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Originally Posted On: https://sloanestreetsurgery.co.uk/articles/deciphering-liquid-biopsy-a-revolution-in-cancer-screening/

You may have read about “breakthrough advances in cancer detection” that aim to revolutionise how we identify many types of cancer even before symptoms occur.

A reliable test that detects cancer early would be a paradigm shift in medical screening and represent a groundbreaking advance. There is no doubt that earlier identification of cancer leads to better treatment and outcomes for patients.  A good quality test would also offer comfort to healthy patients seeking reassurance that they are not affected by cancer. Liquid biopsy tests are promising to offer this sort of early detection, and this article explores them and claims about their performance in more depth. Importantly these tests are different from testing your own genes looking for susceptibilities to certain diseases, such as the brca1 and 2 genes which are associated with breast cancer. That is another form of screening, and not considered in this article.

What are liquid biopsy tests and what do they look for?

Liquid biopsy aims to identify cancerous tumours via a blood test which looks for either circulating tumour cells (CTCs) or circulating tumour DNA (ctDNA).

Liquid biopsy tests are already used in patients with established cancers to help understand the severity of the cancer and to guide treatments.  These are very different from tests offered to healthy people as “screening tests” and it is the screening of people without a diagnosis of cancer that this article focusses on.

Liquid biopsy tests are also offered by some companies to screen healthy people. The test most comprehensively studied in this regard is the “Galleri” test offered by a company called Grail (aptly named because a perfect test that identifies cancer early is something of a holy grail to doctors and patients!) This test has been extensively studied in large trials including in the NHS (the Galleri study). The grail test is not available to patients in the UK, but it is in the USA.

Another company, Datar genetics, also offer liquid biopsy screening test to otherwise healthy people. Their test is called “Trucheck”, and some GPs are offering this test in private practices in London.

Are these tests suitable for screening healthy people?

These tests represent an exciting medical advance, so inevitably doctors and patients are excited by what appears to be an amazing step forward. If they work well, they will change the face of cancer diagnostics.

The challenge though is understanding if these tests offer early detection of cancers at a good enough level for widespread use. When it comes to screening for cancer in healthy people the stakes are high; inaccurate tests have serious consequences. Broadly there are two main ways these tests can fail. If a test has a false negative result, it can tell people who do have cancer that they don’t; and this can potentially delay them seeking the help they need by being falsely reassuring. Another way a test can fail is by generating false positives which tell people they are sick when they are not, and lead to a lot of over investigation and worry.

Finally, it is possible that these tests could detect cancer at a stage earlier than conventional tests…so it could be years before you find out if the test was right or wrong, with lots of worry and testing in that gap.

Making a good decision about how to advise our patients considering these tests is very important. To support this we have sought the opinion of leading oncologists and geneticists who have carefully reviewed the data and seen the relevant companies’ stands at conferences.

Whilst these tests hold hope for the future, they are widely considered to be insufficiently accurate to be used in asymptomatic patients. That’s to say that if they were used, they would run the risk of telling too many people they are healthy when they’re not and too often tell people there is a problem when there isn’t, and finally even if they are right, they may lead to detection of a problem that doesn’t show up on conventional tests for some years.

The Trucheck test being offered by Datar genetics is less well studied than the Grail/Galleri test and Datar have failed to provide adequate information to reassure most doctors of its usability. Oncologists and geneticists raise what we see as highly valid questions on Datar’s datasets and the conclusions drawn from them and are already meeting patients in whom these types of tests have failed, leading to worry and anxiety. There are also good news stories, but the ratio of good to bad is not where we need it to be.

So, is there any environment where they are useful?

Yes, reviewing the data it is apparent that whilst using the Grail/Galleri test for asymptomatic patients doesn’t work well enough yet, it does for some patients who have symptoms.

In patients with vague symptoms where a doctor has a suspicion of an upper gut cancer and normal scans, a trial showed the Galleri test to be very helpful in directing a pathway to make a diagnosis. In summary, like so many medical tests, this one works best when trying to answer a specific question rather than as a screen of healthy people.

The Road Ahead

Researchers and healthcare professionals are working hard and fast to address the challenges that these exciting and revolutionary tests present. More fine tuning of the tests and more clinical trials will be crucial in determining their true effectiveness and impact on cancer diagnosis and outcomes.

Additionally, the integration of the Galleri test into healthcare systems presents complexity regarding how best to follow up positive results.

Conclusion

Liquid biopsy testing stands at the forefront of a new era in cancer detection, offering hope for earlier diagnosis and improved patient outcomes. Its ability to detect a wide array of cancers through a simple blood test represents a significant advancement in medical technology. However, we feel these tests are not ready for widespread use as a screening test yet, due to concerns about their accuracy.

The journey to widespread use of Liquid biopsy for screening requires refinement of the tests and ongoing research. With a commitment to refining accuracy, minimising ethical concerns, and integrating the test into existing healthcare systems, we will hopefully see a future where early cancer detection is a reality that saves lives. We are watching this space closely and will adopt this exciting new technology as soon as it is safe to do so.