Newly Approved Blood Test for Colorectal Cancer Is Not as Good as Colonoscopy

In July 2024 the Food and Drug Administration (FDA) approved a blood test (SHIELD) to detect colorectal cancer or precancer in persons with average risk of such cancer.[1] The blood test, which surveys DNA patterns, can detect colorectal cancer at stage II and more severe stages with reasonable sensitivity and specificity. The test, however, is not nearly as sensitive as colonoscopy in detecting earlier forms of cancer (advanced precancer or stage I cancer).

Background on colorectal cancer and screening

Each year, about 53,000 people in the United States die from colorectal cancer. The five-year survival rate among persons with localized disease is 91%, compared with just 14% for those whose cancer has spread elsewhere in the body; 76% of colorectal cancer-related deaths occur in persons who are not up to date with recommended screening.[2]

The standard for screening involves colonoscopy at recommended intervals based on age and an individual’s risk of colorectal cancer. Colonoscopy is an examination of the inside of the large intestine (colon) with an illuminated, flexible tube with a camera on the end. Unlike the new blood test, colonoscopy requires adjustment of the diet prior to the procedure; a laxative-based bowel prep to clear the colon; and, frequently, conscious sedation or, less often, general anesthesia during the procedure. During a colonoscopy, potential cancers may be identified visually; polyps and other abnormalities are either biopsied or fully removed. The presence of cancer is confirmed by microscopic examination of the removed tissue.

Other screening approaches include fecal (stool) tests, flexible sigmoidoscopy (a procedure that uses a shorter tube than colonoscopy) and radiological imaging (for example, computed tomography [CT] scanning), all of which are less invasive and extensive than colonoscopy.[3]

Fecal tests detect high levels of blood or cancer-related DNA in the stool as markers for colorectal tumors; abnormal findings require confirmation by colonoscopy.

Both sigmoidoscopy and colonoscopy can irritate or injure the colon, particularly in older patients, and more so with colonoscopy. Estimated rates of colon perforation or major bleeding related to colonoscopy are 14 and 34 per 10,000 procedures, respectively.[4]

Shield, the new blood test, looks at a venous sample of blood for cancer indicators on cell-free DNA (cfDNA, which has presumably leaked from the tumor into the bloodstream[5]), including small chemical group alterations and larger gene patterns.[6] Such blood-based phenomena are being studied as potential early-detection biomarkers for various cancers.[7] As with the fecal tests, abnormal findings with the blood test require confirmation by colonoscopy.[8]

Pivotal trial of the Shield test[9]

Results from the main trial supporting approval of the Shield test were published in the New England Journal of Medicine (NEJM) in March 2024. The study was funded by Guardant Health, which manufactures and markets the test.

To test the safety and efficacy of the new cfDNA test, 7,861 individuals from 265 sites in 38 states were screened with the test, and the findings were compared with colonoscopy findings. The subjects were at “average risk” of colorectal cancer, meaning that they had neither direct or family history of such cancer nor other risk factors, such as inflammatory bowel disease. The subjects were age 45 to 84 years (mean age of 60 years) and were selected to mirror the U.S. adult population regarding sex, race and ethnicity.

Compared with colonoscopy screening, the cfDNA blood test detected any cancer (stages I through IV) 83% of the time (54 of 65 cases detected by colonoscopy) and accordingly missed detection of such cancers 17% of the time. Stage I cancer was successfully detected 65% of the time (11 of 17 cases). Earlier advanced precancerous lesions (tumors at least 10 millimeters in size that can develop into cancer) were detected with the cfDNA test just 13% of the time (147 of 1,116 cases); thus, 87% (n=969) of precancers detected by colonoscopy were missed by the cfDNA test.

According to the NEJM article, other available non-invasive (blood- or stool-based) tests correctly identify colorectal cancer approximately 68% to 94% of the time. For precancerous lesions, these non-invasive tests perform better than the cfDNA test but still only detect such lesions 22% to 43% of the time. The highest rate (43%) of precancer detection is for a multitarget stool DNA test (COLOGUARD).

The researchers concluded that the cfDNA test offers an additional option for non-invasive colorectal cancer testing that “may improve screening participation and early detection.” Overall, current adherence rates for recommended colorectal cancer screening are about 60%, well below public health population screening goals. The NEJM article further noted that non-invasive detection of precancerous lesions remains a challenge and that more work is needed to improve the cfDNA test and validate its role in colorectal cancer screening.

In May 2024 an FDA advisory committee supported approval of this cfDNA colorectal cancer screening test. Their deliberations, however, highlighted concerns about the low sensitivity of the test for detecting precancerous lesions and stage I cancer. The advisory committee also recommended that post-marketing data be collected about patient outcomes related to use of this new test.[10]

What You Can Do

Stool- or blood-based screening for colorectal cancer should not be relied upon as a replacement for regular colonoscopy at the recommended intervals. Although such tests are more convenient than colonoscopies, they are much less sensitive, especially for detection of precancerous lesions and stage I cancer. Moreover, abnormal findings require confirmation by colonoscopy. Nonetheless, non-invasive colorectal cancer screenings are far better than not being screened at all. Discuss with your primary care clinician the best screening test options for you.

According to the U.S. Preventative Services Task Force’s most recent recommendations, issued in 2021, regular colorectal cancer screening should begin around the age of 45 years and conclude around the age of 75 years.[11] Those recommendations also state that average-risk individuals should be screened by colonoscopy every 10 years or by other forms of screening more frequently — for example, by fecal or blood test every one to three years. A 2023 UpToDate review notes that regular (every 10 years) colonoscopy is the preferred method of screening if it can be tolerated, in part because it allows for immediate polyp removal.[12]
 

References

[1] Kolata G. F.D.A. approves blood test for colon cancer detection. New York Times. July 29, 2024. https://www.nytimes.com/2024/07/29/health/colon-cancer-blood-test-shield.html. Accessed September 3, 2024.

[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.

[3] Davidson KW, Barry MJ, Mangione CM, et al. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325(19):1965-1977.

[4] Tuvshintogs E. Colorectal cancer screening: ACP guidance statement. Am Fam Physician. 2020;102(4):250-253.

[5] Kolata G. F.D.A. approves blood test for colon cancer detection. New York Times. July 29, 2024. https://www.nytimes.com/2024/07/29/health/colon-cancer-blood-test-shield.html. Accessed September 3, 2024.

[6] 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.

[7] Vittone J, Gill D, Goldsmith A, et al. A multi-cancer early detection blood test using machine learning detects early-stage cancers lacking USPSTF-recommended screening. NPJ Precis Oncol. 2024;8(1):91.

[8] Guardant Health. Press release: FDA advisory committee panel strongly recommends approval of Shield blood test for colorectal cancer screening as a primary non-invasive screening option. May 23, 2024. 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. Accessed September 3, 2024.

[9] 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.

[10] Food and Drug Administration. Brief summary of the Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee. May 23, 2024. https://www.fda.gov/media/178968/download. Accessed September 3, 2024.

[11] Davidson KW, Barry MJ, Mangione CM, et al. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325(19):1965-1977.

[12] Doubeni C. Screening for colorectal cancer: strategies in patients at average risk. UpToDate. November 30, 2023.