The National Health Service (NHS) is exploring a revolutionary blood test that can detect more than 50 distinct types of cancer before symptoms appear termed GalleriTM.
Thousands of individuals will take part in the experiment, which began on September 13, 2021, to assess how effectively the Galleri test works in the health system in the hopes of transforming cancer care in the United Kingdom.
Based on research published in Annals of Oncology1, a blood-based test proved accuracy and high specificity in detecting several cancer types with diverse biological markers, even at early stages, paving the way for a ‘New Paradigm’ for cancer screening.
PSA for prostate cancer, mammography for breast cancer, colonoscopy for colon cancer, Pap smears for cervical cancer, and low-dose CT for individuals at high risk for lung cancer are the only five established screening paradigms. These tests are being used to screen people for various types of cancer. Hence, being able to screen for many cancers simultaneously would be a substantial change.
Cancers for which there is no screening test account for the majority of cancer fatalities in the United States and around the world. One of the most critical opportunities we have to decrease cancer’s severity is to detect cancer early, when treatment is more fruitful. These findings imply that the multi-cancer detection test, when used in combination with existing screening tests, could have a great influence on how cancer is discovered and, ultimately, on public health.
How does the Galleri blood test work?
The test works by detecting chemical alterations in pieces of genetic material, called cell-free DNA (cfDNA), that slip into the bloodstream from tumors. Some cancer tumors are known to release DNA into the bloodstream long before symptoms occur.
Each patient’s blood is drawn and analyzed for DNA known as cell-free DNA (cfDNA), which tumors (and other cells) lose into the bloodstream. Genomic sequencing is used to detect chemical changes to DNA called “methylation” that regulate gene expression, and these results are used by a classifier designed with machine learning (artificial intelligence) to discover abnormal methylation patterns that indicate the presence of cancer. Additionally, the machine learning classifier can predict the location of cancer in the body.
Galleri employs advanced genetic sequencing technology and artificial intelligence to scan for patterns of chemical changes in cfDNA that come from cancer cells but are not seen in healthy cells in order to only identify cfDNA that suggests the presence of cancer.
What do we know so far?
So far, Galleri research has yielded promising results. GRAIL, the corporation that developed the Galleri blood test, has reported the test can detect 50 different forms of cancer with a 0.5 percent false positive rate1. This indicates that out of every 200 persons tested, one person may have a positive result even if they do not have cancer.
Up to this point, only patients who have already been diagnosed with cancer have been tested with the blood test. The test accurately detected cancer in 51.5 percent of the participants in this group1. This provides an idea of how sensitive the test is. The Galleri test was able to accurately identify the location of the tumor 89 percent of the time, which is crucial for selecting which diagnostic tests the patient will require to confirm his or her diagnosis.
An impediment for this type of test is the difficulty of detecting relatively low quantities of abnormal DNA flowing in the blood.
Because the quantity of tumor-derived cfDNA tends to grow as a cancer progresses, these blood tests are more effective at detecting advanced stages of cancer. Judging the data so far, the test was not very successful at spotting stage 1 cancer, which is cancer that is few and hasn’t spread to the rest of the body.
Furthermore, the number of cancers examined, particularly for some rarer cancer types, has been quite limited.
The NHS trial will give researchers the chance to evaluate the test on a much larger sample of people, with more time to follow up on those who do not test positive and a chance to address some of the important concerns and smooth out some of the flaws.
What is the focus of the NHS study?
The Galleri test will be used in the NHS study to see if it can accurately and reliably predict cancer in patients who aren’t suspected of having it, and if it can detect cancer at an earlier stage than would otherwise be the case.2
It will be run by The Cancer Research UK and King’s College London Cancer Prevention Trials Unit, led by director Professor Peter Sasieni, and is being coordinated by GRAIL in collaboration with NHS England.
The research will initially enlist 140,000 adults aged 50 to 77 years old, who will be identified through NHS records and encouraged to participate.
The research will provide information on how effective and suitable the test is throughout our broad population, and the team is determined to ensure that volunteers of various backgrounds and ethnicities are recruited.
The focus of the research is to discover if the test can decrease the proportion of cancer cases diagnosed late in stages 3 or 4 when compared to individuals whose samples aren’t tested. It will also assist in identifying the test’s negative effects. This involves keeping track of the number of individuals who test positive but are never diagnosed with cancer, as well as whether any tumors are missed due to false negatives.
Is the Galleri test hope or hype?
What makes cancer detection so complicated? When searching for comparatively rare diseases like cancer, even accurate testing does not perform as effectively. As a result, false positives occur, prompting costly follow-up as well as an emotional toll. As a result, the limited screens that are suggested focus for commonly occurring cancers in higher-risk populations. Furthermore, as strange as it may sound, some slow-growing tumors aren’t harmful, thus identifying them leads to pricey overmedication. There’s also something known as “lead-time bias,” which occurs when screening results in an earlier diagnosis but not necessarily a better fate. It’s a tough notion that takes some thought experimentation to grasp.
All of this requires a detailed evaluation and compromise when it comes to screening, particularly if casting a wide net identifies more tumors but with the risk of more false or unproductive positive results. However, multi-cancer blood tests like Grail’s and others in development by businesses are particularly promising because they have the potential to change the testing math enough to allow for broader screening.
Galleri, as previously stated, has a very low false-positive rate in validation experiments, especially when compared to many other screening techniques. Along with the fact that it searches for numerous cancer types rather than just one, these tests should be more broadly applied with fewer false positives. As a result of early detection, cancer cases may be more treatable and possibly less expensive. Earlier cancers can often be treated with surgery and radiation. In later phases, expensive drugs that don’t always work are often the only option. Grail’s test may also be more likely to detect worrisome tumors, according to the initial findings.
The main impediment to widespread use of these fascinating features is evidence, as well as the fact that the medical profession has been wounded previously by the promise of early detection. Before anyone can definitely say that this time is different, further well-controlled evidence and expert evaluation are required to verify these tests.
The next few years could provide useful information and boost implementation. Grail is conducting research in a variety of populations, with more to come. The trial in the United Kingdom is an excellent method to obtain practical value out of the test while also providing useful data.
The United States should join the initiative, especially since it pays for a large portion of cancer costs through Medicare. More large trials with more people could help compare tests, evaluate their use in more populations, and ultimately answer the question of whether blood screening saves lives.
None of this will be simple or cheap, and the research will not provide definitive answers right away. However, the prospective reward is significant enough to justify the effort.
“Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set”, by Eric Klein et al. Annals of Oncology. https://doi.org/10.1016/j.annonc.2021.05.806
NHS Galleri Trial. https://digital.nhs.uk/services/nhs-digitrials/nhs-galleri-trial