Understanding a Positive Cologuard Test Result
A positive Cologuard test indicates the presence of abnormal DNA markers and/or blood in the stool that requires follow-up colonoscopy to determine if colorectal cancer or precancerous lesions are present. 1
What Cologuard Detects
- Cologuard is a multitarget stool DNA (mt-sDNA) test that combines detection of DNA alterations (KRAS mutations, aberrant NDRG4 and BMP3 methylation) with an immunochemical test for occult blood 1
- It is designed to detect both colorectal cancer and precancerous lesions, though it is more sensitive for cancer than for precancerous lesions 1, 2
- Cologuard has higher sensitivity than FIT (fecal immunochemical test) for detecting colorectal cancer (92.3% vs 73.8%) and advanced precancerous lesions (42.4% vs 23.8%) 1, 2
Clinical Significance of a Positive Result
- A positive result requires follow-up with colonoscopy to examine the entire colon 1
- The positive predictive value varies based on patient population:
- In some studies, the positive predictive value for colorectal cancer was only 1.3%, and for precancerous lesions plus colorectal cancer was 7.7% 3
- Other studies show that among patients with a previously negative colonoscopy and subsequent positive Cologuard, 30% had advanced adenomas on follow-up colonoscopy 4
- Specificity of Cologuard (86.6%) is lower than FIT (94.9%), meaning it has more false positives 1, 2
Important Considerations
- A positive Cologuard does not definitively mean cancer is present; it indicates an increased risk that requires diagnostic evaluation 1
- The test can detect DNA markers from various sources in the digestive tract, not just the colon 1
- The clinical significance of a positive test with a negative follow-up colonoscopy remains uncertain 1
- Evaluation of the upper gastrointestinal tract is not indicated for patients with positive Cologuard and negative colonoscopy, as the risk ratio of incident aerodigestive cancer is not higher than those with negative Cologuard and negative colonoscopy 1
Limitations to Consider
- Cologuard is less sensitive for detecting advanced adenomas (42.4%) compared to its sensitivity for cancer (92.3%) 1, 2
- False positives can occur due to various factors, including the detection of DNA from non-cancerous sources 1
- The test is not appropriate for high-risk individuals who should undergo direct colonoscopy, including those with:
- Personal history of colorectal cancer or advanced adenomas
- Family history of colorectal cancer in a first-degree relative diagnosed before age 60
- Personal history of inflammatory bowel disease
- Known or suspected hereditary colorectal cancer syndromes 2
Follow-up Recommendations
- Any positive Cologuard test should be followed by a complete diagnostic colonoscopy 1
- Patients should be informed that a positive test does not necessarily mean cancer is present, but that follow-up is essential to determine the cause 1
- The colonoscopy should be performed in a timely manner to evaluate for the presence of colorectal cancer or precancerous lesions 1, 2
- If the follow-up colonoscopy is negative, patients can return to routine screening according to average-risk guidelines 1, 2