Discordant Results

Follow-up colonoscopy findings may be negative for colorectal cancer (CRC) after a positive multitarget stool DNA (mt-sDNA) screening result (discordant results). However, the incidence of aerodigestive cancers (ADC), cancers of the digestive tract and lungs, were uncommon among average-risk individuals with negative colonoscopy results, regardless of concordance with mt-sDNA results.1

Approximately 93% of discordant and 92% of concordant cases had ≥3 years of follow-up1

Neither colonoscopy and mt-sDNA discordant nor concordant groups had increased risk of aerodigestive cancer (ADC) above the rate expected for the general population1

Data suggests that additional diagnostic testing in patients with high-quality colonoscopies who had false-positive mt-sDNA test results is not warranted1

PATIENT CHARACTERISTICS AND SCREENING COLONOSCOPY FINDINGS1

Discordant (n=205)a Concordant (n=1011)a P value
Age
Median (IQR), years 68 (65-71) 67 (65-70) 0.005
50-64 years, n (%) 43 (21) 246 (24) 0.303
65-85 years, n (%) 162 (79) 765 (76)
Sex
Men, n (%) 107 (52) 520 (51) 0.842
Women, n (%) 98 (48) 491 (49)
Race
White, n (%) 194 (95) 937 (93) 0.514
Black, n (%) 4 (2) 20 (2)
Other, n (%) 7 (3) 754 (5)
Ethnicity
Hispanic, n (%) 1 (0.5) 11 (1.1) 0.428
Negative colonoscopy findings
Nonadvanced adenomab 84 (41) 308 (30) <0.001
No colorectal neoplasia 121 (59) 703 (70)

Table adapted from Berger, 20201

  • A retrospective, cohort study of subjects aged ≥50 years at average risk for CRC with negative screening colonoscopy resultsa with either positive mt-sDNA (discordant) or negative (concordant) results were followed to determine whether subsequent ADC had been identified1
  • Patient characteristics of sex and race were similar between the groups with discordant and concordant results1
  • While statistically significantly different, median age was similar between the two groups (68 years vs 67 years for the groups with discordant and concordant results, respectively)1
  • Participants with a positive mt-sDNA had nonadvanced adenomas on colonoscopy more frequently than participants with negative mt-sDNA tests (41% vs 30%; P<0.001)1

RISK OF AERODIGESTIVE CANCERS IN PATIENTS WITH DISCORDANT mt-sDNA RESULTS1,c

Graph summarizes the risk of aerodigestive cancers in patients with discordant mt-sDNA results. Evidence from the United States Multisociety Task Force suggests that asymptomatic patients with a positive FIT-fecal DNA test and a negative high-quality colonoscopy do not need additional testing.
  • Retrospective cohort study
  • 205 persons with false-positive mt-sDNA results
  • Followed for a median of 5.3 years
  • Incidence of cancers in digestive and respiratory systems is similar to expected rate

US MSTF

"Evidence suggests that asymptomatic patients with a positive FIT-fecal DNA test and a negative high-quality colonoscopy do not need additional testing."2

  • Within the false-positive group, there were five ADCs (2.4%), giving an incidence rate of 0.5% per year (95% CI: 0.2-1.2% per year). The expected number of ADCs within this group was six, resulting in a risk ratio (RR) of 0.8 (95% CI: 0.3-1.9; P=0.599) relative to the Surveillance, Epidemiology, and End Results (SEER) population1
  • Among the group with true negative results, 11 ADCs (1.1%) resulted in an incidence rate of 0.2% per year (95% CI: 0.1-0.4% per year). The expected number of ADCs for this group was 30, resulting in an RR of 0.4 (95% CI: 0.2-0.7; P<0.001) relative to the SEER population1
  • The study limitations include a predominantly White study population, selection of population based on availability of patient records, and relatively small study population with limited number of ADCs1

Learn more about the full Indications/Contraindications for the mt-sDNA test. Please see complete prescribing information for the Cologuard® test in the Cologuard Clinician Brochure.

FIT: fecal immunochemical test; mt-sDNA: multitarget stool DNA.

Related Topics

Footnotes

  1. An additional two discordant and 12 concordant participants were lost to follow-up evaluation within 6 months of informed consent (0-6.0 months).
  2. Nonadvanced adenoma defined as colorectal adenomas or sessile serrated polyps <1.0 cm in diameter, without high-grade dysplasia or without ≥25% villous component.
  3. Observed cases (n=5): one CRC, one pancreas cancer, one parotid cancer, and two lung cancer.

List of definitions

ADC: aerodigestive cancer; CRC: colorectal cancer; FDA: Food and Drug Administration; FIT: fecal immunochemical test; IQR: interquartile range; mt-sDNA: multitarget stool DNA; RR: risk ratio; SEER: Surveillance, Epidemiology and End Results; US MSTF: United States Multisociety Task Force.


References

  1. Berger BM, Kisiel JB, Imperiale TF, et al. Low incidence of aerodigestive cancers in patients with negative results from colonoscopies, regardless of findings from multitarget stool DNA tests. Clin Gastroenterol Hepatol. 2020;18(4):864-871.
  2. Rex DK, Boland CR, Dominitz JA, et al. Colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on colorectal cancer. Am J Gastroenterol. 2017;112(7):1016-1030.