Blood Test Detects 79% of Colorectal Cancers in Screening Study

A blood-based circulating tumor DNA (ctDNA) test detected colorectal cancer (CRC) with 79.2% sensitivity and 91.5% specificity, according to a recent prospective study.¹ These findings suggest the investigational test may be a viable noninvasive screening option, although its ability to detect advanced precancerous lesions remains limited.

The population-based, observational study is published in JAMA.

A circulating tumor DNA (ctDNA) blood test demonstrated high sensitivity and specificity for colorectal cancer (CRC) detection in a large average-risk population, study finds. | Image credit: Ahmet Aglamaz - stock.adobe.com

“This study was designed as a large, prospective diagnostic accuracy evaluation of a blood-based CRC screening test, with blinded comparison to colonoscopy in an average-risk screening population,” wrote the researchers of the study. “It enrolled a geographically and demographically diverse cohort across 201 sites, approximating the racial and ethnic distribution of the US.”

CRC is the second leading cause of cancer-related deaths globally, with more than 1.9 million new cases and 930,000 deaths estimated in 2020 alone.² Increased access to screening options—including stool-based tests, visual exams, and emerging blood-based tests—can help detect CRC at its most treatable stages and reduce both incidence and mortality.³

The study enrolled asymptomatic adults aged 45 to 85 years at average risk for CRC between May 2020 and April 2022 across 201 centers in US states and the United Arab Emirates.¹ Participants were required to complete a standard of care colonoscopy following a blood draw. Both study personnel and participants were blinded to test results to reduce bias, and blood samples were collected through site-based or mobile phlebotomy. The primary outcomes included sensitivity for CRC, specificity for advanced colorectal neoplasia, and both positive and negative predictive values. Sensitivity for advanced precancerous lesions was evaluated as a secondary end point.

Among the 27,010 participants in the evaluable cohort, the mean (SD) age was 58.1 (8.2) years and 55.8% identified as women. The investigational blood-based test demonstrated a sensitivity of 79.2% (95% CI, 68.4% to 86.9%) for detecting CRC and a specificity of 91.5% (95% CI, 91.2% to 91.9%) for advanced colorectal neoplasia. The test achieved a negative predictive value of 90.8% (95% CI, 90.7% to 90.9%) and a positive predictive value of 15.5% (95% CI, 14.2% to 16.8%) for advanced colorectal neoplasia. All primary end points met the prespecified acceptance criteria. However, the test’s sensitivity for advanced precancerous lesions was 12.5% (95% CI, 11.3% to 13.8%) falling short of the predefined threshold.

However, the researchers noted several study limitations. First, it evaluated the one-time diagnostic accuracy of the blood-based test but did not compare it with other colorectal cancer screening methods in terms of patient acceptance or long-term effectiveness. Additionally, the impact of this testing approach on incidence and mortality in CRC, as well as the optimal screening interval, remains unknown and will require further investigation through future studies and modeling analyses.

Despite these limitations, the researchers believe the study’s strengths include its large and diverse population enrolled across urban and rural areas in the US, covering a wide range of practice settings. Additionally, the study utilized a decentralized trial platform that combined direct-to-participant and site-based enrollment helped increase participation from underrepresented regions and address COVID-19–related challenges.

“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.

References

1. Shaukat A, Burke CA, Chan AT, et al. Clinical validation of a circulating tumor DNA–based blood test to screen for colorectal cancer. JAMA. Published online June 02, 2025. doi:10.1001/jama.2025.7515

2. Colorectal cancer. World Health Organization. July 11, 2023. Accessed June 3, 2025. https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer

3. Steinzor P. 5 things to know about colorectal cancer. AJMC®. May 7, 2025. Accessed June 3, 2025. https://www.ajmc.com/view/5-things-to-know-about-colorectal-cancer