By Ethan Covey

A circulating tumor DNA (ctDNA)–based blood test demonstrated its ability to accurately detect colorectal cancer among a population of average-risk individuals, according to a study recently published in JAMA (2025;334[1]:56-63). However, the test struggled to detect advanced precancerous lesions.

While colorectal cancer screening is recommended for average-risk adults starting at age 45, it is widely underused.

“Despite the availability of multiple screening modalities, only an estimated 59% of eligible individuals aged 45 years or older were up to date with guideline-recommended screening in 2021, well below the 80% national goal,” the authors of the study wrote.

Reasons for the suboptimal uptake of screening include the invasive nature of procedures, potential discomfort and risks, and resource utilization associated with colonoscopy. Preparing for and participating in a colonoscopy can cause missed work and requires transportation assistance. In addition, some individuals have an aversion to handling stool, which can complicate stool testing methods. Finally, socioeconomic, racial and geographic barriers have been identified that significantly reduce access to screening among certain populations.

Many, if not all, of these factors may be addressed by the use of a noninvasive, blood-based ctDNA screening test.

The test, which was evaluated in the PREEMPT CRC (Prevention of Colorectal Cancer Through Multiomics Blood Testing) study, is an investigational, qualitative, next-generation sequencing, in vitro diagnostic test that detects patterns of CpG (cytosine followed by guanine) dinucleotide methylation associated with advanced colorectal neoplasia, including colorectal cancer and advanced precancerous lesions. The test is conducted on plasma derived from whole blood samples.

From May 2020 through April 2022, the study enrolled 48,995 asymptomatic adults aged 45 to 85 years from 201 sites in 49 U.S. states and the United Arab Emirates. A total of 27,010 participants were included in the evaluable cohort (median age, 57; 55.8% female).

Among this group, the assay achieved a sensitivity of 79.2% for colorectal cancer detection and a specificity of 91.5% for advanced colorectal neoplasia—including both cancer and advanced precancerous lesions. The negative predictive value for advanced colorectal neoplasia was 90.8%, and the positive predictive value for advanced colorectal neoplasia was 15.5%.

However, a notable limitation emerged: Sensitivity for advanced precancerous lesions was only 12.5%, falling substantially short of the prespecified acceptance criterion. This underscores that while ctDNA detection performs adequately for established colorectal cancer, its ability to identify high-risk adenomas remains limited.

“[The] blood-based test demonstrated acceptable accuracy for colorectal cancer detection, but detection of advanced precancerous lesions remains a challenge, and ongoing efforts are needed to improve test sensitivity,” the study authors wrote.