Estimating risk of endometrial malignancy and other intracavitary uterine pathology in women without abnormal uterine bleeding using IETA‐1 multinomial regression model: validation study

To estimate the ability of the International Endometrial Tumor Analysis (IETA)-1 polynomial regression model to estimate the risk of endometrial cancer and other intracavitary uterine pathology in women without abnormal uterine bleeding.This is a retrospective study, in which we validated the IETA-1 model on the IETA-3 study cohort (n = 1745). IETA-3 is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in seven ultrasound centers from 2011 until 2018. The ultrasonography was performed either as part of routine gynecological examination, follow-up of non-endometrial pathology, in the workup before fertility treatment, or before treatment for uterine prolapse or ovarian pathology. Ultrasonographic findings were described using IETA terminology and were compared with histology or with results of clinical and ultrasound follow-up if endometrial sampling was not performed. The IETA-1 model, which was created using data from patients with abnormal uterine bleeding, predicts four histological outcomes: 1) endometrial cancer (EC) or endometrial intraepithelial neoplasia (EIN), 2) endometrial polyp or intracavitary myoma, 3) hyperplasia without atypia, endometritis, or proliferative or secretory endometrium, and 4) endometrial atrophy. The predictors in the model are age, body mass index, and seven ultrasound variables (endometrial visibility, endometrial thickness, color score, cysts in the endometrium, non-uniform echogenicity of the endometrium, presence of a bright edge, presence of a single dominant vessel). We analyzed the discriminative ability of the model (area under the receiver operating curve, AUC; polytomous discrimination index, PDI) and evaluated calibration of its risk estimates (observed/expected ratio, O/E).The median age of the women in the IETA-3 cohort was 51 years (range: 20 - 85), and 51% (887/1745) of the women were postmenopausal. Histology showed EC or EIN in 29 (2%) women, endometrial polyps or intracavitary myomas in 1094 (63%), hyperplasia without atypia, endometritis, or proliferative or secretory endometrium in 144 (8%), and endometrial atrophy in 265 (15%) women. Insufficient material (n = 5, 0.3%) was classified as a separate benign outcome. For 208 (12%) women who did not undergo endometrial sampling but were followed up for at least 1 year without clinical or ultrasound signs of endometrial malignancy, the outcome was classified as benign. The IETA-1 model had an AUC of 0.81 (95% CI: 0.73 - 0.89, n = 1745) for discrimination between EC/EIN and benign endometrium, and the O/E for EC/EIN was 0.51 (95% CI: 0.32 - 0.82). The AUC of the IETA-1 model to discriminate between endometrial atrophy and all other intracavitary uterine conditions was 0.96 (95% CI: 0.95 - 0.98). The PDI of the model was 0.68 (95% CI: 0.62 - 0.73). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95%CI 0.75 - 0.91) versus 0.62 (95% CI: 0.52 - 0.73) when using endometrial thickness as the only predictor (difference in AUC 0.21, 95%CI: 0.08 - 0.32). For postmenopausal women with measurable endometrial thickness (n = 848), the IETA-1 model gave an AUC of 0.81 (95% CI: 0.71 - 0.91) while the AUC for endometrial thickness was 0.70 (95% CI: 0.60 - 0.81) (difference in AUC 0.11, 95%CI: 0.01 - 0.20).The IETA-1 model discriminated well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimated the risk of malignancy. It also discriminated well between the four outcome categories. This article is protected by copyright. All rights reserved.