NHS-Galleri Trial Misses Primary Endpoint; Secondary Analysis Shows Fewer Stage IV Cancers

A new Lancet correspondence revisiting the promise and pitfalls of multi-cancer blood tests arrives as the strongest evidence yet on one of the field’s best-known products raises a basic question: how ready are these tests for broad screening? Grail’s landmark NHS-Galleri trial, the first large randomized study of a multi-cancer early detection blood test in people without symptoms, failed its primary endpoint, even as secondary analyses pointed to fewer Stage IV cancers.

The trial, conducted in England with NHS England and funded by Grail, enrolled 142,250 participants, generally ages 50 to 77. It randomized them to usual care plus annual Galleri testing or usual care alone. Participants gave three blood samples about 12 months apart. The pre-specified primary endpoint was a reduction in combined late-stage cancer diagnoses — Stage III and Stage IV — across a pre-specified group of 12 cancers, measured through one year after the last screening appointment.

When full results were presented at the 2026 American Society of Clinical Oncology annual meeting, the study did not show a statistically significant reduction in that primary endpoint, meaning it missed its main goal. Grail said a pre-specified secondary analysis found a 14% overall reduction in Stage IV cancers for the same 12 cancers, and a 16% increase in Stage I and II cancers detected after three rounds of screening. Julie Gralow, ASCO’s chief medical officer, said in press material: “While the Galleri-NHS study results show some encouraging trends toward tumour downstaging, it is important to recognize that the trial did not statistically reduce late-stage cancers by its predefined primary endpoint.”

That distinction matters in cancer screening. Studies that are not randomized can look encouraging simply because they find cancers earlier, without proving patients are better off — a problem known as lead-time bias. A reduction in advanced cancers is a tougher and more policy-relevant measure than just detecting more cancers. Screening programs typically need that kind of evidence, and ultimately evidence of fewer deaths, before health systems broadly embrace them.

Galleri is a methylation-based circulating cell-free DNA blood test. In simple terms, it looks for cancer-related signals in fragments of DNA circulating in the blood and then predicts where in the body the cancer may have started. Earlier Galleri studies, including CCGA and PATHFINDER, helped show that the test could detect cancer signals, but they were not randomized population-screening trials. NHS-Galleri is the first large randomized test of whether this kind of screening changes the stage at which cancers are diagnosed in an asymptomatic population.

Grail has said the primary endpoint was missed because the drop in Stage IV cancers was offset by an increase in Stage III diagnoses, particularly in the first, or prevalent, screening round. That may sound like a technical distinction, but it is central to how screening tests are judged: finding more cancers, or shifting some very advanced cancers into a slightly earlier stage, is not the same as clearly reducing the overall burden of late-stage disease.

The timing gives the findings added weight beyond the academic debate. Galleri is already sold in the United States by prescription as an add-on screening test, generally for adults 50 and older. But broader questions about coverage, recommendations and routine use remain unsettled, and regulators are still weighing the evidence. Grail has said a Food and Drug Administration advisory committee is scheduled to review its premarket approval application for Galleri on Sept. 23.

That makes NHS-Galleri newly relevant in the U.S. as well as in Britain. For supporters of multi-cancer early detection tests, the trial offered signs of potential benefit, including fewer Stage IV cancers in a secondary analysis. For skeptics, it underscored how high the bar is for a screening test meant for healthy people. The study’s initial report was not designed to answer the biggest question of all — whether screening with Galleri reduces cancer deaths — and longer follow-up will be needed to determine whether any stage shift translates into a mortality benefit.