Risk prediction models for endometrial cancer: development and validation in an international consortium
Menée à partir de données portant sur 9 062 témoins et 6 665 femmes ménopausées atteintes d'un cancer de l'endomètre et de type caucasien (âge : 45 à 85 ans) puis validée à partir de données portant sur un total de 164 222 femmes supplémentaires, cette étude évalue la performance de modèles, basés sur des facteurs épidémiologiques, pour identifier les femmes présentant un risque élevé de cancer de l'endomètre puis examine l'intérêt d'intégrer des facteurs génétiques dans ces modèles pour les rendre plus performants
Background : Endometrial cancer risk stratification may help target interventions, screening, or prophylactic hysterectomy to mitigate the rising burden of this cancer. However, existing prediction models have been developed in select cohorts and have not considered genetic factors.
Methods : We developed endometrial cancer risk prediction models using data on postmenopausal white women aged 45-85 years from 19 case-control studies in the Epidemiology of Endometrial Cancer Consortium. Relative risk estimates for predictors were combined with age-specific endometrial cancer incidence rates and estimates for the underlying risk factor distribution. We externally validated the models in three cohorts: Nurses’ Health Study (NHS), Nurses’ Health Study II (NHS II) and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
Results : Area under the receiver operating characteristic curves for the epidemiologic model ranged from 0.64 (95% CI: 0.62, 0.67) to 0.69 (95% CI: 0.66, 0.72). Improvements in discrimination from the addition of genetic factors were modest (no change in AUC in NHS,; PLCO: 0.64 to 0.66). The epidemiologic model was well calibrated in NHS II (overall E/O = 1.09; 95% CI: 0.98, 1.22) and PLCO (overall E/O = 1.04; 95% CI: 0.95, 1.13) but poorly calibrated in NHS (overall E/O = 0.55; 95% CI: 0.51, 0.59).
Conclusion : Using data from the largest, most heterogeneous study population to date, prediction models based on epidemiologic factors alone successfully identified women at high risk of endometrial cancer. Genetic factors offered limited improvements in discrimination. Further work is needed to refine this tool for clinical or public health practice and expand these models to multiethnic populations.
Journal of the National Cancer Institute , article en libre accès, 2022