PSA and genetic data combined improves detection of prostate cancer

Polygenic scores (PGS) can enhance the accuracy of prostate cancer screening tests to detect aggressive cancers and help avoid some unnecessary biopsies.

Prostate cancer is the most common cancer in men, with 52,000 men diagnosed per year in the UK. Prostate specific antigen (PSA), an enzyme that can be raised in people who have prostate cancer, has been used in screening tests for decades. However, the test has many limitations and can both incorrectly suggest that a patient has prostate cancer, or fail to detect some cancers. This can result in unnecessary biopsies and missed cancer diagnoses.

'PSA is really the best blood cancer marker in all of medicine, but it's not like a pregnancy test where everybody who's positive is pregnant [...] Just like some men are tall and some are short, some are high PSA secreters and some are low PSA producers.' said Dr William Catona, prostate cancer surgeon and professor of urology at Northwestern University's Feinberg School of Medicine, Chicago, who was not involved in the latest research.

To improve the PSA test's accuracy, researchers at Stanford University, California, studied the genomes of nearly 100,000 men without prostate cancer, finding 128 variants that affect PSA levels. Their results are published in Nature Medicine.

Using these markers they developed a risk score, predicting whether a patient's genetics were likely to cause high, normal or low PSA levels. They then created a 'PGS-adjusted PSA' score, combining individual genetic information with other patient factors to test whether PSA levels were irregular and indicated the presence of cancer.

Using the PGS-adjusted PSA score led to 31 percent of unnecessary biopsies being avoided in patients of European ancestry. The adjusted score also predicted aggressive cancers more successfully than when genomic information was not included. The adjusted score did miss nine percent of men who did in fact have prostate cancer, though most of these were not aggressive cancers.

Researchers used data from five cohorts including the UK Biobank, and other cohorts from the USA and Sweden. Of the variants linked to PSA levels discovered, the vast majority were only found to be significantly linked to PSA levels in men of European ancestry. Variants detected were on genes that affected gene expression and the immune response. The PGS score developed was not found to improve prediction of cancer in men of African ancestry.

Dr Linda Kachuri, lead author of the study and assistant professor of epidemiology and population health at Stanford University, noted that the majority of patients in the study were of European ancestry, and said: 'Ideally, we want to come up with a single score that works well for everybody, across the spectrum of ancestry'.

The score will be tested in a larger, more diverse cohort next.