Grant Number:	1U01CA319216-01 Interpret this number
Primary Investigator:	Wright, Jason
Organization:	Tufts Medical Center
Project Title:	Comparative Modeling of Uterine Cancer
Fiscal Year:	2026

Uterine cancer is one of the few cancers for which incidence and mortality are both rising. From 2019-2023, mortality from uterine cancer increased on average by 1.4% annually, the largest mortality increase for any female cancer and the only CISNET cancer site with increasing mortality. Despite the growing burden of uterine cancer in the U.S., the disease remains understudied and cancer control efforts have lagged. There are currently no routinely utilized screening or prevention strategies. With the rise of more aggressive histologic subtypes associated with decreased survival, the timeliness of diagnosis and access to care have taken on increased urgency, yet guidance is lacking to expedite these. Similarly, despite the increasing availability and uptake of new treatments, decision-making to guide the molecular profiling and precision treatment of uterine cancer is not yet standardized. Finally, as uterine cancer incidence and death rise disproportionately among women under age 50, there is a need to better understand the tradeoffs inherent to decisions about fertility-sparing treatment approaches. To explore population-level effects of cancer control and prevention activities, we previously developed, calibrated and validated three natural history models of uterine cancer. In this CISNET Uterine Cancer proposal, we will refine and apply these calibrated population-level natural history models to clinical scenarios in which decision-making is uncertain. First, we will explore how secular changes in epidemiologic risk factors including the rising obesity rate and declining hysterectomy rate influence current and future incidence and mortality. Second, we will assess primary and secondary prevention strategies. Third, we will evaluate strategies to improve early diagnosis and timely treatment. Fourth, we will compare health and economic outcomes of available and emerging therapeutic strategies. Finally, we will evaluate benefits and tradeoffs of fertility-conserving treatment in young women. The broad, long-term objectives of this work are (1) Continuous refinement and expansion of comparative natural history models of uterine cancer; (2) Use of these models to discern the causes of recent trends in uterine cancer incidence and mortality; and (3) Estimation of the impact of strategies aimed at reducing incidence (prevention) and improving survival (screening, diagnosis, treatment) on future cancer burden. At the completion of this work, these data will be widely disseminated to patients and providers and have the potential to significantly impact the clinical care of women with uterine cancer and to guide cancer control strategies. Further, these models will serve as an invaluable resource for the uterine cancer community as new clinical questions and challenges emerge.





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