Impact of the Sessile Serrated Polyp Pathway on Predicted Colorectal Cancer Outcomes

Background and Aims: Approximately 20%–30% of colorectal cancers (CRCs) arise from the serrated polyp pathway. CRC screening options have differential sensitivity to detect sessile serrated polyps (SSPs). We used the Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC-AIM) to assess how the detection of SSPs impacts predicted life years gained (LYG), CRC incidence, and CRC mortality with multitarget stool DNA (mt-sDNA) or fecal immunochemical test (FIT) screening. Methods: A simulated cohort of average-risk US individuals underwent triennial mt-sDNA or annual FIT screening between ages 45–75 years. SSP-attributed CRCs were modeled at 0% (base case), 14.3%, 20%, and 30%, in combination with 4 adherence & attendance scenarios: S1: 100% stool-screening adherence/100% follow-up colonoscopy attendance after a positive stool test; S2: reported stool-screening adherence (mt-sDNA = 71%; FIT = 43%)/100% follow-up colonoscopy attendance; S3: reported stool-screening adherence/reported follow-up colonoscopy attendance (mt-sDNA = 72%; FIT = 47%); and S4: reported stool-screening adherence/72% follow-up colonoscopy attendance. Outcomes were per 1000 individuals. Sensitivity analyses used ranges of stool-screening adherence or follow-up attendance. Results: At S1, S2, S3, and S4, LYG with FIT at the base case (0% SSP-attributed CRC) was 346.7, 279.3, 126.6, and 196.1, respectively, and with mt-sDNA was 324.6, 311.8, 215.8, and 215.8, respectively. Among the 4 adherence/attendance scenarios, modeling SSP-attributed CRCs decreased LYG by 4.9–20.9 with FIT and 2.0–5.1 with mt-sDNA. At S3 and 30% SSP-attributable CRCs, mt-sDNA had 95.1 more LYG, 21.5% greater CRC incidence reduction, and 22.2% greater CRC mortality reduction than FIT. Conclusion: Incorporating SSPs and real-world adherence into the CRC-AIM modeling analyses yielded more practice-relevant estimates of CRC screening outcomes and should be applied in future studies to afford more appropriate assessment of comparative effectiveness estimates between guideline-endorsed screening options.