{"entity":{"id":"paper-nhs-galleri-primary-nejm-2026","kind":"paper","name":"Effect of Screening with Multicancer Early-Detection Test on Late-Stage Cancer Diagnosis","aka":[],"tldr":"The main result of the NHS-Galleri trial: among 142,250 people in England, three yearly rounds of the Galleri blood test added to usual care did not reduce the number of cancers found at stage III or IV.","summary":"Sasieni and colleagues report the primary endpoint of NHS-Galleri, the randomised controlled trial in England in which people aged 50 to 77 gave blood at up to three annual visits and were randomised 1:1 to have it tested with GRAIL's methylation-based multi-cancer early detection test (intervention) or stored (control). The primary endpoint was stage III or IV cancer among 12 prespecified cancer types; a key secondary endpoint was stage IV cancer among the same 12.\n\n71,122 participants were randomised to the intervention group and 71,128 to control. The incidence rate of stage III or IV cancer did not differ significantly (incidence rate ratio 1.03; 95% CI 0.92 to 1.14; P = 0.63). The incidence rate ratio for stage IV cancer after three rounds was 0.86 (95% CI 0.74 to 1.00). Fewer than 1% of participants had trial-related adverse events and none were serious. The authors conclude that further follow-up is warranted to see how the stage III or IV and stage IV differences evolve.","asOf":"2026-10-29","links":[{"label":"NEJM 2026: NHS-Galleri primary endpoint","url":"https://doi.org/10.1056/NEJMoa2505723"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42776074/"},{"label":"ClinicalTrials.gov NCT05611632","url":"https://clinicaltrials.gov/study/NCT05611632"},{"label":"ISRCTN91431511","url":"https://www.isrctn.com/ISRCTN91431511"}],"tags":[],"related":["paper-nhs-galleri-performance-nat-med-2026","paper-nhs-galleri-design-cancers-2022"],"cancers":[],"sections":["early-detection"],"technologies":["mced","liquid-biopsy","cfdna-methylation-testing"],"targets":[],"drugs":["galleri"],"companies":["grail"],"institutions":[],"pathways":[],"terms":["stage-shift","screening"],"trials":["nhs-galleri"],"people":["peter-sasieni","charles-swanton"],"bottlenecks":["b-early-detection","b-overdiagnosis"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/NEJMoa2505723","pmid":"42776074","authors":"Sasieni P, Johnson P, Round T, et al.","paperType":"rct","findings":["71,122 randomised to blood testing and 71,128 to stored blood; three annual screening rounds plus at least 12 months of follow-up.","Stage III or IV cancer among 12 prespecified types (primary endpoint): incidence rate ratio 1.03 (95% CI 0.92 to 1.14), P = 0.63.","Stage IV cancer (key secondary endpoint): incidence rate ratio 0.86 (95% CI 0.74 to 1.00).","Fewer than 1% had trial-related adverse events; none serious."],"whatItMeans":"This is the first randomised answer to whether a multi-cancer blood test changes outcomes, and for its main question the answer was no: adding the test to NHS care for three years did not lower the number of cancers diagnosed at stage III or IV. The stage IV result is a secondary finding with a confidence interval that touches no effect, and deaths have not yet been reported, so the trial continues to follow participants.","caveats":["Three screening rounds; the authors say further follow-up is needed to see how the stage differences evolve.","Cancer deaths, the outcome that matters most, are not reported in this paper.","One test (Galleri) in one health system; results do not transfer automatically to other multi-cancer tests.","Funded by GRAIL."],"changedPractice":false,"participants":142250},"route":"/key-papers/paper-nhs-galleri-primary-nejm-2026/","neighbours":{"paper":[{"id":"paper-nhs-galleri-design-cancers-2022","kind":"paper","name":"NHS-Galleri: design of the largest randomised trial of a multi-cancer blood test","route":"/key-papers/paper-nhs-galleri-design-cancers-2022/"},{"id":"paper-nhs-galleri-performance-nat-med-2026","kind":"paper","name":"Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial","route":"/key-papers/paper-nhs-galleri-performance-nat-med-2026/"}],"section":[{"id":"early-detection","kind":"section","name":"Early Detection & Screening","route":"/fronts/early-detection/"}],"technology":[{"id":"cfdna-methylation-testing","kind":"technology","name":"Cell-free DNA methylation tests","route":"/technologies/cfdna-methylation-testing/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mced","kind":"technology","name":"Multi-cancer early detection (MCED)","route":"/technologies/mced/"}],"drug":[{"id":"galleri","kind":"drug","name":"Galleri","route":"/drugs/galleri/"}],"company":[{"id":"grail","kind":"company","name":"GRAIL","route":"/companies/grail/"}],"term":[{"id":"screening","kind":"term","name":"Screening","route":"/terms/screening/"},{"id":"stage-shift","kind":"term","name":"Stage shift","route":"/terms/stage-shift/"}],"trial":[{"id":"nhs-galleri","kind":"trial","name":"NHS-Galleri","route":"/trials/nhs-galleri/"}],"person":[{"id":"charles-swanton","kind":"person","name":"Charles Swanton","route":"/people/charles-swanton/"},{"id":"peter-sasieni","kind":"person","name":"Peter Sasieni","route":"/people/peter-sasieni/"}],"bottleneck":[{"id":"b-overdiagnosis","kind":"bottleneck","name":"Overdiagnosis and false alarms","route":"/bottlenecks/b-overdiagnosis/"},{"id":"b-early-detection","kind":"bottleneck","name":"The hardest cancers are found late","route":"/bottlenecks/b-early-detection/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}