At an academic function, a guest asks what I do and I say, “public hospital doctor”, which seems more benign than “oncologist”. When he asks me to elaborate, his eyes widen as he exclaims, predictably, “Wow, isn’t that depressing?” By now, I have form in explaining that being an oncologist is sobering but not depressing because, in the space between diagnosis and outcome, there is a lot of good one can do – not only through treating the disease but having empathy for the patient.
Next he asks if “they” will find a cure for cancer. Thinking of all the hard-working (and poorly paid) researchers, I say there is much to celebrate and much more to aspire to. He nods thoughtfully.
We spend the rest of the dinner in companionable conversation but my occupation has been on his mind. Before leaving, he leans towards me. “Can you suggest an ‘everything’ test for cancer?”
No such thing, I say, and he looks disappointed.
I thought of that conversation when reading about the failure of just the kind of blood test on which he had pinned his hopes.
The highest goal of cancer medicine is early detection, leading to the outcome with the greatest meaning to the patient: a cure. For oncologists like me, it would be a different world if we could accurately predict individual risk, detect cancer before it metastasised and reassure patients that early intervention saved lives.
To this end, the American company Grail (get it?) launched a blood test called Galleri to detect what it called a “signal” shared by more than 50 types of cancer. The signal was circulating DNA, the term for minute fragments of cancer DNA present in the bloodstream.
The company markets the blood test as a screening tool “since cancer can develop at any time”. Two weeks after doing the US$949 test, the patient receives an easy-to-read result: cancer signal detected or no cancer signal detected. Ninety-nine per cent of people will screen negative, the 1% who test positive will need a battery of tests to confirm whether they have cancer.
Naturally, for a cancer test that has not yet been approved by the FDA but made it into a Super Bowl ad, there were quite a few disclaimers – but I was drawn to one particularly bold claim: “The Galleri test is intended to detect cancer signals and predict where in the body the cancer signal is located.”
Grail then joined forces with Britain’s NHS to conduct the world’s largest prospective randomised controlled trial (the gold standard of trials) to study whether its blood test can reduce the likelihood of a late-stage cancer diagnosis in an asymptomatic population.
Launched in 2021, the study enrolled 142,000 healthy people between the ages of 50 and 77 in the UK. All participants provided three blood samples over two years. Half were randomly assigned to have their samples tested and, if they tested positive, receive a cancer workup. The other half received usual healthcare, typically based on history and examination to elicit clues.
The logic was that if having the blood test caught cancers early, fewer people would progress to late-stage disease.
The trial did not meet its primary endpoint of reducing late-stage (stage 3 and 4) cancer diagnoses. This is the most important outcome of a clinical study, so the failure to meet it is headline news.
The company responded by saying it was expanding its sales force based on “strong” results, with a statement saying the trial “demonstrates a substantial reduction in stage 4 cancer diagnoses, increased stage 1 and 2 detection of deadly cancers, and four-fold higher cancer detection rate”. Investors have been less magnanimous, causing the company’s share price to plummet by nearly half. The company now faces investor scrutiny and a potential class action.
Moonshot approaches to cancer are not new. Thanks to the persistence of researchers and the generosity of patients, oncologists have access to convincingly good therapies that offer quality of life and longevity. Many of my cancer patients who are well today would not have lived had they been diagnosed at the start of my career.
But what we have here is the world’s largest trial of its kind failing to demonstrate population-level benefit for a blood test to detect cancer. This tells us there is a difference between finding more cancers and saving lives – a very difficult thing for most people to wrap their head around but important from a public health perspective.
For instance, if some cancers are detected at stage 3 rather than 4, that does not necessarily mean less onerous treatment or prolongation of survival. And it’s one thing to detect a cancer at stage 1 and 2 but another to claim that this saves lives because it’s possible the cancer may never have posed a lethal problem.
This conundrum is evident in my very elderly patients who fall and undergo a CT scan which rules out a nasty fracture but finds a tiny cancer. Left alone, these cancers would never declare themselves in the remaining lifetime but the discovery triggers interventions that are far more stressful than the condition. Some people step back but most want something done.
In certain situations, a circulating DNA blood test is a promising test – and Australian researchers are at the forefront of showing us how to harness it.
But for now, healthy people should know there is no blood test (or “total body scan”) for cancer that saves lives.
Which brings us back to a few things we can all do to modify the risk of developing cancer. Reduce processed foods, curb alcohol, don’t smoke and get regular exercise.
It’s not the kind of announcement to send stock prices soaring but, when it comes to impact, the evidence is well and truly in.
