S254 What Do "False-Positive" Stool Tests Really Mean? Data From the New Hampshire Colonoscopy Registry (2022)

Introduction: Accurate understanding of the frequency of meaningful ‘true positive’ and ‘false positive’ mt-sDNA and FIT results is essential to optimizing the use of these important, common colorectal cancer (CRC) screening tests. We utilized the statewide, population-based New Hampshire Colonoscopy Registry (NHCR) to investigate colonoscopy outcomes using 3 distinct definitions of a ‘positive’ colonoscopy, and present the corresponding false discovery rate and positive predictive values (PPV). Methods: Data from Exact Sciences Laboratories and the NHCR identified patients with mt-sDNA+ tests followed by colonoscopy resulting from routine care (8/15-12/20). We calculated false discovery rates (FDR) (# positive stool tests with negative colonoscopy divided by all positive stool tests) and the corresponding PPVs for both mt-sDNA+ and FIT+ cohorts using 3 definitions of positive colonoscopy: 1) Detection of colorectal advanced adenomatous Polyps and Cancer: DeeP-C Study (CRC, adenomas >1 cm or with 25%+ villous elements, high grade dysplasia or any serrated polyp [traditional serrated adenoma, sessile serrated polyp (SSP) or hyperplastic polyp (HP)] >1 cm) 2) Polyps requiring < 10 year follow up per USMSTF guidelines: includes DeeP-C findings (above) and 1 or more SSPs < 1 cm (with/without dysplasia) or 1 or more tubular adenomas < 1 cm. 3) Clinically Significant: Above DeeP-C and USMSTF findings and the remaining clinically significant serrated polyps: 5-9 mm proximal HPs. Results: When using the strictest definition of positive colonoscopy, DeeP-C, the FDR was 71.9% for mt-sDNA+ and 81.7% for FIT+. Using the USMSTF definition, the FDR decreased to 33.2% for mt-sDNA+ and 47.6% for FIT+. Finally, adding 5-9 mm proximal HPs to the USMSTF < 10 year definition resulted in the lowest FDRs: 32.2% for mt-sDNA+ and 47.1% for FIT+ results. These decreasing FDRs correspond to increasing PPVs of 28.1% for mt-sDNA+ and 18.3% for FIT+ (DeeP-C) to 67.8% for mt-sDNA+ and 52.9% for FIT+ (DeeP-C + USMSTF + CSSP, Table). Conclusion: Our analysis demonstrates a substantial decrease in FDRs (and corresponding increases in PPV) when using a definition of positive colonoscopy that includes additional significant precancerous findings such as adenomas or SSPs. These data present a more comprehensive and clinically relevant understanding of false positive outcomes at colonoscopies following positive stool tests, and to our knowledge this is the first such assessment of these outcomes. Table 1. - False discovery rates and positive predictive value (PPV) according to different definitions of positive colonoscopy False discovery rate (“negative” colonoscopy) mt-sDNAN=549 FITN=410 # % # % Deep-C* 395 71.9 335 81.7 DeeP-C* + USMSTF** < 10 yrs 182 33.2 195 47.6 DeeP-C*+ USMSTF** < 10 yrs + CSSP*** 177 32.2 193 47.1 Positive Predictive Value (PPV) # % # % Deep-C* 154 28.1 75 18.3 DeeP-C* + USMSTF** < 10 yrs 367 66.8 215 52.4 DeeP-C*+ USMSTF** < 10 yrs + CSSP*** 372 67.8 217 52.9 *DeeP-C: Detection of colorectal advanced adenomatous Polyps and Cancer3**USMSTF: United States Multi-Society Task Force on Colorectal Cancer Screening8***CSSP: all clinically significant serrated polyps, including all traditional serrated adenomas and sessile serrated polyps, all hyperplastic polyps >10 mm, and hyperplastic polyps 5-9 mm in the proximal colon