Force (USPSTF) is updating its 2016 colorectal cancer screening recommendations.OBJECTIVE To provide updated model-based estimates of the benefits, burden, and harms of colorectal cancer screening strategies and to identify strategies that may provide an efficient balance of life-years gained (LYG) from screening and colonoscopy burden to inform the USPSTF. DESIGN, SETTING, AND PARTICIPANTS Comparative modeling study using 3 microsimulation models of colorectal cancer screening in a hypothetical cohort of 40-year-old US individuals at average risk of colorectal cancer.EXPOSURES Screening from ages 45, 50, or 55 years to ages 70, 75, 80, or 85 years with fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy alone or with FIT, computed tomography colonography, or colonoscopy. All persons with an abnormal noncolonoscopy screening test result were assumed to undergo follow-up colonoscopy. Screening intervals varied by test. Full adherence with all procedures was assumed. MAIN OUTCOME AND MEASURESEstimated LYG relative to no screening (benefit), lifetime number of colonoscopies (burden), number of complications from screening (harms), and balance of incremental burden and benefit (efficiency ratios). Efficient strategies were those estimated to require fewer additional colonoscopies per additional LYG relative to other strategies.RESULTS Estimated LYG from screening strategies ranged from 171 to 381 per 1000 40-year-olds. Lifetime colonoscopy burden ranged from 624 to 6817 per 1000 individuals, and screening complications ranged from 5 to 22 per 1000 individuals. Among the 49 strategies that were efficient options with all 3 models, 41 specified screening beginning at age 45. No single age to end screening was predominant among the efficient strategies, although the additional LYG from continuing screening after age 75 were generally small. With the exception of a 5-year interval for computed tomography colonography, no screening interval predominated among the efficient strategies for each modality. Among the strategies highlighted in the 2016 USPSTF recommendation, lowering the age to begin screening from 50 to 45 years was estimated to result in 22 to 27 additional LYG, 161 to 784 additional colonoscopies, and 0.1 to 2 additional complications per 1000 persons (ranges are across screening strategies, based on mean estimates across models). Assuming full adherence, screening outcomes and efficient strategies were similar by sex and race and across 3 scenarios for population risk of colorectal cancer. CONCLUSIONS AND RELEVANCEThis microsimulation modeling analysis suggests that screening for colorectal cancer with stool tests, endoscopic tests, or computed tomography colonography starting at age 45 years provides an efficient balance of colonoscopy burden and life-years gained.

BACKGROUND AND AIMS: Current guidelines recommend surveillance for patients with nondysplastic Barrett’s esophagus (NDBE) but do not include a recommended age for discontinuing surveillance. This study aimed to determine the optimal age for last surveillance of NDBE patients stratified by sex and level of comorbidity. METHODS: We used 3 independently developed models to simulate patients diagnosed with NDBE, varying in age, sex, and comorbidity level (no, mild, moderate, and severe). All patients had received regular surveillance until their current age. We calculated incremental costs and quality-adjusted life-years (QALYs) gained from 1 additional endoscopic surveillance at the current age versus not performing surveillance at that age. We determined the optimal age to end surveillance as the age at which incremental cost-effectiveness ratio of 1 more surveillance was just less than the willingness-to-pay threshold of $100,000/QALY. RESULTS: The benefit of having 1 more surveillance endoscopy strongly depended on age, sex, and comorbidity. For men with NDBE and severe comorbidity, 1 additional surveillance at age 80 years provided 4 more QALYs per 1000 patients with BE at an additional cost of $1.2 million, whereas for women with severe comorbidity the benefit at that age was 7 QALYs at a cost of $1.3 million. For men with no, mild, moderate, and severe comorbidity, the optimal ages of last surveillance were 81, 80, 77, and 73 years, respectively. For women, these ages were younger: 75, 73, 73, and 69 years, respectively. CONCLUSIONS: Our comparative modeling analysis illustrates the importance of considering comorbidity status and sex when deciding on the age to discontinue surveillance in patients with NDBE.

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10513 Background: Universal germline genetic testing is recommended for all patients with pancreatic ductal adenocarcinoma (PDAC). In addition to treatment implications for the patient, it is valuable for family members of the PDAC patient to undertake germline testing to understand their familial cancer risk. We evaluated the potential effectiveness of cascade testing of first-degree relatives (FDRs) of PDAC patients to guide MRI-based screening for PDAC. Methods: We used a microsimulation model of PDAC to estimate the potential life expectancy (LE) benefit of cascade genetic testing of FDRs of PDAC patients. Analysis was performed for eight mutations of interest (ATM, BRCA1, BRCA2, PALB2, Lynch, TP53, CDKN2A, STK11) with relative risk of PDAC ranging from 1.6 – 24. FDRs were defined by their sex, age, and information state (not informed, informed but not tested, test negative, or test positive). Family size and composition, communication of genetic testing results, and uptake of cascade testing were based on published studies. For each FDR group, we simulated multiple MRI-based screening strategies, defined by starting age (FDR age at patient diagnosis to age 75) and frequency (once or annual until age 75), and identified the strategy that resulted in the highest LE. Results: Each PDAC patient would have an average of 4.35 living FDRs. 1.32 of these living FDRs would be informed of the patient’s test results but not undergo testing themselves, and 1.03 would test positive for the mutation of interest. For lower risk mutations (ATM, BRCA2, PALB2), FDRs would only undergo screening if they test positive. For Lynch syndrome, not tested FDRs would undergo screening starting at age 65 or 70, whereas FDRs who test positive would start at 50 or 55. For STK11, the highest risk mutation, FDRs would start screening annually as soon as they are informed of the patient’s test results. The total LE gain for cascade testing of FDRs ranged from 0 (BRCA1) to 1.05 years (STK11). Conclusions: For each PDAC patient identified to have a germline genetic mutation, cascade testing of FDRs could add up to a year life expectancy for the family, in addition to the value of the germline information to the PDAC patient’s care. [Table: see text]