Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether ACE-I or ARB treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer.
Using an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival.
Median patient age was 69. 6 years. During a median followup of 3 years (IQR 1. 3-6. 1) 200 patients (59%) had recurrence and 14 (4. 1%) had stage progression. Of those patients 143 were receiving ACE-I/ARBs at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included CIS (p = 0. 040), bacillus Calmette-Guérin therapy (p = 0. 003) and ACE-I/ARB therapy (p = 0. 009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guérin therapy (HR 0. 68, 95% CI 0. 47-0. 87, p = 0. 002) or ACE-I/ARB therapy (HR 0. 61, 95% CI 0. 45-0. 84, p = 0. 005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45. 6% for patients treated with ACE-I/ARBs and 28. 1% in those not treated with ACE-I/ARBs (p = 0. 009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and CIS) in 85 patients on BCG therapy alone and in 52 in whom it was combined with ACE-I/ARB. Multivariate analysis revealed that patients treated with bacillus Calmette-Guérin alone (HR 2. 19, 95% CI 1. 01-4. 77, p = 0. 04) showed worse recurrence-free survival compared to patients treated with bacillus Calmette-Guérin and ACE-I/ARB (stage Ta HR 0. 45, 95% CI 0. 21-0. 98, p = 0. 04).
Pharmacological inhibition of the renin-angiotensin system is associated with improved outcomes in patients with bladder cancer. Renin-angiotensin system inhibitor administration in nonmuscle invasive bladder cancer cases should be studied in a prospective randomized trial.
The Journal of urology. 2015 Jul 11 [Epub ahead of print]
Michael L Blute, Timothy J Rushmer, Fangfang Shi, Benjamin J Fuller, E Jason Abel, David F Jarrard, Tracy M Downs
Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin Carbone Comprehensive Cancer Center, Madison, Wisconsin. , Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin Carbone Comprehensive Cancer Center, Madison, Wisconsin. , Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin Carbone Comprehensive Cancer Center, Madison, Wisconsin. , Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin Carbone Comprehensive Cancer Center, Madison, Wisconsin. , Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin Carbone Comprehensive Cancer Center, Madison, Wisconsin. , Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin Carbone Comprehensive Cancer Center, Madison, Wisconsin. , Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin Carbone Comprehensive Cancer Center, Madison, Wisconsin.