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Polygenic Risk Score and Upgrading in Patients With Prostate Cancer Receiving Active Surveillance.

Louisa B Goss1,2, Menghan Liu1, Yingye Zheng1

  • 1Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington.

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|December 12, 2024
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Summary
This summary is machine-generated.

A high polygenic risk score (PRS) is linked to a higher risk of prostate cancer upgrading in patients on active surveillance. This genetic risk may help identify individuals who could benefit from more intensive monitoring strategies.

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Area of Science:

  • Genetics
  • Oncology
  • Urology

Background:

  • Active surveillance is the standard for low-risk prostate cancer (PCa), but frequent monitoring is burdensome.
  • Stratifying patients for intensive versus passive surveillance could optimize care and reduce patient burden.
  • Polygenic risk scores (PRS) may offer a tool to identify patients at higher risk of disease progression.

Purpose of the Study:

  • To examine the association between a polygenic risk score (PRS) and the risk of prostate cancer upgrading.
  • To investigate the relationship between PRS and other prostate tumor characteristics in patients undergoing active surveillance.

Main Methods:

  • A prospective multicenter cohort study included 1220 patients with localized prostate cancer on active surveillance.
  • Multi-ancestry PRS, including variants associated (PRS-451) and not associated (PRS-400) with prostate-specific antigen (PSA), were analyzed.
  • The primary outcome was PCa upgrading; secondary outcomes included prostate volume, PSA, and biopsy findings.

Main Results:

  • Higher PRS was significantly associated with an increased hazard of PCa upgrading during follow-up.
  • PRS-400 showed associations with smaller prostate volume and a higher percentage of biopsy cores with cancer.
  • Incorporating PRS-400 into a clinical model slightly improved its predictive ability for disease progression.

Conclusions:

  • In patients on active surveillance, elevated PRS is associated with an increased risk of prostate cancer upgrading and potentially multifocal disease.
  • PRS, particularly when excluding PSA-associated variants, may provide insights into tumor aggressiveness, indicated by smaller prostate size.
  • While PRS shows potential for informing active surveillance strategies, its definitive impact on clinical decision-making requires further evaluation.