Polygenic scores could 'turn the tide on prostate cancer'

An at-home spit test to identify patients at risk of prostate cancer, using a polygenic risk score, has been shown to outperform current testing methods.

The initial results of the BARCODE1 study, published in the New England Journal of Medicine, showed that for men with the highest risk of prostate cancer, this new test based on risk-associated genetic variants was more accurate than the standard NHS-applied blood test, which detects the enzyme protein-specific antigen (PSA). In conjunction with additional tools, the new test could improve the screening of prostate cancer, helping ensure that positive cases are identified and false positive cases are excluded.

'With this test, it could be possible to turn the tide on prostate cancer', said Professor Rosalind Eeles, from the Institute of Cancer Research in London, who led the research. 'Building on decades of research into the genetic markers of prostate cancer, our study shows that the theory does work in practice – we can identify men at risk of aggressive cancers who need further tests and spare the men who are at lower risk from unnecessary treatments.'

Currently, men over 50 are eligible for a test to detect PSA, which is expressed at higher levels in prostate cancer. However, for every true positive case identified by the PSA test, there are three false positives. Additionally, the PSA test can highlight cancers which are so slow-growing as to not be life-threatening.

One way to identify men at high risk of prostate cancer is using a polygenic risk score. This score is developed using large-scale datasets to identify many genetic variants – each of which is associated with a small increased risk of prostate cancer – and then combining the data to identify men with the largest number of these variants.

As part of this study, a polygenic risk score made from 130 variants linked with prostate cancer risk was calculated for 6393 men in the UK between 55 and 69 years of age. 745 of these men were found to fall within the top ten percent of risk, as defined by this particular polygenic score.

Prostate cancer was identified in 187 of these patients, and was classified as intermediate or higher risk in 103 of them. Of the high-risk cases, 74 patients would have been missed using the standard diagnostic pathway, which involves a high PSA level and a positive MRI test.

'This study is the strongest evidence to date on the clinical utility of a polygenic score for prostate cancer screening,' said Professor Michael Inouye, from Cambridge University, who was not involved in the research. 'A large proportion of prostate cancer cases detected using a polygenic score would not have been detected using the current diagnostic pathway.'

In an editorial published alongside the study David Hunter, professor of epidemiology and medicine and Oxford and Harvard Universities, said that the polygenic risk score 'would be a useful component of a multimodality screening program' should the infrastructure be made available. This screening method would also include age, family history, PSA and MRI results.

Professor Hunter also highlighted the need to ensure sufficient infrastructure to develop and analyse these kinds of tests, which are currently not provided extensively. One suggestion he made, as part of an integrated solution, was to provide the polygenic risk test 'only for men with a positive PSA result, then use the polygenic risk score to determine who should undergo an MRI, and then use all the information to determine whether biopsy is recommended.'

An additional limitation of the current test is that the 130 variants included in the test were identified only in people with European ancestry, making it less reliable for patients with non-European ancestry (such as people of Black African and Caribbean ancestry). An updated test, called PRODICT, is currently being developed by the same team and aims to apply this polygenic risk approach to more diverse populations.