For reluctant patients only: American Cancer Society now recommends blood-based screening tests for colorectal cancer

An update to the American Cancer Society’s colorectal cancer screening guidelines now recommends using a cell-free DNA-based blood test, although with a caveat that it’s not a preferred option. The American Cancer Society only recommends the cell-free DNA (cfDNA)-based blood tests for people without a history of colorectal cancer who decline or haven’t done a stool-based test or a visual exam (i.e., colonoscopy, CT or sigmoidoscopy). A positive result on any test needs to be followed up by a colonoscopy.The cfDNA-based blood screening test uses samples of DNA to identify genomic or epigenomic alternations in DNA from malignant tissues. The U.S. Food and Drug Administration (FDA) approved the test in 2024.The new screening guidelines state that before ordering a blood-based screening test, discuss it with the patient and inform them about the following:Blood-based tests have a lower sensitivity than stool-based or visual tests in detecting advanced precancerous lesions and stage I colorectal cancersA positive result on any test needs to be followed up by a colonoscopyManufacturers of the blood-based tests haven’t specified a testing interval, but U.S. Medicare programs suggest every three yearsEvidence supporting the tests comes from the ECLIPSE study, funded by Guardant Health, the manufacturer of the test (called Shield). The ECLIPSE results were published in the New England Journal of Medicine in 2024. The trial included 7,861 people screened using both the cfDNA test and a colonoscopy. The cfDNA test had a sensitivity for detecting stage I, II or III colorectal cancer was 87.5% and the sensitivity for detecting advanced precancerous lesions was 13.2%. Specificity for colorectal cancer or advanced precancerous lesions was 89.5%. There was a decline in specificity with age, suggesting that people who are older may have more false positives. The American Cancer Society screening guidelines note that these false positives would prompt a colonoscopy and it’s this older age group who have greater risks from colonoscopies.The guidelines also recommend a second test, made by Freenome Holdings, Inc., once it is approved by the FDA. The evidence supporting the second test were published in JAMA in 2025. Canada’s Drug Agency conducted a review of these types of tests in 2019. At the time, Epi ProColon was the only cfDNA-based blood test available. It was not specifically discussed in the American Cancer Society guidelines. Despite this sensitivity and specificity, the guideline committee acknowledged that modeling studies examining the benefit of screening usually assume 100% adherence to screening, which is not the case in real life. The committee decided that tests that may increase the public’s participation in colorectal cancer screening could lead to benefits, namely earlier detection of colorectal cancer and reduced death and disability associated with the disease. This is why it recommended for people who decline preferred tests. “For these individuals, a blood-based test could contribute to increasing screening uptake and reducing the burden of colorectal cancer,” the authors write. “Weighing these factors, the guideline development group determined that blood-based tests could not be recommended as a preferred option for CRC screening at this time and should be offered only to individuals who decline or do not complete preferred screening tests.”Could cfDNA-based blood tests be useful in Canada?The test could help improve colorectal screening outcomes in Canada if it increases the number of people who get screened, researchers from British Columbia and Alberta suggested in a May 2025 modeling paper published in JAMA Oncology. When the researchers’ model assumed high participation and adherence to the cfDNA tests, the screening predicted detection of more cancer cases and reduced colorectal cancer deaths compared to screening with the FIT test. When the researchers tested the model applying the real-world adherence to FIT tests (43%) to the cfDNA test, it identified more cancers than FIT, but failed to reduce more deaths than FIT. The cfDNA test is significantly more expensive than FIT. For example, the cfDNA-based blood test costs more than US$850 out-of-pocket, where a FIT test costs about CAD$75, but is paid for by provincial and territorial healthcare plans for people who qualify for screening.The new American Cancer Society guidelines were published in Cancer.

For reluctant patients only: American Cancer Society now recommends blood-based screening tests for colorectal cancer

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