Epidemiological Classification Changes and Incidence of Early-Onset Colorectal Cancer.

Importance: Previous studies showed an increasing incidence of early-onset colorectal cancer (EOCRC) during a period when cancer registration guidelines were changed. None of these studies simultaneously compared the patterns in colorectal adenocarcinoma (ADC) and neuroendocrine neoplasms (NENs) according to age and stage extension. Objective: To describe patterns in colorectal cancer incidence according to histopathological type and tumor extension at diagnosis in individuals younger than 50 years compared with older patients. Design, Setting, and Participants: This cohort study used data from the French Network of Cancer Registries (FRANCIM) on inhabitants of 7 French administrative areas. The cohort included individuals newly diagnosed with invasive colorectal cancer from 2004 to 2021. This period covered the change in NEN classification published in 2013. Statistical analysis was conducted from November 2024 to March 2025. Main Outcomes and Measures: Age-specific incidence rates of ADC and NENs were primary outcomes. Incidence was calculated and modeled to estimate annual percent changes (APCs) using a flexible multivariable Poisson model. In a sensitivity analysis, Joinpoint regressions consolidated the results. Results: A total of 63 780 patients (35 266 males [55.3%]; mean [SD] age, 63.8 [12.8] years) were diagnosed with all colorectal cancer histologic types (CRC-All). The incidence of EOCRC increased in females (APC, 2.9%; 95% CI, 1.6%-4.3%) and males (APC, 2.6%; 95% CI, 1.2%-4.0%) aged 15 to 39 years but remained stable in those aged 40 to 49 years. In both sexes and all ages, the rates of ADC did not vary while NEN rates increased. In EOCRC, the increase in NENs was marked from 2004 to 2013 (between 10.1% [95% CI, 4.0%-16.5%] per year and 12.6% [95% CI, 7.2%-18.2%] per year) and disappeared thereafter (ranging from -1.1% [95% CI, -1.9% to -0.2%] per year to -1.7% [95% CI, -3.0% to -0.4%] per year). It affected the incidence of colorectal cancer only for patients aged 15 to 39 years, for whom the proportion of NENs was high (29.7% [278 of 935]) compared with 5.7% (132 of 2333) of patients in the 40 to 49 years age class and 1.4% (856 of 60 512) of patients in the 50 years or older age class). In EOCRC, ADC M1 (distant metastasis) incidence increased in both sexes over the entire study period (between 1.2% [95% CI, 0.3%-2.1%] per year and 2.3% [95% CI, 1.0%-3.6%] per year between 2013 and 2021). Conclusions and Relevance: In this cohort study, the 2013 change in NENs classification had a prominent role in EOCRC incidence patterns. Public health decision-makers should consider this artifactual increase.