Discordant Results

Follow-up colonoscopy findings may be negative for colorectal cancer (CRC) after a positive multi-target 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 ADC above the rate expected for the general population1

Data suggests that additional diagnostic testing in patients with negative results from high-quality colonoscopies is not warranted1,2

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
 Non-advanced adenomab 84 (41) 
  308 (30) 
  <0.001
  No colorectal neoplasia 
 121 (59)
 703 (70)  

  • 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 non-advanced adenomas on colonoscopy more frequently than participants with negative mt-sDNA tests (41% vs 30%; P<0.001)1
  • This study cohort had statistically significant differences in demographics compared to participants in the pivotal trial of mt-sDNA, DeeP-C1

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

  • Within the false positive group, there were 5 ADCs (2.4%), giving an incidence rate of 0.5%/year (95% CI: 0.2-1.2%/year). The expected number of ADCs within this group was 6, 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%/year (95% CI, 0.1-0.4%/year). The expected number of ADCs for this group was 30, resulting in a risk ratio (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 Cologuard in the Cologuard Clinician Brochure

To report suspected Adverse Events or product problems, please contact the Exact Sciences Laboratories Customer Care Center at 1-844-870-8870. You can also contact the US Food and Drug Administration (FDA) directly at 1-800-FDA-1088 or visit www.fda.gov/MedWatch.


Related Topics

ADC: aerodigestive cancer, HR: hazard ratio, mt-sDNA: multi-target stool DNA, RR: risk ratio, SEER: Surveillance, Epidemiology and End Results, USMSTF: United States Multi-Society 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.

Footnotes 

a An additional 2 discordant and 12 concordant participants were lost to follow-up evaluation within 6 months of informed consent (0–6.0 mo).

b Non-advanced adenoma defined as colorectal adenomas or sessile serrated polyps <1.0 cm in diameter, without high-grade dysplasia or without ≥25% villous component.

c Observed cases (n = 5): 1 CRC, 1 Pancreas Cancer, 1 Parotid Cancer, and 2 Lung Cancer 

d Expected based on age- and sex-adjusted SEER data1

Last updated: 04/22/2023