1. 83.1% of patients with confirmed colorectal cancer had a positive cfDNA test meeting the accepted standard as outlined by the Food and Drug Administration.

2. Of patients without colorectal cancer, the majority (89.6%) tested negative in the screening blood test, meeting acceptable cut-offs for specificity.

Evidence Rating Level: 2 (Good)

Study Rundown: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in the USA and over 30% of those eligible are not up to date in their screening. Of those who die from CRC, most are not up to date with screening, emphasizing the importance of this preventative measure. The option of implementing a blood-based test would potentially increase screening adherence rates thereby resulting in a reduction of CRC-related morbidity and mortality. This study explored the sensitivity (Sn) for CRC and specificity (Sp) for advanced neoplasia of a blood-based, cell-free DNA (cfDNA) CRC screening test on patients, as compared to the colonoscopy reference standard. The secondary outcome was Sn for the detection of advanced pre-cancerous lesions. Most patients with CRC tested positive in the blood test (83.1%), resulting in a Sn that was determined to meet the accepted standard as outlined by the Food and Drug Administration (FDA). Similarly, the Sp assessment revealed that in patients without a CRC diagnosis, the majority (89.6%) tested negative in the blood test, adhering to the approved FDA requirement. Finally, in patients with a negative colonoscopy, the majority (89.9%) were found to have a negative cfDNA test. Limitations to this study include that the sample of patients with CRC was small, and therefore analytical comparisons of sensitivity according to stage were not appropriately powered. Additionally, features of advanced precancerous lesions may not be detected in the current blood-based screening method. Overall, the results from this study suggest that implementing a blood-based screening test for CRC is a viable research endevaour and further studies comparing the addition of cfDNA in colorectal cancer screening programs will help gauge the level of added utility of using this next generation technique.

Click to read the study in the NEJM

Click to read an accompanying editorial in NEJM

Relevant Reading: Blood test increases colorectal cancer screening in persons who declined colonoscopy and fecal immunochemical test: a randomized controlled trial.

In-Depth [prospective cohort]: This validating cohort trial enrolled 65 patients with colonoscopy-confirmed CRC in addition to a total of 7,861 adult patients without CRC who had an average CRC risk between the ages of 45-84 years old (these participants comprised the clinical validation cohort). Of patients with known CRC, 83.1% had a positive cfDNA test (Sn = 83.1% (95% confidence interval (CI), 72.2% to 90.3%); 16.9% were found to have a negative result. This is in keeping with the accepted standard as outlined by the FDA if the lower boundary of the two-sided Wilson CI is greater than 65%. The Sn of the test to identify screening-relevant CRC was 87.5% (95% CI, 75.3% to 94.1%). Screening-relevant CRC included stage I (Sn 65% (95% CI, 41% to 83%)), stage II (Sn 100% (95% CI, 78% to 100%)), stage III (Sn 100% (95% CI, 82% to 100%)), and stage IV (Sn 100% (95% CI, 72% to 100%)). Of the patients without CRC, 89.6% had a negative cfDNA blood test, resulting in a Sp of 89.6% (95% CI, 88.8% to 90.3%). According to the FDA standards, it is an acceptable screening test if the lower boundary is greater than 85%. Of patients with a negative colonoscopy, 89.9% had a negative cfDNA test, indicating a Sp for no neoplasia of 89.9% (95% CI, 89.0% to 90.7%).

Image: PD

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