Three-Year Interval for the Multi-Target Stool DNA Test for Colorectal Cancer Screening: A Longitudinal Study

Abstract

Data supporting the clinical utility of multi-target stool DNA (mt-sDNA) at the guideline-recommended 3-year interval have not been reported.Between April 2015 and July 2016, candidates for colorectal cancer screening whose providers prescribed the mt-sDNA test were enrolled. Participants with a positive baseline test were recommended for colonoscopy and completed the study. Those with a negative baseline test were followed annually for 3 years. In year 3, the mt-sDNA test was repeated and colonoscopy was recommended independent of results. Data were analyzed using the Predictive Summary Index (PSI), a measure of the gain in certainty for dichotomous diagnostic tests (where a positive value indicates a net gain), and by comparing observed versus expected colorectal cancers and advanced precancerous lesions.Of 2,404 enrolled subjects, 2,044 (85%) had a valid baseline mt-sDNA result [284 (13.9%) positive and 1,760 (86.1%) negative]. Following participant attrition, the year 3 intention to screen cohort included 591 of 1,760 (33.6%) subjects with valid mt-sDNA and colonoscopy results, with no colorectal cancers and 63 advanced precancerous lesions [22 (34.9%) detected by mt-sDNA] and respective PSI values of 0% (P = 1) and 9.3% (P = 0.01). The observed 3-year colorectal cancer yield was lower than expected (one-sided P = 0.09), while that for advanced precancerous lesions was higher than expected (two-sided P = 0.009).Repeat mt-sDNA screening at a 3-year interval resulted in a statistically significant gain in detection of advanced precancerous lesions. Due to absence of year 3 colorectal cancers, the PSI estimate for colorectal cancer was underpowered and could not be reliably quantified. Larger studies are required to assess the colorectal cancer study findings.

Prevention relevance: Understanding the 3-year yield of mt-sDNA for colorectal cancer and advanced precancerous polyps is required to ensure the clinical appropriateness of the 3-year interval and to optimize mt-sDNA's screening effectiveness.

Figure 1.

Study flow diagram. This diagram shows derivation of baseline and analytical cohorts. ^aOf the 154 participants who had early colonoscopy: colorectal cancer was found (n = 1), along with advanced precancerous lesions (n = 11), while 111 participants had clinically insignificant findings, including non-advanced adenomas (n = 41), no findings on colonoscopy (n = 70), and those that could not be categorized (n = 31). ^b400/423 had a valid mt-sDNA result. ^cSubjects excluded were those who did not have documentation or had poor bowel preparation quality (n = 29), those who had a polyp or mass found but no tissue submitted (n = 12), those without documentation of cecal intubation (n = 3), and if a subject had a polyp or mass found but pathology report and verification of lesion could not be retrieved (n = 1).