3. ENDOMETRIAL CANCER
3.6. PREOPERATIVE RISK ASSESSMENT AND PRIMARY TREATMENT
3.6.1. Preoperative risk assessment
The role of preoperative risk assessment is to classify patients into those groups of risk for lymphatic dissemination and disease recurrence in an early step of the diagnostic process in order to define the most optimal surgical management.
Currently, the extent of the surgical staging procedure is guided by the assessment of tumor grade and histological subtype based on the pathological examination of the preoperative endometrial biopsies, and the evaluation of myometrial and cervical invasion and lymph node metastasis based on imaging techniques (Figure 8).
3.6.1.1. Preoperative endometrial biopsies
As most information is not available preoperatively, histological subtype and grade become key factors for risk group assignment 140. Biopsies obtained by aspiration and/or guided by hysteroscopy are not only used to discriminate between EC and non-EC cases but also to assess the tumor grade and histological subtype of the EC cases. However, high discordance rates have been reported on this matter. Regarding EEC tumors, different studies have reported that about 22% to 40% of tumors classified as grade 1 on the
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Introduction
preoperative biopsy were upgraded on the final surgical pathology, as were 26% to 56% of grade 2 tumors. In addition, 8% to 60% of tumors preoperatively defined as grade 3 were found to be downgraded on the final surgical evaluation and/or classified as NEEC in several studies 140–144. Regarding high-risk NEEC histologies, some studies have reported a high concordance between preoperative and postoperative pathological interpretations (93%
of the cases) 140. However, other studies found good correlation for carcinosarcomas (90%), but worse for serous and clear cell carcinomas (67%) 145. These discordances may be partially explained by interobserver variability 146 and the small volume of tissue available for examination in a preoperative biopsy. According to this, hysteroscopy and D&C show a higher accuracy in predicting final post-hysterectomy tumor grade than pipelle biopsy 147,148.
Table 6. Risk stratification system. FIGO 2009 staging is used. G, grade; LVSI, lymphovascular space invasion. Adapted from Colombo et al. 2016 33
Molecular classifications such as the TCGA classification have demonstrated higher prognostic accuracy than the histomorphologic classification. Importantly, several studies have proved a high concordance between molecular alterations in preoperative endometrial
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biopsies and the hysterectomy specimens 149,150 but have not yet been implemented in the routine clinical risk assessment procedure.
3.6.1.2. Magnetic resonance imaging (MRI)
Contrast-enhanced MRI has long been the preferred imaging technique for preoperative risk assessment, particularly for myometrial invasion assessment 69,151,152. The major limitation of imaging techniques is the poor detection of lymph node metastases 153. A recent meta-analysis including 52 studies examining MRI in the assessment of high-risk features of EC found pooled sensitivity (specificity) of 80.7% (88.5%) for ≥50% myometrial invasion, 57%
(94.8%) for cervical invasion, and 43.5% (95.9%) for lymph node metastasis 154. Considering the limited sensitivity of MRI, the authors concluded that patients with negative findings on MRI may not safely abstain from surgical staging. Furthermore, this technology is costly and requires an experienced radiologist to provide accurate interpretation. Some studies suggest that transvaginal ultrasonography has similar accuracy to that of MRI for assessment of myometrial and cervical invasion. This technology is less costly than MRI but cannot be used to determine lymph node metastases 155. If MRI is not available, computed tomography can be also used to assess extrauterine disease.
Various studies have underlined the high accuracy of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in detection of myometrial and cervical invasion and lymph node metastasis. However, its use in preoperative risk assessment of EC remains questionable 156,157.
3.6.2. Primary treatment
The most efficient treatment for EC is surgery. Total hysterectomy (removal of the uterus) and bilateral adnexectomy (removal of both Fallopian tubes and ovaries) is the standard treatment for apparent stage I EC 33,97 (Figure 8). Alternatives to hysterectomy for women who wish future childbearing have been comprehensively reviewed 158. Hysterectomy and adnexectomy were traditionally done with open abdominal surgery (laparotomy). However, laparoscopy is currently the preferred surgical approach, as this technique provide the same clinical outcomes than laparotomy with shorter hospital stays and fewer postoperative complications 159,160. Robotic-assisted laparoscopic surgery appears to facilitate the surgical approach and can be used if available 161.
The necessity of performing a lymphadenectomy (surgical removal of one or more groups of lymph nodes) for the assessment of lymphatic dissemination has been a focus of debate 162, and the decision of the extent of lymphadenectomy varies tremendously between surgeons.
Several randomized trials showed no evidence of benefit in terms of overall or
recurrence-Endometrial cancer disease or early stages in patients with bad prognostic features and/or risk factors. Following this criteria, patients with grade 1 or 2 EEC with less than 50% myometrium invasion are excluded from lymphadenectomy 33,97. Sentinel lymph node assessment may help to determine which early-stage EC patients will benefit from lymphadenectomy and could provide important data to tailor adjuvant therapy 166,167.
Figure 8. Treatment of endometrioid EC. G, grade; RF, risk factors; BT, brachytherapy; RT, radiotheraphy; CH, chemotherapy. Adapted from Oncoguía SEGO 2016 97.
Tumor confined to the uterus
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A complete staging should be performed in patients diagnosed with NEECs, since these tumors present high risk of extrauterine dissemination even when they are found in their initial stages. This includes hysterectomy with bilateral adnexectomy, pelvic and para-aortic lymphadenectomy, omentectomy, and peritoneal biopsies 33,97 (Figure 9).