The accuracy of prostate cancer screening could improve significantly by calculating a person’s risk of developing the disease by using results from two blood markers.
Prostate cancer is the most common form of cancer in men, with more than 10,000 men dying from the disease every year in the UK, despite this, there is currently no national prostate cancer screening programme.
The lack of a prostate cancer screening programme can be partially explained because the current best first-line test – a blood test that detects raised levels of prostate-specific antigen (PSA) – is not completely reliable. It can often miss some harmful cancers and gives false positives.
The new study was published in the Journal of Medical Screening.
Prostate cancer screening algorithm
The researchers developed an algorithm estimating a person’s risk of developing prostate cancer based on age and the levels of two prostate cancer markers, PSA and Hk2 (human kallikrein peptidase).
They tested how well the algorithm could predict prostate cancer by comparing blood samples of men who later died after a prostate cancer diagnosis with those who were never diagnosed with the disease.
The team of researchers discovered that by setting the risk threshold above which men are counted as “screen positive”, the approach would reduce the number of false positives by three quarters compared to the standard PSA test, whilst catching the same proportion of cancer.
Lead author Professor Sir Nicholas Wald (UCL Institute of Health Informatics) 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 (Queen Mary University of London) said: “The approach is innovative for cancer, as it screens people based on their overall risk rather than the results of a single test. This is the same approach used in screening during pregnancy for certain fetal and maternal health conditions.”
Professor Roger Kirby, President of the Royal Society of Medicine and Vice-President of Prostate Cancer UK, who was not involved in the study, said: “This is a novel approach which utilises the levels of two prostate cancer markers, PSA and hK2 (human kallikrein peptidase) to refine prostate cancer screening. The use of PSA alone has significant drawbacks in terms of screening, but the addition of the hK2 marker in this context carries the genuine promise of significantly reducing the death rate from this most common cancer in men.”
Studying blood samples from over 21,000 men
For the study, the researchers analysed data and blood samples from more than 21,000 men in the prospective BUPA study over 40 years ago.
They analysed several prostate cancer markers in blood samples of 571 men who later died from or with prostate cancer, comparing these with a control group of 2,169 men who were never diagnosed with the disease.
They found that whilst hK2 was a weak marker during the prostate cancer screening process, it was relatively independent of PSA, so the two generated a more accurate test. The researchers categorised the results of the total PSA and hK2 based on how far away from average they were according to the participant’s age. They also included age in their assessment of risk.
Following this analytical process, the researchers found that all men 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” following their prostate cancer screening process. Furthermore, they learned that if men aged 55 and over had prostate cancer screening at least five times yearly using this risk cut-off, 90% of cancer cases would be detected, with only 1.2% of cases being false positives.
If a PSA test had been used in the prostate cancer screening process 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%. By comparison, if the risk-based approach had been adjusted to have a detection rate of 86%, the false positive rate would have been 0.5% – a reduction of three quarters.
