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Targeted prostate cancer screening: Are we there yet?

by Katie Roberts | Analysis

20 October 2021

1 comment 1 comment

prostate cancer biopsy
Prostate cancer biopsy histopathology.

Prostate cancer screening is back in the news, as headlines suggest that yearly prostate checks could benefit some men at higher risk of cancer.

It’s a hotly debated topic. Many studies have investigated the benefits of a blood test – called the PSA (or prostate specific antigen) test in picking up prostate cancer in men without symptoms, but overall they point to the test not being reliable enough to save lives in the general population.

But what about a more targeted approach, where screening is offered to people on the basis of things other than their age and sex?

Here’s a rundown of the latest study, what it means and what we still need to know.

Why targeted screening?

The latest study, which we part funded, isn’t the first to investigate whether the PSA test can be used to screen for prostate cancer.

In 2018, our researchers reported that offering a one-off PSA test to men without symptoms didn’t save lives and could do more harm than good.

Now, researchers are exploring whether a more targeted approach may be more successful. This would involve identifying people at a higher risk of prostate cancer and offering them screening.

“Picking up cancers early, when they are more much likely to be curable, is a vital part of the mix as we try to improve the lives of cancer patients,” says Professor Kristian Helin, chief executive of The Institute of Cancer Research, London

“Mass screening isn’t a good option in prostate cancer because of the risk of overdiagnosis, but in men who have a high inherited risk of aggressive disease it makes much more sense.”

Which brings us to the IMPACT trial.

Who was screened?

The IMPACT trial looked at whether targeted screening could benefit people with an inherited condition called Lynch syndrome.

Lynch syndrome affects 1 in 279 people. People with this particular condition – caused by faults in a number of genes (MLH1, MSH2, MSH6 and PMS2) – are at an increased risk of bowel cancer, with around 7 in 10 people developing the disease.

There’s also some evidence that Lynch syndrome can also increase someone’s risk of developing other cancers, including prostate cancer.

And it’s this group the IMPACT team were interested in for this study. Led by scientists at The Institute of Cancer Research, the IMPACT study involved 828 men aged 40 to 69 from families with suspected genetic increased risk of prostate cancer.

The team wanted to know if regular PSA testing could pick up prostate cancer in these men. Men with faults in these particular genes (carriers) were matched with a control group that didn’t carry the same genetic faults (non-carriers).

What did the IMPACT study find?

Researchers, led by Professor Ros Eeles, found that annual PSA testing picked up 8 times as many prostate cancers in men with faults in the MSH2 gene than in those without the mutations after one round of screening.

Of the 305 men with faults in the MSH2 gene, 13 (4.3%) were diagnosed with prostate cancer – while only one non-carrier out of 210 (0.5%) was diagnosed with prostate cancer.

For MSH6 carriers, 4 of 135 men (3%) were diagnosed with prostate cancer, while none of 177 non-carriers had a prostate cancer diagnosis.

An extremely promising start. But, when it comes to screening, detecting more cancers isn’t enough.

What more is needed?

In screening, it’s crucial that cancers are found early. This is because when cancer is detected at an early stage, treatment is more likely to be successful.

But the real test of a screening intervention is if it can save lives. To measure this and be sure of the result in trials, you need lots of people. So this can be difficult with this type of targeted approach, when the genetic faults involved are rare.

For small high-risk groups like this, while a trial might not be able to show with certainty that deaths are avoided, it seems reasonable that it at least shows that it’s able to shift cancer diagnosed at a late stage, to an early one in order to increase chances that people with survive their cancer.

It’s also important to look at the potential harms of screening. Because, as strange as it may sound, finding more cancers isn’t necessarily a ‘good’ thing. This seems like a counter-intuitive statement – but not all cancers pose the same level of danger. And some cancers won’t ever cause someone problems.

Diagnosing and treating these cancers won’t save a person’s life. But it may subject them to unnecessary worry and treatment, and all the side effects that come with it.

Harms like these, and others, are why it’s crucial to weigh up the benefits and harms carefully before deciding to introduce a screening programme, including programmes designed for people at high risk.

This study has given us the first piece of the puzzle, which is showing that PSA testing can effectively detect prostate cancers in men with Lynch syndrome. But when it comes to assessing the benefits of regular PSA testing for men with Lynch syndrome, there are still a few missing pieces.

The IMPACT trial is still running, and the team are planning another 5-year follow-up to compare treatment outcomes in the men taking part.

They’ll also be evaluating the benefits (detecting cancers earlier) and harms (such as overdiagnosis and false positives) of annual PSA testing in men with Lynch syndrome, which will give us a crucial piece of evidence for whether a screening programme should be introduced for this group.

A promising start

It’s an important time in prostate cancer research, with research teams across the world working to improve prostate cancer diagnosis and detect the disease earlier.

And, thanks to researchers like Eeles, we’re learning more and more about how screening could fit into this picture. As well as investigating whether men with Lynch syndrome could benefit, Eeles and her team are also looking at other groups with a higher prostate cancer risk – specifically men with faults in the BRCA genes.

Commenting on the results, Professor Charles Swanton, Cancer Research UK’s chief clinician, says: “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.”

Katie 


    Comments

  • linda johnston
    30 October 2021

    My husband was diagnosed with advanced ca prostate at the start of 2020 despite having what was then deemed a ‘low PSA’, 6.9, with few symptoms. A few years earlier his PSA was 4 and no action was deemed necessary by his GP ? He was placed on the rapid access cancer pathway just before Christmas 2019. Clearly PSA was not a good guide for my husband as it was not indicative of the activity within his body. Surely this indicates that even a slightly raised PSA warrants further investigation. Nothing is perfect but there has to be a way to ‘assess’ all men before cancer gets to the advanced stage ? Women have smear tests and breast screening – surely prevention is better than ‘cure’.

    Comments

  • linda johnston
    30 October 2021

    My husband was diagnosed with advanced ca prostate at the start of 2020 despite having what was then deemed a ‘low PSA’, 6.9, with few symptoms. A few years earlier his PSA was 4 and no action was deemed necessary by his GP ? He was placed on the rapid access cancer pathway just before Christmas 2019. Clearly PSA was not a good guide for my husband as it was not indicative of the activity within his body. Surely this indicates that even a slightly raised PSA warrants further investigation. Nothing is perfect but there has to be a way to ‘assess’ all men before cancer gets to the advanced stage ? Women have smear tests and breast screening – surely prevention is better than ‘cure’.