.tmb-propic-md.jpg?Culture=en&sfvrsn=c25d2b2f_9 "Professor Louis Chesler (Profile pic)")
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A spit test, where a sample can be collected at home, is more accurate at identifying future risk of prostate cancer for some men than the current standard PSA blood test, a new study reports.
Results of the BARCODE 1 study, which have been published in the New England Journal of Medicine, calculated the risk of prostate cancer from DNA extracted from saliva – called a polygenic risk score. For the men with the highest risk score, the study found this to be a better tool than the blood test which measures levels of a protein called prostate-specific antigen (PSA), which can be elevated if someone has prostate cancer.
The current PSA test is used to identify men who are at higher risk of prostate cancer – due to their age or ethnicity – and men presenting with symptoms. Men with a high PSA result will be sent for further tests to detect cancer.
The PSA test falsely indicates prostate cancer in men three out of four times and detects cancers which grow so slowly they are unlikely to ever be life-threatening – meaning that men may undergo unnecessary MRI scans, invasive biopsies, and treatments.
Trialling the new DNA test
Researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust trialled their new DNA test which looks for genetic variants linked to prostate cancer.
For the men with the highest genetic risk, the test falsely identified fewer people with prostate cancer than the PSA test, picked up people with cancer who would have been missed by the PSA test alone, and picked up a higher proportion of the aggressive cancers than the PSA test. The test also accurately identified men with prostate cancer that was missed by an MRI scan.
The research received funding from the European Research Council, the Bob Willis Fund, Cancer Research UK, The Peacock Trust and the National Institute for Health and Care Research (NIHR) Biomedical Research Centre (BRC) at The Royal Marsden and The Institute of Cancer Research (ICR).
The study calculated the polygenic risk score (PRS) of 6,142 European men recruited from their GP surgeries, aged 55-69 – an age at which risk of prostate cancer is increased. The score is based on 130 genetic variations in the DNA code that are linked to prostate cancer, and it was developed by studying the DNA of hundreds of thousands of men.
Identifying the men at highest risk
The men with the highest 10 per cent of risk scores – who have inherited many of these variants and are most at risk of developing the disease – were invited to further screening.
Following an MRI and prostate biopsy, 187 (40 per cent) of the 468 men with a high PRS were diagnosed with prostate cancer. This compares with the PSA test, in which 25 per cent of men with a high PSA level will actually have prostate cancer.
Of these 187 men, 118 (63.1 per cent) had a PSA level below 3.0ug/L, which is considered ‘normal’ and would usually indicate that no further screening is required.
Previous studies have shown that the PSA blood test picks up many people who have cancers that are not of concern and would not require treatment. The PRS saliva test identified a higher proportion of aggressive cancers – which are fast growing and likely to spread – than the PSA test. Of the 187 cancers detected, 55.1 per cent were aggressive cancers compared with 35.5 per cent identified by a PSA test, in a recent study.
More accurate than an MRI scan
The PRS test is also more accurate than an MRI scan for these men with high genetic risk, as 125 men (66.8 per cent) had prostate cancer confirmed by a biopsy that was not detected by the MRI.
As the PSA test is often inaccurate, the PRS saliva test could offer an additional screening tool to be offered to men at higher risk of prostate cancer, or those presenting with symptoms. Future research will follow-up the men with high PRS scores to monitor if they go on to develop prostate cancer.
Since the BARCODE 1 study began, an international research team has identified more risk variants for men of Asian and African ancestry, and the ICR team have developed an updated version of the test, called PRODICT®, which can be used in this population. They have launched a new study using PRODICT®, which includes more genetic variants that indicate cancer than the original test.
Saving the NHS £500million a year
The £42million TRANSFORM trial launched by the charity Prostate Cancer UK, which is being partly led by the team at the ICR, will directly compare the saliva test to the PSA blood test and MRI scan, to assess whether those with a low genetic risk may benefit from an alternative screening tool.
The research team estimates that the spit test could identify up to 12,350 people earlier, saving the NHS around £500 million a year.
Professor Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research, London, and Consultant in Clinical Oncology and Cancer Genetics at The Royal Marsden NHS Foundation Trust, said:
“With this test, it could be possible to turn the tide on prostate cancer. We have shown that a relatively simple, inexpensive spit test to identify men of European heritage at higher risk due to their genetic makeup is an effective tool to catch prostate cancer early. Building on decades of research into the genetic markers of prostate cancer, our study shows that the theory does work in practice – we can identify men at risk of aggressive cancers who need further tests and spare the men who are at lower risk from unnecessary treatments.
“We’re now excited to be rolling out our updated test, PRODICT®, to diverse populations – as Black men are twice as likely to develop prostate cancer – and younger groups, as those with a genetic predisposition are more likely to be diagnosed at younger ages.
“We are also currently comparing the saliva test to other potential screening options, as part of the TRANSFORM trial, to assess the most cost-effective and accurate way to screen men for prostate cancer.”
Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said:
"Early detection of cancers significantly increases the chance of a cure. With prostate cancer cases expected to double by 2040, it's crucial to establish a robust way of picking up clinically significant cases of prostate cancer at an earlier stage. The current PSA test often leads to unnecessary treatments and, more concerningly, fails to detect some cancers. There is an urgent need for a better screening test. This research represents a promising advancement towards that goal and underscores the life-saving potential of genetic testing."
Katie Willis, daughter of Bob Willis, former England Cricket Captain who died from prostate cancer, and co-founder of The Bob Willis Fund, said:
"The Bob Willis Fund has proudly supported this important work for the past three years. The potential of genetics to significantly improve early diagnosis of prostate cancer in men is huge. Although the PSA test is effective for some, it did not work for Dad. If this research can save even one life, establishing the Fund would have been a worthwhile endeavour for our family. We commend Professor Eeles and her team at the ICR for their outstanding efforts and look forward to our continued partnership together.”
Naser Turabi, Director of Evidence and Implementation at Cancer Research UK, said:
“Prostate cancer is the second biggest cancer killer of men in the UK, taking around 12,000 lives a year. Right now, there’s no reliable method to detect aggressive prostate cancer, but this study brings us a step closer to finding the disease sooner in those people who need treatment.
“It’s encouraging to see that genetic testing might help to guide a more targeted approach to screening based on someone’s risk of developing prostate cancer. More research is now needed to confirm if this tool can save lives from the disease so that it can be rolled out to improve diagnosis.”
CASE STUDY – ‘Because of this study, two lives have been saved in my family’
Dheeresh Turnbull, 71, from Brighton, was diagnosed with prostate cancer through the BARCODE 1 study four years ago, after receiving an unexpected letter through the door from his local GP inviting men over 60 to take part in the research trial.
He said: “Once I agreed to go onto the trial, I underwent some tests. When my results came back, I was sent a letter to say I was in the top genetic risk category, and I was referred to The Royal Marsden. Further tests revealed that I had prostate cancer, and I was told that a relatively low PSA score can still be harbouring a life-threatening tumour if the person falls in a certain genetic group. I have no family history of prostate cancer, so I was completely shocked. I would never have been diagnosed at this stage if I hadn’t joined the trial.
"Because the saliva test revealed that I had a high genetic risk of developing the disease, my younger brother, who would have been too young to join the study directly, signed up and discovered that he also had an aggressive tumour in the prostate. It’s incredible to think that because of this study two lives have now been saved in my family.”