Assessing the Clinical Utility of Published Prostate Cancer Polygenic Risk Scores in a Large Biobank Data Set

Area of Science:

• Genetics
• Oncology
• Epidemiology

Background:

• Polygenic risk scores (PRSs) are genetic tools developed to predict prostate cancer risk.
• Evaluating the real-world performance of existing PRSs is crucial for clinical application.

Purpose of the Study:

• To compare the performance of 16 PRSs in identifying men at risk of developing prostate cancer.
• To assess the ability of top-performing PRSs in differentiating aggressive prostate cancer.

Main Methods:

• A case-control study utilizing 16 published PRSs applied to Michigan Genomics Initiative (MGI) patients.
• Case data were matched with the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry for clinical and pathological details.
• Performance was evaluated using area under the covariate-adjusted receiver operating characteristic curve (aAUC) and logistic regression for disease aggressiveness.

Main Results:

• The predictive performance (aAUC) of the 16 PRSs for prostate cancer risk ranged from 0.51 to 0.67.
• No significant association was found between PRS and prostate cancer aggressiveness based on biopsy data.
• The study included 18,050 patients: 2,740 prostate cancer cases and 15,310 controls.

Conclusions:

• Prostate cancer PRSs demonstrate moderate effectiveness in identifying individuals at increased risk of developing the disease.
• Current PRSs have limitations in distinguishing between indolent and aggressive prostate cancer, necessitating further refinement.