University of Leicester
Browse
RADONC-D-21-01064_R1.pdf (722.06 kB)

Use of angiotensin converting enzyme inhibitors is associated with reduced risk of late bladder toxicity following radiotherapy for prostate cancer

Download (722.06 kB)
journal contribution
posted on 2022-03-21, 16:47 authored by SL Kerns, A Amidon Morlang, SM Lee, DR Peterson, B Marples, H Zhang, K Bylund, D Rosenzweig, W Hall, K De Ruyck, BS Rosenstein, RG Stock, A Gómez-Caamaño, A Vega, P Sosa-Fajardo, B Taboada-Valladares, ME Aguado-Barrera, C Parker, L Veldeman, V Fonteyne, R Bultijnck, CJ Talbot, RP Symonds, K Johnson, T Rattay, A Webb, M Lambrecht, D de Ruysscher, B Vanneste, A Choudhury, RM Elliott, E Sperk, C Herskind, MR Veldwijk, T Rancati, B Avuzzi, R Valdagni, D Azria, MP Farcy Jacquet, J Chang-Claude, P Seibold, C West, M Janelsins, Y Chen, E Messing, G Morrow, E Briers, A Dunning, S Gutiérrez-Enríquez, R Paul Symonds, H Stobart, T Ward, CM West
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.

History

Citation

Radiotherapy and Oncology Volume 168, March 2022, Pages 75-82

Author affiliation

Leicester Cancer Research Centre, University of Leicester

Version

  • AM (Accepted Manuscript)

Published in

Radiotherapy and Oncology

Volume

168

Pagination

75 - 82

Publisher

Elsevier

issn

0167-8140

eissn

1879-0887

Acceptance date

2022-01-12

Copyright date

2022

Available date

2023-01-22

Language

eng

Usage metrics

    University of Leicester Publications

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC