Galleri Reports Multi-Cancer Early Detection Test Performance Across 3 Screening Rounds

The Galleri multi-cancer early detection (MCED) blood test (GRAIL) had a positive predictive value (PPV) ranging from 45.8% to 58.0% across 3 annual screening rounds in the randomized NHS-Galleri trial, according to findings published in Nature Medicine. The test detects tumor methylation patterns in cell-free DNA isolated from peripheral blood.

The trial (NCT05611632) randomized 142,250 participants in England aged 50 to 77 years 1:1 to MCED testing added to usual care or to a control arm. The trial did not meet its primary endpoint of reducing the incidence of stage III/IV cancer diagnoses, which was reported separately. The new analysis covers prespecified secondary test performance endpoints in the intervention arm; the analyses were descriptive, with no hypothesis testing.

Positive results were returned for 1.03%, 0.80%, and 0.90% of evaluable participants in rounds 1, 2, and 3, respectively. PPV was 58.0% in round 1, 50.4% in round 2, and 45.8% in round 3. Specificity ranged from 99.50% to 99.60%. Episode sensitivity ranged from 26.7% to 37.2% for all cancers and from 47.6% to 63.4% for 12 prespecified cancer types.

In aggregate, 937 participants had MCED-detected primary cancers, and 68.3% of these were diagnosed at stage I to III. The first or second predicted cancer signal origin was accurate in 91.1% to 93.6% of true-positive results across rounds. As the investigators expected, PPV, cancer detection rate, and episode sensitivity decreased after the prevalent first round. The study was funded by GRAIL, which participated in study design, data interpretation, and manuscript drafting.

Limitations included 12 months of follow-up and overlap with the end of the COVID-19 pandemic, the authors noted. They wrote that a negative MCED result should not be interpreted as ruling out any particular cancer and that MCED testing is intended to complement, not replace, existing screening programs. Analyses of cancer-specific mortality and overdiagnosis will be reported in future publications.

Source: Neal RD, Dolly S, Johnson P, et al. Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial. Nat Med. Published online September 22, 2026. doi:10.1038/s41591-026-04652-8