Colorectal Neoplasia Detection in Individuals With Positive Multitarget Stool DNA Tests

Abstract

Background: The US Preventive Services Task Force (USPSTF) includes multitarget stool DNA (mt-sDNA) testing as a colorectal cancer (CRC) screening option in average-risk individuals, but data on colonoscopy outcomes after positive mt-sDNA tests in community settings are needed. Aim: The aim of this study was to investigate colonoscopy outcomes and quality following positive mt-sDNA in the population-based New Hampshire Colonoscopy Registry. Methods: We compared colonoscopy outcomes and quality between age-matched, sex-matched, and risk-matched patients from 30 endoscopy practices with and without a preceding positive mt-sDNA test. Main outcomes were colonoscopy findings of CRC, advanced noncancerous neoplasia, nonadvanced neoplasia, or normal examination. Quality measures included withdrawal time, bowel preparation quality, examination completion, and percentage of average-risk individuals with normal colonoscopies receiving a USPSTF-recommended 10 year rescreening interval. Results: Individuals with positive mt-sDNA tests (N=306, average age 67.0 y; 61.8% female) were significantly more likely than colonoscopy-only patients (N=918, 66.2 y; 61.8% female) to have CRC (1.3% vs. 0.4%) or advanced noncancerous neoplasia (27.1% vs. 8.2%) (P<0.0001). Neoplasia was found in 68.0% of patients having colonoscopy after a positive mt-sDNA test, (positive predictive value, was 68.0%), versus 42.3% of patients with colonoscopy only (P<0.0001). No significant differences in colonoscopy quality measures were observed between cohorts. Conclusions: Colonoscopy after a positive mt-sDNA test was more frequently associated with CRC and colorectal neoplasia than colonoscopy alone. Positive mt-sDNA tests can enrich the proportion of colonoscopies with clinically relevant findings. Follow-up recommendations suggest that endoscopists do not inappropriately shorten rescreening intervals in mt-sDNA-positive patients with normal colonoscopy. These findings support the clinical utility of mt-sDNA for CRC screening in community practice.

Serrated Polyp Yield at Colonoscopy in Patients with Positive FIT, Positive mt-sDNA, and Colonoscopy Only: Data from the New Hampshire Colonoscopy Registry

“…Since serrated polyps progress through methylation, it would be reasonable to expect that colonoscopies after a positive mt-sDNA test, with two methylated markers, might have a higher yield of serrated polyps compared to those after positive FIT. (21,22) We found that patients in our population with preceding mt-sDNA+ stool tests were more likely to have serrated polyps at colonoscopy than patients with preceding FIT+ tests or patients who had a colonoscopy without a preceding stool test. Specifically, nearly 1 in 5 (17.9%) mt-sDNA+ patients had CRSPs with no synchronous large (> 1 cm) adenomas or CRC detected at colonoscopy, compared to 1 in 10 (9.9%) FIT+ patients and 8.0% of colonoscopy-only patients.…”

“…Positive stool tests prior to colonoscopy are known to enrich polyp findings at colonoscopy ( 5 ). However, the likelihood of specific polyp findings at colonoscopy may not be the same for different stool tests, which employ single (FIT, FOBT) or multiple (mt-sDNA) markers to screen-detect relevant colorectal neoplasia.…”

“… 20 ). Because serrated polyps progress through methylation, it would be reasonable to expect that colonoscopies after a positive mt-sDNA test, with two methylated markers, might have a higher yield of serrated polyps compared with those after positive FIT ( 5, 21 ).…”

“…Although some patients with positive results on either stool test had normal or insignificant findings, our results show that patients with either positive test, and with positive mt-sDNA in particular, had higher prevalence of clinically significant lesions than those who had colonoscopy without preceding stool tests. Because mt-sDNA is less likely to be positive for small polyps than for larger polyps ( 5, 16 ), it is unlikely that mt-sDNA is detecting polyps for which colonoscopic removal would not have been recommended, with or without a preceding stool test. The same would be true for FIT, although the sensitivity of FIT for advanced polyps is less than that of mt-sDNA ( 16 ).…”

“…Stool tests were developed to detect early stages of colorectal cancer as well as precancerous polyps, which can then be removed during subsequent colonoscopy, which should be performed for all patients with positive stool tests. Past research has found that patients with either positive FIT or positive mt-sDNA tests are more likely to have polyps found during colonoscopy than those without preceding stool tests ( 5 ). Thus, the use of these tests for screening can increase the number of individuals referred for colonoscopy who have important lesions which need to be resected.…”