A new hope for early cancer detection — but is it reliable?

On holiday abroad two years ago, he got a bout of food poisoning after which he spent a week in CUH. “During that week they incidentally found I had kidney cancer. I’d never have known but for the food poisoning.”

While a cancer diagnosis is never a happy thing, Flynn knows he has had a lot of luck and that, in a very personal way, he has experienced the importance of early cancer detection. He is now chief medical officer with Certior Health, a Blanchardstown-based company that has partnered with Indian cancer research company Datar Cancer Genetics, to provide a blood-based cancer-screening test called Trucheck.

“I’m the type of patient who will really benefit from this test, somebody asymptomatic with a silent cancer. With Trucheck you get an opportunity for early diagnosis where treatment’s most effective and less invasive,” says Flynn.

Launched in Ireland in July 2023, the company claims the test can distinguish 70 types of cancers accounting for 81% of all cancer cases.

Daniella De Paula, clinical scientist at Certior Health, explains that Trucheck evaluates blood samples to detect circulating tumour cells (CTCs) — cancer cells that escape from the tumour and enter the bloodstream.

“It can detect solid tumours. It’s not intended to detect haematolymphoid cancers — tumours that affect the blood, bone marrow, lymph, and lymphatic system, such as leukaemia,” says De Paula.

Flynn says screening programmes only cover 14% of cancers diagnosed in Ireland in any one year. “Currently, 86% of cancers diagnosed aren’t subject to a screening test. The advantage of Trucheck is that it has the potential to detect 81% of cancers diagnosed in Ireland in any one year. It has a far broader scope than a screening test.”

Trucheck is not the only new blood test promising early detection of cancer — several others are in various stages of development, chiefly in the US. Examples are Guardant Health’s Shield blood test — according to the company’s website it is demonstrated to be accurate at detecting colorectal cancer — and Freenome’s blood-based test for early detection of lung cancer. Freenome is currently enrolling up to 20,000 individuals in a validation trial.

Grail’s Galleri test

Some blood tests screen for multiple cancers (MCED — multi-cancer early detection) such as Exact Sciences’ Cancerguard, and Grail’s Galleri.

Speaking to the Irish Examiner from Cleveland, Ohio, Dr Eric Klein, a scientist with healthcare company Grail which developed Galleri, says the MCED test is trying to fill a major unmet need: “In the US, we screen for five cancers: Breast, colorectal, cervical and prostate cancers, and lung cancer in smokers. All of these programmes have been shown to reduce cancer-related mortality.

“Despite this we still have more than 600,000 cancer deaths a year in the US. Seventy per cent of the cancer deaths are from cancers we don’t screen for because there’s no existing screening. This is the big unmet need. And it’s in the background of the World Health Organisation predicting a 50% increase in cancer worldwide over the next 15 years.”

Explaining that the Galleri test is “designed to detect an array of cancers, including the 12 most aggressive that account for two-thirds of cancer deaths”, Klein says a study of the test in more than 6,000 “mostly asymptomatic” people found 1.5% of these participants had a cancer signal detected, and it found cancer in about 1% of participants including types for which there is no established screening method.

“The false positive rate for the test is 0.5% — meaning one in 200 people don’t actually have cancer, despite a cancer signal being detected,” says Klein. He compares it to a false positive rate for mammography, which he says is about 11%.

Klein — who worked for 35 years in the field of urological cancers — says adding the Galleri MCED test to the cancer-detecting toolkit “doubled the numbers of cancers detected over standard-of-care screening”.

While different blood-based tests may each deploy different mechanisms for detecting cancer, the Galleri test works by looking for tiny fragments of cancer DNA in the bloodstream.

The idea of using liquid biopsy for cancer detection — through blood, or potentially urine or saliva — has been around for decades, says Paul Mullan, professor of molecular oncology at Queen’s University Belfast (QUB): “Advances in technology in the last five to 10 years mean we’re increasingly able to do it more sensitively and accurately, by being able to sequence low levels of tumour DNA circulating in blood. We’re able to detect mutations and methylation [a chemical modification of DNA] much quicker, and at much lower levels. Tests are much more sensitive, they may have many markers, or even measure different types of markers together, so we can get much more information back.”

Mullan says while tests like Galleri “look very promising”, there is a long way to go before they are accurate or sensitive enough to be rolled out in the general population: “Early detection of cancer, in particular, is a high bar to jump over. We cannot afford to make mistakes. And where you’re measuring methylation or mutation, the tumour may be so small and release such little signal that it’s going to be very difficult to detect.”

He also points to the complexity of the information coming back for analysis from some tests, which “may require specialist expertise that regular hospital labs may not have”.

Not for general public

Prof Lorraine O’Driscoll, research director at Trinity St James’s Cancer Institute, says while the emergence of MCED tests represents great hope, much more research is needed: “I think it’s very positive, but for the tests to be useful we’d want to be at the stage where regulators — FDA in the US, EMA in Europe and HPRA in Ireland — are saying: ‘Yes, we believe the evidence is strong enough now to take this on board’.”

Dr Antoinette Perry, associate professor in cell and molecular biology at UCD, also sees the tests as promising, but believes using them for early detection is very challenging: “If you look at the performance metrics for early stage detection for any kind of diagnostic test, you have ‘sensitivity’ — how good is it at catching people with the disease. And ‘specificity’ — how good is it at only catching people who have the disease and not giving false positives?

“Looking at these tests, their sensitivity at picking up various cancers in the early stages is not very high. On the other hand, their specificity tends to be quite high. Sensitivity is the issue, and the only way to address this is through different technological advancements that will get better at picking up really tiny tumour DNA or cells in the blood.”

O’Driscoll would like the tests to be at the stage where health insurance companies are willing to reimburse the cost — these tests are expensive. Galleri, for example, costs upwards of $900 and Trucheck, €1,450. Currently, says O’Driscoll, the tests are for “rich informed people but not the general public”.

About 100 to 120 people here have taken the Trucheck test for cancer detection.

“We’re looking to expand that through partnering with established medical organisations around Ireland,” says founder and director of Certior Health, Declan Malone. He confirms that 80% of those taking the test have a strong family history of cancer, while the remaining 20% “are proactive about preventive health”.

Work is being done on the development of such tests by scientists here, too. In 2022, the All-Ireland Cancer Liquid Biopsies Consortium (CLuB) — a collaboration between TCD, QUB and NUIG — was selected for funding under the North-South Research Programme of the Government’s Shared Island Fund. CLuB’s work is focused on identifying and developing minimally invasive, cost-effective blood tests to complement surgical biopsies for cancer diagnosis and treatment selection.

Mullan is the lead investigator on the QUB side of the collaboration: “We’re very interested in liquid biopsy — blood detection — of cancers, particularly the difficult-to-diagnose ones: Ovarian, pancreatic, lung, triple-negative breast cancer. The stage of detection for a lot of these cancers can be quite late when it has had more chance to spread and develop resistance to treatment. Generally speaking, the earlier you can detect and remove cancer, the better the outcome.”

Ovarian cancer detection

Mullan says their work is most advanced in developing a blood test for ovarian cancer detection: “It’s a PCR-type test, a bit like some covid tests. It looks at a few different markers at the same time, focusing on changes in DNA methylation.”

A spin-off company from QUB, Genome Diagnostics, is currently developing the test (called OvaME).

“We’re hoping the finalised test will arrive towards the end of 2024. Then it has to be tested — validated in many independent samples — so it’s a long process. As to when it will be released publicly, there’s no timeframe at present.”

O’Driscoll leads the TCD side of the collaborative research CLuB group. While Mullan’s team in QUB is looking at DNA in blood samples donated by patients, O’Driscoll’s team is examining extracellular vesicles (EVs) in the same blood samples.

“EVS are little packages of information that are released from cancer cells into the blood, like little mini-maps of the cancer,” she says.

A third element involves a research group studying circulating tumour cells (CTCs), breakaway cells from the tumour and in the bloodstream.

O’Driscoll says studying three component parts from the same blood samples gives much more information than would be garnered by studying just one alone. “We’re not going after one single thing, hoping that has all the answers. We’re studying everything being released into the blood by the tumour,” she says.

A fourth group in Galway is “doing big data and number crunching” around the massive amounts of information generated, says O’Driscoll. It is also looking at “which component part gives the strongest signal for cancer.”

Mullan says the combined approach could allow researchers to detect cancers earlier and more accurately, ultimately improving patient survival rates long-term.

Tissue biopsy still king

When it comes to cancer screening, tissue biopsy continues to be the gold standard.

“But for tissue biopsy you have to know something’s there,” says O’Driscoll, who hopes the disadvantages of tissue biopsy can be overcome by liquid biopsy. “Tissue biopsy can be quite uncomfortable whereas a blood test is minimally invasive. Also, every cell type in the tumour isn’t necessarily the same as the other so, depending on where the tissue biopsy is taken from, it may not represent the whole tumour.

“Blood is a richer source because the tumour cell is releasing a lot of information into it,” she says, adding that tissue biopsy is time-consuming, must be done in a hospital setting and isn’t easily repeated (unlike blood tests).

The only drawback, says O’Driscoll, is that early cancer-detecting blood tests are not yet reliable enough: “More big-study research is needed to get to that point.”

She predicts a different timeline for different cancers: “For some in the next five years — but to complement tissue biopsy, not to replace it. For others, probably more than a decade.”

O’Driscoll has a vision: “That the person at the tip of Kerry or Derry can have a blood test taken by a nurse locally and sent in [for analysis]. But we have to be comfortable that the tests are reliable, the best possible. When that happens, I think it’ll be a game-changer.”

A tumour was found but I had no symptoms 

Arizona-based Valerie Caro, aged 56, read about the Galleri test in 2022. Speaking to the Irish Examiner, she says: “I do conventional screening, but thought it [would be] great to have a baseline for other cancers with a simple blood test.

“I received my results in about 10 days. I was called by two doctors who informed me a cancer signal [had been] detected in my gall bladder or pancreas. The next step was to get an MRI. The MRI didn’t show cancer, but the radiologist said my gall bladder was ‘angry’ and needed to come out.

“After the pathology report, it was confirmed I had a 4.5cm cancerous tumour in my gall bladder. I had no symptoms. I was surprised because cancer doesn’t run in my family.

“I had a second surgery to confirm all cancer was removed around the gall bladder. Then I went through a six-month chemotherapy cycle as insurance that all cancer cells were gone.

“I’m great now, my life is active. I meet with my care team twice a year to confirm I’m cancer-free.

“If I hadn’t taken the test? My gall bladder was ‘kissing my liver’ when the cancer was discovered. Since I had no symptoms, I’d guess it would have travelled to my liver and then to my lungs. It’d likely be a significantly different outcome. I’ve been told I’m very lucky to have found the cancer at the stage I did.”

• May 22, 2024: Two statistics have been updated in this article since original publication.