Almost one in six deaths from prostate cancer could be prevented if targeted screening was used for men at a higher genetic risk for the disease, according to a new computer modeling study led by University College London.
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Prostate cancer is the most common cancer among men and is one of the leading causes of cancer-related death. In the UK, around 130 new cases are diagnosed every day and more than 10,000 men die from the disease every year.
Currently, there is no national screening program for prostate cancer in the UK. Men can be screened using a blood test that checks for elevated levels of prostate-specific antigen (PSA), but the test is not reliable because it cannot accurately differentiate between harmful and harmless cancers. This leads to both harmful cancers going undetected and men with harmless cancers undergoing operations unnecessarily.
As recently reported in PLOS Medicine, Nora Pashayan and colleagues used computer modeling to assess the advantages and disadvantages of introducing four-yearly PSA screening for all men aged 55 to 69 years, as compared with introducing targeted screening of men with a higher genetic risk for this type of cancer.
Screening at-risk men could save countless lives
The findings suggested that the optimal approach would be to screen men who are at a slightly increased genetic risk, which represents almost half of the men in that age group.
The researchers say this would be the most beneficial approach in terms of preventing deaths, whilst reducing the amount of unnecessary treatment procedures. The reason is that men who are at an increased genetic risk are more likely to benefit and less likely to be harmed by screening.
Prostate cancer is a leading cause of death from cancer in men in the UK, but screening is not performed because the harm of overdiagnosis is thought to outweigh the benefits. Our study shows that targeted screening can reduce unnecessary diagnoses while helping to prevent people dying from the disease by enabling earlier detection."
For the study, the team created a hypothetical cohort of 4.5 million men (representative of the number of men aged 55 to 69 in England) and simulated the outcomes of introducing screening into this population.
They compared prostate cancer deaths averted, unnecessary diagnoses and screening costs for three groups: no screening, universal age-based screening and more targeted screening using a range of genetic risk thresholds.
What did the findings suggest?
The team concluded that the best approach would be to screen men who are at a 4-7% increased risk over the course of the next ten years.
While screening all men in the 55 to 69 age group would result in the most deaths averted (20%), it would also be more expensive and result in many unnecessary diagnoses, with nearly one-third of the cancers detected being harmless.
Screening at a genetic risk threshold of 4% would prevent nearly one-sixth of deaths, whilst providing the greatest benefits in terms of quality-adjusted life years. Compared with screening all men in this age group, it would also reduce the number of unnecessary diagnoses of harmless cancers by about one third.
Screening at a genetic risk threshold of 4-7% risk would also be significantly more cost-effective than screening all men. It would reduce costs by between one- fifth at the 4% risk threshold and almost half at the 7% risk threshold, whilst maintaining the benefits of screening.
Under the scenarios the team simulated, men aged 55 to 69 would be screened four times a year once they had reached the risk threshold. This would mean more men being screened the older they get, since the risk for the disease increases with age.
“We now have the tools that help us identify men with clinically important disease”
Pioneering research led by University College London has already led to a change in how prostate cancer is diagnosed. As of last December, MRI is now the first-line approach to diagnosing men with suspected prostate cancer. The change was introduced following two clinical UCL-led trials that showed MRI scans could significantly and safely reduce the numbers of men needing an invasive biopsy.
I feel we now have the tools that help us identify men with clinically important disease - applying these tools to the right patient has to be the future. That is why this work is so important in helping us know who and when to screen.”
Mark Emberton, UCL Medical Sciences.
Callender, T., et al. (2019). Polygenic Risk-Tailored Screening for Prostate Cancer: A Benefit-Harm and Cost- Effectiveness Modelling Study. PLOS Medicine. https://doi.org/10.1371/journal.pmed.1002998.