IETA Ultrasonic Features Combined with GI-RADS Classification System and Tumor Biomarkers for Surveillance of Endometrial Carcinoma: An Innovative Study

Abstract

Objectives: We were the first to combine IETA ultrasonic features with GI-RADS and tumor biomarkers for the surveillance of endometrial carcinoma. The aim was to evaluate the efficacy of single IETA ultrasonography GI-RADS classification and combined tumor biomarkers in differentiating benign and malignant lesions in the uterine cavity and endometrium. Methods: A total of 497 patients with intrauterine and endometrial lesions who had been treated surgically between January 2017 and December 2021 were enrolled; all of them had undergone ultrasound examinations before surgery. We analyzed the correlation between the terms of ultrasonic signs of the uterine cavity and endometrial lesions defined by the expert consensus of IETA and the benign and malignant lesions and then classified these ultrasonic signs by GI-RADS. In addition, the tumor biomarkers CA125, CA15-3, CA19-9 and HE4 were combined by adjusting the classification. The results of the comprehensive analysis were compared with pathological results to analyze their diagnostic efficacy. Results: (1) The statistic analysis confirmed that there were seven independent predictors of malignant lesions, including thickened endometrium (premenopause ≥ 18.5 mm, postmenopause ≥ 15.5 mm), non-uniform endometrial echogenicity (heterogeneous with irregular cysts), endometrial midline appearance (not defined), the endometrial-myometrial junction (interrupted or not defined), intracavitary fluid (ground glass or "mixed" echogenicity), color score (3~4 points) and vascular pattern (focal origin multiple vessels or multifocal origin multiple vessels). (2) In traditional ultrasound GI-RADS (U-T-GI-RADS), if category 4a was taken as the cut-off value of benign and malignant, the diagnostic sensitivity, specificity, PPV, NPV and diagnostic accuracy were 97.2%, 65.2%, 44.0%, 98.8% and 72.2%, respectively, and the area under the ROC curve (AUC) was 0.812. If 4b was taken as the cut-off value, the diagnostic sensitivity, specificity, PPV, NPV diagnostic accuracy and AUC were 88.1%, 92.0%, 75.6%, 96.5% and 91.2%, 0.900, respectively. The diagnostic sensitivity, specificity, PPV, NPV diagnostic accuracy and AUC were 75.2%, 98.5%, 93.2%, 93.4%, 93.4% and 0.868, respectively, when taking category 5 as the cutoff point. In modified ultrasound GI-RADS (U-M-GI-RADS), if 4a was taken as the cut-off value, The diagnostic efficacy was the same as U-T-GI-RADS. If 4b was taken as the cut-off value, the diagnostic sensitivity, specificity, PPV, NPV, diagnostic accuracy and AUC were 88.1%, 92.3%, 76.2%, 96.5%, 91.3% and 0.902, respectively. If 4c was taken as the cutoff point, the diagnostic sensitivity, specificity, PPV, NPV diagnostic accuracy and AUC were 75.2%, 98.7%, 94.3%, 93.4%, 93.6% and 0.870, respectively. The diagnostic sensitivity, specificity, PPV, NPV diagnostic accuracy and AUC were 66.1%, 99.7%, 98.6%, 91.3%, 92.4% and 0.829, respectively, if taking category 5 as the cutoff point. (3) In the comprehensive diagnostic method of U-T-GI-RADS combined tumor biomarkers results, the AUC of class 4a, 4b and 5 as the cutoff value was 0.877, 0.888 and 0.738, respectively. The AUC of class 4a, 4b, 4c and 5 as the cutoff value in the comprehensive diagnostic method of U-M-GI-RADS combined tumor biomarkers results was 0.877, 0.888, 0.851 and 0.725, respectively. There was no significant difference in diagnostic efficiency between the two comprehensive diagnostic methods. Conclusions: In this study, no matter which diagnostic method was used, the best cutoff value for predicting malignant EC was ≥GI-RADS 4b. The GI-RADS classification had good performance in discriminating EC. The tumor biomarkers, CA125, CA19-9, CA15-3 and HE4, could improve the diagnostic efficacy for preoperative endometrial carcinoma assessment.

Keywords: endometrial cancer/carcinoma (EC); endometrium lesion; gynecologic imaging reporting and data system (GI-RADS); the international endometrial tumor analysis (IETA); tumor biomarkers; uterine cavity lesions.

Figure 1

Images of benign IETA ultrasonographic features. (A) Homogeneous hyperechoic; (B) Three-layer pattern; (C) Homogeneous isoechoic; (D) Endometrial midline appearance: “linear” and endometrial–myometrial junction: “regular”; (E) The “bright edge” sign, the echo formed by the interface between an intracavitary lesion and the endometrium; (F) Homogeneous with regular cysts; (G) Vascular pattern: single vessel (without branching); (H) Vascular pattern: circular vessels.

Figure 2

Images of malignant IETA ultrasonographic features. (A) Heterogeneous with irregular cysts and endometrial–myometrial junction: “interrupted”; (B) Endometrial midline appearance: “not defined” and endometrial–myometrial junction: “not defined”; (C) Intracavitary fluid: “ground glass”; (D) Intracavitary fluid: “mixed” echogenicity; (E,F) Vascular pattern: Multiple vessels (focal origin); (G) Vascular pattern: Multiple vessels (multifocal origin); Color score: moderate amount of color/moderate vascularity (3 points); (H) Color score: abundant color/abundant vascularity (4 points).

Figure 3

The ROC curves of various malignant ultrasound signs and their combination. (A) The ROC curve of endometrial thickness malignant signs; AUC: 0.826, SE: 0.025, 95% CI (0.777, 0.874). (B) The ROC curve of non-uniform endometrial echogenicity malignant signs “ heterogeneous with irregular cysts”; AUC: 0.688, SE: 0.032, 95% CI (0.625, 0.751). (C) The ROC curve of endometrial midline appearance malignant signs “not defined”; AUC: 0.732, SE: 0.028, 95% CI (0.677, 0.786). (D) The ROC curve of endometrial–myometrial junction malignant signs “interrupted or not defined”; AUC: 0.898, SE: 0.021, 95% CI (0.856, 0.939). (E) The ROC curve of intracavitary fluid malignant signs “ground glass or mixed echogenicity”; AUC: 0.643, SE: 0.033, 95% CI (0.577, 0.709). (F) The ROC curve of color score malignant signs “3~4 points”; AUC: 0.847, SE: 0.027, 95% CI (0.795, 0.900). (G) The ROC curve of vascular pattern malignant signs: multiple vessels (focal origin) or multiple vessels (multifocal origin); AUC: 0.825, SE: 0.028, 95% CI (0.770, 0.881). (H) The ROC curve of combination of multiple ultrasonic malignant signs; AUC: 0.962, SE: 0.012, 95% CI (0.938, 0.986).

Figure 3

The ROC curves of various malignant ultrasound signs and their combination. (A) The ROC curve of endometrial thickness malignant signs; AUC: 0.826, SE: 0.025, 95% CI (0.777, 0.874). (B) The ROC curve of non-uniform endometrial echogenicity malignant signs “ heterogeneous with irregular cysts”; AUC: 0.688, SE: 0.032, 95% CI (0.625, 0.751). (C) The ROC curve of endometrial midline appearance malignant signs “not defined”; AUC: 0.732, SE: 0.028, 95% CI (0.677, 0.786). (D) The ROC curve of endometrial–myometrial junction malignant signs “interrupted or not defined”; AUC: 0.898, SE: 0.021, 95% CI (0.856, 0.939). (E) The ROC curve of intracavitary fluid malignant signs “ground glass or mixed echogenicity”; AUC: 0.643, SE: 0.033, 95% CI (0.577, 0.709). (F) The ROC curve of color score malignant signs “3~4 points”; AUC: 0.847, SE: 0.027, 95% CI (0.795, 0.900). (G) The ROC curve of vascular pattern malignant signs: multiple vessels (focal origin) or multiple vessels (multifocal origin); AUC: 0.825, SE: 0.028, 95% CI (0.770, 0.881). (H) The ROC curve of combination of multiple ultrasonic malignant signs; AUC: 0.962, SE: 0.012, 95% CI (0.938, 0.986).

Figure 4

The ROC curve of serum tumor biomarkers. (A) The ROC curve of CA125 positive value; AUC: 0.566, SE: 0.033, 95% CI (0.502, 0.630). (B) The ROC curve of CA15-3 positive value; AUC: 0.513, SE: 0.032, 95% CI (0.450, 0.575). (C) The ROC curve of CA19-9 positive value; AUC: 0.618, SE: 0.033, 95% CI (0.553, 0.683). (D) The ROC curve of HE4 positive value; AUC: 0.628, SE: 0.036, 95% CI (0.558, 0.698).

Figure 4

The ROC curve of serum tumor biomarkers. (A) The ROC curve of CA125 positive value; AUC: 0.566, SE: 0.033, 95% CI (0.502, 0.630). (B) The ROC curve of CA15-3 positive value; AUC: 0.513, SE: 0.032, 95% CI (0.450, 0.575). (C) The ROC curve of CA19-9 positive value; AUC: 0.618, SE: 0.033, 95% CI (0.553, 0.683). (D) The ROC curve of HE4 positive value; AUC: 0.628, SE: 0.036, 95% CI (0.558, 0.698).