False Positive Rate for Cologuard
Cologuard has a false positive rate of approximately 13-14% (specificity of 86.6-87%) in average-risk screening populations, meaning roughly 1 in 7 people without colorectal cancer or advanced lesions will receive a positive result. 1
Specific Performance Data
The pivotal trial of 9,989 participants established the following specificity rates for Cologuard:
- 86.6% specificity among participants with nonadvanced or negative findings on colonoscopy 1, 2
- 89.8% specificity among those with completely negative colonoscopy results 1, 2
- This translates to a false positive rate of 13.4% to 10.2% depending on the reference population 1
For comparison, FIT (fecal immunochemical test) demonstrated significantly better specificity of 94.9-96%, resulting in fewer false positives 1, 2
Age-Related Variation in False Positives
Specificity decreases with advancing age, dropping to only 83% in persons aged >65 years, meaning older adults experience higher false positive rates approaching 17% 1
This age-related decline in specificity is clinically important when counseling patients about expected outcomes, particularly in the Medicare population 1
Clinical Implications of False Positives
When Cologuard returns a positive result but colonoscopy is negative:
- No further evaluation of the upper gastrointestinal tract is indicated in asymptomatic patients with high-quality negative colonoscopy 1
- The US Multi-Society Task Force specifically recommends against upper endoscopy workup in this scenario 1
- Patients can return to routine average-risk screening intervals after negative colonoscopy 3
The guideline evidence is clear that incident aerodigestive cancers occurred at similar rates (2.4% vs 1.1%) in patients with discordant results (positive Cologuard, negative colonoscopy) compared to concordant negative results, with no statistically significant difference in risk ratios 1
Cost and Efficiency Considerations
The higher false positive rate has important programmatic implications:
- More colonoscopies are required per cancer detected with Cologuard compared to FIT due to lower specificity 1
- The test costs approximately $500-600, roughly 10 times the cost of annual FIT 1
- Annual FIT is more effective and less costly than Cologuard every 3 years in organized screening programs 1
Common Pitfalls to Avoid
Do not pursue extensive additional testing when Cologuard is positive but colonoscopy is negative, as this leads to unnecessary procedures, patient anxiety, and healthcare costs without demonstrated benefit 1, 3
The DNA component of Cologuard (as opposed to the FIT component alone) is what lowers specificity and increases false positives, detecting DNA alterations that may not represent clinically significant colorectal pathology 1