NHS-Galleri Data Show Fewer Stage IV Cancers, but Primary Endpoint Missed

Topline results from the randomized NHS-Galleri trial (NCT05611632; ISRCTN91431511) found that adding annual multi-cancer early detection (MCED) blood testing (Galleri) to standard-of-care screening in England’s National Health Service did not achieve the prespecified primary endpoint of a statistically significant reduction in combined stage III–IV cancers, although the sponsor reported a favorable trend over time in a prespecified subset of cancers.¹

GRAIL reported that the trial enrolled 142 000 demographically representative, asymptomatic participants aged 50 to 77 years and evaluated annual MCED screening over 3 years. In the prespecified group of 12 “deadly” cancers (anus, bladder, colorectal, esophagus, head and neck, liver/bile duct, lung, lymphoma, myeloma/plasma cell neoplasm, ovary, pancreas, stomach), the company stated that adding the Galleri test to standard screening produced a “substantial and clinically meaningful” reduction in stage IV diagnoses compared with standard-of-care screening alone, with stage IV diagnoses decreasing with each sequential screening round and a greater than 20% reduction in the second and third rounds. Similar reductions were reported across all cancers, according to the company’s topline summary.¹

In addition, GRAIL said that annual screening with the Galleri test plus standard screening resulted in a four-fold improvement in overall cancer detection rate compared with standard screening alone for breast, colorectal, cervical, and high-risk lung cancers. The company also reported an increase in the absolute number of stage I–II cancers detected in the 12 prespecified cancer types that are “typically found in late stages,” and fewer cancers detected via emergency presentation—an outcome associated with poorer prognosis and higher resource use.¹

The sponsor noted that the Galleri test’s positive predictive value, specificity, and cancer-signal-of-origin (CSO) accuracy were consistent with ranges previously reported from North American studies, and that no serious safety concerns were reported among participants who received the Galleri test.¹

Investigators and the sponsor highlighted the clinical importance of shifting diagnoses away from metastatic disease. In the press release, chief investigator Charles Swanton, MD, PhD, emphasized that once distant metastases are established, treatment often shifts toward long-term disease control and symptom management, whereas earlier-stage disease may be treated with curative intent.¹

“As an oncologist, I see how profound the difference is between Stage III and Stage IV disease,” Swanton, a thoracic medical oncologist at University College Hospital, London, said. “When cancer is detected before distant metastatic spread, we can often treat with curative intent, combining surgery, radiotherapy, and systemic therapy in an effort to eradicate all disease. Once distant metastases are established, treatment typically shifts toward long-term disease control and symptom management; durable cures become uncommon in most solid tumors. Reducing the proportion of patients diagnosed with metastatic disease is therefore not merely a statistical aim, it dramatically increases the number of patients for whom eradication of disease and cure is possible.”¹

However, the topline readout also underscored an evidence gap central to MCED adoption: the prespecified primary endpoint (combined stage III–IV reduction) was not met, and mortality outcomes were not reported in the topline release.¹ Broader MCED literature has emphasized that evaluation frameworks for MCED tests differ from single-cancer screening and that clinical utility—including downstream workup, overdiagnosis, and patient-centered outcomes—remains a key focus for ongoing trials.²

GRAIL said additional analyses are underway and that detailed results will be submitted for presentation at the ASCO 2026 Annual Meeting. The company also cited a higher-than-anticipated incidence of stage III cancers in the trial and reported that time to diagnostic resolution appears to improve over time as clinicians gain experience with test-directed workups. GRAIL stated it plans to extend trial follow-up by 6 to 12 months as the dataset matures.¹

The NHS-Galleri trial is positioned as a population-screening study to inform a potential national program in England. In the US, GRAIL stated that its Galleri premarket approval application is under FDA review and incorporates NHS-Galleri metrics focused on test performance, clinical validation, and potential clinical benefit from detection at stages I through III, including reductions in stage IV diagnoses. As with other MCED approaches, the Galleri test is offered as an adjunct—not a replacement—to guideline-recommended single-cancer screening.¹

References:

1. Landmark NHS-Galleri Trial Demonstrates a Substantial Reduction in Stage IV Cancer Diagnoses, Increased Stage I and II Detection of Deadly Cancers, and Four-Fold Higher Cancer Detection Rate. News release. GRAIL. February 19, 2026. Accessed February 20, 2026. https://grail.com/press-releases/landmark-nhs-galleri-trial-demonstrates-a-substantial-reduction-in-stage-iv-cancer-diagnoses-increased-stage-i-and-ii-detection-of-deadly-cancers-and-four-fold-higher-cancer-detection-rate/
2. Hackshaw A, Cohen J, Reichert A, et al. New genomic technologies for multi-cancer early detection: Rethinking the scope of cancer screening. Cancer Cell. 2022;40:109-113. doi:10.1016/j.ccell.2022.01.014