Multi-cancer early detection tests for general population screening: a systematic literature review.
Level 2 - randomized trial
Systematic review of predominantly observational diagnostic accuracy studies with no completed randomized trials
PubMed 39898371 · doi:10.3310/DLMT1294
What was done
A systematic review was conducted across electronic databases (MEDLINE, EMBASE, and trial registers through September 2023) and manufacturer sources to evaluate the clinical effectiveness of blood-based multi-cancer early detection tests in asymptomatic adults aged 50–79 years. Outcomes included test accuracy, cancer detection by site and stage, diagnostic resolution time, mortality, harms, quality of life, and acceptability. Risk of bias was assessed using QUADAS-2, and findings were synthesized narratively.
What was found
Thirty-six studies met criteria (1 ongoing randomized trial, 13 completed cohort studies, 17 completed case-control studies, and 5 ongoing observational studies) evaluating tests detecting 3 to over 50 cancer types. Specificity was consistently high (>96%), but sensitivity varied widely: Galleri reported sensitivity 20.8–66.3% and specificity 98.4–99.5% (3 studies); CancerSEEK sensitivity 27.1–62.3% and specificity 98.9–99.1% (2 studies); SPOT-MAS sensitivity 72.4–100% and specificity 97.0–99.9% (2 studies); Trucheck sensitivity 90.0% and specificity 96.4% (1 study); and Cancer Differentiation Analysis sensitivity 40.0% and specificity 97.6% (1 study). Sensitivity was lower for stage I–II versus stage III–IV cancers. No meaningful evidence was found for mortality, harms, quality of life, or acceptability.
Why it matters
While multi-cancer blood tests consistently demonstrate high specificity, their ability to detect early-stage treatable cancer remains uncertain, and clinical utility for reducing cancer-related mortality is unproven.
Limits
There were no completed randomized controlled trials. Most included studies had a high risk of bias, primarily from inadequate follow-up of participants with negative test results. Only one study evaluated an asymptomatic general screening population, and critical patient outcomes (mortality, overdiagnosis, screening harms, and quality of life) were not reported.
Cited by
- supports Function lab testing detects early signals associated with more than 50 types of cancer.