New Blood Test Algorithm Shows Sensitivity, Specificity in CRC Screening

In June 2025, the NCCN updated its CRC screening guidelines to include Shield blood-based screening as a recommended option for testing once every 3 years among individuals who are at risk of having the disease.

The latest screening algorithm for the Shield™ blood test (Shield V2) demonstrated positive sensitivity and specificity outcomes in the detection of colorectal cancer (CRC), according to a press release from the developer, Guardant Health, Inc.¹

Shield V2 reached all primary end points as part of a study assessing an expanded cohort of individuals who enrolled on the ECLIPSE study (NCT04136002), which was published in the New England Journal of Medicine.² The updated test demonstrated a sensitivity and specificity rate of 84% and 90%, respectively, in the detection of CRC. Additionally, the rate of the sensitivity of detecting stage I CRC was 62%.

Additional data revealed a sensitivity rate of 100% for stage II disease, 96% for stage III disease, and 100% for stage IV disease. The test also demonstrated 13% sensitivity for detecting advanced adenomas.

“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 at Guardant Health, stated in the press release.¹ “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 June 2025, the NCCN updated its CRC screening guidelines to include Shield blood-based screening as a recommended option for testing once every 3 years among individuals who are at risk of having the disease.³ Furthermore, the FDA approved the Shield blood test as a primary screening option among adults who are 45 years or older and at an average risk of having CRC in July 2024.⁴ Supporting findings for the approval came from the ECLIPSE study.

“The persistent gap in [CRC] screening rates shows that the existing screening options do not appeal to millions of people. 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,” Daniel Chung, MD, gastroenterologist at Massachusetts General Hospital and a professor of Medicine at Harvard Medical School, stated in a press release on the FDA approval.⁴ “With increased screening rates and early cancer detection, many more lives can be saved.”

Developers engineered Shield as a non-invasive, blood-based screening test that can highlight the presence of CRC-associated alterations in the blood. A positive result following testing with Shield may indicate the presence of CRC or advanced adenocarcinoma; it is recommended that patients undergo colonoscopy evaluation in this case.

The prospective, observational ECLIPSE study evaluated the performance of the Shield test in the detection of CRC among average-risk populations across more than 200 clinical trial sites in urban and rural settings within 37 states. The study’s primary end points were the sensitivity of CRC detection and specificity of advanced neoplasia detection.⁵ Secondary end points included the positive predictive value of CRC detection, negative predictive value of CRC detection, and sensitivity and specificity of advanced adenocarcinoma detection.

Individuals 45 to 84 years old intended to undergo screening colonoscopy and considered to be at an average risk of having CRC were eligible for inclusion in this study. Additional eligibility criteria included having willingness to consent to blood draw pre-bowel preparation administration before undergoing colonoscopy within 60 days of the investigational blood draw. Those with a history of CRC, a known diagnosis of inflammatory bowel disease, or prior colonoscopy within 9 years before study entry were ineligible for enrollment.

References

1. Guardant Health announces clinical result update for Shield blood-based colorectal cancer screening test. News release. Guardant Health, Inc. September 4, 2025. Accessed September 5, 2025. https://tinyurl.com/bdzb98ss
2. Chung DC, Gray DM, 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
3. National Comprehensive Cancer Network (NCCN) updates colorectal cancer screening guidelines to include Shield blood-based screening. News release. Guardant Health, Inc. June 2, 2025. Accessed September 5, 2025. https://tinyurl.com/e842yrem
4. 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://tinyurl.com/mr2c3uhm
5. Evaluation of the ctDNA LUNAR Test in an average patient screening episode (ECLIPSE). ClinicalTrials.gov. Updated August 11, 2025. Accessed September 5, 2025. https://tinyurl.com/kbr56fww