A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening.
Level 2 - randomized trial
Prospective diagnostic accuracy validation study with a consistently applied reference standard (colonoscopy)
PubMed 38477985 · doi:10.1056/NEJMoa2304714
What was done
A prospective clinical validation study evaluated the diagnostic performance of a cell-free DNA (cfDNA) blood-based test for colorectal cancer screening in an average-risk screening-eligible population compared with screening colonoscopy. Among 10,258 enrolled participants, 7,861 met eligibility criteria and were evaluable. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions). The secondary outcome was sensitivity for advanced precancerous lesions.
What was found
Sensitivity for colorectal cancer was 83.1% (95% CI, 72.2 to 90.3). Sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3 to 94.1), and sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3 to 15.3). Specificity for any advanced neoplasia was 89.6% (95% CI, 88.8 to 90.3), with 10.4% having a positive test. Specificity for negative colonoscopy was 89.9% (95% CI, 89.0 to 90.7).
Why it matters
This blood-based test provides a noninvasive screening alternative that detects over 80% of colorectal cancers, potentially improving screening adherence. However, its low sensitivity for precancerous polyps limits its effectiveness for cancer prevention compared to structural exams.
Limits
The test missed 86.8% of advanced precancerous lesions, limiting its ability to prevent cancer development. Out of 10,258 enrolled participants, 2,397 (23.4%) were unevaluable. The abstract does not assess long-term adherence, optimal screening intervals, cost-effectiveness, or mortality reduction. The study was funded by Guardant Health.
Cited by
- supports A recently published study evaluated a blood-based test for colon cancer screening that showed approximately 80% sensitivity and 90% specificity.