In a 66-year-old woman like Maggie, a stone of weight loss over a couple of months, accompanied by nausea, right-sided chest pain and indigestion, represents cancer until proven otherwise. The problem was: where? The clinical examination was unremarkable. A battery of blood and urine tests failed to provide any clue, as did a chest X-ray. A stool sample to detect a bowel tumour came back resoundingly negative. Gastroscopy, where a camera on a fibre-optic cable allows direct inspection of the stomach, also drew a blank. Cancers of the pancreas or ovary are notoriously difficult to identify; an urgent CT scan of her chest, abdomen and pelvis proved clear.
All of this took many weeks to perform and was still ongoing last month when the impending Galleri trial was in the news. Galleri is a test that aims to detect minute traces of genetic material that leaks from tumours into the bloodstream. Preliminary studies suggest it is able to identify more than 50 different cancer types and to correctly predict the organ of origin 90 per cent of the time. It has been developed by a California-based biotechnology firm, Grail. The name is well-chosen: a single blood test that could pinpoint the cause in a case such as Maggie’s is a holy grail indeed.
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We’re some way off having it in clinical practice. The headline-grabbing initial data masks a slew of uncertainties. Galleri was trialled on samples from 1,264 patients, half of whom had already been diagnosed with cancer, with the other half constituting a control group not known to have the disease. Overall, Galleri detected genetic material from tumours in just 44 per cent of the cancer cases.
The more advanced the cancer, the better Galleri performed, but the more advanced the cancer, the better we are able to diagnose it already. Galleri was poor at picking up early disease – where the chance of cure is highest – identifying only 18 per cent of stage one cases.
It is one thing to demonstrate performance against known disease, quite another to do so in patients such as Maggie. This will be one of the arms of the forthcoming NHS trial, in which Galleri will be used in 25,000 people like her undergoing investigation for suspected cancer. The results will show whether it adds anything significant to our current investigative methods.
More contentiously, the other arm of the trial will use Galleri in 140,000 people without symptoms, as a screening tool. Might Galleri become a routine test offered to everyone of a certain age, that could identify cancer before symptoms develop? Such a prospect would give Grail a huge market for its product, far bigger than if Galleri were to be used purely as a diagnostic test. It would also fit well with the NHS’s target to diagnose 75 per cent of cancers at the earliest stages by 2028 – up from the present level of around 55 per cent.
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Here, I suspect, there will be disappointment. Galleri’s poor performance in stage one disease reflects how little detectable genetic material small, localised tumours release into the bloodstream. And although its false positive rate – the numbers of samples in the control group it incorrectly flagged as having cancer – is less than 1 per cent, once you start deploying it on millions of healthy people, even that low rate will generate thousands of erroneous alarms. Those folk will have to undergo often invasive investigations before they can be given the all-clear, and the anxiety generated will be huge.
Maggie’s case continues to defy diagnosis. The only thing that turned up on examination was a large fatty lump on the side of her chest. This had all the hallmarks of a benign lipoma but now that common cancers have been excluded, something rare becomes more likely. Lipomas very occasionally undergo malignant change, so an MRI to investigate it is planned. In the meantime, Maggie continues to live with gnawing uncertainty. We both know something is wrong. But we don’t yet have the answer.
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This article appears in the 28 Jul 2021 issue of the New Statesman, Summer special