e22570 Background: Blood-based multi-cancer early detection (MCED) tests analyze cfDNA biomarkers to screen for multiple cancers via a single blood draw . Early detection could improve outcomes by identifying cancers at earlier stages, but initial studies report widely varying accuracy. Methods: We reviewed published studies (through Jan 2026) of blood-based MCED tests in asymptomatic adults, including prospective screening cohorts and diagnostic-accuracy designs. Two reviewers extracted data (sensitivity, specificity, predictive values, stage distribution) and assessed study quality (QUADAS-2). Because of heterogeneity across test platforms and study designs, we summarize findings systematically. Results: 20 studies (109,872 participants) evaluated mainly cfDNA-based MCED assays (e.g., Galleri, CancerSEEK), largely in case–control or single-arm cohorts; few true population-screening trials were available (notable: PATHFINDER n=6,621; CCGA substudy n=4,077; a real-world Galleri series >111,000 tests). Risk of bias was frequently high (case enrichment, partial verification). Reported sensitivity ranged 9.5–100% and specificity 65.7–100%. In CCGA, Galleri showed overall sensitivity 51.5% and specificity 99.5%, with pronounced stage dependence (16.8% stage I vs 90.1% stage IV). In PATHFINDER, 35/92 positives were confirmed cancer (PPV 38%); specificity 99.1%, NPV 98.6%. In a separate real-world cohort, 63% of evaluated signal-positives had cancer; among asymptomatic patients completing workup PPV was 49.4%. MCED-detected cancers were skewed to advanced stages (PATHFINDER: 48% stage I–II vs 73% by usual care; Galleri series n=124; 28% stage I–II, 48% stage IV). Modeling predicts modest early-stage gains (+10–20%) and reduced metastatic incidence (45%), but mortality benefit is unproven. Positive results commonly triggered imaging and invasive procedures (49% biopsy/surgery; 82% TP vs 30% FP); serious adverse events were rare, and long-term harm from false positives appears limited. Conclusions: Published evidence indicates that blood-based MCED tests have very high specificity (99%) but only moderate sensitivity, especially for early-stage disease . In asymptomatic screening, only 30–50% of positive tests yield a cancer diagnosis (PPV) higher than most single-cancer screens, yet many positives prove false. Most initially detected cancers are late-stage; empirical stage-shift or mortality benefit remains to be demonstrated. Larger prospective trials (e.g. NHS-Galleri) with long-term follow-up are needed to determine the true clinical impact of MCED screening and to weigh potential benefits against the burden of false-positive workups.
Prajapati et al. (Thu,) studied this question.