OBJECTIVE: To develop a preoperative risk model, using endometrial biopsy results and clinical and ultrasound variables, to predict the individual risk of lymph-node metastases in women with endometrial cancer. METHODS: A mixed-effects logistic regression model for prediction of lymph-node metastases was developed in 1501 prospectively included women with endometrial cancer undergoing transvaginal ultrasound examination before surgery, from 16 European centers. Missing data, including missing lymph-node status, were imputed. Discrimination, calibration and clinical utility of the model were evaluated using leave-center-out cross validation. The predictive performance of the model was compared with that of risk classification from endometrial biopsy alone (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer) or combined endometrial biopsy and ultrasound (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer/deep myometrial invasion/cervical stromal invasion/extrauterine spread). RESULTS: Lymphadenectomy was performed in 691 women, of whom 127 had lymph-node metastases. The model for prediction of lymph-node metastases included the predictors age, duration of abnormal bleeding, endometrial biopsy result, tumor extension and tumor size according to ultrasound and undefined tumor with an unmeasurable endometrium. The model's area under the curve was 0.73 (95% CI, 0.68-0.78), the calibration slope was 1.06 (95% CI, 0.79-1.34) and the calibration intercept was 0.06 (95% CI, -0.15 to 0.27). Using a risk threshold for lymph-node metastases of 5% compared with 20%, the model had, respectively, a sensitivity of 98% vs 48% and specificity of 11% vs 80%. The model had higher sensitivity and specificity than did classification as high-risk, according to endometrial biopsy alone (50% vs 35% and 80% vs 77%, respectively) or combined endometrial biopsy and ultrasound (80% vs 75% and 53% vs 52%, respectively). The model's clinical utility was higher than that of endometrial biopsy alone or combined endometrial biopsy and ultrasound at any given risk threshold. CONCLUSIONS: Based on endometrial biopsy results and clinical and ultrasound characteristics, the individual risk of lymph-node metastases in women with endometrial cancer can be estimated reliably before surgery. The model is superior to risk classification by endometrial biopsy alone or in combination with ultrasound. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

3rd Faculty of Medicine Charles University Prague Czech Republic

Center of Obstetrics and Gynecology Vilnius University Hospital Santaros Klinikos Vilnius Lithuania

Clinic of Obstetrics and Gynecology University of Milan Bicocca San Gerardo Hospital Monza Italy

Department of Clinical Science and Education Karolinska Institutet Stockholm Sweden

Department of Development and Regeneration KU Leuven Leuven Belgium

Department of Epidemiology CAPHRI Care and Public Health Research Institute Maastricht University Maastricht The Netherlands

Department of Gynecological Oncology Catholic University of the Sacred Heart Rome Italy

Department of Gynecological Oncology European Institute of Oncology Milan Italy

Department of Obstetrics and Gynecology 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Obstetrics and Gynecology Clinica Universidad de Navarra Pamplona Spain

Department of Obstetrics and Gynecology National Cancer Institute Milan Italy

Department of Obstetrics and Gynecology Queen Charlotte's and Chelsea Hospital Imperial College London London UK

Department of Obstetrics and Gynecology Skåne University Hospital Lund University Malmö Sweden

Department of Obstetrics and Gynecology Sodersjukhuset Stockholm Sweden

Department of Obstetrics and Gynecology University Hospital Leuven Leuven Belgium

Department of Obstetrics and Gynecology Ziekenhuis Oost Limburg Genk Belgium

Department of Pelvic Cancer Karolinska University Hospital Stockholm Sweden

Department of Public Health and Primary Care KU Leuven Leuven Belgium

Department of Woman and Child Health and Public Health Fondazione Policlinico Universitario Agostino Gemelli IRCSS Rome Italy

Department of Women's and Children's Health Karolinska Institutet Stockholm Sweden

Institute for the Care of Mother and Child Prague Czech Republic

Nuffield Department of Primary Care Health Sciences University of Oxford Oxford UK

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