AGA Clinical Practice Update

Noninvasive Colorectal Cancer Screening Options: Expert Advice

Jim Kling

March 14, 2022

A new expert commentary from the American Gastroenterological Association focuses on noninvasive screening options for colorectal cancer (CRC), as well as approaches to ensure quality in noninvasive screening programs. The commentary was published in Gastroenterology.

The American Cancer Society reported in its Cancer Facts & Figures 2021 report that lifetime risk of CRC in the United States is 4%, and those with above average risk are recommended to undergo CRC screening at an earlier age, with colonoscopy as a screening modality. Between 75% and 80% of the U.S. population is considered at average risk, and this is the group covered by the expert commentary. In this group, CRC rates jump from 35.1 to 61.2 cases per 100,000 people between the ages of 45-49 years and 50-54 years. Early-onset (before 50) CRC accounts for 12% of all cases and 7% of CRC-related deaths.

The authors noted that the U.S. Preventive Services Task Force made a grade B recommendation for individuals to begin screening at age 45, regardless of screening method, and their modeling suggests that screening initialization at 45 rather than 50 years increases life-years gained by 6.2% at the cost of a 17% increase in colonoscopies.

According to the commentary authors, a hybrid approach combining annual fecal immunochemical testing (FIT) at age 45-49, followed by colonoscopy between ages 50 and 70, could result in substantial gains in life-years while prioritizing colonoscopies for advancing age, which is associated with increased risk of advanced adenomas (AA) and CRC.

Exploring Options

For stool-based CRC screening, FIT has generally replaced guaiac fecal occult blood testing because of better patient adherence and fewer restrictions on medicine and diet. FIT can produce a quantitative result measured in micrograms of hemoglobin per gram, or qualitatively positive above a threshold of 20 mcg per gram. The MTsDNA (Cologuard) test combines FIT with two DNA methylation markers, KRAS mutation screening, and a measurement of total human DNA, with use of an algorithm of combined results to determine positivity. It is approved only for average-risk individuals aged 45-85.

In cases where MTsDNA tests positive, but colonoscopy reveals no findings, an aerodigestive cancer could be present. However, this is considered rare based on a study that revealed that 2.4% of patients with discordant results developed an aerodigestive cancer during a median 5.4 years of follow-up, compared with 1.1% of cases with negative MTsDNA and negative colonoscopy. The difference was not statistically significant. The commentary authors suggest that no further testing is required after a negative high-quality colonoscopy and that patients can resume screening at normal intervals with any of the recommended tests.

The Septin 9 blood test (Epi proColon) is another screening option, and is FDA approved for average-risk individuals older than 50 years. It detects methylation of the promoter region of the Septin 9 gene. It has a 48% sensitivity and 91.5% specificity for CRC, as well as a sensitivity of 11.2% for AA. One model found that Septin 9 screening every 1 or 2 years could lead to more quality-adjusted life-years gained and prevention of more deaths than annual FIT, but with more colonoscopies. CRC screening guidelines do not endorse Septin 9, but screening studies are in progress to assess its performance.

Ensuring Quality

"The linchpin for effective noninvasive screening programs is adherence, and several measures of adherence are required," the authors wrote. To ensure high quality of noninvasive screening programs, it is important to create metrics and employ continuous monitoring of compliance, and to initiate changes when adherence and outcomes lag. Important metrics include patient compliance, rapid reporting of test results, timely implementation of follow-up colonoscopies, and systems put in place to restore patients to appropriate CRC screening intervals.

The authors suggested several specific metrics and attainable performance goals. The ratio of tests completed within 1 year to tests ordered should reach 90% or more. Outreach should be conducted to patients who do not complete testing within 1 month of the order. All patients should be contacted with 2 weeks of test results, and those who test negative should be made aware of the appropriate interval for future screening, along with the method of contact.

At least 80% of patients who receive a positive test should be offered a colonoscopy date within 3 months, and all within 6 months, because delay past that time is associated with greater risk of AA, CRC, and advanced-stage CRC. Within 6 months of a positive noninvasive test, at least 95% of patients should have undergone a colonoscopy, unless they are too ill, have moved, or cannot be reached. "Quality metrics for noninvasive screening programs should be set and program performance should be measured and ideally reported publicly," the authors summarized. "Poor adherence at any level should trigger review of established protocols and facilitate change to ensure high-quality screening."

Two authors disclosed relationships with Freenome and/or Check-Cap, but the third disclosed no conflicts.

This article originally appeared on, part of the Medscape Professional Network.


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