A new blood test for prostate cancer that offers greater accuracy than prostate-specific antigen (PSA) has been put to the test by researchers at the University of East Anglia (UEA) in collaboration with colleagues at Imperial College London (ICL) and King’s College London.
They said that the test, developed by Oxford BioDynamics in collaboration with UEA, ICL, and Imperial College NHS Trust, could detect prostate cancer with 94% accuracy, significantly better than PSA testing.
The possibility of using such a test for a screening programme was hailed by cancer charities, who lament that PSA testing is not reliable enough for effective screening – which is why there is currently no national screening programme in the UK. According to the NHS, about three-quarters of men with a raised PSA level do not have cancer, whereas around 1 in 7 men who do would have a normal PSA result.
The researchers set out to assess the accuracy of the Prostate Screening EpiSwitch (PSE) test, which uses 3D genomics to detect cancer-specific chromosome conformations in a person's blood sample. Their study, published in Cancers, aimed to determine whether combining the EpiSwitch test with traditional PSA testing would increase overall diagnostic accuracy.
Existing Test Methods Insufficiently Accurate
They evaluated the dual testing methods in a pilot study of whole blood samples from 147 men. One cohort comprised 109 men enrolled in the same team's PROSTAGRAM screening pilot study, which compared the screening value of PSA, ultrasound, and MRI for prostate cancer diagnosis. That found that all three existing tests had similar accuracies – leading to "a high rate of referral for biopsies which often yield no cancer or insignificant disease" – demonstrating the major problem with prostate screening attempts in the past.
Of the 109 men from the PROSTAGRAM cohort, 21 had cancer and 88 acted as cancer-free controls. The team also assessed the test in a second cohort of men from Imperial College NHS Trust, 29 patients with established prostate cancer and 9 cancer-negative controls.
PSE Has 'Remarkable' Accuracy
Results showed an overall accuracy forEpiSwitch of 94% – vastly superior to PSA testing alone. PSA alone at a cut-off of >3 ng/mL showed a low positive predicted value (PPV) of 0.14 and a high negative predicted value (NPV) of 0.93. In contrast, EpiSwitch alone showed a PPV of 0.91 and an NPV of 0.32. Combining PSA and Episwitch tests significantly increased the PPV to 0.81, although reduced the NPV to 0.78. Integrating PSA as a continuous variable (rather than a dichotomised 3 ng/mL cut-off), with EpiSwitch in a new multivariant stratification model, the PSE test yielded a combined PPV of 0.92 and NPV of 0.94 when tested on the independent prospective cohort – a result that the team described as "remarkable".
They said: "When tested in the context of screening population at risk, PSE yields a rapid and minimally invasive prostate cancer diagnosis." They added that: "Due to its high PPV that significantly exceeds current screening modalities – due to its non-invasive nature and low costs – the PSE test can be utilised for both diagnostic and screening purposes, minimising unnecessary referrals for expensive and invasive MRI and/or biopsy testing.
"Further prospective larger scale studies of the new PSE test in a population screening cohort with low cancer prevalence would be an immediate next step in confirming and expanding PSE test utility."
New Test Offers 'Real Benefit' for Both Diagnosis and Screening
Lead author Dmitry Pshezhetskiy, a professorial research fellow at UEA's Norwich Medical School, said: "Prostate cancer is the most common cancer in men and kills one man every 45 minutes in the UK. There is currently no single test for prostate cancer, but PSA blood tests are among the most used, alongside physical examinations, MRI scans, and biopsies. However, PSA blood tests are not routinely used to screen for prostate cancer, as results can be unreliable. Only about a quarter of people who have a prostate biopsy due to an elevated PSA level are found to have prostate cancer. There has, therefore, been a drive to create a new blood test with greater accuracy.
"When tested in the context of screening a population at risk, the PSE test yields a rapid and minimally invasive prostate cancer diagnosis with impressive performance. This suggests a real benefit for both diagnostic and screening purposes."
Dr Jon Burrows, chief executive officer at Oxford Biodynamics, said: "There is a clear need in everyday clinical practice for a highly accurate blood test that can screen men for prostate cancer and accurately identify those at risk, while sparing those who up to now would be subject to unnecessary, expensive and invasive procedures."
Asked by Medscape News UK to comment on the research, Simon Grieveson, assistant director of research at Prostate Cancer UK, said: "Earlier this year, research revealed that over 10,000 men each year are diagnosed too late, when their prostate cancer is incurable.
"That's why we welcome promising new research like this into new possible tests which could help diagnose men accurately and at an earlier stage. However, we now need to see this tested in far greater numbers of men before we can determine just how effective this approach could be.
"We desperately need a screening programme for prostate cancer and Prostate Cancer UK is committed to driving the research and evidence required to make screening a reality and to save thousands of men’s lives."
Cancer Research UK's senior health information manager, Claire Knight, concurred. She told Medscape News UK: "There is no national screening programme for prostate cancer because the current test we have, the PSA test, isn't reliable enough. So, it's encouraging to see more research into new methods, but we need larger, longer-term studies to fully understand how effectively this will work in practice."
The study was funded by Oxford BioDynamics. EH, MS, MD, RP, JG, TN, CK, and AA are employees of Oxford BioDynamics. AA is a company director. Oxford BioDynamics holds patents on the EpiSwitch technology. The remaining authors declared no conflicts of interest.
