T. Van den Bosch

Prospective geographical and temporal validation of three published mathematical models to calculate risk of endometrial malignancy in patients with postmenopausal bleeding

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness

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

<b><i>Objectives:</i></b> The aim of this study was to develop a model that can discriminate between different etiologies of abnormal uterine bleeding. <b><i>Design:</i></b> The International Endometrial Tumor Analysis 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 (<i>n</i> = 2,417) were recruited. The histology was obtained from endometrial sampling, D&C, hysteroscopic resection, hysterectomy, or ultrasound follow-up for >1 year. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> The median age in 2,417 women was 50 (interquartile range 43–57). 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 (<i>c</i>-statistic 0.88 95% CI: 0.85–0.91) and between all benign histologies. The probabilities for each of the four outcomes were over- or underestimated depending on the centers. <b><i>Limitations:</i></b> 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 is advisable. <b><i>Conclusions:</i></b> 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 and locally recalibrate the model.

Circulating Transcripts and Biomarkers in Uterine Tumors: Is There a Predictive Role?

Uterine cancer comprises endometrial carcinoma and the uterine sarcoma. Endometrial carcinomas are the most frequent variant and have early symptoms and a solid diagnostic work up, resulting in a rather fair prognosis. However, in case of advanced stage disease and relapse, treatment options are limited and prognosis is impaired. Uterine sarcomas are rare, often lacking symptoms and no diagnostic tool for correct pre-operative diagnosis are available. Prognosis is poor. Circulating biomarkers as a liquid biopsy could be beneficial as a diagnostic tool in uterine sarcomas. For both carcinomas and sarcomas, circulating biomarkers could be of use in predicting early disease recurrence. This review in endometrial carcinoma and uterine sarcoma focus on circulating biomarkers; such as proteins; circulating tumor cells; circulating tumor DNA; microRNA; and immune cells.

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

ABSTRACTObjectivesTo assess the ability of the International Endometrial Tumor Analysis (IETA)‐1 polynomial regression model to estimate the risk of endometrial cancer (EC) and other intracavitary uterine pathology in women without abnormal uterine bleeding.MethodsThis was a retrospective study, in which we validated the IETA‐1 model on the IETA‐3 study cohort (n = 1745). The IETA‐3 study is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in one of seven ultrasound centers between January 2011 and December 2018. The ultrasonography was performed either as part of a routine gynecological examination, during follow‐up of non‐endometrial pathology, in the work‐up 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 of at least 1 year 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) EC or endometrial intraepithelial neoplasia (EIN); (2) endometrial polyp or intracavitary myoma; (3) proliferative or secretory endometrium, endometritis, or endometrial hyperplasia without atypia; and (4) endometrial atrophy. The predictors in the model are age, body mass index and seven ultrasound variables (visibility of the endometrium, 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‐characteristics curve (AUC); polytomous discrimination index (PDI)) and evaluated calibration of its risk estimates (observed/expected ratio).ResultsThe median age of the women in the IETA‐3 cohort was 51 (range, 20–85) years 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%), proliferative or secretory endometrium, endometritis, or hyperplasia without atypia in 144 (8%) and endometrial atrophy in 265 (15%) women. The endometrial sample had insufficient material in five (0.3%) cases. In 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 malignant (EC or EIN) and benign endometrium, and the observed/expected ratio for EC or EIN was 0.51 (95% CI, 0.32–0.82). The model was able to categorize the four histological outcomes with considerable accuracy: the PDI of the model was 0.68 (95% CI, 0.62–0.73) (n = 1532). The IETA‐1 model discriminated very well between endometrial atrophy and all other intracavitary uterine conditions, with an AUC of 0.96 (95% CI, 0.95–0.98). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95% CI, 0.75–0.91), compared with 0.62 (95% CI, 0.52–0.73) when using endometrial thickness alone to predict malignancy (difference in AUC, 0.21; 95% CI, 0.08–0.32). In 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 endometrial thickness alone gave an AUC of 0.70 (95% CI, 0.60–0.81) (difference in AUC, 0.11; 95% CI, 0.01–0.20).ConclusionThe IETA‐1 model discriminates well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimates the risk of malignancy. It also discriminates well between the four histological outcome categories. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound features using MUSA terms and definitions in uterine sarcoma and leiomyoma: cohort study

ABSTRACTObjectivesTimely and accurate preoperative diagnosis of uterine sarcoma will increase patient survival. The primary aim of this study was to describe the ultrasound features of uterine sarcoma compared with those of uterine leiomyoma based on the terms and definitions of the Morphological Uterus Sonographic Assessment (MUSA) group. A secondary aim was to assess the interobserver agreement for reporting on ultrasound features according to MUSA terminology.MethodsThis was a retrospective cohort study of patients with uterine sarcoma or uterine leiomyoma treated in a single tertiary center during the periods 1997–2019 and 2016–2019, respectively. Demographic characteristics, presenting symptoms and surgical outcomes were extracted from patients' files. Ultrasound images were re‐evaluated independently by two sonologists using MUSA terms and definitions. Descriptive statistics were calculated and interobserver agreement was assessed using Cohen's κ (with squared weights) or intraclass correlation coefficient, as appropriate.ResultsA total of 107 patients were included, of whom 16 had a uterine sarcoma and 91 had a uterine leiomyoma. Abnormal uterine bleeding was the most frequent presenting symptom (69/107 (64%)). Compared with leiomyoma cases, patients with uterine sarcoma were older (median age, 65 (interquartile range (IQR), 60–70) years vs 48 (IQR, 43–52) years) and more likely to be postmenopausal (13/16 (81%) vs 15/91 (16%)). In the uterine sarcoma cohort, leiomyosarcoma was the most frequent histological type (6/16 (38%)), followed by adenosarcoma (4/16 (25%)). On ultrasound evaluation, according to Observers 1 and 2, the tumor border was irregular in most sarcomas (11/16 (69%) and 13/16 (81%) cases, respectively), but regular in most leiomyomas (65/91 (71%) and 82/91 (90%) cases, respectively). Lesion echogenicity was classified as non‐uniform in 68/91 (75%) and 51/91 (56%) leiomyomas by Observers 1 and 2, respectively, and 15/16 (94%) uterine sarcomas by both observers. More than 60% of the uterine sarcomas showed acoustic shadows (11/16 (69%) and 10/16 (63%) cases by Observers 1 and 2, respectively), whereas calcifications were reported in a small minority (0/16 (0%) and 2/16 (13%) cases by Observers 1 and 2, respectively). In uterine sarcomas, intralesional vascularity was reported as moderate to abundant in 13/16 (81%) cases by Observer 1 and 15/16 (94%) cases by Observer 2, while circumferential vascularity was scored as moderate to abundant in 6/16 (38%) by both observers. Interobserver agreement for the presence of cystic areas, calcifications, acoustic shadow, central necrosis, color score (overall, intralesional and circumferential) and maximum diameter of the lesion was moderate. The agreement for shape of lesion, tumor border and echogenicity was fair.ConclusionsA postmenopausal patient presenting with abnormal uterine bleeding and a new or growing mesenchymal mass with irregular tumor borders, moderate‐to‐abundant intralesional vascularity, cystic areas and an absence of calcifications on ultrasonography is at a higher risk of having a uterine sarcoma. Interobserver agreement for most MUSA terms and definitions is moderate. Future studies should validate the abovementioned clinical and ultrasound findings on uterine mesenchymal tumors in a prospective multicenter fashion. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.