Franka Loeve

The MISCAN-COLON simulation model for the evaluation of colorectal cancer screening

A general model for evaluation of colorectal cancer screening has been implemented in the microsimulation program MISCAN-COLON. A large number of fictitious individual life histories are simulated in each of which several colorectal lesions can emerge. Next, screening for colorectal cancer is simulated, which will change some of the life histories. The demographic characteristics, the epidemiology and natural history of the disease, and the characteristics of screening are defined in the input. All kinds of assumptions on the natural history of colorectal cancer and screening and surveillance strategies can easily be incorporated in the model. MISCAN-COLON gives detailed output of incidence, prevalence and mortality, and the results and effects of screening. It can be used to test hypotheses about the natural history of colorectal cancer, such as the duration of progressive adenomas, and screening characteristics, such as sensitivity of tests, against empirical data. In decision making about screening, the model can be used for evaluation of screening policies, and for choosing between competing policies by comparing their simulated incremental costs and effectiveness outcomes.

National Polyp Study data: Evidence for regression of adenomas

The data of the National Polyp Study, a large longitudinal study on surveillance of adenoma patients, is used for testing assumptions on the adenoma‐carcinoma sequence. The observed adenoma and colorectal cancer incidence in the National Polyp Study were compared with the simulated outcomes of the MISCAN‐COLON model of epidemiology and control of colorectal cancer for the U.S. population based on expert opinion. Variants of this model were explored in order to identify assumptions on the adenoma‐carcinoma sequence that are consistent with the study observations. The high observed adenoma detection rates at surveillance and low observed colorectal cancer incidence in the National Polyp Study could only be explained by assuming a high incidence rate of adenomas accompanied by regression of adenomas. The National Polyp Study data suggest that adenoma prevalence results from a dynamic process of both formation as well as regression of adenomas. This lowers the expectations for the effects of colorectal cancer screening strategies that focus on adenoma detection.

Colorectal cancer risk in adenoma patients: A nation‐wide study

Colorectal cancer incidence after adenoma removal has been studied in selected populations of adenoma patients. Our study estimates the trend in colorectal cancer incidence after adenoma removal in actual clinical practice. From PALGA, a nationwide network and registry of histo‐ and cytopathology in the Netherlands, we extracted data of all patients diagnosed with colorectal adenomas between 1 January 1988 and 1 October 1998. The data were used to calculate population‐based colorectal cancer incidence rates after adenoma removal. A total of 78,473 adenoma patients were followed for a mean of 4.5 years after the first adenoma removal. The colorectal cancer incidence ratio compared with the general population matched by age and gender was 38.4 (37.3–39.5) in the first year after adenoma removal and 1.5 (95% confidence interval (CI): 1.4–1.6) after Year 1. The incidence ratio decreased from 2.8 (2.5–3.1) in Year 2 to 0.9 (0.6–1.2) in Years 9–11. This time trend is the opposite of the upward time trend that was expected after adenoma removal. Adenoma patients in the Netherlands are at increased risk for colorectal cancer compared to the general population. The high cancer incidence in Years 1–5 after polypectomy can be explained by a colonoscopic sensitivity for cancer of approximately 90%.

Impact of systematic false-negative test results on the performance of faecal occult blood screening

The impact of systematic false-negative test results on mortality reduction and on programme sensitivity of annual faecal occult blood testing in ages 50-84 years is explored using a microsimulation model. We made calculations for test sensitivities of 80, 50 and 30%. In order to reproduce a cancer detection rate of 2.2 per 1000 at the first screening, the corresponding mean preclinical sojourn times had to be 1.42, 2.30 and 3.84 years, respectively. The fraction systematic results among the false-negative results is varied between 0 and 100%. With 80% test sensitivity, the reduction in mortality due to screening decreases from 25% without systematic results to 23% when all false-negative results are systematic and the programme sensitivity decreases from 63 to 58%. With 30% test sensitivity, mortality reduction decreases from 21 to 11% and programme sensitivity decreases from 52 to 27%. The impact of systematic false-negative test results is important if annual FOBT screening is considered.