The study was published as a preprint on medRxiv.org and has not yet been peer reviewed.
Key Takeaways
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Among men with lower urinary tract symptoms, a simple genetic risk score (GRS) can distinguish those who need a workup for prostate cancer from those who don’t.
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By incorporating the score into routine care, 40% of men with lower urinary tract symptoms could avoid unnecessary testing for prostate cancer.
Why This Matters
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Assessment of prostate cancer risk in men with lower urinary tract symptoms is currently based on presenting clinical features alone.
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The GRS can help distinguish which men have the greatest risk of prostate cancer. Those with the lowest genetic risk could safely avoid invasive investigation, while those with the greatest risk could be fast-tracked for further investigation.
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The study is “the first to demonstrate the potential clinical application of genetic risk scores” in men with symptoms that could indicate prostate cancer, the authors conclude.
Study Design
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A genetic risk score for prostate cancer was derived using the 269 known risk variants.
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Using UK Biobank data, the GRS was calculated for 6779 men who presented to their general practitioner for nocturia, urinary frequency, or poor stream; 241 were diagnosed with prostate cancer within 2 years.
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Cancer incidence was correlated with baseline GRS.
Key Results
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In the 241 men with a prostate cancer, the mean GRS was 23.51, vs 22.92 in the 6537 men not diagnosed with prostate cancer within 2 years (OR = 2.54).
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An integrated risk model including both age and GRS applied to symptomatic men predicted prostate cancer with an AUC of 0.768, outperforming the diagnostic accuracy of PSA with an AUC of 0.72.
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The negative predictive value of the combined model exceeded 99%.
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Of men presenting with symptoms, those 40 years and younger in the bottom four GRS quintiles, 50 years and younger in the bottom two GRS quintiles, and 50 to 60 years in the bottom GRS quintile had a 2-year prostate cancer incidence below 1%.
Limitations
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The study was mostly to White men due to the lack of ethnic diversity in the biobank data.
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The cohort was enriched for younger men.
Disclosures
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The work was supported by the Higgins family.
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The investigators had no relevant financial relationships.
This is a summary of a preprint research study, “Applying a Genetic Risk Score for Prostate Cancer to Men With Lower Urinary Tract Symptoms in Primary Care to Predict Prostate Cancer Diagnosis: A Cohort Study in the UK Biobank,” led by Harry Green of the University of Exeter Medical School in England. The study has not been peer reviewed. The full text can be found at medRxiv.org.
M. Alexander Otto is a physician assistant with a master’s degree in medical science. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape and is an MIT Knight Science Journalism fellow. Email: [email protected].
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