An ultrasound-based risk model to predict lymph node metastases before surgery in women with endometrial cancer: a model development study

Linda S E Eriksson, Elisabeth Epstein, Antonia C Testa, Daniela Fischerova, Lil Valentin, Povilas Sladkevicius, Dorella Franchi, Filip Frühauf, Robert Fruscio, Lucia A Haak, Gina Opolskiene, Floriana Mascilini, Juan Luis Alcazar, Caroline Van Holsbeke, Valentina Chiappa, Tom Bourne, Pelle G Lindqvist, Ben Van Calster, Dirk Timmerman, Jan Y VerbakelThierry Van den Bosch, Laure Wynants

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: To develop a pre-operative risk model using endometrial biopsy results, 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 was developed on 1501 prospectively included women with endometrial cancer subjected to transvaginal ultrasound examination before surgery. Missing data, including missing lymph node status, was imputed. Discrimination, calibration and clinical utility were evaluated using leave-center-out cross-validation. The predictive performance was compared with risk classification from endometrial biopsy alone (high-risk = endometrioid cancer grade 3/non-endometrioid cancer) or combined endometrial biopsy and ultrasound (high-risk = endometrioid cancer grade 3/non-endometrioid cancer/deep myometrial invasion/cervical stromal invasion/extrauterine spread).

RESULTS: Lymphadenectomy was performed in 691 women, of which 127 had lymph node metastases. The model 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 AUC was 0.73 (95% CI 0.68 to 0.78), calibration slope 1.06 (95% CI 0.79 to 1.34) and calibration intercept 0.06 (95% CI 0.15 to 0.27). Using risk thresholds for lymph node metastases 5% vs. 20% the model had sensitivity 98% vs. 48% and specificity 11% vs. 80%. The model had higher sensitivity and specificity than high-risk according to endometrial biopsy alone (50% vs. 35% and 80% vs. 77%) or combined endometrial biopsy and ultrasound (80% vs. 75% and 53% vs. 52%). 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, clinical and ultrasound characteristics, the individual risk of lymph node metastases in women with endometrial cancer can be reliably estimated before surgery. The model is superior to risk classification by endometrial biopsy alone or in combination with ultrasound. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalUltrasound in Obstetrics and Gynecology
DOIs
Publication statusE-pub ahead of print - Dec 16 2019

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    Eriksson, L. S. E., Epstein, E., Testa, A. C., Fischerova, D., Valentin, L., Sladkevicius, P., Franchi, D., Frühauf, F., Fruscio, R., Haak, L. A., Opolskiene, G., Mascilini, F., Alcazar, J. L., Van Holsbeke, C., Chiappa, V., Bourne, T., Lindqvist, P. G., Van Calster, B., Timmerman, D., ... Wynants, L. (2019). An ultrasound-based risk model to predict lymph node metastases before surgery in women with endometrial cancer: a model development study. Ultrasound in Obstetrics and Gynecology. https://doi.org/10.1002/uog.21950