MCED (Multi-cancer early detection) tests

Multi-cancer early detection (MCED) tests are blood assays interrogating plasma cell-free DNA - chiefly methylation patterns and fragmentomics - to detect a shared "cancer signal" across many tumour types and predict the tissue of origin. The most advanced is GRAIL's Galleri, which uses targeted methylation sequencing across more than 100,000 genomic regions. In the PATHFINDER cohort study (Schrag 2023), Galleri detected a cancer signal in 1.4% of 6,621 adults aged >=50, with specificity 99.1% and a positive predictive value of 38%; the underlying case-control CCGA validation (Klein 2021) reported specificity 99.5%, tissue-of-origin accuracy 88%, and overall sensitivity of about 51%, rising sharply with stage. SYMPLIFY (Nicholson 2023) showed a positive predictive value of 75.5% in symptomatic primary-care patients. Galleri is marketed in the US as a laboratory-developed test; GRAIL submitted a PMA to the FDA on 29 January 2026 (informed by PATHFINDER 2, presented at ESMO October 2025), and headline NHS-Galleri results (February 2026) missed the primary stage-shift endpoint but showed fewer stage-IV diagnoses in a pre-specified subgroup of 12 deadly cancers. Confounders include benign inflammation, recent biopsy, pregnancy and clonal haematopoiesis.