Shield Blood Test Yields High Sensitivity, Specificity for CRC Screening in Expansion Cohort of Average-Risk Adults

The latest colorectal cancer (CRC) screening algorithm for Guardant Health’s Shield blood-based test has shown high specificity and met all primary end points in an expanded cohort of average-risk patients in the observational ECLIPSE study (NCT04136002), according to a positive clinical readout shared by the drug’s developer.1

Shield demonstrated a sensitivity of 84% for detecting CRC with 90% specificity. Moreover, the test’s sensitivity for the detection of stage I CRC was 62%.

“We are pleased with the performance of the new algorithm in detecting stage I CRCs. Today’s update shows yet again that Shield delivers best-in-class performance,” AmirAli Talasaz, co-chief executive officer of Guardant Health, stated in a news release. “We will continue to leverage our first mover advantage, rapidly growing database, and innovation engine to push Shield to higher levels of performance over time.”

In July 2024, the FDA granted full approval to the Shield blood test for CRC screening in adults 45 years of age and older who are at average risk for the disease.2 This regulatory decision makes Shield the first blood test to receive FDA approval as a primary screening option for CRC and the first blood test for CRC screening that meets Medicare coverage requirements.

“The persistent gap in colorectal cancer screening rates shows that the existing screening options do not appeal to millions of people,” Daniel Chung, MD, gastroenterologist at Massachusetts General Hospital and professor of medicine at Harvard Medical School, stated in a separate news release. “The FDA's approval of the Shield blood test marks a tremendous leap forward, offering a compelling new solution to close this gap. This decision will help make screening tests more broadly accessible and propel blood-based testing and CRC screening into a new era. With increased screening rates and early cancer detection, many more lives can be saved.”

Following this decision, the National Comprehensive Cancer Network updated its Guidelines for CRC Screening in June 2025 to include Shield as the first FDA-approved blood test for primary screening of CRC.3

These regulatory decisions were supported by findings from the ECLIPSE study.1

ECLIPSE was a nonrandomized, prospective, multisite registrational study that evaluated the performance of Shield for detecting CRC in over 20,000 patients with average-risk CRC who were intended to undergo screening colonoscopy.1,2Patients were required to be aged 45 to 84 years, be willing to consent to blood draw pre-bowel preparation administration prior to undergoing colonoscopy within 60 days of the date of the investigational blood draw, and be willing to undergo 2 years of follow-up. 4,5

Of note, the clinical validation cohort featured 10,258 participants, 7861 of whom were evaluable for the study.4

The study’s primary outcomes were the sensitivity of CRC detection and the specificity of advanced neoplasia detection.5 The secondary outcome was sensitivity for detection of advanced precancerous lesions.4

Initial findings from ECLIPSE, which were published in The New England Journal of Medicine, demonstrated that Shield displayed sensitivities of 62%, 100%, 96% and 100% for stage I, II, III, and IV CRC.1 Notably, the sensitivity for detecting advanced adenomas was 13%.

In the clinical validation cohort, Shield displayed an overall CRC sensitivity rate of 83.1% (95% CI, 72.2%-90.3%) among eligible patients.4 The sensitivity rate for stage I to III disease was 87.5% (95% CI, 75.3%-94.1%). The sensitivity rate for advanced precancerous lesions was 13.2% (95% CI, 11.3%-15.3%).

Among patients who did not have CRC or advanced precancerous lesions detected on colonoscopy, the specificity rate for any advanced neoplasia was 89.6% (95% CI, 88.8%-90.3%). The specificity for a negative colonoscopy was 89.9% (95% CI, 89.0%-90.7%).

The overall performance of the test places it within the sensitivity range of current guideline-recommended noninvasive screening methods, which range from 67% to 92%.4,6

Guardant Health anticipates that commercial insurance coverage for eligible patients will continue to expand following future guideline inclusion by organizations like the American Cancer Society and the United States Preventive Services Task Force.2

References

1. Guardant Health announces clinical result update for Shield blood-based colorectal cancer screening test. News release. Guardent Health. September 4, 2025. Accessed September 5, 2025. https://investors.guardanthealth.com/press-releases/press-releases/2025/Guardant-Health-Announces-Clinical-Result-Update-for-Shield-Blood-Based-Colorectal-Cancer-Screening-Test/default.aspx
2. Guardant Health’s Shield blood test approved by FDA as a primary screening option, clearing path for Medicare reimbursement and a new era of colorectal cancer screening. News release. Guardant Health, Inc. July 29, 2024. Accessed September 5, 2025. https://investors.guardanthealth.com/press-releases/press-releases/2024/Guardant-Healths-Shield-Blood-Test-Approved-by-FDA-as-a-Primary-Screening-Option-Clearing-Path-for-Medicare-Reimbursement-and-a-New-Era-of-Colorectal-Cancer-Screening/default.aspx
3. National Comprehensive Cancer Network (NCCN) updates Colorectal Cancer Screening Guidelines to include Shield blood-based screening. News release. Guardant Health. June 2, 2025. Accessed September 5, 2025. https://investors.guardanthealth.com/press-releases/press-releases/2025/National-Comprehensive-Cancer-Network-NCCN-Updates-Colorectal-Cancer-Screening-Guidelines-to-Include-Shield-Blood-Based-Screening/default.aspx
4. Chung DC, Gray DM 2nd, Singh H, et al. A cell-free DNA blood-based test for colorectal cancer screening. N Engl J Med. 2024;390(11):973-983. doi:10.1056/NEJMoa2304714
5. Evaluation of the ctDNA LUNAR test in an average patient screening episode (ECLIPSE). ClinicalTrials.gov. Updated July 3, 2024. Accessed September 5, 2025. https://clinicaltrials.gov/study/NCT04136002
6. FDA advisory committee panel strongly recommends approval of Shield blood test for colorectal cancer screening as a primary non-invasive screening option. News release. Guardant Health, Inc. May 23, 2024. Accessed September 5, 2025. https://investors.guardanthealth.com/press-releases/press-releases/2024/FDA-Advisory-Committee-Panel-Strongly-Recommends-Approval-of-Shield-Blood-Test-for-Colorectal-Cancer-Screening-as-a-Primary-Non-Invasive-Screening-Option/default.aspx