Grant Number:	1U01CA319117-01 Interpret this number
Primary Investigator:	Inadomi, John
Organization:	Utah State Higher Education System--University Of Utah
Project Title:	Comparative Modeling to Inform Colorectal Cancer Control Strategies
Fiscal Year:	2026

PROJECT SUMMARY/ABSTRACT Colorectal cancer (CRC) is the second leading cause of cancer mortality in the United States (US), despite decades of progress in screening, treatment, and surveillance. Critical challenges persist across the CRC control continuum and fall into three interrelated categories: (1) differential access to care, including geographic and resource-driven barriers, and individual preferences; (2) changing risk, including rising early-onset CRC incidence with uncertain mechanisms; and (3) evolving technologies, including new screening tests and biomarker-guided treatment strategies that may shift the balance of benefits, harms, and costs. For example, there is evidence of widening rural-urban differences in CRC incidence and access to CRC care, including longer travel times for both screening and treatment. Early-onset CRC, diagnosed before age 50 years, is increasing and is now the leading cause of cancer death in this age group, but we still have a limited understanding of the causes and mechanisms underlying these trends. Uncertainty about these mechanisms translates into uncertainty about the best strategies to mitigate the burden of early-onset CRC. Finally, the rapid development and diffusion of new technologies for screening and treatment can tip the balance of benefits, costs, and harms of screening. Each of these challenges has implications for screening and treatment. Healthcare systems require rigorous evidence to support the implementation of screening strategies that must be made with incomplete information, based on studies conducted across heterogeneous populations. Gaps in available evidence mean that screening strategies cannot be directly informed by empirical studies alone. The Cancer Intervention and Surveillance Modeling Network colorectal cancer group (CISNET-CRC) provides a uniquely powerful platform to address these challenges, using well-established CRC microsimulation models to synthesize evidence across multiple sources. CISNET-CRC models simulate both the onset and progression of CRC in the absence of screening (natural history) and compare outcomes with the introduction of screening, enabling comparative evaluation of alternative screening strategies across multiple birth cohorts and population subgroups. These models have been used to help develop US national screening strategies. Our proposed research builds on established CISNET-CRC models and comparative modeling infrastructure by extending these models to simulate alternative mechanisms of increasing CRC risk, new screening modalities, and emerging treatments, enabling us to apply empirical evidence to address the highest-priority CRC control questions facing the US today. We will develop and apply state-of-the-art methods to estimate and describe model uncertainty and, importantly, approaches for communicating this uncertainty.





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