New risk algorithm would improve screening for prostate cancer

Date:
March 8, 2022
Source:
University College London
Summary:
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 kalliknein
peptidase). They found that, by setting a risk threshold above
which men are counted as 'screen positive', the approach would
reduce the number of false positives by three quarters compared to
a standard PSA test, while catching the same proportion of cancers.



FULL STORY ========================================================================== 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.


========================================================================== 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, but there
is currently no national screening programme.

That is partly because the current best first-line test -- a blood test
that detects raised levels of the prostate-specific antigen (PSA) --
is not wholly reliable, missing some harmful cancers as well as giving
false positives. False positives include not just false alarms where
there is no cancer but the discovery of harmless cancers that are
unnecessarily treated.

In a new study, published in the Journal of Medical Screening, 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 kalliknein 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.

They found that, by setting a risk threshold above which men are counted
as "screen positive," the approach would reduce the number of false
positives by three quarters compared to a standard PSA test, while
catching the same proportion of cancers.



==========================================================================
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 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 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." For the study, the researchers looked at data and blood samples from more than 21,000 men recruited into the prospective BUPA
study over 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, comparing these with
a control group of 2,169 men who were never diagnosed with the disease.

They noted that while hK2 was a relatively weak marker for prostate
cancer on its own, it was relatively independent of PSA so the two
together yielded a more accurate test.

They categorised the results of the total PSA and hK2 tests based on how
far away from average they were according 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 found that if men aged 55 and over
were screened at least five 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 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%. 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.

Professor Wald is one of a number of researchers at UCL seeking to
improve how prostate cancer is detected and screened.

In 2019, findings from the PRECISION trial, led by Professor Caroline
Moore (UCL Division of Surgery and Interventional Science), resulted
in new National Institute of Clinical Excellence (NICE) guidance that
all men with a positive PSA result should have an MRI scan prior to
biopsy. This step has been shown to preserve the detection of aggressive cancers whilst reducing over-diagnosis and unnecessary treatment of insignificant cancers.

In the latest study, 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. However, the levels of PSA are not elevated enough to be
useful in screening this far ahead of disease diagnosis.

The study involved researchers at UCL, Queen Mary University of London
and St George's, University of London.


========================================================================== Story Source: Materials provided by University_College_London. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Nicholas J Wald, Jonathan P Bestwick, Joan K Morris. Multi-marker
risk-
based screening for prostate cancer. Journal of Medical Screening,
Mar.

7, 2022; DOI: 10.1177/09691413221076415 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220307190651.htm

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