SimCRC Stanford University / Massachusetts General Hospital / University of Minnesota

Summary

The Simulation Model of Colorectal Cancer (SimCRC; Stanford University, Massachusetts General Hospital, University of Minnesota) describes discrete event state transitions in continuous time. State transitions can depend on the age and sex of the individual, lesion location within the large intestine, and calendar time. For each simulated individual, SimCRC first generates a time of birth and a time of death from causes other than colorectal cancer (CRC). Next, SimCRC generates adenomas within the individual, with the age of onset for each adenoma drawn from a cumulative probability function. The probability function depends on age, sex and an individual risk index that captures whether a person tends to produce more (or fewer) adenomas than average. Once initiated, each adenoma is assigned a location in the large intestine according to the location distribution of adenomas in autopsy studies.

Natural History Model

SimCRC simulates three adenoma categories (small [1 to <6 mm], medium [6 to <10 mm], and large [10+ mm]) in six locations (cecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum). All adenomas start small and can transition through larger size categories. Each adenoma is randomly assigned an adenoma-specific growth index that allows between-adenoma variability in the probability of transitioning to larger sizes. The timing of transitions between adenoma size categories depends on age, sex, and adenoma location.

Medium and large adenomas may progress to preclinical CRC, although most will not in an individual’s lifetime. Adenoma progression depends on the individual’s age and sex, as well as on the adenoma’s size category and location. Progression through preclinical cancer stages I through stage IV depends on the location of the cancer. At each preclinical stage, SimCRC allows for the detection of cancer by symptoms, with the likelihood of symptomatic detection varying by stage and location.

Colorectal Cancer Mortality Model

After clinical detection, SimCRC simulates the survival time to death from CRC using relative survival estimates from the Surveillance, Epidemiology, and End Results (SEER) Program, following estimates common to the three CISNET CRC models.¹ CRC survival time depends on age, calendar year, stage at detection, cancer location (colon or rectum), and sex. For individuals with synchronous CRCs at the time of diagnosis, SimCRC uses the stage-specific survival of the cancer with the most advanced stage. For all individuals with CRC, the date of death is set to the earliest of the date of death from CRC and the date of death from other causes. The risk of death from other causes is based on data from U.S. life tables.^2-3

Screening Model

Overlaid on the natural history of colorectal disease (no disease to adenoma to preclinical cancer to clinical cancer) is a screening mechanism that allows for the detection of adenoma(s) and preclinical CRC(s). The likelihood of detection is a function of the screening modality (e.g., fecal immunochemical test [FIT], colonoscopy or sigmoidoscopy) and the sensitivity of the test for lesions of a given size, and in the case of endoscopic tests, the reach of the scope. When modeling screening strategies, the chance that a screening test is performed depends on the screening algorithm (e.g., age to begin screening, age to end screening, and screening interval) and assumptions about adherence. Simulated persons diagnosed with CRC (by symptoms or by screening) are assigned a cancer-specific mortality rate, which depends on age, sex, stage at diagnosis, location of cancer (colon vs. rectum), and year of diagnosis.

Surveillance Model

We assume all adenomas detected during colonoscopy are completely removed via polypectomy, although the model also has the ability to simulate incomplete resection. We assume that individuals with an adenoma detected are recommended to undergo colonoscopic surveillance. The frequency of surveillance is allowed to vary by the size and number of adenomas detected at the 2 most recent colonoscopies, thereby enabling the option for surveillance to be performed consistent with the 2020 U.S. Multi-Society Task Force on Colorectal Cancer guidelines.⁴ Simulated individuals are allowed to be adherent or non-adherent with surveillance. The model can also be run assuming no surveillance of individuals who have had adenomas detected.

References

1. Rutter CM, Johnson EA, Feuer EJ, Knudsen AB, Kuntz KM, Schrag D. Secular trends in colon and rectal cancer relative survival. Journal of the National Cancer Institute. 2013 Dec 4;105(23):1806–13.
2. Arias E, Xu J, Kochanek K. United States Life Tables, 2021. National Vital Statistics Reports. 72(12):1–63.
3. Human Mortality Database. Human Mortality Database. 2025 [cited 2025 Mar 19]. U.S.A. Total population. Available from: https://www.mortality.org/Country/Country?cntr=USA
4. Gupta S, Lieberman D, Anderson JC, Burke CA, Dominitz JA, Kaltenbach T, et al. Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer. Gastrointestinal Endoscopy. 2020 Mar 1;91(3):463-485.e5.