title: Renin-Angiotensin Inhibitors Decrease Recurrence after Transurethral Resection of Bladder Tumor in Patients with Nonmuscle Invasive Bladder Cancer.
abstract: OBJECTIVE
  Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guérin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker 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 angiotensin converting enzyme inhibitor/angiotensin receptor blocker 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 angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guérin therapy alone and in 52 in whom it was combined with angiotensin converting enzyme inhibitor/angiotensin receptor blocker. 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 angiotensin converting enzyme inhibitor/angiotensin receptor blocker (stage Ta HR 0.45, 95% CI 0.21-0.98, p = 0.04).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blute
authors.affiliation: 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.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Rushmer
authors.affiliation: 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.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Fuller
authors.affiliation: 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.
authors.forename: E Jason
authors.initials: EJ
authors.lastname: Abel
authors.affiliation: 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.
authors.forename: David F
authors.initials: DF
authors.lastname: Jarrard
authors.affiliation: 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. Electronic address: downs@urology.wisc.edu.
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Downs
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015653:Cystectomy / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D057605:Natural Orifice Endoscopic Surgery / Q000379:methods*; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000453:epidemiology; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D014521:Urethra; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000601:surgery*; D014922:Wisconsin / Q000453:epidemiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: angiotensin converting enzyme inhibitors; angiotensin receptor antagonists; local; neoplasm recurrence; renin-angiotensin system; urinary bladder neoplasms