Blood-based ctDNA tests are gaining attention as a non-invasive alternative for colorectal cancer screening, offering high specificity and reasonable accuracy for detecting established cancers. However, a large meta-analysis shows their biggest limitation remains unchanged: poor detection of precancerous lesions, the very targets that enable true cancer prevention.
While next-generation methylation assays are improving cancer detection rates, sensitivity for advanced precancerous lesions remains strikingly low. This creates a fundamental gap—ctDNA can help identify cancer once it is present, but lacks the ability to reliably intercept the disease earlier in its progression. In real-world screening populations, this also translates into low positive predictive value, despite strong negative predictive performance.
The implication is less about performance—and more about positioning. ctDNA may improve screening adherence due to its convenience, but it does not yet replicate the preventive power of colonoscopy or stool-based testing.