Researchers have helped develop a new blood test to detect prostate cancer with greater accuracy than current methods, the Prostate Screening EpiSwitch (PSE) blood test being 94% accurate, and beating the currently used prostate-specific antigen (PSA) blood test.
The research team says the new test shows significant potential as an accurate and rapid cancer screening diagnostic.
The test was developed by Oxford Biodynamics in collaboration with the University of East Anglia, Imperial College London and Imperial College NHS Trust.
Professor Dmitry Pshezhetskiy, from 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 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.”
The UEA team evaluated the new PSE test, which combines the traditional PSA test with an epigenetic EpiSwitch test, in a pilot study involving 147 patients, and published in the journal Cancers.
They compared its results with those of the standard PSA test, and found that PSE significantly enhances overall detection accuracy for at-risk men.
Pshezhetskiy said: “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, CEO at Oxford Biodynamics, said: “There is a clear need in everyday clinical practice for a highly accurate blood test to 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.”
Study details
Circulating Chromosome Conformation Signatures Significantly Enhance PSA Positive Predicting Value and Overall Accuracy for Prostate Cancer Detection.
Dmitri Pchejetski, Ewan Hunter, Mehrnoush Dezfouli, Matthew Salter, Ryan Powell, Jayne Green, Tarun Naithani, Christina Koutsothanasi, Heba Alshaker, Jiten Jaipuria, Martin Connor, David Eldred-Evans, Francesca Fiorentino, Hashim Ahmed, Alexandre Akoulitchev, Mathias Winkler.
Published in Cancers on 29 January 2023
Summary
Prostate cancer occurs in one out of six men during their lifetime. Because its symptoms are not specific, it is often diagnosed late. The widely used prostate-specific antigen (PSA) blood test does not have sufficient accuracy, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance in some men with cancer. We have developed an epigenetic test for prostate cancer that detects cancer-specific chromosome conformations in the blood of the patient. In this study, we combined this epigenetic test with the PSA test and used two cohorts of patients to determine whether they have better diagnostic accuracy when used together. Our results demonstrate that the new combined test (termed PSE test) allows significant increase in prostate cancer detection compared to PSA or epigenetic test alone. This new PSE test is accurate, rapid, minimally invasive, and inexpensive. If successful in larger trials, it may significantly improve prostate cancer diagnosis.
Abstract
Background
Prostate cancer (PCa) has a high lifetime prevalence (one out of six men), but currently there is no widely accepted screening programme. Widely used prostate specific antigen (PSA) test at cut-off of 3.0 ng/mL does not have sufficient accuracy for detection of any prostate cancer, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance in some men with PCa. We identified circulating chromosome conformation signatures (CCSs, Episwitch® PCa test) allowing PCa detection and risk stratification in line with standards of clinical PCa staging. The purpose of this study was to determine whether combining the Episwitch PCa test with the PSA test will increase its diagnostic accuracy.
Methods
n = 109 whole blood samples of men enrolled in the PROSTAGRAM screening pilot study and n = 38 samples of patients with established PCa diagnosis and cancer-negative controls from Imperial College NHS Trust were used. Samples were tested for PSA, and the presence of CCSs in the loci encoding for of DAPK1, HSD3B2, SRD5A3, MMP1, and miRNA98 associated with high-risk PCa identified in our previous work.
Results
PSA > 3 ng/mL alone showed a low positive predicted value (PPV) of 0.14 and a high negative predicted value (NPV) of 0.93. EpiSwitch alone showed a PPV of 0.91 and a NPV of 0.32. Combining PSA and Episwitch tests has significantly increased the PPV to 0.81 although reducing the NPV to 0.78. Furthermore, integrating PSA, as a continuous variable (rather than a dichotomised 3 ng/mL cut-off), with EpiSwitch in a new multivariant stratification model, Prostate Screening EpiSwitch (PSE) test, has yielded a remarkable combined PPV of 0.92 and NPV of 0.94 when tested on the independent prospective cohort.
Conclusions
Our results demonstrate that combining the standard PSA readout with circulating chromosome conformations (PSE test) allows for significantly enhanced PSA PPV and overall accuracy for PCa detection. The PSE test is accurate, rapid, minimally invasive, and inexpensive, suggesting significant screening diagnostic potential to minimise unnecessary referrals for expensive and invasive MRI and/or biopsy testing. Further extended prospective blinded validation of the new combined signature in a screening cohort with low cancer prevalence would be the recommended step for PSE adoption in PCa screening.
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