Statement on the NHS–GRAIL Galleri Trial

We were disappointed to learn that the Galleri multi-cancer early detection (MCED) test, developed by GRAIL, did not meet the primary endpoint in its large randomized trial conducted in partnership with the National Health Service (NHS).¹

The study was designed to determine whether use of the Galleri test could shift cancer diagnoses from late stage (stage III/IV) to earlier stage (stage I/II) disease in a screened population.² While the trial did not meet this primary endpoint, investigators reported a shift from stage IV to stage III cancers in the Galleri arm.³

Only limited high-level results have been released publicly. Without more detailed data—including performance by tumor type, sensitivity by stage, interval cancer rates, and downstream clinical outcomes—it is not yet possible to determine whether the findings reflect limitations of the study design, the test itself, implementation factors, or broader challenges inherent to MCED approaches. There is currently no public information on outcomes by individual cancer type, so we cannot assess whether certain cancers may have benefited more than others.

WHAT THIS MEANS FOR CANCER SCREENING

These results underscore the difficulty of developing and validating cancer screening tests. Early validation studies suggested that circulating tumor DNA–based approaches could detect multiple cancers, but demonstrating meaningful stage shift in a real-world population requires very large, long-duration trials. In this case, approximately 142,000 participants were followed over three years.²

Large-scale prospective studies are essential to determine whether earlier detection meaningfully changes stage at diagnosis and, ultimately, patient outcomes.

The findings also draw attention to the current regulatory landscape in the United States, where some assays are offered as laboratory-developed tests (LDTs) and may be marketed prior to completion of large, randomized trials demonstrating clinical utility.⁴ Prospective validation remains critical for evaluating any screening intervention.

BIOLOGICAL CHALLENGES OF BLOOD-BASED MCED TESTS

Blood-based MCED tests rely on detecting very small amounts of tumor-derived material shed into circulation. For very small or early lesions, particularly in biologically aggressive cancers, circulating tumor DNA levels may be extremely low. This has long been recognized as a potential limitation of tumor DNA–based detection—especially for cancers such as pancreatic cancer, where tumors can progress rapidly even when small.

Lustgarten’s early detection strategy is intentionally broader. In addition to tumor-derived signals, we support research focused on detecting amplified host responses to early tumors or precancerous changes. These include immune and inflammatory signatures, systemic metabolic alterations, and structural or microenvironmental changes within the organ itself. Such signals may be more robust and detectable earlier than tumor DNA alone.

LOOKING AHEAD

No single approach is likely to solve early detection across all cancer types. Progress will require continued biological insight, technological innovation, and rigorous prospective validation. We remain committed to advancing foundational research on disease initiation and progression alongside novel detection strategies that have the potential to identify pancreatic cancer at its earliest, most treatable stages.

These results should not be generalized to other multi-cancer early detection tests currently in development, as technologies, targets, and validation strategies differ. Each platform must ultimately be evaluated based on its own prospective clinical evidence.

Footnotes

1. GRAIL announcement regarding NHS-Galleri trial results (2025).
2. NHS-Galleri trial: randomized study of approximately 142,000 participants evaluating stage shift in a screening population, conducted in partnership with the National Health Service.
3. Public summary statements reporting a shift from stage IV to stage III diagnoses in the intervention arm, though not meeting the predefined primary endpoint of increased stage I/II detection.
4. U.S. Food and Drug Administration regulatory framework regarding laboratory-developed tests (LDTs).