Targeted screening for patients at highest genetic risk of prostate cancer increased clinical management, radical treatment
Offering targeted screening to participants in the 90th percentile of genetic risk as determined by a polygenic risk score resulted in finding prostate cancer warranting clinical management in 55.1% of patients and radical treatment in 21.4%, a U.K. study found.
A polygenic risk score for prostate cancer found a higher percentage of clinically significant disease than would have been found by prostate-specific antigen (PSA) or MRI screening, a study found.
To identify common germline variants in persons with prostate cancer and calculate a polygenic risk score associated with prostate cancer risk, researchers recruited patients ages 55 to 69 years from primary care centers in the United Kingdom, extracted DNA from saliva, and created a polygenic risk score from 130 variants known to be associated with prostate cancer risk. Patients with a polygenic risk score in the 90th percentile or higher were invited to undergo prostate cancer screening with multiparametric MRI and transperineal biopsy, regardless of their PSA level. Results were published in the New England Journal of Medicine on April 9.
Among 40,292 invited patients, 8,953 (22.2%) expressed interest and 6,393 had their polygenic risk score calculated. From this group, 745 (11.7%) had a polygenic risk score in the 90th percentile or higher and were invited to undergo screening. Of these 745 participants, 468 (62.8%) had MRI and prostate biopsy. Prostate cancer was found in 187 participants (40.0%), with a median age of 64 years at diagnosis (range, 57 to 73 years). Among the patients with prostate cancer, 103 (55.1%) had disease that was classified as intermediate or higher risk according to 2024 National Comprehensive Cancer Network (NCCN) criteria, indicating the need for treatment.
The study authors wrote that cancer would not have been detected in 74 (71.8%) of these patients according to the prostate cancer diagnostic pathway currently used in the U.K., which is based on high PSA level and positive MRI results. Forty of the participants with cancer (21.4%) had disease that was classified as unfavorable intermediate risk or as high or very high risk based on the NCCN criteria.
The study showed that “almost all the participants with a polygenic risk score in the 90th percentile or higher, those with a family history of disease, and those of older age and with a polygenic risk score not in the lower percentiles had an absolute risk above a threshold of 3.8%,” the study authors concluded. “This finding supports the use of polygenic risk score together with established risk factors in screening for prostate cancer.”
An accompanying editorial pointed out the many problems with current prostate cancer screening, such as false-positive PSA results, and noted that treatments for prostate cancer are associated with substantial morbidity. If a screening program started with an assessment of a polygenic risk score, a substantial number of clinically significant cases would be discovered that otherwise would have been missed, but this would require investing in genome arrays, storing genetic data on populations, and counseling on the risk of many other diseases, the editorial said.