Cell-free DNA blood test for the early detection of colorectal cancer

April 2024 Health Innovation Andrea Enguita

Early detection of colorectal cancer (CRC) could prevent more than 90% of CRC-related deaths. Recently published in the New England Journal of Medicine, the use of a cell-free DNA (cfDNA) blood-based test showed high sensitivity and accuracy for the detection of CRC in average-risk screening populations, offering new prospects for early intervention and improved outcomes.

Colorectal cancer (CRC) is the third most common cancer worldwide, accounting for approximately 10% of all cancer cases and is the second leading cause of cancer-related deaths worldwide.1 Early detection could prevent more than 90% of CRC-related deaths, yet more than one-third of the screening-eligible population is not up to date with screening. The detection of CRC using a blood-based test could improve screening adherence, allow its earlier detection and reduce CRC-related mortality. Building upon these insights, the ECLIPSE (Evaluation of the ctDNA LUNAR Test in an Average Patient Screening Episode) study was conducted to assess the performance of a cell-free (cf)DNA blood-based test to detect asymptomatic and early-stage CRC in a population eligible for CRC screening.2


This study included patients aged 45 to 84 years at average risk for CRC and undergoing routine screening with colonoscopy. Standard-care screening colonoscopy was preferably performed within 60 days after enrolment. However, due to procedural delays resulting from the COVID-19 pandemic, an extended timeline for colonoscopy was permitted. Whole-blood samples (30 to 80 ml) were collected in Streck cfDNA blood-collection tubes, processed to plasma, and stored at -80°C until the cfDNA blood-based assay (Shield, Guardant Health) was performed. The panel employed in the assay analysed cfDNA genomic alterations, aberrant methylation status, and fragmentomic patterns. The results were categorised into a binary format, either “abnormal signal detected” indicating a positive test, or “normal signal detected” indicating a negative test. The coprimary outcomes were sensitivity for CRC and specificity for advanced neoplasia in average-risk participants, 45 to 84 years of age, as compared with the colonoscopy reference standard.2

Study findings

In total, 7,861 patients were assessed in this study. Among participants diagnosed with CRC through colonoscopy, 83.1% tested positive for cfDNA, while 16.9% tested negative, yielding a sensitivity of 83.1% (95% confidence interval [CI]: 72.2-90.3) for detecting CRC. The sensitivity for detecting stage I, II or III CRC was 87.5% (95% CI: 75.3-94.1), while it was 13.2% (95% CI: 11.3-15.3) for advanced precancerous lesions. Among participants without any advanced colorectal neoplasia (CRC or advanced precancerous lesions) detected on colonoscopy, 89.6% tested negative for the cfDNA blood-based test, while 10.4% tested positive, resulting in a specificity for any advanced neoplasia of 89.6% (95%CI: 88.8-90.3). The specificity for negative colonoscopy (indicating no CRC, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95%CI: 89.0-90.7).2

In conclusion, the findings from the ECLIPSE study showed promising results from the cfDNA blood-based test for the detection of CRC in average-risk screening populations. In these patients, this test exhibited 83% sensitivity for CRC, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions.2


  1. Fact sheets for colorectal cancer. World Health Organisation (WHO).
  2. Chung DC, Gray DM, Harminder S, et al. A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening. N Engl J Med 2024;390:973-83.