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The results of the BARCODE1 trial, published by The New England Journal of Medicine assesses the use of a polygenic risk score in screening for prostate cancer.
Prof Michael Inouye, Professor of Systems Genomics & Population Health, University of Cambridge, said:
“This study is the strongest evidence to date on the clinical utility of a polygenic score for prostate cancer screening. It shows that a polygenic score can improve early detection of clinically significant prostate cancer, including those warranting radical treatment. A large proportion of prostate cancer cases detected using a polygenic score would not have been detected using the current diagnostic pathway. The authors appropriately discuss the study’s limitations and further research required (e.g. cost effectiveness). Taken together, I suspect we will look back on this as a landmark study that really made the clinical case for polygenic scores as a new tool that moved health systems from disease management to early detection and prevention.”
When asked how long it would take to know if this could be used clinically?
“This is a big step along the path to clinical implementation, but it is still a long road. Realistically, it will likely be years for the NHS to use polygenic scores routinely. It will require investment in infrastructure, generation of genomic data, training for healthcare practicians and potentially access to counselling for patients. There are more targeted ways to use polygenic scores clinically which may make for good next steps. To me, the study really makes me start to believe that these investments are worth it.”
Mr Ben Lamb, Consultant Urological and Robotic Surgeon, Barts Health and UCLH NHS Trusts, and Clinical Senior Lecturer, Barts Cancer Institute, Queen Mary University of London (QMUL), said:
“This is a very interesting study that assesses the utility of polygenic risk score in the detection of prostate cancer. The population may not be representative of those most at risk of prostate cancer, or of poorer health outcomes in general (e.g. black men, men in areas of deprivation), and further research is needed to test the results in these populations. Further research is also needed to understand longitudinal risk for men with a higher polygenic risk score i.e. their risk of developing cancer over time.
“Interestingly, the best rate of detection of significant prostate cancer arose when the saliva test, PSA test and MRI tests were all positive. The saliva test may help to direct resources to those men most likely to have significant prostate cancer, but at present it does not replace these investigations, which we know are powerful tools in reassuring some men and recommending biopsy (and performing a better biopsy) in others.
“The saliva test is less invasive than a blood test, or an MRI, and may be more acceptable for larger populations.”
Dr Oliver Pain, Sir Henry Wellcome Postdoctoral Research Fellow, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, said:
“This study uses solid data and analyses and its findings fit nicely with the previous literature suggesting that polygenic scores can improve estimation of prostate cancer risk. It goes a step further than previous research in this area by providing a direct comparison with the current diagnostic pathway, showing that stratifying individuals by their polygenic score helped to identify people with clinically significant prostate cancer who would have otherwise been missed. As stated by the authors, the main limitation of this study is that it is restricted to individuals of European ancestry. Previous research has shown that the polygenic score they have used performs worse in non-European individuals, limiting the generalisability of this study’s conclusions. However, this is a common limitation of the field, not just this study, and there is progress being made with polygenic scores performing better across ancestral populations as the training data (GWAS) becomes more ancestrally diverse and polygenic scoring methods develop to improve their ability to be transferred across populations. There is evidence that progress is being made in this area for prostate cancer specifically, although there is a lot more work to be done (https://elifesciences.org/articles/78304, https://doi.org/10.1371/journal.pcbi.1011990).
“In general, this study fits with others coming out for other diseases, and it is great step forward, but I would say we need research demonstrating the predictive utility of polygenic scores for prostate cancer in a more representative sample before we can start implementing them in the clinical setting.”
Dr Chantal Babb de Villiiers, Senior Policy Analyst at PHG Foundation, said:
“The BARCODE study results contribute valuable insights into the use of polygenic scores for risk stratification of prostate cancer, and how they can supplement risk prediction with known risk factors. The follow-up of the entire cohort will provide crucial data for evaluating the clinical and economic impact of using polygenic scores. Whilst some polygenic scores are showing promise in very specific scenarios, it is important to approach their implementation with caution and ensure thorough validation. We need further research to determine the best combination of these risk factors as well as how to effectively implement stratified screening.”
Professor Rhian Gabe, Professor of Biostatistics and Clinical Trials, Queen Mary University of London (QMUL), said:
“The test evaluated in this high quality study has exciting results in terms of detection, the hopes for an optimal future prostate cancer screening strategy and deserves larger-scale evaluation. Excitingly, this will happen in the TRANSFORM trial of prostate cancer screening where the test will also be evaluated in terms of acceptance, impact on prostate cancer deaths and incidence by comparing it with other promising strategies involving PSA testing and MRI.”
Dr Samuel Lambert, Assistant Professor of Health Data Science, University of Cambridge, said:
“The results of the BARCODE1 study are a major achievement, clearly illustrating the value of targeting prostate cancer screening to individuals defined as high-risk using a polygenic risk score. Targeting screening to the high-polygenic score population identified significant cancers that would not have been detected using existing thresholds, a comparable rate to previous trials targeting screening to individuals with pathogenic BRCA1/2 variants.
“A current limitation is that the polygenic risk score in this study could only be used in individuals of European ancestry due to limitations in the diversity of available genome-wide association study data. This limitation is likely to be overcome in the long term, with data from new studies like Our Future Health in the UK that have prioritised diversity in their recruitment and linked health records to genetics data. Diverse studies like Our Future Health will allow researchers to better identify the variants associated with disease in all ancestries.”
Prof Dusko Ilic, Professor of Stem Cell Sciences, King’s College London (KCL), said:
“Polygenic risk scores (PRS) offer moderate discriminatory power when used alone. The study used a score based on 130 SNPs and showed that men in the top 10% of the PRS distribution had significantly higher risk. However, when added to established factors like age, PSA level, and MRI findings, the predicting clinically significant prostate cancer improved only modestly. Notably, further stratification within the top decile (e.g., 90th vs. 99th percentile) did not significantly improve predictive accuracy, suggesting diminishing returns at extreme PRS levels.
“Furthermore, there is no direct evidence yet that using PRS improves long-term outcomes such as mortality or quality-adjusted life years. Modelling suggests benefit, but empirical confirmation is needed.
“While the results are promising, especially in identifying significant cancers that would otherwise be missed, major caveats remain:
“So, while PRS could supplement existing screening in high-risk individuals, the evidence is insufficient to recommend a standalone screening program based solely on PRS at this time.”
Dr Britta Stordal, Associate Professor in Cancer Research, Middlesex University, said:
“McHugh et al show that through the use of their BARCODE1 genetic risk score they are able to identify men who are at a higher risk of prostate cancer. 74 men had their prostate cancer diagnosed as a result of participating in this clinical trial that would not have been detected with current standard care on the NHS. This work is possible due to extensive previous research into genetic risk for prostate cancer in European populations. A similar risk score for men of Black African or Caribbean ancestry is urgently needed as we know that these men have a much higher prostate cancer risk than those of European ancestry.”
‘Assessment of a Polygenic Risk Score in Screening for Prostate Cancer’ by J.K. McHugh et al. was published in The New England Journal of Medicine at 22:00 UK time Wednesday 9 April 2025.
DOI: 10.1056/NEJMoa2407934
Declared interests
Prof Michael Inouye: Trustee of the Public Health Genomics (PHG) Foundation, Scientific Advisory Board of Open Targets, and research collaborations with AstraZeneca, Nightingale Health, and Pfizer. All of these are not related to the study. It’s also worth noting that, while the study is obviously driven by the Institute of Cancer Research in London, one of the coauthors (Pashayan) is a colleague at Cambridge.
Prof Dusko Ilic: I declare no interest.
Prof Rhian Gabe: I am Co-Lead of the TRANSFORM trial of prostate cancer screening, we are collaborating with Professor Eles to evaluate her PRS test.
Dr Samuel Lambert: No conflicts of interest to disclose.
Dr Britta Stordal: No conflicts of interest to declare.
For all other experts, no reply to our request for DOIs was received.