The analysis of cancer screening trials in which the outcome is the incidence of late-stage disease.

The National Health Service-Galleri randomized trial seeks to determine the extent to which a blood-based multi-cancer screening test can lead to a reduced incidence of a variety of cancers that are at a late stage as of the time of initial diagnosis. In February 2026, the investigators of this trial issued a news release indicating that after several years of follow-up, for a group of 12 pre-specified forms of cancer there was a lower incidence of stage IV cancer among patients in the intervention arm of the trial than in the control arm. The release stated that a group of participants whose stage IV cancer could not have been influenced by the screening - those with stage IV disease already present as of the initial screening exam - had been excluded from this analysis. We argue that while it is appropriate to restrict such an analysis to persons without prevalent stage IV cancer at the start of the trial, a valid result will be obtained only after accounting for the counterparts of these cases that are present in the trial's control arm. We describe how this can be accomplished, and the assumptions needed for such a strategy to succeed.