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

Author(s): Peter Sasieni, Ph.D.1; Peter Johnson, M.D., F.R.C.P.2; Thomas Round, Ph.D.3; Jane Warwick, Ph.D.1; Helen Jones, B.N.4; Saoirse Dolly, M.B., B.S., Ph.D.5; Lennard Lee, B.M., B.Ch., D.Phil.6; Yujin Lee, M.Sc.1; Harpal Kumar, M.Eng., M.B.A., F.Med.Sci., F.R.C.R.7; Wei Liang, Ph.D.7; Rebecca Smittenaar, Ph.D.7; Richard D. Neal, M.B., Ch.B., Ph.D.8; Charles Swanton, M.B., B.S., Ph.D., F.R.C.P.9,10;
Source: DOI: 10.1056/NEJMoa2505723
Original Article
Professional photo of Anjan J Patel, MD

Dr. Anjan Patel's Thoughts

This is a large, well-designed negative trial. In more than 142,000 adults aged 50 to 77 in England, adding three annual rounds of the Galleri multicancer blood test to usual care did not reduce stage III/IV diagnoses across 12 prespecified cancers. There's an intriguing but non-significant trend toward fewer stage IV cancers, so longer follow-up is the real story to watch, and safety wasn't an issue (fewer than 1% had trial-related adverse events, none serious). For now this doesn't support routine MCED screening outside a trial, so have that conversation ready when patients ask about ordering it.

BACKGROUND

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

METHODS

In a randomized, controlled trial conducted in England, we obtained peripheral blood from persons 50 to 77 years of age 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 risk) were measured after three screening rounds and least 12 months of follow-up after the last participant’s third visit. Research Summary Effect of a Multicancer Early-Detection Test on Late-Stage Diagnosis

RESULTS

Overall, 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.

CONCLUSIONS

In 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.) Quick Take Multicancer Early-Detection, Late-Stage Cancer 2m 22s

Author Affiliations

1Queen Mary University of London, London; 2NHS England, London; 3King’s College London, London; 4EMS Healthcare, Cheshire, United Kingdom; 5Guy’s and St. Thomas’ NHS Foundation Trust, London; 6University of Oxford, Oxford, United Kingdom; 7GRAIL Bio UK, London; 8University of Exeter, Exeter, United Kingdom; 9University College London, London; 10Francis Crick Institute, London

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