medwireNews: Offering targeted screening on the basis of a high polygenic risk score led to the detection of a high proportion of clinically significant prostate cancer in the BARCODE1 trial published in The New England Journal of Medicine.
The researchers point out that just under three-quarters of these cases “would have been missed with the standard diagnostic pathway used in the United Kingdom (high PSA [prostate-specific antigen] level and positive MRI [magnetic resonance imaging] results).”
Editorialist David Hunter, from the University of Oxford in the UK, says these findings indicate that “if available, a polygenic risk score for prostate cancer would be a useful component of a multimodality screening program that assesses age, family history of prostate cancer, PSA, and MRI results as triage tools before biopsy is recommended.”
He continues: “To make this integrated program a reality, however, changes to infrastructure would be needed to make running and analyzing a regulated genome array as easy as requesting a PSA level or ordering an MRI. Clearly, we are far from that future.”
A total of 40,292 men aged 55–69 years and of European ancestry who were registered at one of 69 primary care centers in the UK were invited to participate in the BARCODE1 study, and 8953 (22.2%) expressed an interest in participating.
The team used germline DNA extracted from saliva to derive “polygenic risk scores from 130 variants known to be associated with an increased risk of prostate cancer” for 6393 of the men. Of these, 745 (11.7%) had a score in the 90th percentile or higher, and 468 (62.8%) underwent MRI and prostate biopsy.
Prostate cancer was detected in 187 (40.0%) of the participants, and just over half (55.1%) had disease with a Gleason score of at least 7 points that was classified as intermediate risk or higher according to the 2024 National Comprehensive Cancer Network (NCCN) criteria, while 21.4% had disease classified as unfavorable intermediate, high, or very high risk and therefore required radical treatment.
Of the 103 men with clinically significant prostate cancer, 71.8% had disease that would not have been detected with the current UK screening recommendations, report Rosalind Eeles (Institute of Cancer Research, London, UK) and co-investigators.
Using various criteria, they estimated overdiagnosis rates of 15.6% to 20.8%, which are “similar to the overdiagnosis estimates in two PSA-based screening studies,” write the authors.
They continue: “Further screening will be key in ascertaining the incidence of prostate cancer over time among currently unaffected persons at high risk. Follow-up of the whole cohort is continuing in order to evaluate the prostate cancer incidence and tumor characteristics among the participants with polygenic risk scores below the 90th percentile.”
Eeles and colleagues also highlight the need for further research “[t]o evaluate fully the implementation of polygenic risk score alongside established risk factors in a national screening program,” specifically “research into the recommended age at which to obtain a polygenic risk score, tests of replication in persons of non-European ancestry, and an evaluation of economic effects.”
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