Assessment of a Polygenic Risk Score in Screening for Prostate Cancer
Powered by Evidence Published in The New England Journal of Medicine (NEJM), 2025
Moving Beyond One-Size-Fits-All Screening
Traditional prostate cancer screening has largely relied on age-based prostate-specific antigen
(PSA) testing, applying similar screening strategies to broad populations of men regardless of
individual inherited risk. While PSA-based screening has enabled earlier detection in some cases,
it has also contributed to overdiagnosis and unnecessary interventions in lower-risk individuals,
while potentially missing opportunities for earlier identification of men at higher genetic risk.
Advances in genomic medicine now allow prostate cancer risk to be assessed with greater
precision—before disease develops.
What Is a Polygenic Risk Score (PRS)?
A Polygenic Risk Score (PRS) estimates a man’s inherited risk of prostate cancer by analyzing
the combined effect of hundreds to millions of common genetic variants (depending on the test);
the BARCODE1 study used 130 validated variants.
PRS can identify men at substantially higher or lower genetic risk years before clinical disease
develops—often beyond what age, family history, or single-gene (monogenic) testing alone can
capture.
This enables a risk-guided screening approach, where screening intensity and timing can be
aligned with an individual’s genetic risk profile rather than relying solely on age-based
thresholds.
Key Evidence from the NEJM BARCODE1 Study
The study, titled “Assessment of a Polygenic Risk Score in Screening for Prostate Cancer,”
evaluated the role of PRS in identifying men at increased risk for clinically significant prostate
cancer (PrCa).
Key findings include:
• A 2025 New England Journal of Medicine (BARCODE1) study evaluated a PRS-
guided prostate cancer screening strategy, targeting men in the top 10% of inherited genetic risk.
• Men with PRS ≥90th percentile were offered multiparametric MRI and transperineal
biopsy irrespective of PSA level, shifting screening upstream from biomarkers to genetic
risk.
• Among those screened, 40% were diagnosed with prostate cancer, and 55% had
intermediate- or high-risk disease requiring clinical management according to NCCN criteria.
• More than 70% of clinically significant cancers would have been missed using the
current UK diagnostic pathway (as defined in the study) based on elevated PSA and
positive MRI.
• Overall, the study supports PRS as a powerful risk-stratification tool that enriches
screening for biologically significant prostate cancer and enables a move toward
precision, risk-based screening, while underscoring the need for broader validation
across diverse populations.
What This Means Clinically
Traditional PSA screening measures a downstream biomarker that can be elevated for many non-
cancerous reasons. In contrast, PRS assesses inherited genetic susceptibility, identifying men
who are biologically predisposed to develop aggressive disease—often before PSA becomes
abnormal.
Avigena’s Approach
Avigena integrates polygenic risk scores (PRS) with monogenic (single-gene) risk, family
history, and clinical context within a physician-led, evidence-based preventive genomics
program.
By combining common genetic risk (polygenic) with rare high-impact genetic variants
(monogenic), Avigena supports a more comprehensive assessment of inherited prostate cancer
risk. This integrated approach is designed to inform personalized screening and early detection
strategies, while ensuring that all clinical decisions remain with the treating healthcare
professional.
Reference
McHugh JK et al. Assessment of a Polygenic Risk Score in Screening for Prostate Cancer.
The New England Journal of Medicine, April 2025.
DOI: 10.1056/NEJMoa2407934
Read the full article on the NEJM website
This content is provided for educational purposes only and does not constitute medical advice.
Screening decisions should always be made in consultation with a qualified healthcare
professional.