Explaining secular trends in colorectal cancer incidence and mortality with an empirically-calibrated microsimulation model

Colorectal cancer is the fourth most common cancer and the second leading cause of cancer death in the United States. Incidence and mortality from the disease have fallen over time. Several factors have contributed to the incidence and mortality trends, including trends in the risk factors for the disease, the dissemination of screening, and the adoption of chemotherapy. To assess the relative contribution of these factors in explaining the trends, we developed a comprehensive population-based microsimulation model of colorectal cancer. The model tracks the formation of adenomas and their progression to invasive cancer and incorporates the effects of risk factors, screening, and treatment on the underlying disease process.; In Chapter 1 we describe the development and calibration of the natural history model. Using a likelihood-based approach, we simultaneously fit the model output to age-specific data on adenoma prevalence by number from autopsy studies, the distribution of findings on colonoscopy by location and size/histology from screening studies, and the incidence of cancer by stage and location from the Surveillance, Epidemiology and End Results Program.; In Chapter 2 we use the model to estimate what incidence and mortality might have been over the past 35 years had trends in risk factors, screening, and chemotherapy not occurred. We found that these three factors together yielded a 12% reduction in incidence and a 15% reduction in colorectal cancer mortality. Screening alone explains 89% and 80% of the overall reductions in incidence and mortality respectively; 17% of the overall mortality reduction is attributable to chemotherapy alone. Risk factor trends alone explain a comparatively small proportion of the overall incidence and mortality reductions.; Finally, in Chapter 3 we explore whether heterogeneity in the rates of adenoma growth alter the conclusions about the effectiveness and cost-effectiveness of colorectal cancer screening. We found that heterogeneity mitigates the reductions in incidence and mortality attributable to screening and may lead to more favorable incremental cost-effectiveness ratios but that it does not change the conclusions about which screening strategy is the most effective at reducing the incidence of colorectal cancer and which strategy yields the greatest reduction in colorectal cancer mortality.