Clinical Data Bolster Efficacy of Blood-Based Colorectal Cancer Screening

A recent clinical readout update for Guardant Health's blood-based colorectal cancer (CRC) screening, the Shield test, has provided further validation of its diagnostic performance in a real-world, average-risk population.¹ The data, derived from an expanded cohort of the landmark ECLIPSE study (NCT04136002), reaffirms the test's utility as a primary screening option and is particularly noteworthy for its performance metrics in detecting early-stage disease.

Study Findings and Performance Metrics

The clinical validation assessed the latest algorithm (V2) for the blood-based test, building on the initial findings of ECLIPSE. The study, a prospective, observational, multicenter trial conducted across over 130 sites in the United States, was designed to evaluate the performance of the liquid biopsy test against a standard-of-care screening colonoscopy.

Key findings from the updated analysis include:

• Overall Colorectal Cancer Sensitivity: The test demonstrated an overall sensitivity of 84% for the detection of CRC.
• Specificity for Advanced Neoplasia: The test maintained a high specificity of 90% for advanced neoplasia (CRC or advanced precancerous lesions), which is critical for minimizing false positives and unnecessary follow-up procedures.
• Stage-Specific Sensitivity: The data provides crucial insights into the test's ability to detect cancer at different stages. The sensitivity for stage I CRC was 62%, with sensitivities of 100% for stage II and 96% for stage III.
• Advanced Adenoma Detection: Sensitivity for advanced adenomas was 13%.

These results are particularly significant in the context of improving screening adherence. Traditional screening methods, such as colonoscopy, are highly effective but can be associated with patient discomfort, procedural risks, and logistical barriers that lead to low screening rates. By offering a noninvasive, blood-based alternative, the Shield test aims to address the persistent screening gap and detect more cancers at earlier, more treatable stages.

“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,” said AmirAli Talasaz, Guardant Health co-CEO, in a press 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 March 2024, the FDA approved the Shield test.² The approval was supported by earlier data from ECLIPSE published in The New England Journal of Medicine.³

Clinical Implications and Guidelines

The performance data from the ECLIPSE study underscores the potential of cell-free DNA (cfDNA) technology to expand the arsenal of available screening tools for clinicians. The National Comprehensive Cancer Network (NCCN) recently updated its CRC screening guidelines to include this blood test as the first of its kind to be recommended for primary screening.⁴ This guideline inclusion is a pivotal step that is expected to facilitate greater patient access and improve screening rates.

For a clinical audience, the value proposition of a high-performing liquid biopsy is clear: it provides a convenient and accessible option that can be offered during a routine office visit, potentially reaching millions of individuals who are not up to date with their recommended screening. While a positive result necessitates a follow-up colonoscopy for a definitive diagnosis, the high specificity of the test helps to ensure that this is a clinically appropriate and judicious next step.

The data also highlights the importance of patient stratification and shared decision-making. Clinicians must weigh the performance characteristics of different screening modalities against an individual patient’s risk factors, preferences, and ability to adhere to a screening regimen. For many average-risk patients, a less invasive option with strong performance metrics could be the catalyst for initiating or resuming screening.

Looking Ahead

While the current data focuses on CRC screening, Guardant Health is also leveraging the Shield platform for other applications. The company has a pipeline of activities, including a multicancer detection (MCD) test that has received a Breakthrough Device Designation from the FDA and is included in the National Cancer Institute's Vanguard study. This suggests a broader strategic focus on using cfDNA technology to address a range of unmet needs in oncology, from early detection to treatment selection and recurrence monitoring.

This article was generated with assistance from Google Gemini and NotebookLM. It was edited and reviewed by Targeted Oncology staff. If you have any questions about the use of AI, please contact us.

REFERENCES:

1. Guardant Health Announces Clinical Result Update for Shield Blood-Based Colorectal Cancer Screening Test. News release. Guardant Health. September 4, 2025. Accessed September 4, 2025. https://tinyurl.com/2ma37dyd

2. US FDA approves Guardant Health’s blood-based cancer test. News release. Reuters. July 29, 2024. Accessed September 4, 2025. https://tinyurl.com/yyu94wk2

3. Chung D, Gray D, Singh H, et al. A cell-free DNA blood-based test for colorectal cancer screening. N Engl J Med. 2024;390:973-983. doi:10.1056/NEJMoa2304714

4. Colorectal Cancer Screening NCCN Guidelines Version 2.2025. Accessed September 4, 2025. https://tinyurl.com/44rfpx66