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Study: Prostate cancer screening may benefit people with Lynch syndrome

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Contents

Study findings Guidelines
Strengths and limitations Clinical trials
What does this mean for me? Related resources
Questions for your doctor Peer support
   

STUDY AT A GLANCE
What is this study about?

The IMPACT trial is an international study looking at how well (prostate-specific antigen) screening for cancer works for people with inherited mutations. This report shared early results of screening in people with .

Why is this study important?

Globally, cancer is a leading cause of death in men, and researchers are beginning to recognize the importance of identifying genetic mutations that increase the risk of this disease.

is caused by an inherited mutation in an , , , or gene. This syndrome increases a person’s risk for colorectal, endometrial, and other cancers. Some research suggests that people with are also at increased risk for cancer and possibly for more aggressive cancer.

However, no studies have looked at whether screening for cancer among people with helps to find the disease in its early stages when it is most treatable. The goals of the IMPACT trial are to better understand the risk of cancer in men with and to determine whether screening with a test can detect early cancer.

Study findings

The IMPACT trial included 644 men ages 40-69 with an inherited mutation in an , or gene.  

Participants were screened for cancer with a blood test when they enrolled in the study. Researchers recommended biopsy for men whose levels were above 3.0 ng/mL. Biopsy samples were then classified based on pathology (visual appearance and presence or absence of cancer cells) as benign (no cancer cells) or high-, intermediate- or low-risk cancers.

Results from participants with were compared to results from age-matched people without an inherited mutation.

screening identifies cancer more often among people with MHS2 and mutations.

  • Among participants (men with or without ), 18 (1.9%) were diagnosed with cancer.
  • Tenfold more people with a mutation in a gene (17 of 643, 2.6%) were diagnosed with cancer than those who were age-matched and in the control group without a mutation (1 of 318, 0.3%).
  • People with an or MSH 6 mutation had similar rates of cancer (4.3% and 3.0%, respectively).
  • No one with an mutation had cancer.
     
  Participants with an inherited mutation Participants without an inherited mutation*
Gene cancer Total % cancer Total %
All 12 643 2.6% 1 318 0.3%
13 305 4.3%      
4 134 3.0%      
0 03 0%      

 

 

 

 

 


*Participants without an inherited mutation for a particular gene were age-matched to a participant with an inherited mutation to control for other factors related to age.

It is important to note that this initial screening was done at the beginning of the IMPACT trial. The study is designed to screen participants for five years and follow up on cancer results for 10 years, and will likely detect additional cancer during that time.

cancers identified by screening among people with are often high-risk cancers

Of the 17 people with diagnosed with cancer, most (11 of 17, 65%) had aggressive, high-risk cancers.

  • 59% of people with an or mutation had high-risk cancers.
  • The only person without a mutation who had cancer had low-risk cancer.
    Pathology of cancer
Gene All cancers High-risk Intermediate-risk Low-risk
13 7 (54%) 3 (23%) 3 (23%)
4 3 (75%) 0 1 (25%)
or 17 10 (59%) 3 (18%) 4 (23%)
No mutation 1 0 0 1 (100%)

 

 

 

 

 


The results from this first round of screening in people with show that screening using levels and follow-up biopsies is an effective way to detect cancer, especially those that are high-risk and aggressive and could be life-threatening. This study is ongoing—all participants will be screened annually for at least five years and followed for at least 10 years.

Strengths and limitations

Strengths

  • This is a large, , international study enrolling men in eight countries. It is the largest study of men with who are screened for cancer and followed up in a clinical trial. The results are expected to be more reliable due to the study size.
  • This is the first study to examine the effectiveness of screening for cancer in people with .
  • The results confirm previous studies that found that people with (specifically those with a mutation in and ) are at increased risk for cancer and an aggressive form of the disease.

Limitations

  • This study looked at people with inherited mutations specifically in genes (, and ). It did not include people with an inherited or mutation.
  • No people with mutations were included. However, mutations in cause cancer in the way they affect the gene. Men with mutations would likely have similar risks and results as men with mutations. 
  • Because no people with a mutation were included, this study does not clarify the risks for cancer nor the benefit of testing in men with this mutation.
  • Few cancers were diagnosed during this first initial screening; therefore the documented rate of cancer is less reliable. Additional data is needed to confirm these results. Because this reports the cancer status of participants as they enter the study (their first screening), little time has passed. More cases are expected to be diagnosed in time and as a result of additional screening.
  • Because most men (94%) in the study were of European ancestry, these conclusions may not apply as well to people of other ancestries.

What does this mean for me?

If you have a known mutation in an or gene, you may benefit from testing to screen for cancer. Although people with mutations were not included in the study, their cancer risk is believed to be similar to people with an gene mutation, and they may therefore also benefit from testing. If you have a family history of cancer but you do not know if you have an inherited mutation in a gene that increases your risk of cancer, genetic counseling and testing might help you determine if screening is right for you.

Even though this early research supports using screening for cancer in men with and mutations, national guidelines do not yet include this recommendation. Current guidelines suggest that people with mutations speak with their doctor about the benefits and risks of screening for cancer and consider yearly testing and digital rectal exam beginning at age 40. Not all insurance providers cover the cost of screening.

Reference

Bancroft EK, Page EC, Brook MN, et al.  A prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international study. Lancet Oncology 2021; 22: 1618–31. Published online October 19, 2021.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 11/10/22

This article is relevant for:

People with Lynch syndrome

This article is also relevant for:

People with a genetic mutation linked to cancer risk

People with a family history of cancer

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IN-DEPTH REVIEW OF RESEARCH

Study background

is caused by an inherited mutation in one of the mismatch repair genes—, , , or —which are associated with increased risk of colorectal, endometrial and ovarian and other cancers. Growing evidence suggests that men with have a slightly increased risk of cancer, but no studies have yet examined whether this group might benefit from screening for the disease.

The Institute of Cancer Research in the UK started the IMPACT trial (Identification of Men with a genetic predisposition to Cancer). This research asks whether screening men with a high genetic risk for cancer is effective and leads to improved survival.

The IMPACT study includes a large group of men with who are screened and followed for cancer. Two other studies in the US are also looking at screening in people with , which will add important information to the IMPACT study.

This is the first study to examine the usefulness of screening for cancer in people with . This report summarizes initial findings from participants at the time of entry to the study.

Researchers of this study wanted to know

Researchers of this study wanted to look at the usefulness of the (prostate-specific antigen) test for detecting cancer. They also wanted to determine how often people with are diagnosed with cancer and how aggressive their cancer was at the time of diagnosis.

Populations looked at in this study

Men ages 40-69 who had genetic testing for a mutation in an MSH1, or gene were eligible for this study. Individuals with an inherited mutation in one of these genes and age-matched people without an inherited mutation were included.

  • The average age of participants was 52.8 years old.
  • The majority of participants reported European ancestry (94% European ancestry, 1% African or Caribbean ancestry, 4% Asian ancestry, 1% mixed ancestry and 1% unknown ancestry).
  • Education level varied: 20% had a technical or vocational qualification and 41% were university graduates.
  • 19% had a family history of cancer.
  • 22% had previous urinary symptoms.
  • 38% had a previous test.

Study design

From 2012 to 2020, 828 men were recruited for the study. Of those, 644 had a mutation in one of the mismatch repair genes (, or ) and 184 did not. To boost the sample size in the group without an inherited mutation, the researchers also included 134 people without mutations who participated in the IMPACT trial. For comparison, each person who tested positive for an inherited mutation was matched to a similarly aged person who did not have that mutation.

Researchers tested participants for blood levels. or men whose levels were above a threshold of 3.0 ng/mL, researchers recommended that they have a biopsy.

Biopsy samples were then classified based on pathology( including Gleason score, T score, N/M and other visual appearance) as benign (no cancer cells) or high-, intermediate- or low-risk cancers. If the biopsy indicated cancer was high risk (having features associated with a likelihood of spreading and being life-threatening), the participants were offered treatment according to current guidelines. If pathologists detected low-risk cancer, participants received an and a second biopsy after three to six months.

Researchers compared how often cancer was diagnosed among participants with a mutation to those without a mutation.

This study is ongoing. Researchers will continue to screen participants yearly for at least five years and follow up on cancer diagnosis for at least 10 years.

Study findings

In this study, 56 men (6%) had prostate-specific antigen levels above 3.0 ng/L after initial screening, prompting a referral for a biopsy. Of these individuals, 35 consented to have a biopsy.

  • Among the 18 men (51%) who underwent biopsies and received a cancer diagnosis:
    • 13 (4.3% of total cohort) had an inherited mutation. This is a statistically significant difference.
      • The average age at diagnosis was 58 years.
    • 4 (3.0% of total cohort) had an inherited mutation. This is a statistically significant difference.
      • The average age at diagnosis was 63 years.
    • 1 participant without an inherited mutation had cancer. His age at diagnosis was 66 years.
  • 11 of 13 (85%) individuals with an mutation had tumors that were classified as high-risk cancers (n=8) or intermediate risk (n=3).
  • 3 of 4 (75%) individuals with an mutation had tumors that were classified as high-risk cancer (n=3).
  • The cancer found in the individual who was in the control group was low risk and not clinically significant (treatment would not have an effect).
  • Only 3 of 18 (17%) individuals diagnosed with cancer reported urinary symptoms.

These findings support previous research indicating that people with , especially those with mutations in an or gene, are at increased risk for cancer and are more likely to have aggressive forms of the disease. More than three-quarters of the tumors among carriers and carriers were clinically significant (treatment would have an effect), supporting the idea that the prostate-specific antigen test is useful for detecting high-risk cancers and would not result in for this group.

Strengths and limitations

Strengths

  • This trial is an international collaboration among 34 genetic and urology clinics in eight countries. It is the largest cohort of men with who have been screened for cancer and were followed in a clinical trial.
  • This is the first study to examine the usefulness of cancer screening in people with .
  • This study compared levels and cancer among age-matched people without mutations to those with mutations. This design allows the researchers to determine whether cancer cases are found more frequently among those with and whether the of cancer is riskier.

Limitations

  • Few cancers were diagnosed during this study. Future screening data from the ongoing IMPACT study and other similar studies are needed to confirm and strengthen these results.
  • Follow-up data is not available yet for these participants, so the impact of screening on survival is not known.
  • Most men (94%) were of European ancestry, so the results may not be generalizable to non-European populations.
  • No people with mutations were included. However, given the mechanism by which mutations in affect the gene function, researchers predict that men with an mutation would have similar results as men with an mutation.  
  • Because no one with a mutation was included, this study does not clarify the risks for cancer nor the benefit of testing in men with this mutation.

Context

is associated with an increased risk of colorectal, endometrial, ovarian, stomach, small bowel, ureter and kidney cancers. Research over the last decade has also pointed to an increased risk for other cancers, including cancer. Other studies have found contradictory results with no increased risk of cancer for people with . However, few studies have examined risk based on mutations in specific genes.

The first screening round from the IMPACT trial confirms that is associated with an increased risk of cancer and that some mutations carry more risk than others. This study supports previous studies showing that a mutation in the gene conveys a greater risk of cancer in people with .

screening is the most effective cancer . However, its limitations have been well documented. Some professional groups do not support routine screening due to overdetection and treatment because it leads to too many "" results, meaning suspicious levels even though no cancer is found. However, this study suggests that levels can help identify people with cancer among those with higher risk, including those with an inherited mutation.

Based on the results of the previous IMPACT study in people with mutations, the NCCN updated its guidelines to include annual prostate-specific antigen screening for men with a mutation beginning at age 40. If researchers find similar results in people with , the NCCN guidelines for this population may be updated as well.

Conclusions

Initial results for people with enrolled in the IMPACT trial confirm that individuals with an inherited mutation in or have an increased risk for cancer. These findings also support the use of prostate-specific antigen testing in people with to detect , aggressive disease.

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posted 11/10/22

Expert Guidelines
Expert Guidelines

The NCCN suggests that individuals with inherited mutations linked to talk with their doctor about the benefits and risks of screening beginning at age 40. Those people who elect to have screening should consider having yearly screenings rather than every other year.

Updated: 11/10/2022

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • What is my risk for cancer based on my mutation?
  • What are the benefits and risks of screening for cancer?
  • At what age should I begin screening for cancer?
  • How do I get a test?
  • What type of surveillance should I have for cancer considering my personal and family history?

Open Clinical Trials
Open Clinical Trials

The following are studies looking at ways to screen for cancer in people at high risk: 

  • NCT05129605:  Cancer Genetic Risk Evaluation and Screening Study (PROGRESS). This study will look at how enhanced cancer screening using  will improve early detection rates and further understanding of how inherited mutations can lead to development of cancer.
  • NCT03805919: Men at High Genetic Risk for  Cancer. This is a  cancer screening study using  in high risk men. This study is open to men with an inherited mutation in any of the following genes: , HOXB13,  or FANCA.

Updated: 06/13/2022

Peer Support
Peer Support

The following organizations offer peer support services for people with, or at high risk for cancer:

Updated: 01/30/2022

Who covered this study?

MedPage Today

Time for targeted PSA screening for men with rare pathogenic variants? This article rates 4.0 out of 5 stars

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