A study looking at screening for men who are at an increased risk of developing prostate cancer (IMPACT)

The research team found that the PSA blood test may be useful to help diagnose prostate cancer in men with some genetic changes.

Study design
This study was for men who hadn’t been diagnosed with prostate cancer. Some people taking part had changes in certain genes, and some didn’t.  

The genes the research team were interested in were:

• BRCA1
• BRCA2
• MLH1
• MSH2
• MSH6

The men taking part have a PSA blood test once a year for at least 5 years. 

If their PSA level was greater than 3.0 nanograms per millilitre (ng/ml), they could have a biopsy to check for cancer cells.

If their PSA level was less than or equal to 3.0 ng/ml, they didn’t have any more tests until the PSA test the following year.

The research team looked at various things for each group, including the number of men who:

• had a PSA level of greater than 3.0 ng/ml 
• were diagnosed with prostate cancer
• had prostate cancer that was classed as medium (intermediate) or high risk 

Results

Results for BRCA 1 and BRCA2 genes
Around 3,000 men joined this part of the study between 2005 and 2013:

• 919 had a BRCA1 gene change
• 709 didn’t have a BRCA1 gene change
• 902 had a BRCA2 gene change
• 497 didn’t have a BRCA2 gene change

 

In 2019, the research team published some results for this part of the study. The results were for people having their 4th annual PSA test. 

They found that, in total:

• 527 men had had a PSA level greater than 3.0ng/ml  
• 357 men had had a prostate biopsy
• 112 men had been diagnosed with prostate cancer 

They looked at the number of men in each group who had prostate cancer. 

They found there wasn’t much difference between those who had a BRCA1 gene change and those who didn’t:

• 31 out of 919 men (3.4%) who had a BRCA1 gene change
• 19 out of 709 men (2.7%) who didn’t have a BRCA1 gene change

But there was a bit more of a difference between those who had BRCA2 gene change and those who didn’t:

• 47 out of 902 men (5.2%) who had a BRCA2 gene change
• 15 out of 497 men (3.0%) who didn’t have a BRCA2 gene change

They looked at the number of men whose prostate cancer was intermediate or high risk. It was higher in those who had a BRCA gene change than those who didn’t. And the average age at diagnosis was lower in these men.

Results for MLH1, MSH2 and MSH6 genes
Around 1,000 men joined this part of the study between 2012 and 2020:

• 204 had an MLH1 gene change
• 199 didn’t have an MLH1 gene change
• 305 had an MSH2 gene change
• 210 didn’t have an MSH2 gene change
• 135 had an MSH6 gene change
• 177 didn’t have an MSH6 gene change

 

In 2021, the team published some results for this part of the study. The results were for people having their first annual PSA test. 

They found that, in total:

• 56 men had a PSA level greater than 3.0ng/ml  
• 35 men had a biopsy
• 18 men had been diagnosed with prostate cancer

They looked at the number of people in each group who had been diagnosed with prostate cancer. 

They found that no one with an MLH1 gene change (or the group who didn’t have an MLH1 gene change) had prostate cancer. 

But there was a difference between those who had an MSH2 gene change, and those who didn’t:

• 13 out of 305 men (4.3%) who had an MSH2 gene change
• 1 out of 210 men (0.5%) who didn’t have an MSH2 gene change

And a difference between those who had an MSH6 gene change, and those who didn’t:

• 4 out of 135 men (3.0%) who had an MSH6 gene change
• None of the 177 men who didn’t have an MSH6 gene change

They also looked at the number of men who had intermediate or high risk prostate cancer. It was higher in those with a genetic change. And the average age at diagnosis was lower in these men.

Conclusion
The study team concluded that annual PSA tests may help diagnose prostate cancer in men with changes in the BRCA2, MSH2 or MSH6 genes. 

It is hard to draw firm conclusions because of the small number of people diagnosed with prostate cancer. This is especially true for the MLH1, MSH2 and MSH6 groups who had only had one PSA test when these results were published.

The team suggest that regular PSA testing should be considered for men with these gene changes. This is called targeted screening. But they need the results of further annual PSA tests before they can say for sure whether targeted screening will be useful for these men. 

In 2020, The European Association of Urology (EAU) recommended that men with a BRCA2 gene change should have an annual PSA tests. 

Future results
The study team continue to follow up the men who took part in this study. They plan to publish further results about diagnosing prostate cancer earlier, to assess if using a PSA test affects how long people live.

Where this information comes from    
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed ) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.