Dynamic contrast-enhanced ultrasound improves diagnostic performance in endometrial cancer staging

Objectives: To compare the sensitivity and specificity of conventional two-dimensional transvaginal ultrasound/power Doppler (2D-TVU/PD) alone and 2D-TVU/PD combined with dynamic contrast-enhanced ultrasound (DCE-US) in diagnosing deep myometrial invasion (MI) and cervical stromal involvement (CSI) in women with endometrial cancer (EC), and to assess the association of DCE-US semiquantitative and qualitative variables with International Federation of Gynecology and Obstetrics (FIGO) Stage ≥ IB and 'high-risk' cancer.

Methods: This was a prospective study of 101 consecutive women with biopsy-confirmed EC, undergoing expert ultrasound examination at Karolinska University Hospital, a tertiary referral center. All consenting women underwent DCE-US using a 1.5-2.5-mL intravenous bolus of SonoVue contrast agent, as well as conventional 2D-TVU/PD examination. DCE-US videoclips were analyzed with regard to filling (global or focal), wash-in (prior, simultaneous or after) and wash-out (global or focal) patterns of the contrast agent in the tumor compared with the surrounding tissue, as well as semiquantitative DCE-US parameters (wash-in slope, time-to-peak, peak intensity and area under the time-intensity curve (TIC)) obtained from a TIC. The study cohort was compared with a control cohort of women with EC examined at our center according to the International Endometrial Tumor Analysis protocol using 2D-TVU/PD only, matched at a ratio of 3:1 for FIGO stage and grade. The sensitivity and specificity of 2D-TVU/PD alone in the control cohort and in combination with DCE-US in the study cohort in the diagnosis of deep MI, CSI and high-risk cancer (defined as FIGO Stage ≥ IB and/or Grade 3 endometrioid and/or non-endometrioid histology) were compared, using pathological evaluation after hysterectomy as the 'gold standard'.

Results: After exclusions, 93 women were included in the study cohort and were matched to 279 women in the control cohort. The prevalence of FIGO Stage IA, Grade 1-2 EC was 52% in both cohorts. The sensitivity of 2D-TVU/PD with DCE-US in the study cohort was higher than that of 2D-TVU/PD alone in the control cohort in diagnosing both deep MI (0.74 vs 0.62; P = 0.036) and CSI (0.75 vs 0.51; P < 0.001), whereas the specificity was not significantly different (0.87 vs 0.85 and 0.96 vs 0.95, respectively). Compared with 2D-TVU/PD alone, the specificity of 2D-TVU/PD with DCE-US was higher in detecting high-risk cancer (0.94 vs 0.85; P = 0.024) but the sensitivity did not differ (0.73 vs 0.71). High-risk cancer and FIGO Stage ≥ IB were characterized by a 'focal' filling pattern, with a 'prior' wash-in pattern and a 'focal' wash-out pattern on subjective assessment of DCE-US videoclips. All semiquantitative DCE-US parameters were significantly predictive of FIGO Stage ≥ IB but not of high-risk cancer, despite a clear trend.

Conclusions: Compared with 2D-TVU/PD alone, combining 2D-TVU/PD with DCE-US can significantly improve the detection of deep MI and CSI in women with EC, without increasing the false-positive rate. It can also improve the correct classification of high-risk disease, mainly by increasing specificity, thereby possibly reducing the number of unnecessarily extensive surgeries by almost 10%. Semiquantitative DCE-US parameters, as well as a 'focal' filling pattern, endometrial wash-in prior to the myometrium and a 'focal' wash-out pattern, are all associated with more advanced disease. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.