ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2025
A Polygenic Risk Score for Late Bladder Toxicity Following Radiotherapy for Non-Metastatic Prostate Cancer.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Genetic determinants of fatigue up to 2 years after radiotherapy in prostate cancer patients.Nature communications · 2026Article
- Voxel-Based Dose-Toxicity Modeling for Predicting Post-Radiotherapy Toxicity: A Critical Perspective.Journal of clinical medicine · 2025Article
- Cancer treatment and survivorship statistics, 2025.CA: a cancer journal for cliniciansArticle
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Authors and funding
38 authors.
Funding
Abstract
backgroundLate bladder toxicity is a concern for patients receiving prostate cancer radiotherapy and negatively affects survivors. Few risk factors are known beyond the radiation dose and volume of bladder exposed. A polygenic risk score (PRS) could identify susceptible patients.
methodsA PRS was built using genome-wide association results from the Radiogenomics Consortium (N = 3,988) and then tested in the prospective REQUITE and URWCI studies (N = 2,034). The primary outcome was time to patient-reported gross [grade ≥2, (≥G2)] hematuria, analyzed using Cox proportional hazards regression. Secondary outcomes were ≥G2 urinary retention and frequency. The PRS was externally validated for clinically diagnosed irradiation cystitis in the UK Biobank (N = 8,430). A gene-burden test evaluated rare coding variants.
resultsA 115-variant PRS was associated with a significantly increased risk of ≥G2 hematuria [hazard ratio (HR) per SD = 1.22; P = 0.009] as well as urinary retention (HR per SD = 1.18; P = 0.016) and frequency (HR per SD = 1.14; P = 0.036). When binarized, men in the upper decile (PRShigh) had a >2-fold increased risk of hematuria after adjusting for clinical risk factors [HR = 2.12; P = 0.002; Harrel's concordance index = 0.71 (95% confidence interval, 0.65-0.76)]. A similar effect size was seen in the UK Biobank for clinically diagnosed irradiation cystitis [odds ratio (OR) = 2.15; P = 0.026]. The burden test identified BOD1L1 as a putative novel radiosensitivity gene.
conclusionsThis PRS identifies susceptible patients and could guide the selection of those needing reoptimized treatment plans that spare the bladder beyond currently recommended constraints. IMPACT: PRS-guided treatment planning in radiation oncology could lower the incidence of clinically relevant bladder toxicity and reduce the impact of this outcome on prostate cancer survivors.
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