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). 2021 Apr;14(4):489-496. doi: 10.1158/1940-6207.CAPR-20-0294. Epub 2021 Jan 12.


High-specificity colorectal cancer screening is desirable to triage patients <50 years for colonoscopy; however, most endorsed colorectal cancer screening tests have not been rigorously evaluated in younger populations. This prospective cross-sectional study determined the specificity of the multitarget stool DNA (mt-sDNA) test in an average-risk screening population of 45 to 49 year-olds. Specificity was the primary outcome and was measured in participants without colorectal cancer or advanced precancerous lesions [APL- advanced adenomas (AA), and sessile serrated lesions ≥10 mm], and in the subgroup of participants with negative colonoscopic findings. APL sensitivity was a secondary outcome. The evaluable cohort included those who completed the study without protocol deviations and had a usable mt-sDNA test. Of 983 enrolled participants, 816 formed the evaluable cohort, with a mean age of 47.8 (SD, 1.5) years; 47.7% were women. No participants had colorectal cancer, 49 had APL, 253 had nonadvanced adenomas (NAA), and 514 had negative colonoscopic findings. mt-sDNA test specificity was 95.2% (95% CI, 93.4-96.6) in participants with NAA or negative findings [96.3% (confidence interval (CI), 94.3%-97.8%)] in those with negative findings, and did not differ by sex (P = 0.75) or race (P = 0.36) in participants with NAA or negative findings. Sensitivity for APL was 32.7% (CI, 19.9-47.5%), with most APL (83.7%) measuring 10-19 mm and none having high-grade dysplasia. The area under the ROC curve for discriminating between APL and lesser findings was 0.72 (CI, 0.64-0.81). mt-sDNA's high specificity would help minimize risk from unnecessary diagnostic procedures in this age group. This study shows that mt-sDNA has high specificity among average-risk 45 to 49-year olds, supporting its use as a noninvasive option for colorectal cancer screening. PREVENTION RELEVANCE: This study shows that mt-sDNA has high specificity among average-risk 45-49 year olds, supporting its use as a non-invasive option for colorectal cancer screening.

Trial registration: ClinicalTrials.gov NCT03728348.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics
  • Cross-Sectional Studies
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / genetics*
  • Early Detection of Cancer / methods*
  • Feces / chemistry*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Precancerous Conditions / diagnosis*
  • Precancerous Conditions / epidemiology
  • Precancerous Conditions / genetics
  • Prognosis
  • Prospective Studies
  • ROC Curve
  • United States / epidemiology


  • DNA, Neoplasm

Associated data

  • ClinicalTrials.gov/NCT03728348