Salvage Combination Intravesical Immunotherapy With Bacillus Calmette-Guérin and Interferon-α2B: Impact on Recurrence, Progression, and Survival

Abstract

Background: The population of patients with bladder cancer who have recurrence following an initial instillation of Bacillus Calmette-Guérin (BCG) is critical to study, as treatment delay with repeated courses of intravesical therapy may yield poor prognosis in patients with disease progression. Objective: To evaluate our institution's experience with use of BCG alone and in combination with interferon (INF)-α2B in regard to the rates of bladder cancer recurrence, disease progression, need for eventual cystectomy, and survival in patients with initial BCG failure. Study Design: We identified a combined series of 139 patients who had undergone intravesical instillations of BCG alone (n = 114) or in combination with INF-α2B (n = 25) performed at Brigham and Women's Hospital, Boston, between 2002 and 2007. All patients previously received an initial 6-week course of BCG therapy and subsequently had BCG failure on follow-up cystoscopy. Study outcome measures included: time to cancer recurrence in patients, progression of disease, eventual cystectomy, and patient mortality. Results: At a median follow-up of 64.7 months from initial BCG administration, 84% of patients treated with BCG + INF-α2B had disease recurrence. The average time to recurrence was < 1 year, and 63% of patients had recurrence on the first post-treatment biopsy. Among patients with a positive first biopsy, 52% had disease progression on initial surveillance. Overall, disease progression was seen in 48% of patients receiving BCG + INF-α2B therapy, and 28% of all patients eventually underwent radical cystectomy. All outcomes occurred more frequently in patients undergoing combination intravesical therapy compared with patients given BCG monotherapy. Conclusions: Patients with bladder cancer undergoing salvage intravesical BCG + INF-α2B at our institution had a > 50% chance of disease recurrence and progression, and > 25% of patients eventually proceeded to radical cystectomy. Randomized trials are needed to clarify the issues present in our findings and to determine the appropriate role for concomitant INF therapy in patients when BCG monotherapy has failed.