Polygenic Risk Score Outperforms PSA and MRI in Detecting Clinically Significant Prostate Cancer: NEJM
Researchers have found in a new BARCODE1 study that a polygenic risk score identified a higher proportion of clinically significant prostate cancer compared to PSA or MRI screening, which would have missed 71.8% of cases. Further Overdiagnosis rates were comparable to those seen in previous PSA-based studies. The study was published in The New England Journal of Medicine by Jana K. and fellow researchers. This method might provide a more accurate and focused way of detecting high-risk individuals who would be indicated for more extensive diagnostic assessment.
The UK trial sought to investigate whether germline genetic information could enhance prostate cancer detection earlier, by targeting those with the greatest genetic risk with screening. Through the use of genome-wide association data to determine a polygenic risk score based on 130 established variants, researchers were able to target those in the top 10% of genetic risk and invite them for screening with multiparametric MRI and transperineal biopsy, irrespective of PSA.
Men aged 55 to 69 years were recruited from primary care centers in the UK. Saliva was sampled to yield germline DNA that was then used to compute a polygenic risk score for each participant based on 130 known prostate cancer-associated genetic variants. Of 40,292 men invited to join, 8953 (22.2%) were interested, and 6393 received polygenic risk score testing. The 745 men with a score at or above the 90th percentile (11.7%) were offered intensive screening. This included multiparametric MRI followed by transperineal biopsy, regardless of the participants' PSA levels.
Key Findings
Of 40,292 invited men, 6393 had polygenic risk scoring.
745 men (11.7%) were classified in the top 10% of genetic risk.
468 of these men (62.8%) underwent MRI and biopsy.
187 (40.0%) were found to have prostate cancer.
103 (55.1%) had cancer of intermediate or higher risk that needed treatment.
74 (71.8%) of these high cases would not be detected with existing PSA-based methods.
40 men (21.4%) had high-risk or very high-risk prostate cancer.
This British study offers strong evidence that prostate cancer screening using polygenic risk scores can identify more clinically relevant cancers than conventional PSA-based methods. The approach has the potential to be a revolutionary step towards more personalized and efficient cancer screening. Applying genetic information to select men most likely to gain from more sophisticated diagnostic equipment can contribute to alleviating the population burden of undetected, high-risk prostate cancer.
Reference:
McHugh, J. K., Bancroft, E. K., Saunders, E., Brook, M. N., McGrowder, E., Wakerell, S., James, D., Rageevakumar, R., Benton, B., Taylor, N., Myhill, K., Hogben, M., Kinsella, N., Sohaib, A. A., Cahill, D., Hazell, S., Withey, S. J., Mcaddy, N., Page, E. C., … Eeles, R. A. (2025). Assessment of a polygenic risk score in screening for prostate cancer. The New England Journal of Medicine, 392(14), 1406–1417. https://doi.org/10.1056/nejmoa2407934
