What is the appropriate next step in management for a patient with a positive Cologuard (colorectal cancer DNA stool) test?

Management of a Positive Cologuard Test

A positive Cologuard test requires follow-up with a complete diagnostic colonoscopy, which should be performed within 60 days and no later than 6 months to minimize the risk of advanced-stage disease. 1, 2, 3

Immediate Next Step

• Schedule diagnostic colonoscopy as the definitive follow-up test for any positive Cologuard result, as colonoscopy allows direct visualization of the entire colon and simultaneous removal of any detected lesions 1, 2
• Do not repeat the Cologuard test, as this will likely yield another false positive given the test's 13-14% false positive rate 3
• Do not substitute with CT colonography, flexible sigmoidoscopy, or other non-colonoscopy modalities, as colonoscopy is the gold standard with 89-95% sensitivity for detecting adenomas ≥10mm 1, 3

Timing of Colonoscopy

Complete the colonoscopy within 60 days of the positive result, with an absolute maximum of 6 months. 1, 3

The evidence strongly supports timely follow-up:

• Delays beyond 180 days show a trend toward increased colorectal cancer risk, becoming statistically significant after 270 days (OR 1.48,95% CI 1.05-2.08) 1
• Each additional month of delay increases colorectal cancer incidence and mortality by approximately 0.1 per 1,000 individuals (1.4% monthly increase in mortality) 1
• Delays beyond 6 months are associated with advanced-stage colorectal cancer (adjusted OR 2.09,95% CI 1.43-3.06) and advanced adenomas (adjusted OR 1.31,95% CI 1.04-1.64) 3

Understanding the Test Result

A positive Cologuard does not mean cancer is definitively present—it indicates increased risk requiring diagnostic evaluation. 2

Key performance characteristics to counsel patients about:

• Cologuard has 92.3% sensitivity for colorectal cancer but only 42.4% sensitivity for advanced precancerous lesions 1, 2
• The test has 86.6% specificity, meaning approximately 13-14% of positive results are false positives in patients without significant neoplasia 2, 3
• Positive predictive value ranges from 1.3% to 7.7% depending on the population 2

If Colonoscopy is Negative

Patients with a high-quality negative colonoscopy after a positive Cologuard should return to standard colonoscopy-based surveillance intervals and should NOT undergo further Cologuard testing. 3

This recommendation is based on:

• Colonoscopy supersedes the Cologuard result as the definitive diagnostic test 3
• A subanalysis of the pivotal Cologuard trial found no increased risk of aerodigestive cancers in patients with discordant results (positive Cologuard, negative colonoscopy) compared to concordant negative results (risk ratio 0.8,95% CI 0.3-1.9) 3
• Average-risk individuals should follow colonoscopy every 10 years; if non-advanced adenomas were found and removed, follow surveillance guidelines (typically 5-10 years depending on findings) 3

Upper GI Evaluation

Do NOT routinely perform upper endoscopy after a positive Cologuard with negative colonoscopy. 1, 3

Upper endoscopy is only indicated if:

• Iron-deficiency anemia is present 1, 3
• Specific upper GI symptoms exist (dyspepsia, reflux, weight loss) independent of the Cologuard result 3
• Research shows only 0.14% of patients with positive fecal tests are diagnosed with gastric or esophageal cancer within 3 years, and there is no significant difference in upper GI cancer incidence between positive and negative fecal test results (0.37% vs 0.31%, P=0.65) 4

Common Pitfalls to Avoid

Do not delay colonoscopy while attempting dietary modifications, repeating the test, or pursuing alternative imaging—every month of delay increases cancer mortality risk 1, 3

Do not use Cologuard as a surveillance tool after colonoscopy—it is approved only as a primary screening modality in average-risk adults aged 45-85 years 3

Do not order Cologuard in high-risk patients who should undergo colonoscopy instead, including those with:

• Personal history of colorectal cancer or advanced adenomas 2, 5
• Family history of colorectal cancer in a first-degree relative diagnosed before age 60 5
• Personal history of inflammatory bowel disease 2, 5
• Known or suspected hereditary colorectal cancer syndromes (Lynch syndrome, familial adenomatous polyposis) 2, 5

Quality Colonoscopy Requirements

Ensure the follow-up colonoscopy meets quality standards:

• Complete examination to the cecum 1
• Adequate bowel preparation to detect polyps >5mm 1
• Performed by an endoscopist with acceptable adenoma detection rates 1