Faculty Collaboration Database

Use of angiotensin converting enzyme inhibitors is associated with reduced risk of late bladder toxicity following radiotherapy for prostate cancer. Radiother Oncol 2022 Mar;168:75-82

Date

01/26/2022

Pubmed ID

35077710

Pubmed Central ID

PMC8986577

DOI

10.1016/j.radonc.2022.01.014

Scopus ID

2-s2.0-85123912429 (requires institutional sign-in at Scopus site)   9 Citations

Abstract

BACKGROUND AND PURPOSE: Genome-wide association studies (GWAS) of late hematuria following prostate cancer radiotherapy identified single nucleotide polymorphisms (SNPs) near AGT, encoding angiotensinogen. We tested the hypothesis that patients taking angiotensin converting enzyme inhibitors (ACEi) have a reduced risk of late hematuria. We additionally tested genetically-defined hypertension.

MATERIALS AND METHODS: Prostate cancer patients undergoing potentially-curative radiotherapy were enrolled onto two multi-center observational studies, URWCI (N = 256) and REQUITE (N = 1,437). Patients were assessed pre-radiotherapy and followed prospectively for development of toxicity for up to four years. The cumulative probability of hematuria was estimated by the Kaplan-Meier method. Multivariable grouped relative risk models assessed the effect of ACEi on time to hematuria adjusting for clinical factors and stratified by enrollment site. A polygenic risk score (PRS) for blood pressure was tested for association with hematuria in REQUITE and our Radiogenomics Consortium GWAS.

RESULTS: Patients taking ACEi during radiotherapy had a reduced risk of hematuria (HR 0.51, 95%CI 0.28 to 0.94, p = 0.030) after adjusting for prior transurethral prostate and/or bladder resection, heart disease, pelvic node radiotherapy, and bladder volume receiving 70 Gy, which are associated with hematuria. A blood pressure PRS was associated with hypertension (odds ratio per standard deviation 1.38, 95%CI 1.31 to 1.46, n = 5,288, p < 0.001) but not hematuria (HR per standard deviation 0.96, 95%CI 0.87 to 1.06, n = 5,126, p = 0.41).

CONCLUSIONS: Our study is the first to show a radioprotective effect of ACEi on bladder in an international, multi-site study of patients receiving pelvic radiotherapy. Mechanistic studies are needed to understand how targeting the angiotensin pathway protects the bladder.

Author List

Kerns SL, Amidon Morlang A, Lee SM, Peterson DR, Marples B, Zhang H, Bylund K, Rosenzweig D, Hall W, De Ruyck K, Rosenstein BS, Stock RG, Gómez-Caamaño A, Vega A, Sosa-Fajardo P, Taboada-Valladares B, Aguado-Barrera ME, Parker C, Veldeman L, Fonteyne V, Bultijnck R, Talbot CJ, Symonds RP, Johnson K, Rattay T, Webb A, Lambrecht M, de Ruysscher D, Vanneste B, Choudhury A, Elliott RM, Sperk E, Herskind C, Veldwijk MR, Rancati T, Avuzzi B, Valdagni R, Azria D, Farcy Jacquet MP, Chang-Claude J, Seibold P, West C, Janelsins M, Chen Y, Messing E, Morrow G, REQUITE Consortium

Authors

William Adrian Hall MD Professor in the Radiation Oncology department at Medical College of Wisconsin
Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin-Converting Enzyme Inhibitors
Genome-Wide Association Study
Humans
Male
Prostate
Prostatic Neoplasms
Urinary Bladder