Journal Club: NHS-Galleri (GRAIL)

A note on sourcing: This journal club is based on a conference presentation rather than a peer-reviewed publication. The data below come from the ASCO 2026 late-breaking abstract LBA100 and the accompanying presentation. A full manuscript has not yet been published at the time of this book, so the detailed methodology and subgroup analyses are not yet available for independent scrutiny.

Study Design

NHS-Galleri is the largest randomized controlled trial ever conducted for an MCED test. It was launched in England in 2021 and enrolled 142,924 adults aged 50 to 79 with no symptoms or suspicion of cancer. Participants were randomized to either an intervention arm, in which they underwent testing with Galleri, or to a control arm, in which they did not undergo testing with Galleri and instead underwent “routine” care. In the intervention arm, a “cancer signal detected” result triggered referral into the NHS for diagnostic workup.

The primary objective was a reduction in the combined incidence of stage III and stage IV cancers across 12 prespecified cancers (lung, head & neck, colorectal, pancreas, myeloma/plasma cell neoplasm, liver/bile duct, stomach, esophagus, anus, lymphoma, ovary, and bladder), measured roughly three years after the last participant was randomized. A reduction in stage IV cancer was a secondary objective. So, this trial was built to test whether the test could produce a “stage shift” (catching cancers earlier than they would’ve otherwise been caught) rather than whether the test leads to fewer deaths.

The study measured something called an “incidence rate ratio” (IRR) for each arm. The IRR is the rate of new cancers in the intervention arm divided by the rate in the control arm. Therefore, a value of 1.0 means no difference between the groups, while a value below 1.0 means fewer cancers with screening, and a value above 1.0 means more cancers with screening.

Results

The primary endpoint was not met. Across the 12 prespecified cancers, there were 706 stage III and IV cancers in the intervention arm and 688 in the control arm, for an IRR of 1.03 (95% CI 0.92-1.14, p = 0.63). In the first (prevalence) round, the Stage III and IV IRR was 1.19, which is roughly what would be expected when a relatively sensitive test is first used in a population and pulls forward a backlog of existing cancers. By the second and third rounds, the IRR fell to 0.95 and then 0.88.

The secondary endpoint was positive. The IRR for stage IV cancers was 0.86 in the intervention arm (342 stage IV cancers in the intervention arm vs 397 in the control arm; 95% CI 0.744-.998), and, like the IRR trend seen for stage III and IV cancers, the effect grew with each round of screening (a 9% reduction after year 0, 22% after year 1, and 26% after year 2).

The number of stage I and II cancers was higher in the interventional arm (647 in the interventional arm vs 559 in the control arm; relative risk 1.16, 95% CI 1.03-1.30), as were the number of stage I-III cancers (1,007 in the interventional arm vs 846 in the control arm; RR 1.19, 95% CI 1.09-1.30).

Across all cancer types, 3,637 cancers were diagnosed in the intervention arm and 3,400 in the control arm over three years of screening. Adding the MCED test quadrupled the number of “screen-detected cancers” (1,173 in the interventional arm vs 290 in the control arm). It is my understanding that “screen-detected cancers” are those that are found in individuals without symptoms or signs of cancer. Additionally, adding the MCED test reduced the number of cancers detected clinically (meaning after they caused symptoms or other problems) by 21% (2,464 in the interventional arm vs 3,110 in the control arm), and reduced emergency presentations of cancer by 21% (225 in the interventional arm vs 286 in the control arm). The test’s aggregate performance (99.55% specificity, 52.0% PPV, and 92.5% cancer signal origin accuracy for the top two predicted cancer origin sites) was consistent with what GRAIL has reported in its other studies described in this book. With regard to safety, there were 381 related adverse events in the intervention arm and 333 in the control arm, and no related serious adverse events. Not much information was provided on these adverse events in the conference abstract.

What I Think

The good news:

1. In my opinion, this is the most important dataset in the field, and parts of it are encouraging. Specifically, the 14% reduction in stage IV cancer diagnoses was not just statistically significant but is also clinically meaningful.
2. The fact that testing with Galleri led to fewer emergency presentations and fewer cancers presenting clinically with symptoms suggests the test changed how and when cancers are found in a large, real-world health system (not just in a research cohort).

That said, the headline is the headline. The primary endpoint was not met.

1. The trial was designed and powered to show a reduction in combined stage III and IV cancer across 12 different types of cancers, and it did not. As stated above, the favorable trends in the later rounds and the stage IV reduction are encouraging, but they are, formally, secondary. Reading too much into secondary and exploratory findings from a trial that missed its primary endpoint is exactly the kind of thing I try to be careful about elsewhere in this book.
2. A stage shift is a surrogate endpoint, and it is not the same as showing that screened people live longer than unscreened people, which, to me, is the most important question for cancer screening tests.
3. The sensitivity of the test, particularly by stage, is not reported. While I do not know why these numbers were not presented, I can only assume that this was because the sensitivity for early-stage cancer, as with other tests and studies in this book, was relatively low.
4. The data are from a conference presentation and have not yet been peer-reviewed or published as a full manuscript.