The Microsimulation SCreening Analysis (MISCAN) Colorectal Cancer Model (Erasmus University Medical Center/Memorial Sloan Kettering) describes discrete event state transitions in continuous time. State transitions can depend on the age, sex, and race of the individual, lesion location within the large intestine, and calendar time. For each simulated individual, MISCAN first generates a time of birth and a time of death from causes other than colorectal cancer (CRC). Next, MISCAN generates adenomas within the individual using a non-homogeneous Poisson process. Each individual is assigned a baseline log-risk. A person’s overall risk is a linear function of the baseline log-risk, sex-, race-, and age-specific log-risk. Once initiated, each adenoma is assigned a location in the large intestine according to the observed location distribution of CRC.
MISCAN simulates three adenoma size categories (small [1-5 mm], medium [6-9 mm], and large [10+ mm]) and in six locations. All adenomas start small and can transition through larger size categories. MISCAN simulates two types of adenomas: progressive and nonprogressive. Nonprogressive adenomas grow in size, but never develop into cancer. Progressive adenomas eventually develop into cancer, although other causes of death may occur before the transition to preclinical (or clinical) cancer. The probability that an adenoma is progressive is a function of the age of adenoma onset. Progressive medium and large adenomas can transition to a stage I preclinical (asymptomatic) cancer, although larger adenomas are more likely to progress than medium-sized adenomas.
Preclinical cancers progress through stages I through IV. Stage durations within adenoma stages and within preclinical cancer stages are correlated, but there is no correlation between the duration of adenoma stages and preclinical cancer stages. At each preclinical stage, MISCAN simulates whether there is transition to symptomatic and clinically detected cancer as a function of age, sex, race, and preclinical cancer location. After clinical detection, MISCAN simulates the survival time to death from CRC using relative survival estimates from the Surveillance, Epidemiology, and End Results (SEER) program, following an approach that is common across the three models.1
CRC survival time depends on: age, calendar year, and stage at detection; cancer location (colon or rectum); sex; and (optionally) race (black or white). For individuals with synchronous CRCs at the time of diagnosis, MISCAN uses the stage-specific survival of the cancer with the highest stage present. For all individuals with CRC, their death date is set to the earliest simulated death date (either due to CRC death or other causes).
Risk Factor Modeling: MISCAN includes a risk factor module that allows risk factors to influence CRC incidence by affecting the age-specific incidence of adenomas. Because risk factors are assumed not to influence the progression rate from adenoma to cancer, higher CRC incidence is an immediate result of the higher adenoma incidence. The MISCAN risk module includes obesity, smoking, and red meat consumption as factors related to an increased risk for adenomas, and fruit and vegetable consumption, physical activity, multivitamin use, aspirin use, and hormone replacement therapy as factors related to a decreased risk for adenomas. All risk factors are modeled as dichotomous characteristics.
- Rutter CM, Johnson EA, Feuer EJ, Knudsen AB, Kuntz KM, Schrag D. Secular trends in colon and rectal cancer relative survival. J Natl Cancer Inst. 2013;105(23):1806-13. [Abstract]