Abstract
Description
Within the United States (US), colorectal cancer (CRC) remains the fourth most common malignancy and is responsible for over 50 000 deaths annually, second only to lung cancer in cancer mortality. Despite increased public awareness and increasing screening rates, the US remains far below the 80% screening mark set by the National Colorectal Cancer Roundtable at 59%. The addition of non-invasive blood-based tests for CRC screening could potentially increase screening rates and lower CRC deaths.
I performed a PubMed search using the search term “blood-based colorectal cancer screening.” I was particularly interested in articles that looked at Shield, which is the first and (currently) only blood-based DNA test that is approved by the US Food and Drug Administration (FDA) to screen for CRC. The FDA approval for Shield was based on 1 large cohort trial (ECLIPSE), the results of which were published in Gastroenterology in March 2024.
This brief synopsis will detail the major parts of that study and layout the potential benefits, risks, and cost analysis of implementing this test into routine practice.
Keywords: blood-based screening test, cell-free DNA, colorectal cancer screening, non-invasive screening
Introduction
In July 2024, the United States Food and Drug Administration (FDA) approved Shield, a cell-free DNA blood-based test for colorectal cancer (CRC) screening in average risk patients. This test is designed to detect genomic alterations and abnormal methylation of DNA fragments that are circulating in the blood.1 Prior data from a case-control study reported a sensitivity of 93% at detecting CRC and specificity of 90%.1 Shield has now been tested in a screening population, and the results are discussed below.
Accuracy
The ECLIPSE trial, a prospective cohort study that was sponsored by Guardant Health, who owns the Shield test, was published in the New England Journal of Medicine in March 2024.2 The primary conclusions of the ECLIPSE trial were defined as a sensitivity to detect CRC and a specificity to detect advanced precancerous lesions (APL). Sensitivity to detect APL was listed as a secondary outcome measure.
Shield was tested on a cohort of 10 258 individuals, including 65 people with biopsy-confirmed CRC. Among the 65 people with known CRC, 54 had a positive Shield test, indicating a sensitivity of 83.1% (95% confidence internal of 72.2%- 90.3%) at detecting CRC. A total of 10.4% of participants without any advanced neoplasia on a colonoscopy had a positive Shield test, which indicates a specificity of 89.6% to detect APL. Shield correctly identified only 147 of 1116 participants with APL found on the colonoscopy, which indicates a sensitivity to detect APL of 13.2%.2
Shield can be compared to other CRC screening methods. Cologuard Plus, a multi-target stool DNA test has a sensitivity of 93.9% for detecting CRC and specificity of 90.6% for detecting APL3 and fecal immunochemical tests (FIT) have a pooled sensitivity of 79% and specificity of 94%.4 All of these non-invasive tests must be compared to the colonoscopy, the gold standard, which has a sensitivity of 95% and specificity of 85% for detecting CRC.5
Non-invasive screening methods for CRC tend to have low sensitivity at detecting APL. Cologuard Plus has a 43.4% sensitivity for detecting APL, while FIT testing has reported sensitivities of around 24%.
Benefits
A blood test for CRC screening could be a good option for those who refuse to undergo the colonoscopy procedure and do not wish to undergo screening with other available methods. This could be collected in office and does not require any bowel preparation.
One recent study showed that offering blood-based testing for CRC screening increased screening uptake significantly (30.5% vs 13.1%).6 Another analysis determined that for every 3 persons choosing Shield over colonoscopy or stool tests, 2 or more persons who previously declined screening must take up Shield (with appropriate colonoscopy follow up) to reduce CRC mortality from its current level.7
Harms
Shield has very poor sensitivity at detecting APL, which could lead to false-reassurance and to missing clinically important pre-cancers. Furthermore, Shield correctly identified only 11/17 Stage 1 CRCs with a sensitivity of 65% (95% CI 41%–83%), which raises the concern about its ability to detect CRC when it is at its most treatable and the outcomes are most favorable. Shield has a false-positive rate of around 10%, which can lead to further testing and downstream costs.
Cost
The list price for Shield is $1495, which is substantially higher than the cost of Cologuard, FIT, and the Medicare reimbursement rate for a colonoscopy. Shield is covered by Medicare with $0 out-of-pocket cost for Part B beneficiaries. Costs for individuals without Medicare may vary, and cost-sharing may be involved.8
A cost-effective analysis comparing screening strategies found that FIT and colonoscopy were more effective and less costly than Shield and Cologuard. Cologuard was more effective and less costly than Shield.7 However, in people who will absolutely not participate in colonoscopy screenings or stool tests, Shield is cost-effective as opposed to no screening.
The Bottom Line
The Shield blood test is a recent FDA-approved, blood-based screening option for average-risk adults aged 45 and older, but it is not a substitute for the current United States Preventative Task Force recommended screening modalities, which include stool-based tests and colonoscopies. The recommended screening interval with Shield is 3 years. Shield is less effective and more costly than current alternatives. How this will be incorporated into existing screening guidelines remains to be seen. Shield will likely increase the percentage of adults who participate in CRC screening. The net benefit or harm will ultimately depend on the balance between getting more people screened versus shifting people away from more effective strategies. In my practice I will continue to recommend colonoscopy, FIT, and Cologuard as first-line screening tests and discourage my patients from choosing Shield if they are willing to do one of the more effective alternatives. I would only recommend Shield for people refusing to do colonoscopy or stool-based testing.
Funding Statement
This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare-affiliated entity.
Footnotes
Conflicts of Interest: The author declares no conflicts of interest.
The author is an employee of HCA Florida St Lucie Hospital, a hospital affiliated with the journal’s publisher.
This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare-affiliated entity. The views expressed in this publication represent those of the author and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.
References
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