treated with the standard dose and in 33 (45%) treated with the decreased dose. Median time to recurrence was not attained in the standard dose arm and it was 63 months in the decreased dose arm. Kaplan-Meier estimates for time to recurrence did not reveal differences between the 2 doses (p = 0.405). Tumor progressed in 20 patients (24.7%) with the standard dose and in 19 (26%) with the decreased dose. Four patients (6.1%) with Tis had local extension into the prostatic urethra and ducts, including 3 (8.3%) treated with the standard dose and 1 (3.4%) treated with the decreased dose. Median time to progression was not attained in either arm. Kaplan-Meier estimates for time to progression did not differ significantly (p = 0.7997). Deferred cystectomy for progression was performed in 7 patients (8.4%) treated with the standard dose and in 7 (9.5%) of those treated with the decreased dose. Subgroup analysis by patient age, tumor status, number, size and T stage (T1G3 vs Tis) did not differ significantly. The groups did not differ in disease specific mortality, which was 12.2% in the standard dose arm and 16.4% in the decreased dose arm. Mean disease specific survival +/- SE was 86.96 +/- 4.14 and 83.73 +/- 4.73 months, respectively.
Conclusions: Our results suggest that a 3-fold decreased dose of intravesical BCG is as effective as the standard dose against progression in patients with high risk stages T1G3 and Tis superficial bladder carcinoma but with significantly less toxicity.