Imagine being able to detect signs of more than 50 types of cancer through a simple blood test, potentially before symptoms appear.
That is the promise of Galleri, a multi-cancer early detection (MCED) blood test developed by GRAIL, a US-based biotechnology company, co-founded by Prof. Y.M. Dennis Lo. The technology has generated considerable interest because many potentially deadly cancers, including pancreatic, ovarian, and liver cancers, have no established routine screening tests for the general population. [1]
But a critical question remains: Does finding more cancers through a blood test actually help people live longer?
Recent results from a major UK clinical trial did not demonstrate the expected reduction in advanced cancer diagnoses, yet secondary findings suggest a possible reduction in stage IV diagnoses. Understanding the difference is essential.
What is Galleri, and how does it work?
Galleri looks for cancer-associated signals in fragments of DNA circulating in the bloodstream. It analyzes chemical patterns called DNA methylation using sequencing technology and machine learning. These patterns can indicate whether a cancer signal is present and suggest where it originated.
Unlike screening methods focused on a single cancer, Galleri is designed to identify signals associated with more than 50 cancer types, including pancreatic, ovarian, and liver cancers.
It is very important to know the meaning of the test results. A positive result is not a cancer diagnosis: additional examinations, imaging, and sometimes biopsy are needed. A negative result does not rule out cancer, particularly early tumors that shed little detectable DNA.
Galleri is intended to complement, not replace, recommended cancer screening.
What happened in the landmark UK trial?
The NHS-Galleri randomized trial enrolled approximately 142,250 adults aged 50–77 without cancer symptoms. Participants were offered annual Galleri testing plus usual screening or usual care without Galleri.
The primary goal was to reduce diagnoses of stage III and stage IV cancer combined across 12 prespecified cancer groups. Stage III often describes locally advanced disease; stage IV generally indicates spread to distant organs.
After three annual screening rounds, the trial did not meet this primary endpoint. The Galleri group had approximately 3% more combined stage III–IV diagnoses than the control group, a difference that was not statistically significant. The study therefore did not demonstrate its principal intended benefit. [2]
Why Are Researchers Still Interested?
Across the three screening rounds, the Galleri group experienced approximately 14% fewer stage IV cancer diagnoses, with a 26% reduction during the third screening round. [2] These are potentially encouraging signals, but they are not proof of benefit, particularly in the context of the unsuccessful primary endpoint.
How can stage IV diagnoses decline without a decline in stages III and IV combined? Imagine a cancer that would ordinarily be diagnosed at stage IV but is instead discovered at stage III. The combined stage III–IV count does not change, even though the patient’s treatment options might differ. This is a plausible hypothesis, not a conclusion established by the trial.
Other explanations remain possible: more cancers may be found without preventing advanced disease, some may progress too rapidly for annual screening, and some additional detections may not ultimately benefit patients. Longer follow-up is needed.
How Accurate Is Galleri?
A notable strength is its low false-positive rate of approximately 0.45%. Overall, fewer than 1% of tests returned a positive result, and approximately half of those positive results were associated with a subsequent cancer diagnosis.
Its limitation is sensitivity. Across cancers diagnosed in the relevant screening intervals, Galleri detected approximately one-third. [3] Thus, a negative test should never be interpreted as a guarantee that no cancer is present. A test may produce relatively few false alarms while still missing many cancers.
What Do Newer Studies Tell Us?
GRAIL recently reported another set of results from the PATHFINDER 2, a North American prospective study of approximately 35,878 adults aged 50 or older, which examined Galleri’s performance when added to recommended screening.
GRAIL reported that adding Galleri increased the number of screen-detected cancers by 6.5-fold in the reported comparison, and that about 71% of new cancers detected by Galleri were stages I–III. [4]
These findings support the technology’s ability to identify additional cancers, but they do not mean Galleri is six times better than every conventional screening test. PATHFINDER 2 was not designed as a randomized trial to demonstrate lower cancer mortality or reduced advanced-cancer incidence.
What is still missing?
Earlier detection does not automatically mean longer survival. Some cancers may have spread before a blood signal is detectable. Others may grow so slowly that detecting and treating them creates unnecessary harm. Lead-time bias can make survival after diagnosis appear longer merely because the diagnosis occurred earlier.
The meaningful outcomes are fewer dangerous cancers, fewer cancer deaths, better quality of life, and acceptable rates of unnecessary testing and treatment. The reported stage IV reduction deserves study, but it has not yet established that population screening with Galleri saves lives.
For individuals considering Galleri or other multi-cancer early detection tests, discussing the potential benefits, limitations, costs, and follow-up procedures with a qualified healthcare professional is essential. Recommended cancer screening should continue regardless of the result.
AFCR’s Perspective: From Early Detection to Meaningful Patient Benefit
The development of multi-cancer early detection technologies represents an important scientific achievement. The next challenge is not simply to detect more signals, but to determine what they mean and how to act on them. That calls for an integrated research pathway:
- Molecular early detection: identify signals through DNA, proteins, imaging, and other biomarkers.
- AI-driven risk assessment: distinguish aggressive cancers from those less likely to cause harm.
- Personalized clinical guidance: determine who needs imaging, biopsy, or surveillance.
- Precision intervention: select appropriate treatment or preventive strategies.
- Longitudinal validation: measure advanced disease, mortality, quality of life, and harms.
For people at higher risk of cancer, including those with a family history, earlier detection could open new possibilities. But researchers still need to understand which cancers require urgent attention, what should happen after a positive test, and whether earlier treatment improves outcomes.
This is where collaboration becomes essential. At the Asian Fund for Cancer Research Limited (AFCR), we bring together scientists, clinicians, and other experts to identify promising research opportunities and help innovative approaches move closer to clinical use and meaningful patient benefit.
Ultimately, the goal of cancer research is not simply to find cancer earlier. It is to give more patients the opportunity to live longer, healthier lives.
References:
[2] Sasieni P, Johnson P, Round T, et al. Effect of Screening with Multicancer Early-Detection Test on Late-Stage Cancer Diagnosis. New England Journal of Medicine. Published September 22, 2026. https://doi.org/10.1056/NEJMoa2505723
[3] Neal RD, Dolly S, Johnson P, et al. Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial. Nature Medicine. Published September 22, 2026. https://doi.org/10.1038/s41591-026-04652-8
[4] Nabavizadeh N, McDonnell C, Kurbegov D, et al. Performance and safety of a multi-cancer early detection test: the PATHFINDER 2 study. Nature Medicine. Published September 22, 2026. https://doi.org/10.1038/s41591-026-04618-w
