What are the recommended follow-up screening guidelines for colorectal cancer after a negative Cologuard (multitarget stool DNA test) result and no family history of colon cancer?

Colorectal Cancer Screening After Negative Cologuard Without Family History

After a negative Cologuard (multitarget stool DNA test) result in an average-risk individual with no family history of colon cancer, repeat screening with Cologuard should occur in 3 years, or you may switch to any other recommended screening modality at its appropriate interval. 1

Screening Interval for Negative Cologuard

• The multitarget stool DNA test (Cologuard) is recommended every 3 years for average-risk adults aged 45-75 years. 1, 2

• After a negative result, the next Cologuard test should be performed in 3 years, assuming the patient remains asymptomatic and at average risk. 1

• This 3-year interval applies specifically to the multitarget stool DNA-FIT combination test and is distinct from annual FIT testing alone. 1, 2

Alternative Screening Options After Negative Cologuard

You are not locked into continuing with Cologuard. After a negative result, you may switch to any of these recommended screening modalities at their standard intervals: 1, 2

• Colonoscopy every 10 years (considered the gold standard with ability to detect and remove polyps in one procedure) 1

• Annual fecal immunochemical test (FIT) (high-sensitivity stool-based test) 1

• CT colonography every 5 years 1

• Flexible sigmoidoscopy every 5 years (though this only visualizes the left colon) 1

• High-sensitivity guaiac-based fecal occult blood test (gFOBT) annually 1

Age-Based Screening Recommendations

• Continue regular screening through age 75 if you are in good health with a life expectancy greater than 10 years. 1, 2

• Between ages 76-85, screening decisions should be individualized based on overall health status, prior screening history, and life expectancy. 1

• Screening is generally discouraged after age 85. 1, 2

Critical Follow-Up Requirement

• If any future Cologuard test is positive, you must undergo timely colonoscopy for diagnostic evaluation. This is non-negotiable, as failure to follow up positive stool-based tests with colonoscopy completely negates the screening benefit. 1, 2

• The entire screening paradigm for stool-based tests depends on colonoscopy follow-up of abnormal results to detect and remove precancerous lesions or early cancers. 1

When This Guidance Does NOT Apply

This 3-year interval recommendation is only for average-risk individuals, defined as those without: 1

• Personal history of colorectal cancer, adenomatous polyps, or inflammatory bowel disease 1

• Family history of colorectal cancer in a first-degree relative diagnosed before age 60 3, 4

• Two or more first-degree relatives with colorectal cancer at any age 3, 4

• Known genetic syndromes (Lynch syndrome, familial adenomatous polyposis) 1

If any of these risk factors are present, you would need more intensive screening with colonoscopy at shorter intervals, typically starting at age 40 or 10 years before the youngest affected relative's diagnosis. 3, 4

Practical Considerations

• Modeling studies suggest that annual Cologuard would provide greater life-years gained than the 3-year interval, but would also result in significantly more colonoscopies due to increased false-positive results. 1

• The 3-year interval for multitarget stool DNA testing represents a balance between detection benefit and the burden of follow-up colonoscopies. 1

• Annual FIT testing is estimated to provide similar or greater benefit compared to Cologuard every 3 years, with potentially fewer false-positive colonoscopies. 1, 2