Multicancer Detection Tests for Population-Wide Screening of Asymptomatic Individuals: A Systematic Review.

Abstract

Purpose: Multicancer detection (MCD) tests aim to detect different cancer types using a single test. However, evidence on their potential for screening asymptomatic populations remains limited. We consolidated evidence from prospective cohort studies evaluating blood-based MCD tests in primarily asymptomatic adults to contextualize upcoming randomized controlled trial results.

Materials and methods: We updated and extended a prior review (to September 2023), conducting comprehensive Medline/Embase searches to February 1, 2026. Key outcomes included cancers detected and not detected by MCD tests, false-positive MCD tests, and diagnostic investigation pathways. Risk of bias (RoB) was assessed using a modified Quality Assessment of Diagnostic Accuracy Studies-2 tool.

Results: From 2,723 screened records (244 previously shortlisted to 2023, 2,479 records for 2023-2026), we included 18 articles (12 studies, nine MCD tests); of these, 11 articles had not appeared in prior reviews. Cancer detection rates varied widely between studies, for example, new MCD-test-detected invasive cancers diagnosed ≤12 months post-test ranging from 18.8 (95% CI, 11.0 to 30.1) to 43.8 (95% CI, 29.4 to 62.8) per 10,000 tested, with MCD-test-detected invasive stage I to II cancers ranging from 9.0 (95% CI, 4.2 to 17.2) to 21.0 (95% CI, 11.6 to 35.5) per 10,000 tested. False-positives exceeded MCD-test-detected cancers (eg, approximately 1.6-fold in PATHFINDER, 1.5-fold K-DETEK, 4.2-fold DETECT-A, 8.1-fold SeekInCare studies). Diagnostic investigation pathways were prespecified/suggested in four of eight interventional studies. Where reported, the median time to diagnostic resolution varied from <0.1 months to 4 months for MCD-test-detected cancers, with substantially higher 75th percentiles (3.1-7 months), and similar patterns were observed for false-positive MCD tests. No study was judged to have overall low RoB.

Conclusion: Substantial heterogeneity in cancer yield metrics likely reflects differences in MCD technologies, diagnostic pathways, follow-up duration, and background standard-of-care screening. Long-term follow-up, randomized trials, fully-paired test comparisons, and implementation research are essential to determine the potential of MCD tests for population screening.