What is the likelihood of colorectal cancer if a Cologuard (colon cancer screening test) result is positive?

Likelihood of Colorectal Cancer with a Positive Cologuard Test

A positive Cologuard test has a low positive predictive value for colorectal cancer of only 1.3%, meaning the vast majority of patients with positive results do not have cancer. 1

Understanding Cologuard and Its Performance

Cologuard is a multitarget stool DNA test that combines DNA markers with a fecal immunochemical test (FIT) component. According to the National Comprehensive Cancer Network (NCCN) guidelines, this test has the following performance characteristics:

• Sensitivity for colorectal cancer: 92.3% (higher than FIT alone at 73.8%) 2
• Sensitivity for advanced precancerous lesions: 42.4% (higher than FIT alone at 23.8%) 2
• Specificity: 86.6% among participants with nonadvanced or negative findings (lower than FIT at 94.9%) 2

Positive Predictive Value for Cancer

The positive predictive value (PPV) of Cologuard for colorectal cancer is notably low:

• A 2023 retrospective review found that among 78 patients with positive Cologuard tests who underwent colonoscopy:
  • Only 1.3% had colorectal cancer
  • 6.4% had advanced adenomas (>1 cm size, high-grade dysplasia, or villous features)
  • Combined PPV for cancer and precancerous lesions was 7.7%
  • 68% had either normal colonoscopy or hyperplastic polyps 1

Clinical Implications and Follow-up Recommendations

When a patient has a positive Cologuard result:

1. Colonoscopy is mandatory: The U.S. Multi-Society Task Force on Colorectal Cancer emphasizes that any positive non-invasive screening test requires follow-up with colonoscopy 2

2. Timing of follow-up: Follow-up colonoscopy should be performed within 60-90 days of a positive result:

   • The Veterans Health Administration recommends a 60-day target for completion of diagnostic colonoscopy 2
   • Delays beyond 270 days after a positive stool test are associated with significantly increased risk of colorectal cancer (OR: 1.48) 2

3. Patient counseling: It's important to explain to patients that:

   • A positive result indicates the need for diagnostic colonoscopy but does not mean cancer is present
   • The test has high sensitivity but moderate specificity, leading to many false positives
   • The vast majority (approximately 98.7%) of positive results will not reveal cancer 1

Common Pitfalls to Avoid

1. Misinterpreting positive results: Don't assume a positive Cologuard means high likelihood of cancer. The data clearly shows most positives are false positives.

2. Delaying follow-up: Ensure timely colonoscopy within 60-90 days of a positive result.

3. Inappropriate screening intervals: The NCCN notes that appropriate screening intervals for stool DNA testing cannot be recommended due to limited data 2, 3.

4. Using Cologuard for high-risk patients: Patients with a history of polyps should undergo direct visualization with colonoscopy rather than stool-based testing 3.

5. Ignoring upper GI sources: While some might worry about upper GI bleeding causing false positives, research shows that only 0.14% of persons with positive FIT results were diagnosed with gastric or esophageal cancer within 3 years, so routine upper endoscopy is not recommended 4.

By understanding the true likelihood of cancer with a positive Cologuard result, clinicians can provide appropriate counseling to patients and ensure timely follow-up while avoiding unnecessary anxiety.