.tmb-propic-md.jpg?Culture=en&sfvrsn=c25d2b2f_9 "Professor Louis Chesler (Profile pic)")
Experts at The Institute of Cancer Research, London, have responded to the draft recommendation from the National Screening Committee (NSC) to implement a targeted prostate cancer screening programme for men with a confirmed BRCA1 and BRCA2 variant.
The draft recommendation, which will now go to a public consultation for three months, has recommended that men with a confirmed BRCA1 and BRCA2 variant should have a PSA test every two years, from age 45 to age 61.
Vital step towards reducing deaths
Professor Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research, London, said the move would represent a vital step towards reducing deaths from prostate cancer:
"We're very pleased to see that the National Screening Committee has recommended that PSA testing for men who carry BRCA1 and BRCA2 mutations is introduced. This recommendation is based on research led by my team at The Institute of Cancer Research, which showed that these men face a significantly higher risk of developing prostate cancer and are more likely to experience aggressive forms of the disease. PSA testing picks up cancers at an earlier stage, when they are easier to treat – which will ultimately save lives."
However, Professor Eeles added that cancers could be missed if screening only occurs every two years. Data from the IMPACT screening trial showed that cancers were picked up in each year that BRCA2 carriers were tested, and in all but one of the five consecutive years that BRCA1 carriers were tested.
Professor Eeles added:
"We therefore recommend annual screening, rather than every two years – to avoid the risk that an aggressive cancer could be allowed to grow unchecked for a whole year.
"The NSC has recommended that BRCA carriers be tested from the age of 45 to 61. Our research offered screening for cancers for a wider age range, and I am concerned that if you stop screening at 61 years of age, a large number of cancers will be missed. Of the cancers we found in the IMPACT trial, 49 per cent of them in BRCA1 carriers were between the ages of 61-69, and for BRCA2 carriers 42 per cent were in this age group. We are urging regulatory bodies to act on the evidence, offering all men with a BRCA1 or BRCA2 mutation from the age of 40 – up until the age of 69 – annual PSA testing. This has been the recommendation in Europe, to date, for BRCA2 carriers.
"Today’s recommendation is indeed a vital step toward reducing deaths from prostate cancer. However, unless BRCA testing is expanded, there are thousands of men who will miss out on this screening programme. The NHS needs to offer BRCA testing to more men, starting by offering testing to male relatives of BRCA carriers."
Discovering the BRCA2 gene
The Institute of Cancer Research (ICR) has played a pivotal role in providing the evidence for today’s decision.
It was 30 years ago this year that researchers at the ICR discovered the BRCA2 gene, which plays an essential role in protecting against cancer. Inherited faults in this gene, and in BRCA1, can significantly increase the risk of breast, ovarian, prostate and pancreatic cancers.
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BRCA carriers are at greater risk of prostate cancer
ICR researchers led the IMPACT trial which, in 2019, reported findings that annual PSA testing picked up prostate cancers more often, at a younger age and in more dangerous forms in men with BRCA2 mutations than in non-carriers. The team have been calling for regular PSA testing for these men from the age of 40, ever since.
This year, results from the trial showed that men with BRCA1 mutations should also be offered an annual PSA test. These men are more than three times as likely, compared with non-carriers, to have aggressive prostate cancers that are likely to grow and spread quickly.
Expanding access to BRCA testing
While the decision to screen BRCA carriers for prostate cancer is a vital step toward ensuring that those at greatest risk receive the earliest interventions, there are currently thousands of men who will not know they have a BRCA variant.
There are up to 32,000 men in the UK aged 45-69 who could have the BRCA variant, but testing to date has focused on women, where the evidence around higher cancer risk and mitigations have been clearer for decades.
The NHS needs to expand BRCA testing, and the ICR has been leading the way at improving capacity. The ICR’s BRCA-DIRECT study trialled an innovative patient-centred digital pathway, to reduce the turnaround time for results. Using a new online platform, participants could access their pre-test information, give consent, provide a saliva sample and receive their results in their own time.
Professor Clare Turnbull, Professor of Translational Cancer Genetics at The Institute of Cancer Research, London, said:
"Individuals can only access a BRCA test via the NHS if eligible based on their personal or family history of cancers, as per the Genomic Medicine Service National Test Directory. Only individuals who have had ovarian cancer or particular forms of breast, prostate or pancreatic cancer are eligible, or those who are unaffected but have a close, strong family history of these cancers."
Leading trials to identify markers for other high-risk groups
Black men are also at an increased risk of developing prostate cancer. The NSC has not recommended screening for this group, as they state that there is currently a lack of data.
Researchers at the ICR have identified new genetic variants that could explain some of this increased risk and have built a genetic profile of prostate cancer risk that is applicable to men of diverse ancestries.
At the moment, the PSA test is not a good enough marker of increased risk of disease in this group of men, as they have a naturally higher PSA level than men of European ancestry.
The ICR is leading the PROFILE trial, which is carrying out targeted screening for Black men, men with a family history of prostate cancer, and those with genetic alterations including BRCA. Recruitment is still open for the study, and if you fit into one of these groups, the researchers are inviting people to sign up. The study involves MRI scans, a biopsy and biological samples, to look for new markers that we hope will be better at detecting prostate cancer than a PSA test.
In addition, the ICR is a co-lead on the TRANSFORM trial – the biggest prostate cancer screening study in a generation. The trial will test the most promising prostate cancer screening techniques available – including a saliva test to assess genetic risk of the disease – to identify the safest, most accurate and most cost-effective way to screen men. The TRANSFORM trial will ensure that at least 1 in 10 men invited to take part are Black, in order to build an evidence base for the NSC to consider.
Professor Ros Eeles said:
"We know that Black men are also at a higher risk of developing prostate cancer. At the moment, the PSA test is not a good enough marker of increased risk of disease in this group of men. This is why we at the ICR are leading the PROFILE trial, to look for new markers that we hope will be better at detecting prostate cancer.
"We are also co-leading the TRANSFORM trial, which will compare different methods of detecting prostate cancer using MRI and genetics – and which aims to recruit more Black men than any previous trials, in order to build this evidence base. We’re looking forward to feeding into the consultation process in the coming months."
