Blood-Based ctDNA Test Demonstrates Acceptable Accuracy for Colorectal Cancer Detection

Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths globally, with over 1.9 million new cases and 930,000 deaths reported in 2020 alone. Early detection through regular screening is crucial for reducing both incidence and mortality. While current methods like stool-based tests and visual exams are widely used, there is growing interest in blood-based tests as a less invasive alternative. A prospective study published in JAMA highlights a new blood-based circulating tumor DNA (ctDNA) test that demonstrated 79.2% sensitivity and 91.5% specificity for CRC detection, suggesting it could serve as a viable noninvasive screening tool.

The population-based, observational study by researchers from NYU Grossman School of Medicine (New York, NY, USA) aimed to evaluate the diagnostic accuracy of this investigational test in a large, average-risk screening population. It was conducted between May 2020 and April 2022 across 201 centers in the United States and the United Arab Emirates. All participants were asymptomatic adults aged 45 to 85 years and considered to be at average risk for CRC. The study was conducted under blinded conditions, with both participants and study personnel unaware of the test results, to minimize potential bias. Participants underwent a blood draw followed by a standard-of-care colonoscopy. Blood samples were collected either on-site or through mobile phlebotomy. The ctDNA test is designed to detect mutations linked to colorectal cancer in the bloodstream. The study’s primary outcomes were sensitivity for CRC, specificity for advanced colorectal neoplasia, and both positive and negative predictive values. Sensitivity for detecting advanced precancerous lesions was assessed as a secondary endpoint.

Among 27,010 participants in the evaluable cohort, with a mean age of 58.1 years and 55.8% identifying as women, the blood-based test met all prespecified criteria for its primary endpoints. It showed 79.2% sensitivity for CRC detection and 91.5% specificity for advanced colorectal neoplasia. The test achieved a negative predictive value of 90.8% and a positive predictive value of 15.5%. However, its sensitivity for detecting advanced precancerous lesions was 12.5%, which did not meet the predefined threshold. The researchers acknowledged certain limitations. The study only assessed the one-time diagnostic accuracy of the blood-based test and did not compare it with other existing screening methods in terms of patient acceptability or long-term effectiveness. Additionally, the impact of such blood-based testing on CRC incidence and mortality, as well as the ideal screening interval, remains uncertain and will require further exploration through future studies and modeling. Despite these constraints, the study was strengthened by its large and demographically diverse sample drawn from urban and rural regions in the US. The use of a decentralized trial platform, which allowed for both direct-to-participant and site-based enrollment, was instrumental in maintaining enrollment momentum during the COVID-19 pandemic and reaching underrepresented areas.

“In an average-risk colorectal cancer screening population, a blood-based test demonstrated acceptable accuracy for [CRC] detection, but detection of advanced precancerous lesions remains a challenge, and ongoing efforts are needed to improve test sensitivity,” wrote the researchers.