The results of the randomized NHS-Galleri trial reported by Sasieni et al in The New England Journal of Medicine showed that annual screening with a blood-based multicancer early detection test added to usual care did not result in a significantly lower incidence rate of stage III or IV cancers across 12 prespecified cancer types after three screening rounds.
Study Details
The ongoing prospective trial, conducted in England, evaluated the clinical utility of the Galleri multicancer early detection blood test when added to usual care. The test analyzes methylation patterns in cell-free DNA to detect a cancer signal and predict its tissue or organ of origin.
Eligible individuals were aged 50 to 77 years and had not received a cancer diagnosis or treatment within the previous 3 years or been undergoing evaluation for suspected cancer. A total of 142,250 participants were randomly assigned 1:1 to the intervention group (n = 71,122), in which blood samples underwent multicancer early detection testing, or the control group (n = 71,128), in which samples were stored. Participants were invited for two additional annual blood collections. Those in the intervention group with a positive test result were referred for diagnostic evaluation through established National Health Service urgent cancer referral pathways.
The primary endpoint was the incidence rate of stage III or IV cancer among 12 prespecified cancer types: lung, head and neck, colorectal, pancreatic, myeloma or plasma cell neoplasm, liver or bile duct, stomach, esophageal, anal, lymphoma, ovarian, and bladder cancers. Stage IV cancer among these 12 types was a key secondary endpoint. Participants had 12 months of follow-up after each of the first two screening rounds and a median of 17 months (range = 12–22 months) after the third round.
Key Results
After three screening rounds, 706 participants in the intervention group and 688 in the control group had been diagnosed with stage III or IV cancer among the 12 prespecified types. The corresponding incidence rates were 300.5 and 292.5 per 100,000 person-years, respectively, yielding an incidence rate ratio of 1.03 (95% confidence interval [CI] = 0.92–1.14, P = .63). The incidence rate of stage III or IV cancer therefore did not differ significantly between the groups.
However, the incidence rate of stage IV cancer was lower in the intervention group than in the control group: 145.2 vs 168.5 per 100,000 person-years, respectively (incidence rate ratio = 0.86; 95% CI = 0.74–1.00). The incidence rate ratio for stage IV cancer was 0.91 (95% CI = 0.71–1.18) in the first screening round, 0.78 (95% CI = 0.57–1.06) in the second, and 0.74 (95% CI = 0.57–0.95) in the third.
The investigators concluded: “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.”
Charles Swanton, MB, BS, PhD, FRCP, of University College London and the Francis Crick Institute, London, is the corresponding author for the New England Journal of Medicine article.
DISCLOSURE: The study was supported by Grail. For full disclosures of the study authors, visit nejm.org.
