New era of early cancer detection blood tests on the horizon

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Published: 11 Sep 2022
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Dr Deborah Schrag - Memorial Sloan Kettering Cancer Center, New York City, USA

Dr Deb Schrag speaks to ecancer about PATHFINDER, a prospective study of a multi-cancer early detection blood test.

A validated blood-based multi-cancer early detection (MCED) test uses cfDNA and machine learning to detect a common cancer signal across over 50 cancer types and where the signal is coming from. PATHFINDER is a prospective study in a screening population that evaluated the clinical feasibility of MCED testing.

The study, reported at the ESMO Congress 2022, is the first prospective investigation to show that an MCED test can detect cancer in patients with undiagnosed cancer, as previous studies used tests only in patients already known to have cancer.

A number of further studies are now underway including a major randomised clinical trial enroling 140,000 asymptomatic people in England to investigate the clinical effectiveness of MCED testing on cancer outcomes.

Watch Dr Tom Beer talk about his study on MCED testing, also presented at ESMO 2022.

This study was evaluating a fundamentally new approach to cancer screening. It was exploring using
blood tests to screen for multiple cancers at once. That’s really a paradigm shift in the current
approach for cancer screening. The goal was to really understand how patients and physicians would
cope with this, particularly receiving a blood test that suggested that cancer might be present, and to
understand the diagnostic evaluations that would ensue. So that was the purpose.
This was a cohort study, so over 6,000 adults all over the age of 50 were approached and invited to
participate. Adults could participate if they were over 50 with no special risk factors; they could also
participate if they fell into a high risk group and the high risk group had a history of smoking or a
family history or themselves had a personal history of cancer and were survivors and had survived
more than three years cancer free. So a high risk group and average ordinary adults over 50 who
were receiving their medical care in one of seven US healthcare systems distributed widely across the
United States.

People who were invited to participate came to see their doctor, they had this blood test, they signed
an informed consent, it was a research test. They gave a blood specimen and two weeks later the
patient’s physician received a report that said signal was detected or signal was not detected. If signal
was not detected nothing further, there was no further interaction, but at the end of a year those
patients’ records were examined to see if cancer was found. For the small proportion of individuals
who had a cancer signal detected, this was 1.4% of the population or 92 individuals, the focus was on
them to understand the diagnostic odysseys that would ensue. For these 92 individuals, two, it turned
out upon further questioning, had suspicion of cancer or were undergoing a work-up for cancer that
had started even before they got the test results and those two were put aside to be quite
conservative. Of the remaining 90, the diagnostic evaluations detected cancers in 35 individuals. The
remaining individuals, so 55, no cancer was identified, despite a diagnostic evaluation.

We really wanted to understand what those diagnostic evaluations would entail and the key, I believe
not a surprise, was imaging. Most of these patients had imaging studies, typically CT scans, PET CT
scans. But what was valuable about the test is in addition to simply indicating positive signal or
negative signal, the test provided suggestions as to the site of origin. So it provided two suggestions,
first or second, and in nearly 90% of cases those signal detections were accurate. So, for example,
there’s a signal suggestive of lymphoma; there’s a signal suggestive of breast cancer; there’s a signal
suggestive of lung cancer. This helped direct the physician to organise the evaluation. If it was signal
detected head and neck cancer then of course one could start with an oropharyngeal examination, for
example, by an ENT.

These diagnostic odysseys typically took less than three months; the median was 79 days for
everyone. Of course, shorter for the true positive, for the 35 individuals for whom cancer was found
than for the individuals who were false positive.

What cancers does this test look for?

All types of cancers and that’s the powerful thing. The cancers, of the 35 cancers it was split nearly
down the middle – 17 versus 18 – solid tumour malignancies, so those are cancers like breast, lung,
colorectal but also cancers for which there is no screening – cholangiocarcinoma, uterine cancer,
ovarian cancer, head and neck cancer, pancreas cancer – that was about half and the other half was
cancers of hematologic origin and the most common there was lymphoma, some unusual types of
leukaemia but quite a few lymphomas as well were detected. It is important to note there is no
standard screening test for lymphoma.

How does it work?

The assay looks at methylation in very small bits of abnormal DNA that are shed into the bloodstream.

What could be the implications of these findings?

This particular study was intended to really understand how patients and physicians would respond to
receiving a positive screening test. But what’s really exciting is that this test has already been used in
140,000 adults who receive their care from the UK’s National Health Service. A randomised trial has
completed enrolment – 70,000 individuals had the test and 70,000 completed routine care, routine
screening, which of course does not extend to most types of cancers. In a couple of years we should
have results of that study and that will really look at the clinical utility of this test.

But the current test, the PATHFINDER test, does provide a glimpse of what the future may hold which
is a fundamentally new approach to how we think about cancer screening and, if you will, a one-stop
shopping to screen for lymphoma and uterine cancer and head and neck cancer all at once.

How far away are we from population-wide blood test screening?

I think we’re still a ways away. It is absolutely premature to discontinue the routine cancer screenings
that we know save lives. It’s critical to point out that there are some parts of the world where the most
important thing that we can do is ensure that people have access to mammography, to colorectal
cancer screening, because in many parts of the world organised screening programmes are not fully
implemented, even though the technology exists. So we’re not ready to abandon what we know works

But in the future this approach could be a very powerful alternative. There is much discussion about
the potential for over-diagnosis and identifying cancers that are not meaningful, cancers that will
never hurt an individual in their lifetime – prostate cancer is… perhaps cancers that we don’t want to
even know about, we don’t want to diagnose these cancers. So the key with this technology will be
thoughtful deployment. An individual who is 92 years old who would not accept cancer treatment and
would not want to… is obviously not going to be a good candidate for this test. Again, age is not a
perfect arbiter of anything, of course, but one has to use this technology thoughtfully and issues of
over-diagnosis are very real and an important concern. There’s lots more to learn but I do think that in
the future the problem of some of the cancers that we have not been able to screen for in an
organised way, this is very powerful.

What are the cost indications?

A cost-effectiveness analysis in this space certainly needs to be done. Cost-effectiveness analysis
requires modelling and we need more data to inform the models. We’re not ready to do the cost-
effectiveness analyses until we have more data. But when people succumb to late stage cancers
early and die it doesn’t cost very much because they die quickly of late stage cancers but we’re not
improving extending lives. So the key is to look not only at the cost but at cost in relationship to life
years saved. The critical issue about all cancer screening is that we need to understand the effects on
mortality, not simply diagnoses but mortality. As we have these data, cost-effectiveness models will
be performed that will help inform different countries organise screening programmes as to when and
whether adoption of this test makes sense with respect to the amount of resources that the country
has to spend on healthcare. We’re a long ways away from that at this point but we can glimpse. It
provides a tantalising glimpse of the future.