HCC surveillance decreases all-cause and tumor-specific mortality in patients with compensated cirrhosis regardless of LTx availability. In addition, incidence of HCC and sensitivity of surveillance test also had a substantial impact on the benefits of surveillance. (Hepatology 2018;68:78-88).

Background Real-world adherence to colorectal cancer (CRC) screening strategies is imperfect. The CRC-AIM microsimulation model was used to estimate the impact of imperfect adherence on the relative benefits and burdens of guideline-endorsed, stool-based screening strategies. Methods Predicted outcomes of multi-target stool DNA (mt-sDNA), fecal immunochemical tests (FIT), and high-sensitivity guaiac-based fecal occult blood tests (HSgFOBT) were simulated for 40-year-olds free of diagnosed CRC. For robustness, imperfect adherence was incorporated in multiple ways and with extensive sensitivity analysis. Analysis 1 assumed adherence from 0%-100%, in 10% increments. Analysis 2 longitudinally applied real-world first-round differential adherence rates (base-case imperfect rates = 40% annual FIT vs 34% annual HSgFOBT vs 70% triennial mt-sDNA). Analysis 3 randomly assigned individuals to receive 1, 5, or 9 lifetime (9 = 100% adherence) mt-sDNA tests and 1, 5, or 9 to 26 (26 = 100% adherence) FIT tests. Outcomes are reported per 1000 individuals compared with no screening. Results Each screening strategy decreased CRC incidence and mortality versus no screening. In individuals screened between ages 50–75 and adherence ranging from 10%a-100%, the life-years gained (LYG) for triennial mt-sDNA ranged from 133.1–300.0, for annual FIT from 96.3–318.1, and for annual HSgFOBT from 99.8–320.6. At base-case imperfect adherence rates, mt-sDNA resulted in 19.1% more LYG versus FIT, 25.4% more LYG versus HSgFOBT, and generally had preferable efficiency ratios while offering the most LYG. Completion of at least 21 FIT tests is needed to reach approximately the same LYG achieved with 9 mt-sDNA tests. Conclusions Adherence assumptions affect the conclusions of CRC screening microsimulations that are used to inform CRC screening guidelines. LYG from FIT and HSgFOBT are more sensitive to changes in adherence assumptions than mt-sDNA because they require more tests be completed for equivalent benefit. At imperfect adherence rates, mt-sDNA provides more LYG than FIT or HSgFOBT at an acceptable tradeoff in screening burden.

BackgroundMicrosimulation models of colorectal cancer (CRC) have helped inform national screening guidelines and health policy decision-making. However, detailed descriptions of particular underlying assumptions are not published, limiting access to robust platforms for exploratory analyses. We describe the development and validation of the Colorectal Cancer and Adenoma Incidence and Mortality (CRC-AIM) microsimulation model, a robust model built to facilitate collaborative simulation studies on disease progression and early detection through screening interventions.DesignWe used the Cancer Intervention and Surveillance Modeling Network (CISNET) CRC models, specifically CRC-SPIN, as a foundation for CRC-AIM’s formulas and parameters. In addition, we developed novel submodels and recalibrated various parameters to address gaps and discrepancies in publicly available information. Along with evaluating the natural history and screening detection outcomes from CRC-AIM, we determined the impact of using different life tables (cohort versus period) on natural history outcomes.ResultsCRC-AIM demonstrated substantial cross-model validity when comparing multiple natural history and screening outputs and probability curves to those from CISNET models, particularly CRC-SPIN. Additionally, using period life tables, CRC-AIM’s cumulative probability of developing CRC from ages 40 to 100 (7.1%) lies within the range of the CISNET models (6.7% to 7.2%). Using cohort tables, that probability increases to 8.0%. One notable difference is that, regardless of life table used, the cumulative probability of dying from CRC (3.2% for period; 3.8% for cohort) is slightly higher in CRC-AIM than the CISNET models (2.7% to 2.8%), due to CRC-AIM’s different methodology for determining survival. Additionally, there is substantial overlap (e.g. 94-95% overall agreement for strategies on and off the efficient frontier for stool-based strategies) across multiple screening overlay outputs between CRC-AIM and the CISNET models, especially CRC-SPIN.ConclusionsWe developed and validated a robust CRC microsimulation model, CRC-AIM, and demonstrate the influence of life table choice on downstream outputs. We further describe CRC-AIM’s parameters and include complete component tables to enhance transparency and encourage collaboration.

Colorectal cancer is a growing burden in adults less than 50 years old. In 2018, the American Cancer Society published a guideline update recommending a reduction in the colorectal cancer screening start age for average-risk individuals from 50 to 45. Implementing these recommendations would have important implications for public health. However, the approximate number of people impacted by this change, the average-risk population ages 45–49, is not well-described in the literature. Here, we provide methodology to conservatively estimate the average-risk and screening-eligible population in the United States, including those who would be impacted by a lowered colorectal cancer screening start age. Using multiple data sources, we estimated the current average-risk population by subtracting individuals with symptomatic colorectal cancer, with a family history of colorectal cancer, and with inflammatory bowel disease and hereditary nonpolyposis colorectal cancer from the total population. Within this population, we estimated the number of screening-eligible individuals by subtracting those with previous colorectal cancer screening (45- to 49-year-old) or up to date with colorectal cancer screening (50- to 74-year-old). The total average-risk population is estimated between 102.1 and 106.5 million people, of whom 43.4–45.2 million people are eligible for colorectal cancer screening. Lowering the screening age would add roughly 19 million people to the average-risk population and increase the current number of screening-eligible individuals on immediate implementation by over 60% (from 27 to 44 million). Estimating the population size impacted by lowering the recommended colorectal cancer screening start age enables more accurate decision-making for policymakers and epidemiologists focused on cancer prevention.

BackgroundReal-world adherence to colorectal cancer (CRC) screening strategies is imperfect. The CRC-AIM microsimulation model was used to estimate the impact of imperfect adherence on the relative benefits and burdens of guideline-endorsed, stool-based screening strategies.MethodsPredicted outcomes of multi-target stool DNA (mt-sDNA), fecal immunochemical tests (FIT), and high-sensitivity guaiac-based fecal occult blood tests (HSgFOBT) were simulated for 40-year-olds free of diagnosed CRC. For robustness, imperfect adherence was incorporated in multiple ways and with extensive sensitivity analysis. Analysis 1 assumed adherence from 0%-100%, in 10% increments. Analysis 2 longitudinally applied real-world first-round differential adherence rates (base-case imperfect rates=40% annual FIT vs 34% annual HSgFOBT vs 70% triennial mt-sDNA). Analysis 3 randomly assigned individuals to receive 1, 5, or 9 lifetime (9=100% adherence) mt-sDNA tests and 1, 5, or 9 to 26 (26=100% adherence) FIT tests. Outcomes are reported per 1000 individuals compared with no screening.ResultsEach screening strategy decreased CRC incidence and mortality versus no screening. In individuals screened between ages 50-75 and adherence ranging from 10%-100%, the life-years gained (LYG) for triennial mt-sDNA ranged from 133.1-300.0, for annual FIT from 96.3-318.1, and for annual HSgFOBT from 99.8-320.6. At base-case imperfect adherence rates, mt-sDNA resulted in 19.1% more LYG versus FIT, 25.4% more LYG versus HSgFOBT, and generally had preferable efficiency ratios while offering the most LYG. Completion of at least 21 FIT tests is needed to reach approximately the same LYG achieved with 9 mt-sDNA tests.ConclusionsAdherence assumptions affect the conclusions of CRC screening microsimulations that are used to inform CRC screening guidelines. LYG from FIT and HSgFOBT are more sensitive to changes in adherence assumptions than mt-sDNA because they require more tests be completed for equivalent benefit. At imperfect adherence rates, mt-sDNA provides more LYG than FIT or HSgFOBT at an acceptable tradeoff in screening burden.