Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study.
Level 3 - non-randomized controlled study
Prospective single-arm cohort study evaluating diagnostic workup feasibility
PubMed 37805216 · doi:10.1016/S0140-6736(23)01700-2
What was done
A prospective cohort study (PATHFINDER) enrolled a convenience sample of 6662 adults aged 50 years or older without signs or symptoms of cancer across seven US health networks. Participants provided blood for multicancer early detection (MCED) cell-free DNA methylation testing. If a cancer signal was detected, predicted tissue-of-origin results were returned to physicians to guide clinical evaluation. The primary outcome was the time to and extent of diagnostic testing needed to confirm or rule out cancer.
What was found
Among 6621 participants with analysable results, a cancer signal was detected in 92 (1.4%). Of these, 35 (38%) were diagnosed with cancer (true positives) and 57 (62%) had no cancer diagnosis (false positives). Excluding two participants whose diagnostic assessments began prior to test results, the median time to diagnostic resolution was 79 days (IQR 37-219): 57 days (IQR 33-143) for true positives and 162 days (IQR 44-248) for false positives. Most participants underwent imaging (91% of true positives, 93% of false positives) and laboratory tests (79% of true positives, 88% of false positives). Invasive diagnostic procedures were performed in 82% of true positives and 30% of false positives; surgery occurred in three true-positive participants and one false-positive participant.
Why it matters
This study provides prospective evidence that blood-based multicancer early detection testing is feasible in outpatient settings and can direct targeted diagnostic workups to confirm cancers.
Limits
The study used a convenience sample with limited diversity (91.7% White, 63.5% female). It was an uncontrolled, single-arm study and did not measure clinical utility, morbidity, or mortality benefits, while false positives entailed prolonged diagnostic resolution times (median 162 days).
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- supports When used in healthy adults age 50 and older, the detection rate of early-stage cancer with the Galleri test is approximately 2 per 1,000 people.