Illustration of the prostate organ in blue surrounded by red cancer cells to symbolize prostate cancer
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UK researchers have shown that incorporating a genetic risk score (GRS) for prostate cancer into routine clinical care could help identify patients at greatest risk for the disease who should be prioritized for investigation.

The risk score, developed by a team at the University of Exeter, could also help men classified as being at a very low risk of cancer to avoid invasive investigations, which in turn would reduce patient harm and demand on secondary care services.

They study findings are published in the British Journal of Cancer.

Lead author Dr Harry Green, research fellow at the University of Exeter Medical School, said: “Our study is the first to demonstrate that incorporating genetic risk into GP’s [general practitioner’s] risk assessment of patients’ symptoms of possible prostate cancer could result in faster referral for those at most risk.”

The study included data for 6,777 men without pre- existing prostate cancer who were registered in the UK Biobank—a biomedical database containing in-depth genetic and health information from half a million people—and had consulted their GP about lower urinary tract symptoms (LUTS), such as nocturia, urinary frequency, or poor stream.

All of these symptoms are common in men over 50 years of age and are often present at the time of a prostate cancer diagnosis. However, they are also associated with the incidence of benign prostate enlargement and increase with age, which complicates attempts to accurately diagnose tumors.

Of the men included in the study, 3.5% had a record of a prostate cancer diagnosis within 2 years of visiting their GP with LUTS.

When the researchers applied a genetic risk score to the cohort, based on the 269 known risk variants for prostate cancer, they found that the risk for prostate cancer more than doubled with each standard deviation increase in score.

Put a different way, men with a score in the lowest 20% of the observed range had a less than 1% chance of developing cancer within 2 years whereas those with a score in the highest 20% of the range had an 8.8% chance, a significant difference.

Green and colleagues note that UK guidelines recommend that any individual with a 3% or greater chance of developing cancer should be followed-up, but there are proposals to reduce this threshold to 2%.

At the reduced threshold, the investigators estimated that at least 40% of the cohort with LUTS could avoid referrals. Since GPs make around 800,000 suspected prostate cancer referrals annually in the UK, incorporating genetic risk for cancer into GP triage could mean that 320,000 men could safely avoid referral and unpleasant investigation while the remaining 160,000 could be expedited for faster investigation.

The team calculated that the accuracy of the GRS on its own was 70.3%, but when it was combined with age, this increased to 77.2%. By comparison, the reported diagnostic accuracy of prostate specific antigen (PSA) testing—the current screening tool used for men with LUTS—is around 72%.

The study authors hypothesize that combining the GRS with PSA could further improve accuracy.

“We need more research to find out how PSA and genetic tests would work together and what the implications would be for PSA if genetic testing was introduce,” the study’s lead investigator, Dr Sarah Bailey, senior research fellow at the University of Exeter Medical School, told Inside Precision Medicine.

She added that the team are now looking for more funding to expand the to study to include PSA and genetics together in primary care.

Further research will also be needed to look at how the GRS will work in men of non-European backgrounds, as the current study only included White European men.

“In theory a genetic risk score should perform just as well in men of other ethnicities, but more research is needed to make sure that’s the case, and that men of non-European backgrounds would not be disadvantaged by the genetic testing,” Bailey remarked.

At present, genetic sequencing is not available in UK primary care but the researchers say that current trends suggest that it will become part of routine practice in the future.

Bailey hopes this will mean that the GRS could be used routinely and “patients at the greatest risk of prostate cancer can be fast tracked for investigation in primary care, perhaps without having to wait for a PSA test – they could be referred directly if they experience any lower urinary tract symptoms.”

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