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  1. Home
  3. A Polygenic Risk Score For Late Bladder Toxicity Following Radiotherapy For Non-metastatic Prostate Cancer.
  1. Home
  3. A Polygenic Risk Score For Late Bladder Toxicity Following Radiotherapy For Non-metastatic Prostate Cancer.

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A Polygenic Risk Score for Late Bladder Toxicity Following Radiotherapy for Non-Metastatic Prostate Cancer.

Manzur Farazi1, Xin Yang1, Carson J Gehl1

  • 1The Medical College of Wisconsin, Milwaukee, Wisconsin.

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
|March 3, 2025

View abstract on PubMed

Summary
This summary is machine-generated.

A polygenic risk score (PRS) can identify prostate cancer patients at higher risk for bladder toxicity after radiotherapy. This genetic tool may help personalize treatment to reduce side effects for survivors.

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Area of Science:

  • Radiation Oncology
  • Genetics
  • Urology

Background:

  • Late bladder toxicity is a significant concern for prostate cancer patients undergoing radiotherapy, impacting survivors' quality of life.
  • Known risk factors for bladder toxicity are limited, primarily focusing on radiation dose and bladder volume exposure.
  • A polygenic risk score (PRS) offers a potential method to identify patients genetically predisposed to developing bladder toxicity.

Purpose of the Study:

  • To develop and validate a polygenic risk score (PRS) for predicting late bladder toxicity in prostate cancer patients receiving radiotherapy.
  • To assess the PRS's association with specific urinary side effects, including hematuria, urinary retention, and frequency.
  • To evaluate the PRS's utility in identifying patients who may benefit from personalized treatment strategies.

Main Methods:

  • A PRS was constructed using genome-wide association data from the Radiogenomics Consortium (N=3,988).
  • The PRS was prospectively tested in the REQUITE and URWCI studies (N=2,034), analyzing time to gross hematuria (≥G2) using Cox regression.
  • External validation was performed using UK Biobank data (N=8,430) for clinically diagnosed irradiation cystitis, alongside a gene-burden test for rare variants.

Main Results:

  • The 115-variant PRS significantly correlated with increased risk for hematuria (HR=1.22, P=0.009), urinary retention (HR=1.18, P=0.016), and frequency (HR=1.14, P=0.036).
  • Patients in the highest PRS decile (PRShigh) exhibited over a two-fold increased risk of hematuria (HR=2.12, P=0.002) after adjusting for clinical factors.
  • The PRS demonstrated similar predictive performance for clinically diagnosed irradiation cystitis in the UK Biobank (OR=2.15, P=0.026), and BOD1L1 was identified as a potential radiosensitivity gene.

Conclusions:

  • The developed PRS effectively identifies patients susceptible to developing late bladder toxicity following prostate cancer radiotherapy.
  • This genetic risk assessment tool can inform treatment planning, potentially guiding the selection of patients who require optimized bladder-sparing strategies.
  • Implementing PRS-guided treatment could reduce the incidence and impact of bladder toxicity, improving outcomes for prostate cancer survivors.