Doc, can I have the new DNA test to see if I have cancer?

Many of you will have had patients asking about this test as it was widely reported in the media BBC June 2023 following publication of the initial results of the NHS Symplify Trial last week. It all sounds a bit too good to be true, and in general practice we rapidly tire of ‘miracle medical news’ stories in the media that we are asked about by patients who have had expectations unrealistically raised. So, what is going on with cell free cfDNA and cancer diagnosis, and is it worth all the hype?

My colleague Rob gave us an excellent summary of the test 18 months NB Blog February 2022 when the NHS trials looking at the Galleri Test, as it is called, were first announced.  Put very simply (I need simple when it comes to genetics!) DNA from cancer cells can be detected in the blood giving the potential for earlier diagnosis and treatment. The blood test looks at methylation patterns of DNA, and crucially different cancers have different patterns of methylation. The test can use these methylation patterns of cfDNA to detect multiple different types of cancers, in what is called a Multi Cancer Early Detection Test (MCED). 

That’s the theory, which sounds amazing, but ‘how does it perform in practice?’ is the ‘million dollar’ question that needs answering. The NHS Symplify Trial is the first large scale evaluation of a MCED in symptomatic patients and the greatly anticipated initial results from the trial were presented at the American Society of Clinical Oncology conference last week NIHR June 15^th 2023 thus hitting all the headlines. It is another example in a recent trend of ‘publication by press release’, as the full publication of the paper is pending in the Lancet Oncology. 

So, what did the study do? The first thing to say is that the NHS Symplify Trial was evaluating the test in patients with symptoms suggestive of cancer (other research is looking at the screening potential of the test with the NHS Galleri Trial expected to enrol up to 1M asymptomatic patients).  The Symplify trial enrolled 6,000 patients, with a mean age of 61, who presented to their GP with symptoms suggestive of possible cancer (e.g. change in bowel habit, unexplained weight loss, rectal bleeding etc) and were then referred for investigation. The patients were investigated in the usual way, and they also had the Galleri MCED blood test the result of which was then matched with the outcome from the patients’ investigations. 

Results? The Galleri test detected a cancer signal in 323 people, 244 in whom cancer was actually diagnosed. The positive predictive value of the test was 75.5%, the negative predictive value 97.5% and the specificity 98.4%. These are all good numbers, but the sensitivity of the test was only 66% (i.e. it missed 1/3 of cancers) and crucially the sensitivity was dependent on the stage of the cancer. For Stage 1 cancers (i.e. the ones we most want to diagnose) the sensitivity was only 24%, but it was 95% in stage 4.  Importantly though with a positive test, it was 85% accurate in detecting the source of the cancer. This is perhaps the most significant finding, as it shows real potential for being able to make cancer investigation in suspected cases more targeted, streamlined and quicker thereby reducing treatment delays. 

So, in conclusion, these are promising early results, but from this initial data it seems that the most likely use of the test will be as a diagnostic aid in secondary care to pinpoint the source of the cancer earlier and streamline investigations in patients that we refer with suspected cancer symptoms.  Unfortunately, the test is currently insufficiently sensitive to be used to ‘rule in or rule out’ early stage cancer. Contrary to many of the media reports last week, the test needs to be considered as very much a work in progress whilst we await further research and data from the NHS Symplify Trial and the NHS Galleri Trial.  In the meantime, we can advise our curious and hopeful patients that GPs being able to use a cfDNA blood test to diagnose cancer at an early stage in primary care still seems a long way off.