What are the guidelines for using Cologuard (multitarget stool DNA testing) for colorectal cancer screening?

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Last updated: June 18, 2025View editorial policy

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From the Guidelines

Cologuard testing is recommended for average-risk adults as a non-invasive option for colorectal cancer screening, to be performed every 3 years if results are negative. According to the American Cancer Society guidelines, average-risk adults should begin colorectal cancer screening at age 50 years with one of the following options, including the multitarget stool DNA (mtsDNA) test every 3 years 1. The guidelines emphasize that prevention of colorectal cancer is the greater priority of screening, and screening options may be chosen based on individual risk, personal preference, and access.

When considering Cologuard testing, it is essential to note that patients should not use it if they have a personal history of colorectal cancer, adenomas, inflammatory bowel disease, certain hereditary syndromes, or a family history that puts them at high risk for colorectal cancer. Additionally, patients should not collect a sample if they have diarrhea or blood in their stool from hemorrhoids, cuts, or other causes, as these may lead to false-positive results.

The test works by detecting altered DNA and blood in stool, which may indicate the presence of colorectal cancer or precancerous lesions. Key points to consider when using Cologuard include:

  • It should be performed every 3 years if results are negative
  • A follow-up diagnostic colonoscopy is required if Cologuard results are positive
  • Cologuard may miss some cancers and precancerous lesions, or may indicate that abnormalities are present when they are not (false positives)
  • Patients should discuss with their healthcare provider which screening test is most appropriate for them based on their individual risk factors and preferences, as stated in the guidelines 1.

From the Research

Cologuard Testing Guidelines

  • Cologuard, a multitarget stool DNA test, is recommended by major US guidelines as an option for colorectal cancer screening in average-risk individuals aged 45 years and older 2.
  • The test is approved by the Food and Drug Administration for use in average-risk individuals and is covered by Medicare and most private insurers with no copay or deductible 2.
  • The test detects 11 biomarkers, including point mutations in KRAS, aberrant methylation in NDRG4 and BMP3, and human hemoglobin, and has higher sensitivity but lower specificity for colorectal cancer compared to fecal immunochemical test (FIT) 2.

Screening Intervals and Recommendations

  • Retesting with Cologuard is recommended every 1-3 years, although the optimal testing interval has not yet been determined empirically 2.
  • For average-risk individuals, screening should begin at age 45 and continue until age 75, with options including colonoscopy every 10 years, FIT annually, and CT colonography every 5 years 3.
  • For high-risk individuals, such as those with a positive family history of colorectal cancer, screening should begin at age 40, with more frequent screening intervals depending on the risk factor 3.

Comparison with Other Screening Modalities

  • Cologuard has been compared to fecal occult blood test (FOBT) and has shown higher sensitivity and specificity for detecting colorectal cancer and advanced adenoma 4.
  • The test has also been compared to CT colonography, which provides accurate evaluation for advanced adenomas, but is currently underutilized for colorectal cancer screening 5.
  • FIT is another screening option that offers high specificity and sensitivity, is low-cost, easy to operate, and less likely to be affected by food and drugs, making it a safer and more accurate option for population screening 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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