Galleri blood test for 50 types of cancer: What is it?

The headline findings from Pathfinder - which comprised 6,661 adults over-50 with no signs or symptoms of disease - found that its multi-cancer early detection (MCED) test successfully identified cancer in 35 participants, of whom 29 were being diagnosed for the first time (six had recurrent disease).

In short, for every 189 people screened, one genuine cancer case was found.

Around 80 patients who had a positive blood test result subsequently underwent scans for cancer - but most turned out to be false positives (Image: Getty)

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Of the 29 primary cancers, 14 were picked up at stages one or two when treatment was likely to be most effective and six of these were solid tumours.

This included types for which there is no screening tool available, such as pancreatic, uterine, liver, bone, small intestine, and oropharyngeal - a form of head and neck cancer which affects the back of the throat and tongue.

These are unlikely to have been identified during a routine physical examination.

When the MCED blood test - also known as Galleri - was positive and cancer was actually present, the study showed that the test correctly predicted the tumour location in 34 out of the 35 cases.

At face value, this seems impressive.

As the authors put it: "The Pathfinder study provides early evidence of the feasibility of blood testing to screen for multiple cancers with a single test, a departure from the prevailing framework requiring distinct screening tests for each cancer type."

Cancers detected via MCED and stage at diagnosis. Blue cases are those for which there is no routine screening programme (Image: Lancet)

The study has already been expanded into the Pathfinder2 trial with a larger and more diverse cohort.

Participants in this first round were 92% white, most had college educations, only 268 were smokers, two thirds were female, and had high participation rates in existing screening programmes - all of which suggests that the results cannot be generalised to the wider population.

Analysis is similarly underway in the UK via the NHS Galleri study which has recruited 140,000 adults to evaluate the difference in outcomes between those given normal cancer screening versus those given normal screening plus an annual MCED check.

A third study - the Oxford University-led Symplify trial - is also investigating the use of MCED in primary care for patients presenting with non-specific symptoms like weight loss or fatigue.

The big question is not whether these blood tests can detect cancers - they can - but whether they do it so much better than existing programmes as to be more cost-effective for healthcare services and to achieve a population-level reduction in cancer mortality.

READ MORE: Cancer screening and an ageing population - the dilemma for the NHS

The Pathfinder study cannot answer that: the sample size was too small and the follow up period (12 months) too short.

But it does throw up some interesting data.

People tend to imagine these all-in-one blood tests returning a definitive 'yes' or 'no' result for cancer, but that is not the case.

In total 92 participants had a positive cancer signal, but 57 turned out to be false positives following additional investigations including laboratory tests, scans, and invasive surgical and non-surgical procedures such as colonoscopies - which carry a small risk of bowel perforation.

This means avoidable workload for the health service and unnecessary potential harm for patients.

One man ended up having his testicles removed needlessly after a positive blood test result followed by an abnormal scan, only for no cancer to be detected.

The journey from positive blood test result to diagnostic resolution for patients who were true positives and those who were false positives (Image: Lancet)

False positives are inevitable with any screening programme, however, and the false positive rate in Pathfinder - 0.9% - "compares favourably" with existing single-cancer screening programmes.

Patients who genuinely did have cancer were also much more likely than the false positives - by a rate of 82% to 30% - to have undergone any investigative procedures.

More troubling is the fact that MCED also appears to have missed quite a lot of cases.

Over the 12 month period of the study - from December 2019 to December 2020 - a total of 121 participants enrolled in the trial were diagnosed with cancer.

Of these, 35 were detected via MCED and 38 via other US healthcare screening services (nine by non-standard screening tests, and 29 through routine screening programmes such as bowel and breast screening).

The fact that MCED succeeded in identifying only 35 out of these 121 cases was "somewhat underwhelming", said cancer scientists.

The Pathfinder researchers countered that this may have been skewed by a "healthy volunteer" effect: only 3681 of the participants (56%) had any additional risk factors, such as smoking, genetics or past history of cancer.

In other words, it might perform better against a general (unhealthier) population of over-50s; Pathfinder2 should answer that.

The key question is whether multicancer blood tests can improve diagnosis enough to impact on cancer mortality rates at a population level (Image: Getty)

READ MORE: Cancer and adults under 50 - why are the rates on the increase? 

Another drawback is that non-industry-sponsored research on MCED is "scarce".

The Pathfinder study - while peer-reviewed and published in the Lancet, a highly respected medical journal - was funded by GRAIL, the blood test's manufacturer.

This is not unusual - pharmaceutical companies routinely fund drug trials which inform regulator decision-making - but completely independent academic research would have its own merits.

Most important is whether MCED can actually save enough extra lives, or prolong survival long enough, to supplant existing screening tools.

In an editorial published in the Lancet, Drs Richard Lee and Hilary Robbins - clinicians at the Royal Marsden in London who were not involved in Pathfinder - cautioned that "the exciting data in these studies should not outshine more sobering concerns such as low sensitivity [the number of cancer cases missed by MCED], overlap with existing proven approaches, and unknown mortality benefit and cost-effectiveness".

They stress that any changes in how cancer screening is done "must be based on reduced mortality or other stringent measures".

Given that eight of the primary cancers detected at stages one and two by MCED were non-aggressive blood cancers this "raises important questions regarding the test's ability to reduce cancer mortality at a population level".

For now then the results are more mixed than miraculous.