Using the results from two blood markers can improve the accuracy of risk calculations for prostate cancer, a new study has shown.
Calculating a person’s risk of developing prostate cancer using results from two blood markers would improve the accuracy of screening for the disease, reports a new study led by a UCL researcher.
Research led by UCL, UK, has led to an algorithm that estimates a person’s risk of developing prostate cancer based on age and the levels of two prostate cancer markers, prostate-specific antigen (PSA) and human kalliknein peptidase (hK2).
Writing in the latest edition of the *Journal of Medical Screening*, lead author Professor Sir Nicholas Wald, of UCL Institute of Health Informatics, and colleagues describe comparing blood samples of men who later died after a prostate cancer diagnosis with those who were never diagnosed with the disease, using the algorithm.
They found when they set a risk threshold above which men are counted as “screen positive”, it reduced the number of false positives by three quarters compared to a standard PSA test, while catching the same proportion of cancers.
Prof Wald said: “A key drawback of screening for prostate cancer using a PSA test alone is the higher risk of a false positive, which can lead to an unnecessary, invasive biopsy and the unnecessary treatment of a clinically insignificant cancer that would not have caused harm anyway.
“Our study shows a different screening approach could reduce the number of false positives by three quarters. This would make screening for prostate cancer safer and more accurate, reducing overdiagnosis and overtreatment.
“The next step is to test the feasibility of this approach in practice with a pilot project inviting healthy men for screening. If the project is successful, we believe this approach ought to be considered as part of a national screening programme for all men.”
Co-author Jonathan Bestwick, of Queen Mary University of London, said the approach, which is used in pregnancy screening for certain foetal and maternal health conditions, is innovative for cancer because it screens people on the basis of their overall risk rather than the results of a single test.
For this study, the researchers looked at data and blood samples from more than 21,000 men recruited into the prospective BUPA study more than 40 years ago.
They analysed a number of prostate cancer markers in blood samples of 571 men who later died from or with prostate cancer and compared them to a control group of 2,169 men who were never diagnosed with the disease.
While hK2 was quite a weak marker for prostate cancer on its own, the team found it was relatively independent of PSA. It meant the two together yielded a more accurate test.
All participants who were estimated to have a one in 20 or greater risk of developing prostate cancer in the next five years were counted as “screen positive”.
The team found that if men aged 55 and over were screened at least every five years using this risk cut-off, 90% of cancer cases would be detected. About 1.2% of cases would be false positives.
However, if a PSA test had been used to screen for the disease on its own, in one scenario modelled by the researchers, an 86% detection rate would have been accompanied by a false positive rate of 2%.
The researchers also found that men’s PSA levels were significantly elevated up to 30 years before a prostate cancer diagnosis, suggesting that a cause of prostate cancer plays a role long before it is diagnosed.
Wald N et al. Multi-marker risk-based screening for prostate cancer. *Journal of Medical Screening* 7 March 2022
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