The researchers created an algorithm that predicts a person’s chance of acquiring prostate cancer based on age and levels of two prostate cancer indicators, PSA and hK2 (human kalliknein peptidase). They discovered that by establishing a risk threshold at which men are considered ‘screen positive,’ the approach will lower the amount of false positives by three-quarters while capturing the same proportion of malignancies as a regular PSA test.
According to a new study lead by a UCL researcher, calculating a person’s risk of acquiring prostate cancer using the results of two blood indicators would increase the accuracy of screening for the disease.
Prostate cancer is the most frequent type of cancer in males, with over 10,000 men dying from it each year in the United Kingdom, although there is presently no national screening program in place. This is due in part to the fact that the current best first-line screening, a blood test that detects elevated levels of the prostate-specific antigen (PSA), is not entirely reliable, missing some deadly tumors while also producing false positives. False positives include not just false alarms where no disease exists, but also the detection of innocuous malignancies that are treated unnecessarily.
In a new study published in the Journal of Medical Screening, researchers created an algorithm to estimate a person’s risk of acquiring prostate cancer based on age and levels of two prostate cancer markers, PSA and hK2 (human kalliknein peptidase).
They compared blood samples from men who died after being diagnosed with prostate cancer to those who were never diagnosed with the condition to see how well the algorithm predicted prostate cancer. They discovered that by establishing a risk threshold at which men are considered “screen positive,” the approach would lower the amount of false positives by three-quarters while catching the same proportion of malignancies as a regular PSA test.
The approach is innovative for cancer, as it screens people on the basis of 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.Jonathan Bestwick
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.
“According to our findings, an alternative screening method might cut the amount of false positives by three-quarters. This would make prostate cancer screening safer and more accurate, minimizing overdiagnosis and overtreatment. The next step will be to put this strategy to the test in a pilot project that will invite healthy males for screening. We feel that if the experiment is successful, this technique should be considered as part of a national screening program for all men.”
Co-author Jonathan Bestwick (Queen Mary University of London) said: “The approach is innovative for cancer, as it screens people on the basis of 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 research, commented: “This is a novel approach to prostate cancer screening that uses the levels of two prostate cancer markers, PSA and hK2 (human kallikrein peptidase). In terms of screening, the use of PSA alone has considerable limitations, but the addition of the hK2 marker in this context has the actual promise of considerably lowering the death rate from this most frequent malignancy in men.”
The researchers examined data and blood samples from nearly 21,000 males who participated in the prospective BUPA trial over 40 years ago for the study. They looked at a number of prostate cancer markers in blood samples from 571 men who died from or had prostate cancer, and compared them to a control group of 2,169 men who were never diagnosed with the condition.
They observed that, while hK2 was a relatively poor signal for prostate cancer on its own, it was somewhat independent of PSA, resulting in a more accurate test when the two were combined. They classified the total PSA and hK2 test findings based on how far from the average they were in relation to the participant’s age. They also included age into their assessment of risk.
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.”
The researchers discovered that if males aged 55 and over were checked at least five times a year using this risk cut-off, 90% of cancer cases would be detected, with only 1.2 percent of cases being false positives.
If a PSA test had been used to screen for the disease on its own, the researchers calculated that an 86 percent detection rate would have been accompanied by a 2% false positive rate. In comparison, if the risk-based strategy had been changed to have an 86 percent detection rate, the false positive rate would have been 0.5 percent, a three-quarters drop.
Professor Wald is one of several UCL academics working to enhance how prostate cancer is discovered and screened. The findings of the PRECISION experiment, coordinated by Professor Caroline Moore (UCL Division of Surgery and Interventional Science), resulted in new National Institute of Clinical Excellence (NICE) guidelines in 2019 that all males with a positive PSA test should receive an MRI scan prior to biopsy. This procedure has been demonstrated to preserve the detection of aggressive tumours while decreasing over-diagnosis and wasteful treatment of minor cancers.
Researchers discovered that men’s PSA levels were considerably higher up to 30 years before a prostate cancer diagnosis in the newest study, implying that a cause of prostate cancer plays a role long before it is diagnosed. However, PSA levels are not high enough to be beneficial in screening thus long in advance of illness diagnosis.