Ryan L Steinberg1, Kenneth G Nepple1, Kyla N Velaer2, Lewis J Thomas1, Michael A O'Donnell3. 1. Department of Urology, University of Iowa, Iowa City, IA. 2. Department of Urology, Stanford University, Palo Alto, CA. 3. Department of Urology, University of Iowa, Iowa City, IA. Electronic address: michael-odonnell@uiowa.edu.
Abstract
BACKGROUND: Bacillus Calmette-Guérin (BCG) is the most effective initial intravesical therapy for high-grade non-muscle invasive bladder cancer, but many patients still fail. Combination intravesical BCG and interferon (IFN) will salvage some patients but results remain suboptimal. OBJECTIVE: We hypothesized that further immunostimulation with intravesical interleukin-2 and subcutaneous granulocyte-macrophage colony-stimulating factor may improve response to intravesical BCG and IFN in patient with prior BCG failure(s). METHODS: A retrospective review was performed. Patients received 6 treatments of quadruple immunotherapy (intravesical solution with one-third dose BCG, 50 million units IFN, and 22 million units interleukin-2, along with a 250-mcg subcutaneous sargramostim injection). Surveillance began 4 to 6 weeks after treatment completion. Patients received maintenance if recurrence-free. Success was defined as no recurrence (bladder or extravesical) and bladder preservation. Analysis was performed by Kaplan-Meier method (P<0.05). RESULTS: Fifty-two patients received treatment with a median recurrence follow-up of 16.3 months and overall follow-up of 41.8 months. All patients had at least 1 prior BCG failure and 13% had 2 or more prior failures. Only 3 patients (6%) were unable to tolerate full induction. Treatment success was 55% at 1 year, and 53% at 2 years. Thirteen patients (25%) underwent cystectomy at a median time of 17.3 months with disease progression to T2 in 1 patient and T3 in 2 patients. No patients had positive surgical margins or positive lymph nodes. CONCLUSIONS: In patients with non-muscle-invasive bladder cancer with prior BCG failure, quadruple immunotherapy demonstrated good treatment success in some patients and warrants further evaluation.
BACKGROUND: Bacillus Calmette-Guérin (BCG) is the most effective initial intravesical therapy for high-grade non-muscle invasive bladder cancer, but many patients still fail. Combination intravesical BCG and interferon (IFN) will salvage some patients but results remain suboptimal. OBJECTIVE: We hypothesized that further immunostimulation with intravesical interleukin-2 and subcutaneous granulocyte-macrophage colony-stimulating factor may improve response to intravesical BCG and IFN in patient with prior BCG failure(s). METHODS: A retrospective review was performed. Patients received 6 treatments of quadruple immunotherapy (intravesical solution with one-third dose BCG, 50 million units IFN, and 22 million units interleukin-2, along with a 250-mcg subcutaneous sargramostim injection). Surveillance began 4 to 6 weeks after treatment completion. Patients received maintenance if recurrence-free. Success was defined as no recurrence (bladder or extravesical) and bladder preservation. Analysis was performed by Kaplan-Meier method (P<0.05). RESULTS: Fifty-two patients received treatment with a median recurrence follow-up of 16.3 months and overall follow-up of 41.8 months. All patients had at least 1 prior BCG failure and 13% had 2 or more prior failures. Only 3 patients (6%) were unable to tolerate full induction. Treatment success was 55% at 1 year, and 53% at 2 years. Thirteen patients (25%) underwent cystectomy at a median time of 17.3 months with disease progression to T2 in 1 patient and T3 in 2 patients. No patients had positive surgical margins or positive lymph nodes. CONCLUSIONS: In patients with non-muscle-invasive bladder cancer with prior BCG failure, quadruple immunotherapy demonstrated good treatment success in some patients and warrants further evaluation.