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

ABSTRACT Background and Aims Approximately 20-30% of colorectal cancers (CRC) arise from the serrated polyp pathway. CRC screening options have differential sensitivity to detect sessile serrated polyps (SSPs). We used the CRC-AIM model 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%). 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 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. 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. Conclusions 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.