Research Institute of Oncology, Dept. of Urology, Minsk, Belarus

Introduction & Objectives: Both bacillus Calmette-Guérin (BCG) and interferon-alpha (IFN-α) shows activity against bladder cancer. We performed prospective randomized trial to evaluate efficacy and toxicity of combined intravesical BCG plus IFN-α comparing to BCG and IFN-α monotherapy for non-muscle invasive bladder cancer.

Material & Methods: A total of 149 patients with a mean age 63,2 years were included in the study. Inclusion criteria were non-muscle invasive transitional cell carcinoma with intermediate and high-risk of recurrence and progression. After the transurethral resection of all tumors patients were randomized in three groups. Patients from group 1 (n=60) were treated with a 6-week course of 125 mg BCG (full dose, Russian strain), in the group 2 (n=60) patients received 6 weekly instillations of 125 mg BCG plus 6 million units of IFN-α, patients in group 3 (n=29) received 4 monthly courses of intravesical 6 million units of IFN-α given twice daily during 3 consecutive days. Response was assessed by cystoscopy every 3 months after treatment.

Results: At median follow-up of 30,9 months recurrence observed in 26 patients (43,3%) in BCG group, 8 patients (13,3%) in BCG+IFN-α group and 18 patients (62,1%) in IFN-α group. Progression to muscle invasion occurred in 12% and 7% from group 1 and 3 respectively with no progression in group 2 patients. The 3-year recurrence free survival was higher in BCG+IFN group - 78,5% versus 62,6% in BCG and 40,2% in IFN-α group. There was no significant difference between groups with BCG for recurrence free survival. Monotherapy with IFN-α had significantly lower response rate than BCG groups (p=0,007). Adverse events were experienced by 25%, 11,6% and 6,9% of patients from group 1, 2 and 3, respectively. Toxicity related dropout and treatment delay were similar in both groups with BCG. When comparing adverse events rate there was significant difference between BCG+IFN-α and BCG group (p=0,025). The corresponding rates for moderate to severe adverse events related to treatment were 6,7% for BCG+IFN-α and 21,7% for BCG group (p=0,013). This difference probably related to the modulation of immune reaction on BCG by adding IFN-α.

Conclusions: Monotherapy with IFN-α had lowest complication rate but lower response rate than BCG groups (p=0,007). Combine use of BCG and IFN-α had a significantly less complication rate and severe adverse events rate (p=0,025 and p=0,013 respectively). Intravesical full dose BCG plus IFN-α appears to be much effective then BCG and IFN-α monotherapy, despite no significant difference was received in this study. Longer follow-up is required to validate these findings.