A landmark multi-cancer early detection trial has reported its first results, marking what researchers describe as a pivotal moment for cancer screening. Professor Charles Swanton, lead study author from The Francis Crick Institute and University College London Cancer Institute, said: “This is the first randomised controlled trial of a multi-cancer early detection test to report results, and it represents a landmark achievement for participants and the UK’s National Health Service.”
The NHS-Galleri trial, a collaboration between test developer GRAIL and NHS England, enrolled 142,942 participants aged 50 to 77 with no prior cancer symptoms. Each provided annual blood samples for three years. The study’s primary objective was to demonstrate a statistically significant reduction in late-stage (Stage III–IV) cancer diagnoses when the Galleri blood test was added to standard NHS screening. That primary endpoint was not met; some reports indicated a non‑significant 3% increase in Stage III/IV cancers in the Galleri group compared with the control group.
How the Galleri Test Works
Despite the primary result, the trial yielded encouraging secondary findings that have drawn widespread attention. The Galleri test is a multi-cancer early detection (MCED) blood test that works by identifying cell‑free DNA (cfDNA) shed by cancer cells into the bloodstream. It analyses hundreds of thousands of methylation sites – chemical markers on DNA that can reveal whether a cell is cancerous – to detect patterns indicative of malignancy. The test is designed to screen for a signal shared by more than 50 types of cancer, including many deadly cancers for which no organised screening programmes currently exist, such as pancreatic, ovarian and liver/bile duct cancers.
When a cancer signal is detected, the test can predict the likely origin of the cancer with high accuracy – over 90% in some studies – through a feature called Cancer Signal of Origin (CSO), which helps guide diagnostic follow‑up. The Galleri test has demonstrated high specificity of 99.5% and a low false‑positive rate of 0.45% in some research, though false positives and false negatives can still occur. The trial builds on earlier investigations, including the Circulating Cell‑free Genome Atlas (CCGA) study, which first showed the feasibility of blood‑based MCED tests, and the SYMPLIFY study, which evaluated Galleri as a diagnostic aid in patients with suspected cancer symptoms.
Caution and Next Steps
While the primary goal was not achieved, secondary analyses revealed a substantial reduction in Stage IV cancer diagnoses: a decrease of 14% overall, with more significant reductions of 22% and 26% in the second and third screening rounds respectively for a pre‑specified group of 12 cancer types. The test also increased detection of earlier‑stage cancers (Stage I–II) by 19% and raised the overall cancer detection rate four‑fold compared with standard screening alone. Furthermore, 25% fewer patients were diagnosed with cancer in emergency settings.
Professor Swanton, a clinician scientist who serves as Deputy Clinical Director at The Francis Crick Institute and Chair in Personalised Cancer Medicine at UCL, described the results as “encouraging nevertheless”. His research focuses on understanding cancer evolution, particularly in metastatic and drug‑resistant disease, and he is chief investigator of the CRUK TRACERx study, which investigates lung cancer evolution. His work has been published extensively in journals including The New England Journal of Medicine, Nature, Science and The Lancet Oncology.
Experts have said that annual multi‑cancer early detection testing using the Galleri test is “feasible at scale” within a national health system like the NHS. However, caution has been voiced. Dr Julie Gralow, Chief Medical Officer of the American Society of Clinical Oncology (ASCO), noted that while the trends are encouraging, the trial did not statistically reduce late‑stage cancers by its predefined primary endpoint and stated that the Galleri assay should not yet be included in cancer screening guidelines. Some experts have expressed scepticism, suggesting the findings are being presented more positively than the overall results justify, particularly given the missed primary endpoint. There have also been calls for substantial investment in NHS cancer services to manage potential increases in referrals if MCED tests are deployed. From an insurance perspective, insurers are advised to treat MCED results as screening tools and to continue relying on diagnostic confirmation for underwriting and claims decisions.
GRAIL, the test developer, has said it remains encouraged by the trial’s findings, highlighting the reduction in Stage IV diagnoses and increased early‑stage detection as evidence of the test’s potential. The 25% drop in emergency cancer diagnoses further underscores the possibility that the test could shift detection away from acute presentations, offering a clearer picture of how such technology might alter the landscape of cancer screening.
