Blood-Based Colorectal Cancer Screening: Frequently Asked Questions

Colonoscopy remains the gold standard for colorectal cancer screening—but it is also underused. Prep burden, procedure anxiety, access barriers, and cost all contribute to a persistent screening gap. Blood-based tests offer a lower-barrier alternative, and the landscape has changed meaningfully in the past two years. Here is what pharmacists need to know.

How Many Blood-Based Colorectal Cancer Tests Are FDA-Approved, and What Are They?

There are multiple FDA-approved blood-based colorectal cancer screening tests. Epi proColon was approved in 2016 for those aged 50 or older with average risk of colorectal cancer and detects the Septin9 gene via methylation in blood plasma, with a clinical trial demonstrating 68.2% sensitivity and 80.0% specificity.¹

Shield (Guardant Health) was approved by the FDA in July 2024 as a screening tool for colorectal cancer, detecting changes in DNA sequencing and mutations that cancer cells release into the blood, and is intended for adults 45 and older at average risk. Shield carries Medicare reimbursement coverage, which Epi proColon lacks—a practical distinction that significantly affects real-world utilization.²

A third test—SimpleScreen CRC by Freenome—was approved in July 2026.³ SimpleScreen CRC detects signals associated with colorectal cancer from cell-free DNA in the blood. In a clinical trial, the test detected colorectal cancer with 81.1% sensitivity and advanced precancerous lesions with 13.7% sensitivity, including 30.7% for advanced precancerous lesions with high-grade dysplasia. The test showed 90.4% specificity for advanced colorectal neoplasia.⁴

How Accurate Is the Shield Test?

In a study published in the New England Journal of Medicine, Shield demonstrated 83.1% sensitivity for detection of colorectal cancer, with sensitivity for stages I to III reaching 87.5%. However, its sensitivity for precancerous lesions—advanced adenomas—is considerably lower, which is the central limitation cited by gastroenterology societies.⁵

Based on data from clinical studies, Shield has limited detection of stage I colorectal cancer (55% to 65%) and does not detect 87% of precancerous lesions, meaning one in ten patients with a negative Shield result may have a precancer that would have been detected by colonoscopy.⁵

What Should Pharmacists Tell Patients About a Positive Blood Test Result?

A positive result from either Shield or Epi proColon is not a colorectal cancer diagnosis—it is a signal that warrants follow-up. A positive Shield test requires a colonoscopy to confirm whether an advanced lesion or colorectal cancer is present or whether the result was a false positive.⁶

Pharmacists counseling patients should frame this clearly: the blood test is a step in the screening process, not the endpoint. Patients who test positive and do not follow up with colonoscopy have not completed screening.⁶

Are Blood Tests a Replacement For Colonoscopy?

No—and this is a point of strong consensus among gastroenterology and oncology societies. Expert consensus holds that blood tests should not be considered a replacement for colonoscopy, as they are neither as effective nor as cost-effective and cannot prevent colorectal cancer through polyp removal the way colonoscopy can.⁷

Blood tests serve a different purpose: they lower the barrier to initial screening for patients who decline or cannot access colonoscopy, with the expectation that those who test positive will proceed to colonoscopy. As an on-ramp rather than an alternative, pharmacists have a meaningful place in the screening ecosystem.⁷

How Often Should Patients Be Rescreened if Their Blood Test Is Negative?

Screening interval recommendations differ by test type. Colonoscopy carries a 10-year interval for a negative result in average-risk individuals because it both detects and removes precancerous polyps. Blood-based tests, which do not have this polyp-removal capability and have lower sensitivity for precancerous lesions, carry shorter recommended rescreening intervals—typically 1 to 3 years depending on the test and guideline source.⁶

Pharmacists should verify the specific interval guidance for whichever FDA-approved test a patient has used and flag the distinction from colonoscopy interval when counseling.

What Role Can Pharmacists Play in Improving Colorectal Cancer Screening Rates?

Colorectal cancer is one of the most preventable cancers when caught early, yet screening rates remain below national targets. Pharmacists—particularly those in retail and ambulatory care settings—have routine touchpoints with patients who may be overdue for screening. Identifying patients aged 45 and older, asking about screening status, and explaining that blood-based options are now available for those who have declined colonoscopy are concrete steps that fit within existing medication counseling workflows. Connecting patients to primary care for test ordering or, where pharmacist-ordering protocols exist, facilitating access directly can meaningfully move the needle on a public health gap.

REFERENCES

1. Colon Health Alert: FDA Approves New Screening Test Epi proColon. Colorectal Cancer Alliance. April 19, 2016. Accessed August 3, 2026. https://colorectalcancer.org/article/colon-health-alert-fda-approves-new-screening-test-epi-procolon

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. Guardant. July 29, 2024. Accessed August 3, 2026. 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. FDA approves Freenome’s SimpleScreen CRC blood-based screening test; Abbott to commercialize in the US. News release. Freenome, Inc. July 27, 2026. Accessed August 5, 2026. https://www.freenome.com/newsroom/fda-approves-freenomes-simplescreen-crc/

4. Shaukat A, Burke CA, Chan AT, et al. Clinical Validation of a Circulating Tumor DNA–Based Blood Test to Screen for Colorectal Cancer. JAMA. June 2, 2025. doi:10.1001/jama.2025.7515

5. Chung DC, et al. A cell-free DNA blood-based test for colorectal cancer screening. N Engl J Med. 2024;390(11):973-983.

6. Edwards E. FDA approves blood test to screen for colon cancer. NBC News. July 29, 2024. Accessed August 3, 2026. https://www.nbcnews.com/health/health-news/colon-cancer-blood-test-shield-screening-fda-approved-rcna163630

7. American Gastroenterological Association. FDA Approves First Blood Test for Colorectal Cancer. https://gastro.org/news/fda-approves-first-blood-test-for-colorectal-cancer/