MULTICANCER detection is moving closer to routine clinical use, with research demonstrating how a new low-cost blood test shows strong accuracy across multiple cancers and diseases, highlighting the growing potential of cfDNA based diagnostics for early detection.
Multicancer Detection and cfDNA Background
Multicancer detection using cell-free DNA has emerged as a promising noninvasive strategy, capturing molecular signals released from multiple organs into the bloodstream. However, existing assays are often expensive and limited to single conditions, restricting broader clinical application of multicancer detection technologies.
Methods and Results of Multicancer Detection Study
Researchers developed MethylScan, a cost effective cfDNA methylome sequencing assay, and evaluated its performance in a cohort of 1061 individuals across multiple diagnostic applications. The assay uses methylation sensitive restriction enzymes to enrich hypermethylated cfDNA fragments, followed by sequencing and machine learning based analysis. Primary outcomes included diagnostic accuracy for multicancer detection, liver cancer surveillance, and disease classification, measured using AUROC, sensitivity, and specificity.
For multicancer detection across liver, lung, ovarian, and stomach cancers, the assay achieved AUROC of 0.938 (95% CI: 0.920 to 0.954), with sensitivity of 63.3% (95%: CI 58.9 to 67.9%) at specificity of 98.0%.
For early-stage cancers, AUROC was 0.916 (95% CI: 0.890 to 0.940), with a sensitivity of 55.3% (95% CI: 49.1 to 62.1%) at the same specificity. In liver cancer surveillance, AUROC reached 0.927 (95% CI: 0.889 to 0.959) with a sensitivity of 79.6% (95% CI: 70.6 to 87.8%) at a specificity of 90.4%.
Clinical Implications
These findings suggest multicancer detection using a single blood test may become more accessible and scalable, particularly due to reduced sequencing costs. The ability to simultaneously detect multiple diseases, including cancer and organ injury, could transform screening pathways and enable earlier intervention. Future research should validate performance in larger and more diverse cohorts, refine sensitivity for early-stage disease, and assess real-world clinical utility.
Reference
Zeng W et al. Toward the simultaneous detection of multiple diseases with a highly cost-effective cell-free DNA methylome test. PNAS. 2026;23(15):e2518347123.
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