Parton, Marcus

10545 Background: Approximately 20–30% of colorectal cancers (CRC) arise from the serrated polyp pathway. The multitarget stool DNA (mt-sDNA) test has greater sensitivity to detect sessile serrated polyps (SSPs) than a leading fecal immunochemical test (FIT). However, most modeling analyses do not account for the contribution of the SSP pathway to risk of CRC. We used the CRC-AIM model to assess the impact of the SSP pathway on predicted CRC outcomes with mt-sDNA or FIT screening. Methods: A simulated cohort of average-risk US patients underwent triennial mt-sDNA or annual FIT screening from ages 50–75. The percentage of CRCs arising from the SSP pathway were modeled at 0% (base case), 20%, and 30%, with stool screening adherence based on theoretical (100%) or previously reported (mt-sDNA 71%; FIT 43%) rates. Published SSP sensitivities for mt-sDNA and FIT were used. All other model inputs were identical to CISNET models. Sensitivity analyses used screening adherence rates of 40–70%. Key outcomes were life-years gained (LYG), CRC incidence and CRC mortality per 1000 patients. Results: Including SSPs in the model demonstrated a greater loss of LYG with FIT than mt-sDNA (Table). At 100% adherence, compared with base case, modeling 20% or 30% SSP pathway CRCs resulted in a decrease of 9–15 LYG with FIT and 2–4 LYG with mt-sDNA, a decrease in CRC incidence reduction of 3.9–6.1% with FIT and 0.7–1.1% with mt-sDNA, and a decrease in CRC mortality reduction of 2.6–4.0% with FIT and 0.4–0.8% with mt-sDNA. Using previously reported adherence, compared with base case, modeling 20% or 30% SSP pathway CRCs resulted in a decrease of 13–20 LYG with FIT and 2–5 LYG with mt-sDNA, a decrease in CRC incidence reduction of 4.4–6.9% with FIT and 0.6–1.1% with mt-sDNA, and a decrease in CRC mortality reduction of 3.5–5.4% with FIT and 0.4–0.9% with mt-sDNA. Assuming reported adherence and 30% SSP pathway CRCs, mt-sDNA had 48 more LYG, 14.6% greater CRC incidence reduction, and 12.4% greater CRC mortality reduction than FIT. Assuming 30% SSP pathway CRCs, outcomes favored mt-sDNA vs FIT even after modeling equivalent adherence rates ranging from 40–70%. Conclusions: After incorporating the SSP pathway into the model, outcomes with mt-sDNA neared those of FIT at 100% screening adherence rates and surpassed FIT at more realistic reported screening adherence rates.[Table: see text]

Abstract Background Real‐world data for patients with positive colorectal cancer (CRC) screening stool‐tests demonstrate that adenoma detection rates are lower when endoscopists are blinded to the stool‐test results. This suggests adenoma sensitivity may be lower for screening colonoscopy than for follow‐up to a known positive stool‐based test. Previous CRC microsimulation models assume identical sensitivities between screening and follow‐up colonoscopies after positive stool‐tests. The Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC‐AIM) was used to explore the impact on screening outcomes when assuming different adenoma sensitivity between screening and combined follow‐up/surveillance colonoscopies. Methods Modeled screening strategies included colonoscopy every 10 years, triennial multitarget stool DNA (mt‐sDNA), or annual fecal immunochemical test (FIT) from 50 to 75 years. Outcomes were reported per 1000 individuals without diagnosed CRC at age 40. Base‐case adenoma sensitivity values were identical for screening and follow‐up/surveillance colonoscopies. Ranges of adenoma sensitivity values for colonoscopy performance were developed using different slopes of odds ratio adjustments and were designated as small, medium, or large impact scenarios. Results As the differences in adenoma sensitivity for screening versus follow‐up/surveillance colonoscopies became greater, life‐years gained (LYG) and reductions in CRC‐related incidence and mortality versus no screening increased for mt‐sDNA and FIT and decreased for screening colonoscopy. The LYG relative to screening colonoscopy reached >90% with FIT in the base‐case scenario and with mt‐sDNA in a “medium impact” scenario. Conclusions Assuming identical adenoma sensitivities for screening and follow‐up/surveillance colonoscopies underestimate the potential benefits of stool‐based screening strategies.