Targeted prostate cancer screening can benefit men with inherited cancer syndromes

Lynch syndrome increases the risk of a variety of cancers, the most famous of which is bowel cancer

A new study found that the annual PSA test found that men with Lynch syndrome genes (MSH2 and MSH6 gene defects) are eight times more likely to develop prostate cancer than men without Lynch syndrome genes

Many male cancer cases with Lynch syndrome are "clinically significant", which shows that targeted screening has the potential to save lives

Scientists at the London Cancer Institute believe that targeted screening every year from the age of 40 may enable this high-risk group of prostate cancer to be diagnosed and treated earlier

Identifying patients with Lynch syndrome can also guide their treatment, because there is increasing evidence that immunotherapies that use the immune system to attack cancer may be particularly effective when patients with these mutations relapse

This new research is part of the international IMPACT research, published in the journal The Lancet Oncology, funded by Cancer Research UK, and supported by the Ronald and Rita McCauley Foundation, Royal Marsden National Additional support from the NIHR Biomedical Research Center and ICR Trusted by the Medical Service System Foundation

IMPACT surveyed 828 men with Lynch syndrome families from 34 centers in 8 different countries to assess whether regular PSA testing can effectively detect prostate cancer in men who carry certain genetic variants that increase the risk of the disease.

Among the 828 men who participated in the study, more than 600 had defects in the so-called mismatch repair genes MLH1, MSH2, or MSH6, which are related to Lynch syndrome

PSA screening is not recommended for men in the general population because it has not been proven to be beneficial, and there are concerns that it may lead to overdiagnosis and overtreatment of cases that do not cause major problems

But for men with a higher genetic risk, it may bring more hope

For MSH6 carriers, 4 out of 135 men (3%) were diagnosed with prostate cancer, while none of the 177 non-carriers was diagnosed with prostate cancer (0%)

Men with a defect in the MSH2 gene are 8 times more likely to be diagnosed with prostate cancer than non-carriers, and are diagnosed at a younger age-the average age is 58 years, not 66

Crucially, compared with men who do not carry the MSH2 gene, men with MSH2 gene defects are more often suffering from aggressive and potentially life-threatening tumors, and 85% of them show "clinically significant" diseases

At the same time, the average age of MSH6 carriers is 62, and 75% of them have life-threatening or "clinically significant" tumors

As part of the IMPACT study, future screenings will help determine the benefits and harms of annual screening of men with genetic alterations in MLH1, MSH2, and MSH6, so that experts can conclude if this balance is beneficial , If these groups should be screened

The study found no cancer in men with mutations in MLH1 (another gene associated with Lynch syndrome).

Researchers are planning another five-year follow-up to compare the treatment results of these patients
.
Follow-up screening and cancer testing are also important to determine whether the 3.
0ng/ml PSA threshold used in this study is appropriate
.

Professor Ros Eeles is a professor of tumor genetics at the London Cancer Institute and a clinical oncology and tumor genetics consultant for the Royal Marsden National Medical Service Foundation.
He led the IMPACT research
.
she says:

"Prostate cancer screening is not recommended for the general population, but we believe that it may benefit certain groups of men with a high genetic risk
.
" Our new findings indicate that PSA testing for Lynch syndrome patients is better than the general population.
It is possible to develop life-threatening prostate cancer
.
We believe that men with genetic defects that cause Lynch syndrome may benefit from regular PSA testing starting at the age of 40
.

"Targeted screening may identify aggressive prostate cancer among early men with a high genetic risk, thereby increasing their chances of survival
.
Because these people's cancers are more likely to be aggressive and potentially life-threatening.
, They need thorough treatment
.
I expect that these results, and the evidence of our ongoing follow-up work, will affect future national and international screening guidelines for this population, with the goal of detecting prostate cancer earlier and possibly saving it Life
.
"

Professor Christian Hailin, Chief Executive Officer of the London Cancer Institute said:

"Detecting cancer at an early stage when it is more likely to be cured is an important part of our strategy to improve the lives of cancer patients
.
For prostate cancer, large-scale screening is not a good option because it carries the risk of overdiagnosis, but for those who are genetic It is more meaningful for men with a higher risk of aggressive disease
.
This new study shows that a PSA examination every year can detect a large number of cases of prostate cancer in men with hereditary Lynch syndrome early.
Treatment to improve survival
.
This is an exciting example of the potential of genetic research and how it affects our lives
.
"

Professor Charles Swanton, Chief Clinician of Cancer Research UK, said:

"In general, the PSA test is not reliable enough to be used as a nationwide prostate cancer screening program
.
But this study shows that it has promise as a method to detect high-risk groups
.
What needs to be done now is research, To find out how early this test can diagnose prostate cancer in this group, like any screening program, it needs to be investigated for its potential harm and survival benefits before it can be promoted
.
"

"We currently do not recommend PSA testing for asymptomatic high-risk men, but if you are concerned about your risk of cancer, it is important to communicate with your doctor
.
"

Paul Cunningham, 67, from Plymouth, discovered that he had Lynch syndrome when he was treated for skin cancer in 2016
.
Six weeks ago, he was diagnosed with prostate cancer
.
He said:

"When I went for skin cancer removal surgery, I found out that I had Lynch syndrome.
The nurse noticed that I was also undergoing treatment for bowel cancer and recommended me to undergo surgery
.
My first reaction was despair and frustration— With so many family members dying of cancer, I always thought I would die too-but I discussed this with the genetic counseling team, which was really helpful
.

"Lynch syndrome is a double-edged sword
.
No one wants a higher risk of cancer, but because the doctor is aware of my risk, it means that I am being followed up quickly and transferred to other situations where it may not appear.
place
.
Four weeks ago, I conducted an annual PSA check through the IMPACT study, she was diagnosed with prostate cancer, and now I'm waiting for surgery date
.

"The consultant said that if I had not participated in this study, they might have been staring at me, but thanks to the screening, they had managed to detect my cancer in advance
.
I hope these findings will continue to help others in my place.

.
Now, I just want to finish the treatment and spend more time with my beautiful wife
.
"

Journal Reference :

1. Elizabeth K Bancroft et al.
   A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study .
   The Lancet Oncology , 2021; DOI: 10.
   1016/S1470-2045(21)00522 -2