Abstract A011: Early Onset Cancer Incidence: A Model for the Role of Diagnostic Advances

Abstract Background Recent increases in the diagnosis of certain cancers among younger individuals are generating intense concern. Many studies attribute the increase in early-onset cancer to an etiologic cause but questions have also arisen about the role of earlier diagnosis. Observed trends incidence reflect changes in the incidence of disease diagnosis, which is a product of the development of preclinical disease and its diagnosis after preclinical onset. Etiologic factors will generally relate to the onset of preclinical disease, but the interval from one to clinical diagnosis is also driven by diagnostic technologies and practices which have changed dramatically over the past several decades. In this study we use disease modeling to separate the risk of diagnosis into these two components to study the potential role of diagnostic changes in the observed early-onset incidence trends. Methods We simulate incidence trends from a natural history model that includes healthy, preclinical, and clinical disease states, where the transition from the healthy to the preclinical state represents disease onset and the transition from the preclinical to the clinical state represents diagnosis. We superimpose birth-cohort effects on the rate of disease onset and period effects on the rate of disease diagnosis to identify those that match patterns of incidence by age group and 5-year calendar interval from 2005 to 2019 relative to 2000-2004 for 6 cancers (colon, rectum, female breast, stomach, pancreas, and kidney) with increasing incidence in younger age groups. As a concrete example, we explore whether changes in sensitivity of breast cancer screening technologies between 2000 and 2019 may have contributed to increasing incidence of breast cancer diagnosis in women under 50. Results Two types of effects are broadly consistent with the observed increasing incidence trends in younger individuals: (1) a birth-cohort effect on disease onset that begins around 1970 and becomes more pronounced in later birth years or (2) a period effect consistent with progressive reduction over time in the interval from preclinical onset to diagnosis. An earlier, protective birth-cohort effect is consistent with recent declining trends in incidence in older individuals for colon, rectal, and stomach cancers. Conclusions A disease model provides clues about the possible drivers of cancer incidence trends, suggests constraints on the patterns of exposures that might be implicated etiologically, and indicates that the role of diagnostic changes warrants consideration alongside potential etiologic explanations. Thiswork prompts us to recommend replacing the term "early-onset cancer" with "early-diagnosed cancer" to clarify that the observed trends reflect changes in the incidence of cancer diagnosis. Citation Format: Ruth D. Etzioni, Lukas Owens. Early Onset Cancer Incidence: A Model for the Role of Diagnostic Advances abstract. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31 (23Suppl): Abstract nr A011.