Whether blood-based tests that screen simultaneously for multiple cancers provide clinical benefit beyond usual care was unknown prior to this randomized trial. The investigators assessed whether adding a multicancer early-detection test to standard clinical practice could reduce the incidence of late-stage cancer diagnoses across a prespecified set of cancer types.
This multicenter, randomized, controlled trial was conducted in England. Eligible participants were persons 50 to 77 years of age. Peripheral blood was obtained from participants at up to three annual visits. After the baseline blood collection, participants were randomly assigned in a 1:1 ratio to the intervention group (blood tested) or the control group (blood stored). Participants and trial personnel were initially unaware of the group assignments.
Participants in the intervention group had their collected blood tested with the multicancer early-detection assay. Participants in the control group had their blood samples stored but not tested during the trial period. All participants continued to receive usual care in parallel with trial procedures.
The predefined primary end point for the trial was the incidence rate of stage III or IV cancer among 12 prespecified cancer types. A key secondary end point was the incidence rate of stage IV cancer among the same 12 prespecified cancers. Incidence rates were defined as the number of first eligible events divided by person-years at risk.
The principal comparison between groups measured differences in incidence rates after three screening rounds and after at least 12 months of follow-up following the last participant’s third visit. The trial reports incidence rate ratios with corresponding 95% confidence intervals and hypothesis testing for the primary end point.
A total of 142,250 participants were randomized: 71,122 to the intervention group and 71,128 to the control group. This large-scale randomization provided the basis for the between-group comparisons of late-stage cancer incidence after the planned screening rounds and follow-up period.
After three screening rounds and the prespecified follow-up, the incidence rate of stage III or IV cancer — the trial’s primary end point — did not differ significantly between the intervention and control groups. The reported incidence rate ratio for the primary end point was 1.03 with a 95% confidence interval of 0.92 to 1.14, and the P value was 0.63. Thus, no statistically significant reduction in combined stage III or IV cancers across the 12 prespecified types was observed with the addition of multicancer early-detection testing to usual care.
For the key secondary end point of stage IV cancer, the incidence rate ratio after three screening rounds was reported as 0.86 with a 95% confidence interval of 0.74 to 1.00. This result suggests a between-group difference favoring fewer stage IV cancers in the intervention group, but the confidence interval reaches 1.00, and the trial authors indicate that further follow-up is warranted to clarify how this finding evolves over time.
Trial-related adverse events occurred in fewer than 1% of participants. Importantly, none of the trial-related adverse events that were reported were serious. No additional safety concerns are detailed in the abstract.
In this randomized trial of adults aged 50 to 77, screening with a multicancer early-detection blood test in addition to usual care did not lead to a lower incidence rate of stage III or IV cancers across 12 prespecified cancer types after three screening rounds, compared with usual care alone. A between-group difference in stage IV cancer incidence was observed (incidence rate ratio, 0.86), but the confidence interval reached 1.00; the investigators recommend further follow-up to determine how outcomes for stage III or IV cancers and the observed difference in stage IV cancers change over time. Clinicians and policymakers should consider these findings in the context of additional follow-up data and comprehensive evaluation of benefits, harms, and implementation implications.
The trial was funded by Grail. It is registered as NHS-Galleri on ClinicalTrials.gov (NCT05611632) and also listed under ISRCTN91431511. The full report is published in the New England Journal of Medicine (2026 Oct 8;395(14):1374-1386; doi: 10.1056/NEJMoa2505723).