Researchers believe that men who inherit a higher cancer risk due to ‘Lynch syndrome’ could benefit from regular PSA testing starting at age 40 to detect early signs of prostate cancer.
Lynch syndrome increases the risk of numerous cancers, the most well-known of which being bowel cancer. It affects 175,000 people in the UK, however, only 5% of those who have it are aware of it.
According to new research, annual PSA testing could detect incidences of prostate cancer up to eight times more frequently in men with Lynch syndrome defects in genes like MSH2 and MSH6 than in men without.
Many of the cancer cases in Lynch syndrome men were ‘clinically significant,’ implying that targeted screening could save lives.
Scientists at London’s Institute of Cancer Research believe that starting annual prostate cancer screening at the age of 40 could lead to earlier diagnosis and treatment in this high-risk cohort of men.
When men with these mutations have disease recurrence, accumulating data suggests that immunotherapies that harness the immune system to combat cancer may be especially beneficial in men with these mutations.
Cancer Research UK funded the new study, which is part of the international IMPACT study,, with additional support from the Ronald and Rita McAulay Foundation, the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust, and the ICR. It was published today (19th October 2021) in The Lancet Oncology.
IMPACT is a study involving 828 men from Lynch syndrome families at 34 sites in eight countries to see if frequent PSA testing is an effective strategy to detect prostate cancer in men who have certain genetic changes that enhance their risk.
Prostate cancer screening isn’t recommended for the general population, but we believe it could benefit some groups of men at high inherited risk. Our new findings show that PSA testing in men with Lynch syndrome is much more likely to pick up life-threatening prostate cancer than in the general population. We think that men with the gene faults causing Lynch syndrome are likely to benefit from regular PSA testing from the age of 40.
Ros Eeles
More than 600 of the 828 males in the study have mutations in the mismatch repair genes MLH1, MSH2, or MSH6, which are linked to Lynch syndrome, a genetic disorder that raises the risk of several malignancies, particularly bowel cancer.
PSA screening is not advised for men in the general population since it has not been proven to be useful, and there are worries that it could lead to over-diagnosis and over-treatment of instances that would not have caused substantial issues otherwise.
However, it may hold more promise for males who have a high hereditary risk. In the current trial, men were given a yearly PSA test, and those with a high PSA were given a biopsy to see if they had prostate cancer.
Annual PSA tests were found to be useful in detecting prostate cancer in males who inherited a mutation in the MSH2 or MSH6 genes. Only one non-carrier out of 210 (0.5%) was diagnosed with prostate cancer, despite the fact that 13 (4.3%) of 305 males with MSH2 gene flaws were diagnosed with prostate cancer.
Four out of 135 MSH6 carriers (3%) were diagnosed with prostate cancer, whereas none of the 177 non-carriers received a prostate cancer diagnosis (0 percent).
Men with the MSH2 gene flaw were eight times more likely than non-carriers to be diagnosed with prostate cancer, and they were diagnosed at a younger age, on average 58 years against 66 years.
Importantly, men with the MSH2 gene flaw had a higher rate of aggressive, possibly life-threatening tumors, with 85% demonstrating ‘clinically significant’ disease compared to none in non-carriers. Overdiagnosis in MSH2 carriers is therefore uncommon.
MSH6 carriers, on the other hand, were detected at an average age of 62 years, with 75% having life-threatening, or ‘clinically significant,’ tumors.
Future screening rounds as part of the IMPACT project will assist scientists to determine the benefits and risks of annual screening in males with MLH1, MSH2, and MSH6 gene changes, so they can determine if the balance is favorable and if screening should be implemented.
There were no tumors discovered in men with MLH1 mutations, another gene linked to Lynch syndrome, and more research is needed to determine whether these men are at a higher risk of prostate cancer and might benefit from targeted screening.
Another five-year follow-up is planned to compare treatment outcomes in these individuals. Following screening rounds and cancer diagnosis will be crucial in assessing whether the 3.0ng/ml PSA threshold utilized in this study is suitable.
Professor Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research in London and Consultant in Clinical Oncology and Oncogenetics at The Royal Marsden NHS Foundation Trust leads the IMPACT project. She said:
“Prostate cancer screening isn’t recommended for the general population, but we believe it could benefit some groups of men at high inherited risk. Our new findings show that PSA testing in men with Lynch syndrome is much more likely to pick up life-threatening prostate cancer than in the general population. We think that men with the gene faults causing Lynch syndrome are likely to benefit from regular PSA testing from the age of 40.”
“Targeted screening has the potential to pick out aggressive prostate cancers at an early stage in men at high inherited risk, increasing their chances of survival. And because cancers in these men are more likely to be aggressive and potentially life-threatening, they would need to have radical treatment. I anticipate that these results, and evidence from our ongoing follow-up work, will influence future national and international screening guidelines for this group of men, with the aim of picking out prostate cancer earlier and potentially saving lives.”
Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said:
“Picking up cancers early, when they are more much likely to be curable, is a vital part of our strategy to improve the lives of cancer patients. Mass screening isn’t a good option in prostate cancer because of the risk of over-diagnosis, but in men who have an increased inherited risk of aggressive disease it makes more sense.”
“This new study suggests that screening with an annual PSA test could lead to early detection of significant numbers of prostate cancer cases in men with inherited Lynch syndrome, leading to earlier treatment and increased survival. It’s an exciting example of the potential of genetics research and how it can impact our lives.”
Professor Charles Swanton, Cancer Research UK’s Chief Clinician, said:
“Overall the PSA test is not reliable enough to be used as a national screening programme for prostate cancer. But this research shows it could have promise as a test for people who are at higher risk of the disease. What’s needed now is research to find out how early the test can diagnose prostate cancer in this group and like any screening programme, the potential harms and survival benefits would need to be investigated before it could be rolled out.”
“We don’t currently recommend the PSA test for high risk men who are asymptomatic, but if you’re concerned about your cancer risk it’s important you speak to your doctor.”
In 2016, while getting treatment for skin cancer, Paul Cunningham, 67, of Plymouth, found he had Lynch Syndrome. He was diagnosed with prostate cancer six weeks ago. He said:
“I found out I had Lynch Syndrome when I went into surgery to have my skin cancer removed, and the nurse noticed I was also undergoing treatment for bowel cancer and referred me on. My immediate reaction was doom and gloom with so many family members dying of cancer, I’d always assumed I would too but I talked it through with the genetic counseling team, and that was really helpful.”
“Having Lynch Syndrome is a double-edged sword. No one wants to be at higher risk of cancer, but because doctors are aware of my risk, it means I’ve been fast-tracked and referred where I might not have been otherwise. Four weeks ago, I was diagnosed with prostate cancer after having my annual PSA check through the IMPACT study, and I’m now waiting for a date for surgery.”
“The consultant said that, if I hadn’t been on the study, they probably would have just kept an eye on me, but thanks to the screening, they’ve managed to catch my cancer early. I hope these findings will go on to help others in my position. For now, I’m just looking forward to finishing treatment and spending more time with my beautiful wife.”
