Effect of Screening with Multicancer Early-Detection Test on Late-Stage Cancer Diagnosis.

backgroundWhether screening with blood-based early-detection tests for multiple cancers in addition to usual care has clinical utility is unknown.

methodsIn a randomized, controlled trial conducted in England, we obtained peripheral blood from persons 50 to 77 years of age at up to three annual visits. After baseline blood collection, participants were randomly assigned in a 1:1 ratio to the intervention group (participants whose blood was tested) or the control group (participants whose blood was stored). Participants and trial personnel were initially unaware of the group assignments. The primary end point was stage III or IV cancer among 12 prespecified types of cancer, and a key secondary end point was stage IV cancer among the 12 prespecified types. The differences between the groups in the incidence rate (the number of first eligible events divided by person-years at risk) were measured after three screening rounds and at least 12 months of follow-up after the last participant's third visit.

resultsOverall, 71,122 participants were randomly assigned to the intervention group and 71,128 to the control group. The incidence rate of stage III or IV cancer (primary end point) did not differ significantly between the groups (incidence rate ratio [intervention vs. control], 1.03; 95% confidence interval [CI], 0.92 to 1.14, P = 0.63). The incidence rate ratio for stage IV cancer (a key secondary end point) after 3 screening rounds was 0.86 (95% CI, 0.74 to 1.00). Less than 1% of participants had trial-related adverse events; none were serious.

conclusionsIn this trial, we did not observe a lower incidence rate of stage III or IV cancers across 12 prespecified cancers after three screening rounds with multicancer early-detection testing plus usual care than with usual care alone. Further follow-up is warranted to assess the way in which findings for stage III or IV cancers and the between-group difference in stage IV cancers evolve over time. (Funded by Grail; NHS-Galleri ClinicalTrials.gov number, NCT05611632; ISRCTN number, ISRCTN91431511.).