PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms
In 6,621 adults over 50, the Galleri test flagged a cancer signal in 1.4%, of whom 38% turned out to have cancer; diagnostic work-up took about two months for true positives and over five months for false positives.
PATHFINDER was a single-arm prospective study in which 6,621 adults aged 50 or over at seven US health systems had the Galleri methylation-based multi-cancer early detection (MCED) test in addition to standard screening. A cancer signal triggered clinician-directed diagnostic evaluation guided by the predicted cancer signal origin.
A signal was detected in 92 participants (1.4%); 35 had cancer confirmed, giving a positive predictive value of 38%. Specificity was 99.1% and the cancer signal origin prediction was correct in the large majority of true positives. Median time to diagnostic resolution was 79 days: 57 days for true positives and 162 days for false positives. Almost half of the cancers detected were early stage, and several were in organs without standard screening.
The study established feasibility and the diagnostic pathway and set the stage for the randomised NHS-Galleri trial and the larger PATHFINDER 2.
- Cancer signal detected in 92 of 6,621 (1.4%); 35 true positives, PPV 38%
- Specificity 99.1%; negative predictive value 98.6%
- Median time to diagnostic resolution 79 days (57 for true positives, 162 for false positives)
- Most participants with a false-positive signal underwent imaging and a substantial minority an invasive procedure
A multi-cancer blood test can be run in ordinary clinics, and most positive results can be resolved with imaging. But six in ten positives are false alarms that take months to resolve, and the test misses most cancers. Whether it reduces late-stage cancer or deaths is unknown; that requires randomised trials.
- Single-arm; no control group and no mortality or stage-shift endpoint
- Sensitivity for incident cancers was low because many cancers arose after a negative test
- Participants were largely white, insured and health-literate
- Harm from false positives (anxiety, procedures, cost) was documented but not weighed against benefit
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