Cologuard mt-sDNA Test Could Provide a Noninvasive Screening Option for CRC

February 19, 2021 - Multitarget stool DNA test Cologuard could present a potential noninvasive screening method for colorectal cancer, as it has demonstrated high specificity among average-risk patients aged 45 to 49 years.

Multitarget stool DNA (mt-sDNA) test Cologuard could present a potential noninvasive screening method for colorectal cancer (CRC), as it has demonstrated high specificity among average-risk patients aged 45 to 49 years, according to results from a study published in Cancer Prevention Research.1

The mt-sDNA had a specificity of 95.2% (95% CI, 93.4-96.6) in patients who tested positive for nonadvanced adenomas (NAA) and 96.3% in those who tested negative for colonoscopic findings (95% CI, 94.3-97.8). Specificity did not differ by sex (P = .75) or race (P = .36) in patients who received negative results or those who tested positive for NAA. The sensitivity for detecting advanced precancerous lesions (APL) was 32.7% (95% CI, 19.9-47.5).

Additionally, the majority of APLs (83.7%) measured between 10 mm to 19 mm and did not have high-grade dysplasia. Lastly, the area under the ROC curve meant to discriminate APL from lesser findings was 0.72 (95% CI, 0.64-0.81).

"These new data support the critical role an effective, non-invasive option like Cologuard plays in screening people ages 45 to 49," Kevin Conroy, chairman and CEO of Exact Sciences, said in a press release.2 "Cologuard may appeal to this younger screening population because they can collect sample at home, without missing work or undergoing bowel prep and anesthesia, and only those patients with a positive Cologuard will require a diagnostic colonoscopy."

Although high specificity screenings for CRC would be helpful when triaging patients under the age of 50 years prior to undergoing a colonoscopy, the majority of endorsed tests have not been rigorously evaluated in younger individuals. This unmet need inspired the prospective cross-sectional study, which sought to determine the specificity of Cologuard in average-risk patients between the ages of 45 and 49 years.

The primary outcome of the study was specificity, which was measured in patients without CRC and with APLs, as well as a subgroup of patients who had negative colonoscopic findings.

The evaluable cohort included those with usable mt-sDNA tests and patients who had completed the study without protocol deviations. In total, 983 patients were enrolled to the study, 816 of whom were included in the evaluable cohort. The mean age of the participants was 47.8 years (SD, 1.5) and 47.7% were women. Forty-nine patients had advanced precancerous lesions, 253 had nonadvanced adenomas, and 514 had negative colonoscopic findings. No patients were found to have CRC.

Cologuard became the first stool-based DNA screening test in CRC to receive approval from the FDA in August 2014.3 The regulatory decision was based on data from a trial in which 9989 patients were tested for CRC using Cologuard. The test demonstrated a 92.3% colorectal-detection rate compared with 73.8% in patients who were tested using an immunochemical test (P <.001). Additionally, the test gained inclusion in United States Preventive Services Task Force (USPSTF) screening guidelines for patients over the age of 50 years.

In September 2019, the FDA expanded the approval of Cologuard to include eligible, at-risk individuals who are aged 45 years or older.4

More recently, the test gained further development in November 2020, when the USPSTF issued a grade B recommendation for patients to receive CRC screenings at the age of 45.5 Cologuard was listed in the recommendation as a screening method that can be utilized in average-risk adult patients between the ages of 45 and 75 years.

"This study is among the first to evaluate the use of a CRC screening method in patients between the ages of 45 and 49," Paul Limburg, MD, chief medical officer of screening at Exact Sciences, added in the release. "The American Cancer Society guidelines and the 2020 draft United States Preventive Services Task Force guidelines now say that screening should begin at 45, and these data support the use of Cologuard as a first-line screening option."

Due to the high specificity of mt-sDNA, investigators concluded that Cologaurd may be able to help minimize unnecessary diagnostic procedures in this younger age group.


  1. Imperiale TF, Kisiel JB, Itzkowitz SH, et al. Specificity of the multi-target stool DNA test for colorectal cancer screening in average-risk 45–49 year-olds: a cross-sectional study. Cancer Prev Res (Phila). Published online January 12, 2021. doi:10.1158/1940-6207.CAPR-20-0294
  2. New prospective data demonstrate low false-positive rate for screening average-risk people age 45-49 for colorectal cancer with Cologuard. News release. Exact [KR1] Sciences Corp. January 12, 2021. Accessed February 19, 2021.
  3. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014;370(14):1287-1297. doi:10.1056/NEJMoa1311194
  4. Cologuard gains FDA approval for use in younger Americans, ages 45 to 49. News release. Exact Sciences Crop. September 23, 2019. Accessed February 19, 2021.
  5. Exact Sciences commends task force for draft updated guidelines that include colorectal cancer screening beginning at age 45. News release. Exact Sciences Corp. October 27, 2020. Accessed February 19, 2021.