Supplementary Material for: The risk of endometrial malignancy and other endometrial pathology in women with abnormal uterine bleeding: an ultrasound-based model development study by the IETA group

Objectives: To develop a model that can discriminate between different etiologies of abnormal uterine bleeding. Design: The International Endometrial Tumor Analysis (IETA) 1 study is a multicenter observational diagnostic study in 18 bleeding clinics in 9 countries. Consecutive women with abnormal vaginal bleeding presenting for ultrasound examination (n=2417) were recruited. The histology was obtained from endometrial sampling, D&C, hysteroscopic resection, hysterectomy, or ultrasound follow-up for >1 year. Methods: A model was developed using multinomial regression based on age, body mass index and ultrasound predictors to distinguish between (1) endometrial atrophy, (2) endometrial polyp or intracavitary myoma, (3) endometrial malignancy or atypical hyperplasia, (4) proliferative/secretory changes, endometritis or hyperplasia without atypia and validated using leave-center-out cross-validation and bootstrapping. The main outcomes are the model’s ability to discriminate between the four outcomes and the calibration of risk estimates. Results The median age in 2417 women was 50 (interquartile range 43 to 57). 414 (17%) women had endometrial atrophy; 996 (41%) had a polyp or myoma; 155 (6%) had an endometrial malignancy or atypical hyperplasia; and 852 (35%) had proliferative/secretory changes, endometritis or hyperplasia without atypia. The model distinguished well between malignant and benign histology (c-statistic 0.88 95% CI 0.85 to 0.91), and between all benign histologies. The probabilities for each of the four outcomes were over- or underestimated depending on the centers. Limitations Not all patients had a diagnosis based on histology. The model over- or underestimated the risk for certain outcomes in some centers, indicating local recalibration might be necessary. Conclusions The proposed model reliably distinguishes between four histological outcomes. This is the first model to discriminate between several outcomes, and is the only model applicable when menopausal status is uncertain. The model could be useful for patient management and counseling, and aid in the interpretation of ultrasound findings. Future research is needed to externally validate the model.