Galleri Test: Multi-Cancer Blood Screening Detects 50+ Cancer Types

How Does the Galleri Multi-Cancer Blood Test Work?

The Galleri test works by detecting abnormal methylation patterns in cell-free DNA (cfDNA) circulating in the bloodstream. When cancer cells grow and die, they release fragments of their DNA into the blood. These fragments carry distinctive methylation signatures, which are chemical modifications that affect gene expression without changing the DNA sequence. GRAIL's proprietary machine learning algorithm analyzes over one million methylation sites across the genome to distinguish cancer-derived cfDNA from normal cfDNA, enabling detection of a cancer signal and prediction of the cancer signal origin (CSO), which identifies where in the body the cancer is likely located.

The test is performed on a standard blood draw of approximately 20 milliliters and requires no special preparation by the patient. Results are returned within approximately two weeks, reported as either "Cancer Signal Detected" with a predicted tissue of origin, or "Cancer Signal Not Detected." The tissue of origin prediction accuracy exceeds 88% in cases where a cancer signal is detected, which is critical for directing follow-up diagnostic workup to the appropriate organ system rather than requiring extensive whole-body imaging.

Galleri uses targeted methylation sequencing technology, specifically bisulfite sequencing of selected genomic regions, rather than whole-genome sequencing. This approach was validated in the Circulating Cell-free Genome Atlas (CCGA) study, a large prospective, multi-center, observational study involving over 15,000 participants. The methylation-based approach proved superior to other cfDNA analysis methods including whole-genome sequencing for mutation detection, because methylation patterns provide stronger cancer-type-specific signals and are less affected by clonal hematopoiesis of indeterminate potential (CHIP), a common age-related phenomenon that can cause false positive results in mutation-based liquid biopsies.

How Accurate Is the Galleri Test at Detecting Cancer?

The Galleri test's performance varies significantly by cancer stage, reflecting the biological reality that later-stage cancers shed more cfDNA into the bloodstream. In the CCGA substudy published in Annals of Oncology, the overall sensitivity was 51.5% across all cancer types and stages. Critically, sensitivity increases substantially with stage: approximately 16.8% for Stage I cancers, 40.4% for Stage II, 77% for Stage III, and 90.1% for Stage IV. The specificity is 99.5%, meaning that only about 0.5% of people without cancer receive a false positive result, which is important for minimizing unnecessary follow-up procedures and patient anxiety.

Performance also varies by cancer type. The test performs particularly well for aggressive cancers that shed abundant cfDNA, including pancreatic cancer (sensitivity approximately 83.7% across stages), hepatobiliary cancers, head and neck cancers, and ovarian cancer. For cancers with existing standard screening tests, such as breast cancer detected by mammography and cervical cancer detected by Pap smears, the sensitivity is generally lower, reflecting that these cancers may be caught at very early stages when cfDNA shedding is minimal. Importantly, Galleri is designed to complement, not replace, existing recommended cancer screening programs.

The positive predictive value (PPV), which indicates the probability that a positive result truly represents cancer, is strongly influenced by the prevalence of cancer in the screened population. In the PATHFINDER study of approximately 6,600 adults aged 50 and older, the PPV was 43.1%, meaning that roughly 4 in 10 individuals with a cancer signal detected were subsequently diagnosed with cancer upon diagnostic workup. This PPV is comparable to or better than established screening tests in certain contexts. However, the relatively low sensitivity for Stage I cancers means that a negative result does not rule out cancer, and patients should continue standard screening and remain alert to symptoms.

What Is the NHS-Galleri Trial Studying?

The NHS-Galleri trial is one of the most ambitious cancer screening studies ever conducted. Launched in 2021 by the National Health Service in England in partnership with GRAIL, the trial enrolled approximately 140,000 asymptomatic participants aged 50-77 from 13 NHS regions. Participants were randomized 1:1 to either receive annual Galleri blood tests for three years alongside routine NHS care, or to continue routine NHS care alone. The primary endpoint is whether Galleri screening shifts cancer diagnoses to earlier stages, specifically reducing the proportion of cancers diagnosed at Stage III or IV.

Initial results from the first screening round were presented at the European Society for Medical Oncology (ESMO) Congress in 2023. Among approximately 5,461 participants with positive cancer signals, diagnostic evaluation confirmed cancer in a clinically meaningful proportion. The trial found that 66% of cancers detected by Galleri in the screened group were types for which no standard NHS screening program exists, highlighting the test's potential to fill gaps in existing cancer detection. However, the trial also revealed challenges in the diagnostic workup pathway, with some participants requiring multiple investigations to locate the cancer suggested by the tissue of origin prediction.

The trial's long-term follow-up will be critical for answering the ultimate question: does early detection through multi-cancer screening translate into improved survival? Stage shift is used as a surrogate endpoint because earlier-stage cancers generally have significantly better prognosis and more treatment options, but definitive mortality data will require years of additional follow-up. The NHS has indicated that if the trial demonstrates clear clinical benefit, it will consider incorporating Galleri into the national screening program, potentially transforming cancer detection for millions of people.