When early readouts from the NHS-Galleri trial in February 2026 revealed that the study had missed its primary endpoint, headlines quickly framed the outcome as a setback for multi-cancer early detection (MCED). For a technology often positioned as a potential revolution in cancer screening, the reaction was swift and, in some cases, pessimistic.
This is not a drug trial where missing a primary endpoint automatically means a lack of clinical benefit. Screening trials are different, and they require a much more nuanced interpretation.
—Megan Hall, GRAIL
But for those closely involved in the development of MCED tests, the story is far more complex.
“This is not a drug trial where missing a primary endpoint automatically means a lack of clinical benefit,” Megan Hall, Vice President of Medical and Corporate Affairs and Distinguished Scientist at GRAIL, told DDN. “Screening trials are different, and they require a much more nuanced interpretation.”
What is the Galleri test?
Researchers are looking at the Galleri blood test as a way of detecting a large range of cancers at an early stage. Unlike traditional screening, which targets a single cancer — such as breast, cervical, or colorectal — Galleri is designed to identify dozens of cancer types from a simple blood draw.
The test works by analyzing DNA methylation patterns in circulating cell-free DNA (cfDNA). Methylation is a chemical modification of DNA that can switch genes on or off, and cancer cells often display abnormal methylation signatures long before symptoms appear. By reading these patterns, the Galleri test can not only detect cancer signals but also predict the tissue or organ of origin, guiding doctors toward the most appropriate follow-up diagnostic pathway.
“The goal is to shift diagnosis to a point when cancers are still treatable,” explained Hall. “Detecting cancer early can dramatically improve outcomes, and for many rare or difficult-to-screen cancers, this approach may be the only feasible option for early detection.”
Galleri is the first test of its kind capable of identifying more than 50 different cancer types from a single blood sample. But as Hall emphasized, the goal isn’t simply to catch every cancer.
“It’s to detect the cancers that warrant treatment,” she said. “More aggressive tumors shed more DNA into the bloodstream, which makes them inherently more detectable with this type of assay. Less aggressive or indolent cancers, like early-stage prostate or thyroid cancers, are less likely to appear in the test, reducing the risk of overdiagnosis.”
While this limits sensitivity for some tumors, it also ensures that the cancers Galleri detects are those most likely to pose a serious threat if left untreated. This focus on aggressive cancers also helps to minimize unnecessary follow-up procedures and reduces patient anxiety.
Validating a broad cancer test
Before the NHS-Galleri trial, Galleri had already been extensively studied in prior clinical investigations, including the Circulating Cell-free Genome Atlas (CCGA) study, the original PATHFINDER study, and the larger PATHFINDER 2 study.
PATHFINDER 2 evaluated Galleri’s safety and performance alongside standard screening in 35,878 adults aged 50 and older with no clinical suspicion of cancer across the US and Canada. Early results, published in October 2025, showed that adding Galleri to standard screening produced a more than seven-fold increase in cancer detection, with over half of the newly detected cancers found at an early stage. The test also demonstrated a specificity of 99.6 percent, corresponding to a false-positive rate of just 0.4 percent.
These studies provided the foundation for the first and only prospective, randomized, controlled trial designed to evaluate the clinical utility and performance of an MCED test in a population-based screening setting. The NHS-Galleri trial enrolled more than 140,000 participants in the UK in just over ten months. Participants aged 50-77 provided annual blood samples over three years, with the goal of determining whether the Galleri blood test could reduce late-stage cancer diagnoses when added to standard screening.
The trial’s primary endpoint aimed to demonstrate a significant reduction in stage three and four cancers combined, but it ultimately fell short of that goal. While this result caused a lot of disappointment across the industry, experts have cautioned that the story is far more nuanced.
The decision to combine stages three and four as the primary endpoint was made more than six years ago, when it aligned with the NHS England's Long Term Plan to diagnose 75 percent of cancer at stage one and two. However, during that time, the difference between stage three and four has become increasingly clinically meaningful, as advances in treatment have improved outcomes for many stage three cancers while stage four disease remains far more difficult to treat and, in many cases, incurable.
Across all cancer types combined, the American Cancer Society estimates that five-year relative survival for stage three increased from 54 percent in the mid-1990s to 69 percent in 2015–2021. This has translated to stage three cancers being much more survivable than stage four cancers. For example, in colorectal cancer, five-year survival is more than 50 percent higher at stage three than at stage four. In stomach cancer, survival improves by more than 30 percent. Even in lung cancer, one of the deadliest malignancies, five-year survival for stage three disease is approximately 37 percent, compared with just 10 percent for stage four disease.
“Five years ago, we would define late-stage diagnosis as stage three and stage four, and now it’s predominantly stage four. If we had powered the trial to reduce stage four cancers, the trial would have been heralded as a huge success,” Richard Neal, Co-Chief Investigator of the NHS-Galleri, part-time GP, and Professor of Primary Care at the University of Exeter, told DDN.
What did the trial really show?
For the first time, the data suggest a shift away from stage four disease, with some cancers now being diagnosed at stage three instead. That indicates cancers are being identified earlier in their progression, which has meaningful implications for patients, healthcare systems, and costs.
—Megan Hall, GRAIL
While the study did not demonstrate a statistically significant reduction in stage three and four cancers combined, secondary analyses revealed that there was still a reduction of more than 20 percent in stage four cancers alone, alongside an increase in diagnoses at earlier stages.
“For the first time, the data suggest a shift away from stage four disease, with some cancers now being diagnosed at stage three instead,” Hall said. “That indicates cancers are being identified earlier in their progression, which has meaningful implications for patients, healthcare systems, and costs.”
Neal echoed that view. “I was delighted with the substantial reduction in stage four diagnoses,” he said. “These findings show there is clear potential for this test to make a difference to cancer outcomes in asymptomatic screening populations.”
Notably, the trial also detected early-stage disease in aggressive cancers such as pancreatic and ovarian cancer — malignancies that currently lack effective population screening tools. “These findings provide the first evidence that the use of an MCED test can alter the stage at which cancers are diagnosed,” said Hall.
Overall, annual screening with the Galleri test plus standard of care screening resulted in a four-fold improvement in the cancer detection rate compared to standard of care screening alone in England for breast, colorectal, cervical and high-risk lung cancer.
What does the future hold for the Galleri test?
While Galleri is already available through prescription in the US, GRAIL is pursuing full regulatory approval. The company submitted its premarket approval application to the FDA earlier this year.
“We want to set a high bar,” Hall said. “FDA rigor matters — not just for us, but for the credibility of the entire field.”
This rigor also extends to their clinical testing, which is far from finished. “Our whole clinical program encompasses nine different clinical trials and is enrolling more than 380,000 participants across all of those studies. To our knowledge, it is the largest clinical program in genomic medicine to date.”
Attention is now shifting to the REACH trial, a large US-based trial evaluating the Galleri test in Medicare-eligible adults. The study will enroll approximately 50,000 participants who receive usual care plus the Galleri test, alongside a matched comparator group receiving standard care alone. Unlike the NHS-Galleri trial, REACH is designed with a primary focus on reducing stage four cancer diagnoses, reflecting both clinical insights and changes in the treatment landscape.
The full results from the NHS-Galleri trial are expected to be presented later this year, pending acceptance at the American Society of Clinical Oncology (ASCO) annual meeting.
Looking further ahead, Neal sees the broader trajectory as inevitable. “The natural history is that these tests get better and more refined over time,” he said. “As we define the right screening populations and improve the technology, MCED will almost certainly become part of routine care in high-income Western health systems.”
