The cornerstone of the treatment of endometrial carcinoma is surgery, including hysterectomy and bilateral salpingo-oophorectomy. If the risk for metastases is estimated to be increased, a pelvic and para-aortic lymphadenectomy is also warranted. Preoperative risk assessment is based on the histopathologic analysis of the diagnostic endometrial biopsy or curettage specimen, and the determination of myometrial invasion of the tumor using imaging methods. Deep myometrial invasion (>50% of the myometrial thickness) has been found to be an independent prognostic factor for metastases in endometrial carcinoma. As the extent of the operation is dependent on the results of the preoperative assessment, a good diagnostic performance of the used methods is fundamental.
One hundred consecutive patients presenting with endometrial carcinoma and scheduled for an operation at Tampere University Hospital from 2007 through 2009 were enrolled in this prospective observational study. The primary objective was to evaluate the feasibility of three-dimensional power Doppler angiography (3DPDA) in the preoperative assessment of deep myometrial invasion. All patients were examined preoperatively, and the results were correlated with the final histopathological report of the surgical specimen. The endometrial volume with endometrial and myometrial vascular indices VI (vascularization index), FI (flow index) and VFI (vascularization flow index) were calculated by 3DPDA.
According to multivariate regression analysis, endometrial volume and endometrial FI were the independent predictors of deep myometrial invasion (OR, 1.109; 95% CI, 1.011–1.215 and OR, 1.061; 95% CI, 1.023–1.099. p=0.028 and 0.001, respectively). The distance between the ultrasound probe and the target tissue was found to be a notable confounding factor, which must be acknowledged when evaluating the results. The second objective was to compare the performance of 3D sonography and magnetic resonance imaging (MRI) in a subset of 20 patients. MRI was found to be more sensitive (91.7%) in detecting deep invasion. However, 3D sonography was more specific (87.5%).
A combination of the assessed methods was found to have the best or 80.0% accuracy. The third aim of the study was to evaluate the performance of two ovarian cancer biomarkers, CA125 and HE4, in the preoperative evaluation of endometrial carcinoma. A combination of the markers, a risk score, was found to better predict advanced stage than either of the markers alone with a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 57.1%, 98.7%, 88.9%, 92.6%, and 92.2%, respectively. Patient’s BMI was found to have an influence on the level of HE4. This confounding factor must be taken into account when using HE4 measurement in clinical practice. The last objective of the study was to incorporate angiogenic markers in the preoperative assessment.
Preoperative serum concentrations of endoglin, vascular endothelial growth factor VEGF and its soluble receptor sFLT-1 were measured and correlated with the histopathological features of the tumors. Immunohistochemistry was used to assess the tumoral expression of endoglin, VEGF, and its cell surface receptors VEGFR1 and VEGFR2. Serum concentration of VEGF was found to correlate with the presence of metastases. The tumor microvessel density, assessed by immunohistochemistry, was associated with the degree of vascularization determined by 3DPDA. The results of the present study suggest that endometrial volume measurement and endometrial blood flow assessment by 3DPDA may facilitate the preoperative workup of patients with endometrial carcinoma. In addition, the measurement of serum concentrations of CA125 and HE4 with risk score calculation may further assist identifying the patients with an elevated risk for metastases.