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There's a great deal of hype around the prospects for multicancer early detection (MCED) testing – a single blood test to detect cancer markers even before symptoms appear. This could be a major step-change in medicine, but some experts caution that we're not there yet, and warn of difficulties attached to a potential wider roll out. So do these tests actually live up to the hype?

Galleri Faces Some Controversy

Several MCED tests are marketed directly to consumers, and are also undergoing testing in the NHS. Grail's Galleri test, which looks for altered DNA methylation patterns in blood, is the most advanced. The University of Oxford-led SYMPLIFY study results, published last July, found that the test detected a cancer signal in 323/5461 symptomatic cases, 244 of which received a cancer diagnosis, yielding a positive predictive value of 75.5%, a negative predictive value of 97.6%, sensitivity of 66.3%, and specificity of 98.4%. 

Sensitivity increased with increasing age and cancer stage, from 24.2% in stage I to 95.3% in stage IV. Among those with proven cancer, prediction of site of origin was accurate in 85.2% of cases.

Galleri is currently undergoing a pilot trial in the NHS with 140,000 volunteers without cancer symptoms or signs at baseline. The results are due later this year. Both the test and the trial have attracted controversy, with a paper published in The Lancet earlier this month expressing concerns over low detection rates for early-stage cancers, high false-positive rates, imprecise cancer origin analysis, need for follow-up investigations, high costs, and unproven mortality gains, as well as the existence of possible political influences over the NHS's selection of this particular test over others.

The test claims to detect more than 50 types of cancer, and the hope is that it will pick up tumours that are difficult to identify early – such as head and neck, bowel, lung, and pancreatic cancers – and thus avert typically late-state diagnoses with poor prognosis, which usually lead to expensive treatments.

Tests May Make the 'Worried Well' Even More Worried

However, MCED tests don't detect early disease very well, explained Karol Sikora, consultant oncologist and honorary professor of professional practice at the University of Buckingham Medical School, speaking to Medscape News UK. They are good at picking up advanced cancer but are quite nonspecific and can give false-positive results. "The real problem with all MCEDs is that they make the worried well even more worried!"

So the results of the pilot trial may be disappointing. 

"The data so far doesn't show it's really helpful for stage I or II disease – and there's often no way of telling where the cancer's coming from," he said. "What's a GP supposed to do with someone who's received a positive test but has no symptoms? What am I supposed to do as an oncologist if they're referred to me?"

Who Pays for Further Investigations?

Manufacturers don't have to prove health economic value, only that a test does pick up cancer, he pointed out. Should the NHS pick up the tab for a total body scan and a load of tumour markers just in case when people take a private test that hasn’t been validated by NICE as having a cost-benefit? "It's a real quandary," he said.

Also, if you only have one scan slot, should you give it to a patient with symptoms, coughing up blood perhaps, or to someone who is completely well but has a positive test result? "The priority's got to be those that have symptomatic disease."

"The research is fantastic," he said. But “rolling it out as a public health tool, which is what Galleri is trying to do – it’s too early for that.” Ultimately, though, Sikora does think that such tests might improve the UK's dismal cancer survival statistics. 

"That, of course, is the politics behind it. The NHS wants to show that they're backing this, because it'll solve the problem." It's not going to solve it in a short timescale, however. "A lot more people are going to die because of late-stage diagnosis unless we solve it by increasing conventional diagnostic capacity."

Tests Could Reduce Clinical Costs of Cancer Care

Earlier diagnosis from MCED tests also offers the tantalising prospect of reducing clinical costs of cancer care – estimated at £21 billion in the UK in 2018. Professor Allan Hackshaw, director of the Cancer Research UK and University College London Cancer Trials Centre, told Medscape News UK: "At present, the NHS spends a huge amount on cancer drugs, and advanced radiotherapies, for treating advanced cancers."

These drugs are often not curative, patients may need multiple treatment sequences, and most have side effects that impair quality of life and often need to be addressed with more medication. "Early-stage cancer is easier and cheaper to treat," said Hackshaw. If MCED tests lead to a noticeable reduction in people diagnosed with late-stage/advanced cancer, this should directly improve survival rates. "On a population level, even a 15%-20% reduction in cancer deaths would be a great achievement,” he said. 

MCED tests also offer a screening modality for cancers that have no effective tests (70%-75% of all cancer deaths), and for those that are too rare for population-wide screening. Current single-cancer screening is cost-effective only for breast, lung, colorectal, and cervical cancers. Hackshaw led a modelling study, reported in the British Journal of Cancer in 2021, that suggested that the true-positive to false-positive ratio dropped from 1:18 for current screening tests to 1:1.6 with an earlier version of Galleri. Moreover, the cost of diagnostic investigations among screen positives, per cancer detected, was reduced from £10,452 to £2175 with MCED testing.

MCED tests are likely to prove cost-effective, Hackshaw believes. More research is needed, but "it seems likely that MCED tests can save the NHS much money".