Endometrial carcinoma is a malignant epithelial tumor that forms in the inner lining, or endometrium, of the uterus. Endometrial carcinoma is the most common gynecologic malignancy. Approximately two-thirds of endometrial carcinoma cases are diagnosed with disease confined to the uterus. The complete NCCN Guidelines for Uterine Neoplasms provide recommendations for the diagnosis, evaluation, and treatment of endometrial cancer and uterine sarcoma. This manuscript discusses guiding principles for the diagnosis, staging, and treatment of early-stage endometrial carcinoma as well as evidence for these recommendations.

Abstract

Endometrial carcinoma is a malignant epithelial tumor that forms in the inner lining, or endometrium, of the uterus. Endometrial carcinoma is the most common gynecologic malignancy. Approximately two-thirds of endometrial carcinoma cases are diagnosed with disease confined to the uterus. The complete NCCN Guidelines for Uterine Neoplasms provide recommendations for the diagnosis, evaluation, and treatment of endometrial cancer and uterine sarcoma. This manuscript discusses guiding principles for the diagnosis, staging, and treatment of early-stage endometrial carcinoma as well as evidence for these recommendations.

NCCN Categories of Evidence and Consensus

Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.

Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

All recommendations are category 2A unless otherwise noted.

Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

Overview of Uterine Neoplasms

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 61,380 new uterine cancer cases will occur in 2017, with 10,920 deaths resulting from the disease.1 Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers.2,3 The NCCN Guidelines for Uterine Neoplasms describe malignant epithelial tumors and uterine sarcomas; each of these major categories contains specific histologic groups that require different management (see “Initial Clinical Findings” in the NCCN Guidelines for Uterine Neoplasms, available at NCCN.org).

Risk factors for uterine neoplasms include increased levels of estrogen (caused by obesity, diabetes, and high-fat diet), early age at menarche, nulliparity, late age at menopause, Lynch syndrome, older age (≥55 years), and tamoxifen use.47 Thus, the incidence of endometrial cancer is increasing because of increased life expectancy and obesity. The “Summary of the Guidelines Updates” (available at NCCN.org) describes the most recent revisions to the algorithms, which have been incorporated into this revised Discussion text (see the NCCN Guidelines for Uterine Neoplasms). By definition, the NCCN Guidelines cannot incorporate all possible clinical variations and are not intended to replace good clinical judgment or individualization of treatments. Exceptions to the rule were discussed among the NCCN panel during the process of developing these guidelines.

NOTE: This manuscript highlights only a portion of the NCCN Guidelines on Uterine Neoplasms. The guidelines appearing in this issue of JNCCN discuss important general principles and evidence for diagnosis, staging, and primary/adjuvant treatment of early-stage endometrial carcinoma. Please refer to the complete guidelines online at NCCN.org for recommendations for post-treatment surveillance of early-stage disease, in addition to diagnosis and management of

F1

NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 1.2018

Version 1.2018, 10-13-17 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 2; 10.6004/jnccn.2018.0006

F2

NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 1.2018

Version 1.2018, 10-13-17 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 2; 10.6004/jnccn.2018.0006

F3

NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 1.2018

Version 1.2018, 10-13-17 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 2; 10.6004/jnccn.2018.0006

F4

NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 1.2018

Version 1.2018, 10-13-17 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 2; 10.6004/jnccn.2018.0006

F5

NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 1.2018

Version 1.2018, 10-13-17 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 2; 10.6004/jnccn.2018.0006

F6

NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 1.2018

Version 1.2018, 10-13-17 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 2; 10.6004/jnccn.2018.0006

advanced, metastatic, or recurrent endometrial carcinoma and uterine sarcoma.

Endometrial Cancer

In 2017, 67% of patients with adenocarcinoma of the endometrium were diagnosed with disease confined to the uterus at diagnosis.1 Regional and distant disease comprised 21% and 8% of cases, respectively. Many physicians believe that adenocarcinoma of the endometrium is a more treatable malignancy because the early symptoms of irregular vaginal bleeding (in this predominantly postmenopausal patient population) often trigger patients to seek care when the disease is at an early and treatable stage. However, data show that the mortality rate for uterine cancer has increased more rapidly than the incidence rate.8 This increased mortality may be related to an increased rate of advanced-stage cancers, high-risk histologies (eg, serous carcinomas), and patients being diagnosed at an older age.

Analysis of SEER data suggests that survival is increased in patients who are younger, have early-stage disease, and have lower-grade disease.9 In addition to grade and depth of myometrial invasion, other risk factors associated with poor prognosis include age, lymph node status, tumor size, lymphovascular space invasion (LVSI), and tumor involvement of the lower uterine segment.10,11 To further improve outcome for patients with this disease, physicians need to identify high-risk patients and to tailor treatment appropriately to provide the best long-term survival. The panel suggests that gynecologic oncologists be involved in the primary management of all patients with endometrial cancer.

Genetic Factors

Most endometrial cancer is caused by sporadic mutations. However, hereditary genetic mutations cause endometrial cancer in about 5% of patients, which occurs 10 to 20 years before sporadic cancer.12 Screening of the tumor for defective DNA mismatch repair (MMR) using immunohistochemistry and/or microsatellite instability (MSI) is used to identify which patients should undergo mutation testing for Lynch syndrome (see “Lynch Syndrome” in the NCCN Guidelines for Colorectal Cancer Screening, available at NCCN.org).1218 Universal testing of endometrial tumors for defects in DNA MMR is recommended (eg, MLH1, MSH2, MSH6). MLH1 loss should be further evaluated for promoter methylation to assess for an epigenetic process rather than a germline mutation.16 Genetic counseling and testing is recommended for patients with all other MMR abnormalities and for patients without MMR defects but who have a significant family history of endometrial and/or colorectal cancer (See “Lynch Syndrome [Hereditary Non-Polyposis Colorectal Cancer]” in the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal).

Women with Lynch syndrome are at a higher lifetime risk (up to 60%) for endometrial cancer; thus, close monitoring and discussion of risk-reducing strategies is recommended.13,19,20 In relatives with Lynch syndrome but without endometrial cancer, a yearly endometrial biopsy is recommended to assess for cancer.21,22 This strategy also enables select women to defer surgery (and surgical menopause) and to preserve fertility. Prophylactic hysterectomy/bilateral salpingo-oophorectomy (BSO) can then be done after childbearing is complete or sooner, depending on patient preference.23,24 In addition, interventions to decrease the risk from colorectal cancer may also be appropriate (eg, annual colonoscopy).

Diagnosis and Workup

About 90% of patients with endometrial carcinoma have abnormal vaginal bleeding, most commonly in the postmenopausal period. Diagnosis can usually be made via an office endometrial biopsy.25,26 The histologic information from the endometrial biopsy (with or without endocervical curettage) should be sufficient for planning definitive treatment. Office endometrial biopsies have a false-negative rate of about 10%. Thus, a negative endometrial biopsy in a symptomatic patient must be followed by a fractional dilation and curettage (D&C) under anesthesia.25,27 Hysteroscopy may be helpful in evaluating the endometrium for lesions, such as a polyp, if the patient has persistent or recurrent undiagnosed bleeding.28 Endometrial biopsy may not be accurate for diagnosing malignancies of the uterine wall such as mesenchymal tumors.

For detailed imaging recommendations by stage and planned treatment approach, see “Principles of Imaging” in the full NCCN Guidelines for Uterine Neoplasms at (available NCCN.org). Consideration of chest imaging (chest x-ray) is recommended. Other imaging tests such as CT, MRI, and/or PET/CT may be used to assess disease extent and to evaluate for metastatic disease as indicated based on clinical symptoms, physical findings, or abnormal laboratory findings.2934 In patients with extrauterine disease, a serum CA-125 assay may be helpful in monitoring clinical response.35,36 However, serum CA-125 levels can be falsely increased in women who have peritoneal inflammation/infection or radiation injury, may be normal in women with isolated vaginal metastases, and may not predict recurrence in the absence of other clinical findings.3739 Currently, no validated screening test is available for endometrial carcinoma.40,41

Disease Staging

The FIGO (International Federation of Gynecology and Obstetrics) system is most commonly used for staging uterine cancer. The original 1970 criteria for staging endometrial cancer only used information gained from presurgical evaluation (including physical examination and diagnostic fractional D&C). At that time, many patients were not treated with primary surgery because of obesity or various other medical problems. Thus, the 1970 staging system is rarely used today (eg, when the patient is not a surgical candidate).

Several studies showed that clinical staging was inaccurate and did not reflect actual disease extent in 15% to 20% of patients.4244 This reported under-staging and, more importantly, the ability to identify multiple prognostic factors with a full pathologic review made possible with surgical staging, motivated a change in the staging classification. Therefore, in 1988, FIGO modified its staging system to emphasize thorough surgical/pathologic assessment of data, such as histologic grade, myometrial invasion, and the extent and location of extrauterine spread (including retroperitoneal lymph node metastases).45 FIGO updated and refined the surgical/pathologic staging criteria for uterine neoplasms in 2009.4649 Separate staging systems for malignant epithelial tumors and uterine sarcomas are now available (see the staging section of the algorithm). In 2017, the AJCC Cancer Staging Manual was updated (to take effect January 2018).50

The 2009 FIGO staging system streamlined stages I and II endometrial carcinoma. These revisions were made because the survival rates for some of the previous sub-stages were similar.48 Stage IA is now less than 50% myometrial invasion, and stage IB is 50% or more myometrial invasion. Stage II only includes patients with cervical stromal invasion. Patients with uterine-confined disease and endocervical glandular involvement (mucosal involvement) without cervical stromal invasion are no longer considered stage II.48 Stage IIIC is now subdivided into IIIC1 and IIIC2, because survival is worse with positive para-aortic nodes.48 Although most of the previously published studies discussed in these NCCN Guidelines used the older 1988 FIGO staging system, these have been reinterpreted by the NCCN panel to reconcile with the 2009 staging system.

Peritoneal cytology no longer affects the 2009 FIGO staging, because it is not viewed by some authors as an independent risk factor.49 However, FIGO and AJCC continue to recommend that peritoneal washings be obtained and results recorded, because positive cytology may add to the effect of other risk factors (see “Principles of Evaluation and Surgical Staging” on page 178 [ENDO-C]).51,52

Principles of Evaluation and Surgical Staging for Endometrial Carcinoma

Staging should be done by a team with expertise in imaging, pathology, and surgery. The amount of surgical staging that is necessary to determine disease status depends on preoperative and intraoperative assessment of findings by experienced surgeons. For the 2014 update, the NCCN panel added a new section on surgical staging (see “Principles of Evaluation and Surgical Staging” on page 178 [ENDO-C]). However, this surgical staging section only applies to malignant epithelial tumors and not to uterine sarcomas. Surgical staging with nodal assessment for apparent uterine-confined endometrial cancer is critical to accurately determine the initial FIGO stage. The NCCN sentinel lymph node (SLN) algorithm is recommended if sentinel node mapping is utilized.

Pathology: An expert pathology review will determine the specific epithelial histology of the tumor (ie, various endometrioid histologies, serous carcinoma, clear cell carcinoma, carcinosarcoma, undifferentiated carcinoma). The pathologic assessment of the uterus and the nodes is described in the algorithm; this assessment should also include the Fallopian tubes, ovaries, and peritoneal cytology. If nodal resection was performed, the level of nodal involvement and size of metastasis should be determined. See “Hysterectomy and Pathologic Evaluation” in the algorithm (page 177 [ENDO-B]). The Protocol for Examination of Specimens from Patients With Carcinoma of the Endometrium from the College of American Pathologists (CAP) is a useful guide (http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2013/Endometrium_13protocol_3200.pdf). This CAP protocol was revised in October 2013 and reflects the updated FIGO/AJCC 2009 staging (ie, AJCC Cancer Staging Manual, 7th edition). Estrogen receptor testing is recommended in the setting of stage III, IV, or recurrent endometrioid carcinoma.

As the grade of the tumor increases, the accuracy of intraoperative evaluation of myometrial invasion decreases (ie, assessment by gross examination of fresh tissue). In one study, the depth of invasion was accurately determined by gross examinations in 87.3% of grade 1 lesions, 64.9% of grade 2 lesions, and 30.8% of grade 3 lesions.53 Studies show that in 15% to 20% of cases, the preoperative grade (as assessed by endometrial biopsy or curettage) is upgraded on final fixed pathologic evaluation of the hysterectomy specimen.54

Lymphadenectomy: Previously, a full standard lymphadenectomy (ie, dissection and assessment of both pelvic and para-aortic nodes) was recommended for all patients; however, a more selective and tailored lymphadenectomy approach that may include the SLN algorithm is now recommended by the NCCN Panel to avoid systematic overtreatment.55 No randomized trial data support routine full lymphadenectomy,56 although some retrospective studies have suggested that it is beneficial.5759 Two randomized clinical trials from Europe reported that routine lymph node dissection did not improve the outcome of endometrial cancer patients, but lymphadenectomy did identify those with nodal disease.60,61 However, these findings remain a point of contention.6264 To avoid overinterpretation of these results, it is important to address the limitations of these randomized studies, including selection of patients, extent of lymph node dissection, and standardization of postoperative therapy.65,66 Other concerns include the lack of central pathology review, subspecialty of surgeons, and adequacy of statistical power.

Decisions about whether to perform lymphadenectomy, and, if done, to what extent (eg, pelvic nodes only or both pelvic and para-aortic nodes), can be made based on preoperative and intraoperative findings. Criteria have been suggested as indicative of low risk for nodal metastases: 1) less than 50% myometrial invasion; 2) tumor less than 2 cm; and 3) well or moderately differentiated histology.67,68 However, this may be difficult to accurately determine before final pathology results are available.

Another associated benefit of lymphadenectomy is the diagnosis of those with nodal metastases to guide appropriate adjuvant treatment to improve survival or decrease toxicity. However, one of the trials was not designed to address this question.61 Therefore, there was no standardization of adjuvant treatment after staging surgery with lymphadenectomy. In fact, the use of lymphadenectomy did not translate into an increased use of adjuvant therapy. This may have contributed to the lack of difference in recurrence and survival in the two groups.

The question of whether to add para-aortic lymphadenectomy to pelvic node dissection has been debated. Prior studies have shown conflicting information regarding the risk of para-aortic nodal metastases in patients without disease in the pelvic nodes.44,67,69,70 There was a high rate of lymphatic metastasis above the inferior mesenteric artery, suggesting a need for systematic pelvic and para-aortic lymphadenectomy. Hence, para-aortic lymphadenectomy up to the renal vessels may be considered for selective high-risk situations, including those with pelvic lymphadenectomy or high-risk histologic features. Many surgeons do not do a full lymphadenectomy in patients with grade 1 early-stage endometrial cancer.55

In summary, lymph node dissection identifies patients requiring adjuvant treatment with radiation therapy (RT) and/or systemic therapy.71 A subset of patients may not benefit from lymphadenectomy; however, it is difficult to preoperatively identify these patients because of the uncontrollable variables of change in grade and depth of invasion on final pathology. The NCCN Panel recommends that lymphadenectomy should be done for selected patients with endometrial cancer with para-aortic lymphadenectomy done as indicated for patients at high risk (see “Principles of Evaluation and Surgical Staging” on page 178 [ENDO-C]).6 Lymphadenectomy is contraindicated for patients with uterine sarcoma. SLN mapping can be considered as an alternative to full lymphadenectomy in the setting of apparent uterine-confined disease. The SLN surgical algorithm is described in the next section.

SLN Mapping: The section on surgical staging (see “Principles of Evaluation and Surgical Staging,” page 178 [ENDO-C]) includes recommendations about SLN mapping. SLN mapping may be considered for patients with apparent uterine-confined endometrial cancer to assess whether they have metastatic pelvic lymph nodes.7276 In SLN mapping, dye is injected into the cervix, which travels to the sentinel nodes (see Figures 1–3 in “Principles of Evaluation and Surgical Staging,” page 180).

A surgical SLN algorithm is proposed to decrease the false-negative rate (see Figure 4 in “Principles of Evaluation and Surgical Staging,” page 181).72,77 For example, suspicious or grossly enlarged nodes should be removed regardless of SLN mapping results. In SLN mapping, the surgeon's expertise and attention to technical detail are critical. Patients may be able to avoid the morbidity of a standard lymphadenectomy with SLN mapping.78,79 Because SLNs identify the primary lymphatic pathway, this increases the yield of finding metastatic disease during the mapping process. If SLN mapping fails, a reflex side-specific nodal dissection should be performed.72,80 SLN mapping may be most appropriate for those at low to intermediate risk for metastases and/or for those who may not tolerate a standard lymphadenectomy.76,7985 Recent findings also suggest that indocyanine green may be preferable to blue dyes.8589 Attention to detail and experience are critical to ensure optimal outcomes.

An updated literature review and consensus recommendations for SLN mapping in endometrial cancer were recently released by the Society of Gynecologic Oncology (SGO).76 Close adherence to the NCCN SLN surgical algorithm was found to result in accurate prediction of pelvic lymph node metastasis with a less than 5% false-negative rate. Additionally, results were recently published from the FIRES trial, which compared SLN mapping to lymphadenectomy for endometrial cancer in the largest multicenter prospective study to date (n=385).85 Mapping of at least 1 SLN was successful in 86% of patients; sensitivity was 97.2% (95% CI, 85.0–100), and negative predictive value was 99.6% (95% CI, 97.9–100).

Until recently, much of the data to support SLN mapping wasbased on single-institution studies. A systematic review of 17 studies with small cohorts (n>30 patients) revealed detection rates of 60% to 100%; detection rates for studies with larger cohorts (n>100) were at least 80%. Retrospective application of a surgical algorithm generated 95% sensitivity, 99% predictive value, and a 5% false-negative rate.90 Another recent systematic review and meta-analysis of 55 studies with small cohorts (n>10 patients; n=4915) generated an overall detection rate of 81% with a 50% bilateral pelvic node detection rate and 17% para-aortic detection rate.89

SLN mapping should be done in institutions with expertise in this procedure. If patients have apparent metastatic disease (based on imaging and surgical exploration), removal of nodes for staging purposes is not necessary because it will not change management.29 The main contraindication for SLN mapping is uterine sarcoma. Historically, SLN mapping was controversial in patients with high-risk histology (eg, serous carcinoma, clear cell carcinoma, carcinosarcoma).55,91 However, recently, SLN mapping in patients with high-risk histologies (ie, grade 3, serous, clear cell, carcinosarcoma) has been reported with promising results as a potential alternative to complete lymphadenectomy.80,92

SLN Ultrastaging: Recent data highlight the potential significance and impact of SLN ultrastaging (ie, serial sectioning and immunohistochemistry) to improve the accuracy of detecting micrometastases. Ultrastaging of SLNs can reveal lymph node metastases undetected through conventional histology, and studies suggest that SLN ultrastaging leads to upstaging in 5% to 15% of patients.75,78,82,84,90

In a retrospective analysis of patients with early-stage endometrial cancer (n=780) who underwent SLN mapping with lymphadenectomy versus lymphadenectomy alone, SLN mapping led to the detection of more metastasis (30.3% vs 14.7%; P<.001) and was associated with greater use of adjuvant therapy.93 Long-term follow-up was reported from a prospective multicenter study in 125 patients with early-stage endometrial carcinoma who underwent SLN biopsy. Patients with a positive SLN underwent external beam radiation therapy (EBRT) and chemotherapy at a higher rate than those with a negative SLN. In patients with a detected SLN, recurrence-free survival at 50 months was 84.7%, and no difference was detected between patients with and without a positive SLN (P=.5).94

In a cohort of 508 patients who underwent SLN mapping, ultrastaging detected 23 additional cases of micrometastasis that would have been missed by conventional hematoxylin and eosin staining.95 A multicenter study of 304 women with presumed low- or intermediate-risk disease showed that SLN biopsy and ultrastaging detected metastatic SLNs in a 3-fold greater number of patients than standard lymphadenectomy.96

Although these findings do not appear to be an artifact of uterine manipulation,97 the implications and appropriate management of micrometastases or isolated tumor cells (ITCs) detected via SLN ultra-staging are not yet clear.76,78,84,98100 The prognostic significance of ITCs has been studied in breast cancer,101 in which nodes containing ITCs are excluded from the positive node count per AJCC staging. Studies have recently begun to investigate the significance of ITCs discovered during SLN mapping in early-stage endometrial cancer.

A retrospective review examined 844 patients with endometrial cancer who underwent SLN mapping.102 Most patients with ITCs, micrometastasis, and macrometastasis received adjuvant chemotherapy (83%, 81%, and 89%, respectively). Recurrence-free survival at 3 years was 90% for those with negative SLNs, 86% for ITCs, and 86% for micrometastasis. Only patients with SLN macrometastasis had significantly lower recurrence-free survival (71%; P<.001).

A recent prospective observational study of 519 patients compared outcomes for patients with SLN macrometastasis, micrometastasis, and ITCs, taking into account adjuvant treatment.103 Patients with SLN ITCs had a significantly better 3-year progression-free survival (PFS) compared with patients with SLN macrometastasis (95.5% vs 58.5%), and outcomes were similar between patients with negative SLNs, ITCs, and micrometastasis. Recurrence was detected in only 1 of 31 patients with ITCs (stage IB carcinosarcoma) and adjuvant treatment did not appear to influence outcomes. Based on these early data, it is unclear if patients with SLN ITCs would derive significant benefit from adjuvant treatment. Future evaluation of prognosis/outcome may need to prospectively examine the threshold for and impact of adjuvant therapy for patients with scattered ITCs.

Minimally Invasive Procedures: Over the past decade, practice has trended towards minimally invasive approaches to total hysterectomy (TH)/BSO and lymph node assessment in patients with early-stage endometrial cancer.104 Although these procedures may be performed via any surgical route (eg, laparoscopic, robotic, vaginal, abdominal), the standard in those with apparent uterine-confined disease is to perform the procedure using a minimally invasive approach. Randomized trials, a Cochrane Database Systematic Review, and population-based surgical studies support that minimally invasive techniques are preferred in this setting due to a lower rate of surgical site infection, transfusion, venous thromboembolism, decreased hospital stay, and lower cost of care, without compromise in oncologic outcome.104110 Despite data showing that minimally invasive procedures result in lower perioperative complications and lower cost of care, racial and geographic disparities in access to minimally invasive surgical care have been observed.106,110

A randomized phase III trial evaluated laparoscopy for comprehensive surgical staging; patients (n=2616) with clinical stage I to IIA disease (GOG-LAP2) were assessed.109,111 Patients were randomly allocated 2:1 to laparoscopy or laparotomy. Results from LAP2 indicate that 26% of patients needed conversion to laparotomy because of poor visibility, metastatic cancer, bleeding, increased age, or increased body mass index. Detection of advanced cancer was not significantly different between the groups. However, significant differences were noted in removal of pelvic and para-aortic nodes (8% not removed with laparoscopy vs 4% with laparotomy; P<.0001).112,113 Significantly fewer postoperative adverse events and shorter hospitalization occurred with laparoscopy compared with laparotomy. Recurrence rates were 11.4% for laparoscopy versus 10.2% for laparotomy. The 5-year overall survival (OS) rate was 84.8% for both arms of LAP2.111 Laparoscopic staging was associated with improved postoperative quality of life across several parameters.108

Results were recently published from the LACE trial, which compared outcomes of patients with stage I endometrial carcinoma (n=760) who were randomized to undergo total abdominal or total laparoscopic hysterectomy.105 At a median follow-up of 4.5 years, disease-free survival (DFS) was 81.3% for laparotomy versus 81.6% for laparoscopy, with no significant differences observed between groups for recurrence and OS. Another randomized trial (n=283) comparing laparoscopy versus laparotomy reported shorter hospital stay, less pain, and faster resumption of daily activities with laparoscopy.114 However, laparotomy may still be required for certain clinical situations (eg, elderly patients, those with a very large uterus) or certain metastatic presentations.109,115,116

Robotic surgery is a minimally invasive technology that has been increasingly used in the surgical staging of early-stage endometrial carcinoma due to its potential advantages over laparotomy, especially for obese patients.117121 Prospective cohort and retrospective studies suggest that robotic approaches perform similarly to laparoscopy and result in comparable or improved perioperative outcomes.121124 Oncologic outcomes appear to be comparable to other surgical approaches, although longer-term outcomes are still being investigated.125127 In heavier patients, robotic surgery may result in less frequent conversion to laparotomy when compared with laparoscopic approaches and also appears to be safe and feasible in patients at higher anesthesiologic risk.121,122,128

Costs for robotic equipment and maintenance remain high.117,118,125127,129,130 The SGO, American Association of Gynecologic Laparoscopists (AAGL), and American Congress of Obstetricians and Gynecologists (ACOG) have published guidelines or position statements about robotic surgery.131133 For recent reviews on the robotic-assisted surgery for gynecologic malignancies and associated cost issues, see articles by Sinno and Fader134 and Gala et al. 135

Primary Treatment

These NCCN Guidelines divide pure endometrioid cancer into 3 categories for delineating treatment: 1) disease limited to the uterus; 2) suspected or gross cervical involvement; and 3) suspected extrauterine disease. Most patients with endometrial cancer have stage I disease at presentation, and surgery (with or without adjuvant therapy) is recommended for medically operable patients. As a general principle, endometrial carcinoma should be removed en bloc to optimize outcomes; intraperitoneal morcellation should be avoided.136139

Disease Limited to the Uterus: To stage medically operable patients with endometrioid histologies clinically confined to the fundal portion of the uterus, the recommended surgical procedure includes TH/BSO with surgical staging and lymph node assessment (see “Hysterectomy and Pathologic Evaluation” on page 177 [ENDO-B], and “Principles of Evaluation and Surgical Staging” on page 178 [ENDO-C] and in this discussion [page 185]).62 When indicated, surgical staging is recommended to gather full pathologic and prognostic data on which to base decisions regarding adjuvant treatment for select patients who do not have medical or technical contraindications to lymph node dissection (see “Lymphadenectomy,” page 186 and “SLN Mapping,” page 187). Ovarian preservation may be safe in select premenopausal women with stage I endometrioid cancer.140142 Minimally invasive surgery is the preferred approach when technically feasible and is considered a quality measure by the SGO and the American College of Surgeons (www.sgo.org/quality-outcomes-and-research/quality-indicators; www.facs.org/quality-programs/cancer/ncdb/qualitymeasures).

During surgery, the intraperitoneal structures should be carefully evaluated, and suspicious areas should be biopsied. Although not specifically affecting staging, FIGO recommends that peritoneal cytology should be collected and results should be recorded. Enlarged or suspicious lymph nodes should be excised to confirm or rule out metastatic disease. Retroperitoneal node dissection with pathologic evaluation—in the absence of clinically apparent lymphadenectomy—is useful when using the 2009 FIGO staging criteria, but its routine use has been questioned (see “Lymphadenectomy” on page 186).

Patients with apparent uterine-confined endometrial carcinoma are candidates for sentinel node mapping, which assesses the pelvic nodes bilaterally and may be less morbid than complete lymphadenectomy (see “SLN Mapping” on page 187). Adherence to the NCCN SLN algorithm is critical.

Incomplete Surgical Staging: For patients with incomplete (ie, not thorough) surgical staging and high-risk intrauterine features, imaging is often recommended, especially in patients with higher grade and more deeply invasive tumors.143,144 Surgical restaging, including lymph node dissection, can also be done.67 Based on the imaging and/or surgical restaging results, recommended adjuvant treatment options are provided in the algorithm (see Adjuvant Treatment for “Incompletely Surgically Staged” on ENDO-7, available in these Guidelines at NCCN.org).

Fertility-Sparing Therapy: Although the primary treatment of endometrial cancer is usually hysterectomy, continuous progestin-based therapy may be considered for highly selected patients with grade 1, stage IA (noninvasive) disease who wish to preserve their fertility.145149 Likewise, it may also be selectively used for young patients with endometrial hyperplasia who desire fertility preservation. The guidelines include an algorithm for fertility-sparing therapy in selected patients with biopsy-proven grade 1 (preferably by D&C), stage IA noninvasive endometrioid adenocarcinoma (see “Criteria for Considering Fertility-Sparing Options” on page 176 [ENDO-8]). The panel recommends consultation with a fertility expert. When considering fertility-sparing therapy, all of the criteria must be met as outlined in the algorithm (eg, no metastatic disease). Selected patients may require genetic counseling and testing. Patients should also receive counseling that fertility-sparing therapy is not the standard of care for the treatment of endometrial carcinoma. TH/BSO with surgical staging is recommended after childbearing is complete, if therapy is not effective, or if progression occurs. Fertility-sparing therapy is not recommended for high-risk patients (eg, those with high-grade endometrioid adenocarcinomas, uterine serous carcinoma, clear cell carcinoma, carcinosarcoma, and uterine leiomyosarcoma).

Continuous progestin-based therapy may include megestrol acetate, medroxyprogesterone, or an intrauterine device containing levonorgestrel.145,146,150 A durable complete response occurs in about 50% of patients.145 The use of progestin-based therapy should be carefully considered in the context of other patient-specific factors, including contraindications such as breast cancer, stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis, and smoking.

In patients receiving progestin-based therapies, the NCCN panel recommends close monitoring with endometrial sampling (biopsies or D&C) every 3 to 6 months. TH/BSO with staging is recommended: 1) after childbearing is complete; 2) if patients have documented progression on the biopsies; or 3) if endometrial cancer is still present after 6 to 12 months of progestin-based therapy.149,151 Although some young women who had subsequent negative endometrial biopsies after hormonal therapy were able to become pregnant (35%), their ultimate recurrence rate was high (35%).145,148,152154 In patients with persistent endometrial carcinoma after 6 months of failed hormonal therapy, the panel recommends pelvic MRI to exclude myoinvasion and nodal/ovarian metastasis before continuing on fertility-sparing therapy.

In premenopausal women with stage IA to B endometrial cancer, data suggest that ovarian preservation is safe and not associated with an increased risk of cancer-related mortality; patients were followed up for 16 years.140 Other studies also suggest that ovarian preservation may be safe in women with early-stage endometrial cancer.141,142

Suspected or Gross Cervical Involvement: For patients with suspected or gross cervical involvement (endometrioid histologies), cervical biopsy or pelvic MRI should be performed if not done previously (see “Additional Workup” on page 173 [ENDO-2]).143,144 If negative, patients are assumed to have disease that is limited to the uterus and are treated as previously described (see “Primary Treatment” on page 172 [ENDO-1]). It may be difficult to distinguish primary cervical carcinoma from stage II endometrial carcinoma. Thus, for operable patients with cervical involvement, TH or radical hysterectomy is recommended along with BSO, cytology (peritoneal lavage), and dissection of lymph nodes if indicated (see “Principles of Evaluation and Surgical Staging,” page 178 [ENDO-C] and “Hysterectomy and Pathologic Evaluation,” page 177 [ENDO-B]).62 In these patients, radical or modified radical hysterectomy may improve local control and survival when compared with TH.155,156 Alternatively, the patient may undergo EBRT and brachytherapy (category 2B) followed by TH/BSO and surgical staging. However, preoperative RT is a category 2B recommendation because the NCCN panel feels that upfront surgery is the preferred option for these patients.

Patients Not Suited for Primary Surgery: For uterine-confined disease not suitable for primary surgery, EBRT and/or brachytherapy is the preferred treatment approach. Initial systemic therapy can also be considered for select patients with uterine-confined tumors of endometrioid histology (eg, estrogen and progesterone receptor–positive [ER/PR-positive]). Patients receiving hormonal therapy alone should be closely monitored using endometrial biopsy (eg, consider endometrial biopsies every 3–6 months).40,157 Progesterone-based therapy has been shown to provide some benefit with low toxicity in patients with low-grade tumors.158 Tamoxifen with alternating megestrol159 and aromatase inhibitors has also been used.160163

For suspected gross cervical involvement in patients who are not suited for primary surgery, EBRT and brachytherapy is an effective treatment that can provide some measure of pelvic control and long-term PFS (see “Principles of Radiation Therapy for Uterine Neoplasms,” on page UN-A in these Guidelines at NCCN.org).164167 EBRT and brachytherapy should be administered with (or without) systemic therapy. If rendered operable, local treatment should follow. Systemic therapy alone is also a primary treatment option (category 2B), but should be followed by local treatment consisting of surgery if feasible (EBRT + brachytherapy if inoperable).

Adjuvant Therapy

Uterine-Confined Disease: Thorough surgical staging provides important information to assist in selection of adjuvant therapy for endometrial tumors (see “Principles of Evaluation and Surgical Staging,” page 178 [ENDO-C]). Patients with stage I endometrial cancer who have thorough surgical staging are stratified by adverse risk factors (ie, age, positive LVSI, tumor size, and lower uterine segment or surface glandular involvement).168,169 Recommended adjuvant treatment is shown in the algorithm (see page 183 [ENDO-D]). Note that the treatment algorithm was revised in 2010 based on the updated FIGO staging.48 However, by necessity, much of the discussion in this manuscript has been based on data from patients staged using the older FIGO/AJCC staging system. The implications of stage migration should be considered when evaluating historical data.

The basic concept underlying the recommendations in the NCCN Guidelines is the trend toward selecting more aggressive adjuvant therapy for patients as tumor grade and myometrial and/or cervical invasion worsen, because risk exists on a continuum.170172 In surgical stage I and II endometrial cancer, other pathologic factors that may influence the decision regarding adjuvant therapy include LVSI, patient age, tumor volume, depth of invasion, and lower uterine segment or surface cervical glandular involvement. When administering adjuvant RT, it should be started as soon as the vaginal cuff has healed, no later than 12 weeks after surgery.

Significant controversy centers on how much adjuvant therapy is necessary in patients with surgical stage I endometrial cancer, regardless of intrauterine features, if extrauterine disease has been clearly ruled out. In a large prospective study, the Gynecologic Oncology Group (GOG) reported that the 5-year survival rate for surgical stage I patients with no adverse risk factors other than grade and myometrial invasion (ie, without extrauterine disease, isthmus/cervical involvement, or LVSI) was 92.7%.173 The practice of surgical staging has led to a decrease in the use of adjuvant therapy for stage I endometrial carcinoma, which is reflected in the option of observation in the NCCN Guidelines (see page 174 [ENDO-4]).71,169,170,174176 The NCCN panel recommends observation only for select patients with no residual disease in the hysterectomy specimen.

The recommended postoperative (ie, adjuvant) treatment options for patients with surgical stage II disease (using thorough surgical staging) are shown in the algorithm (see “Adjuvant Treatment” for stage II disease, page 175 [ENDO-5]). The NCCN panel generally agrees on the role of adjuvant therapy for patients with an invasive cervical component if extrafascial hysterectomy is performed. However, for patients with stage II disease who have had a radical hysterectomy with negative surgical margins and no evidence of extrauterine disease, observation or vaginal brachytherapy are options. As with stage I disease, the presence of adverse risk factors should be considered when selecting adjuvant therapy.177

In 2017, the panel removed observation as a recommended option in the adjuvant setting for patients with stage IA, grade 3 disease with additional risk factors and stage IB grade 3 disease without adverse risk factors. For patients with stage IA/IB, grade 3 disease (IA with adverse risk factors and IB without), systemic therapy was added as a category 2B option when performed along with the primary recommendation of vaginal brachytherapy and/or EBRT. For stage IB, grade 3 disease with adverse risk factors, the option of systemic therapy (in addition to EBRT and/or vaginal brachytherapy) was upgraded to a category 2A option.

Adjuvant RT: Several phase III trials have assessed adjuvant therapy in patients with uterine-confined disease. In summary, the use of adjuvant RT improves pelvic control in patients with selected risk factors (and may improve PFS), but RT did not improve OS in any of the trials. However, many of these trials had limitations because most of the patients were low risk (ie, they had low-risk intrauterine pathologic risk factors). Thus, the trials were underpowered for patients with high-risk factors. It is recognized that in patients with uterine-confined disease, there is a spectrum of risk based on intrauterine pathologic findings. Adverse intrauterine pathologic risk factors include high-grade tumors, deep myometrial invasion (and consequently more advanced stage), LVSI, and serous or clear cell carcinoma histologies.

Four trials have evaluated the role of adjuvant external-beam pelvic RT in patients with endometrial carcinoma. In 2 of these trials, the patients were not formally staged (Postoperative Radiation Therapy in Endometrial Carcinoma [PORTEC-1], Aalders).178,179 In the third trial (ASTEC/EN.5), only 50% of the patients were thoroughly staged as part of a companion surgical protocol.60,180 However, formal surgical staging was mandated for all patients in the fourth trial (GOG 99).181 Note that these trials used the older staging system (ie, before 2009).

The PORTEC-1 trial suggested that external-beam pelvic RT provides a therapeutic benefit in selected patients with uterine-confined disease.178,182 Although RT significantly decreased locoregional recurrence, it did not increase OS.183 The Aalders' randomized trial found that RT reduced vaginal (ie, locoregional) recurrences but did not reduce distant metastases or improve survival.179 A recent pooled randomized trial (ASTEC/EN.5) suggested that adjuvant pelvic RT alone did not improve either relapse-free survival (ie, PFS) or OS in patients with intermediate-risk or high-risk early-stage endometrial cancer, but there was a small improvement in pelvic control.180 However, the ASTEC/EN.5 study is very controversial; 51% of the patients in the ASTEC observation group received vaginal brachytherapy.64,184 The Keys' trial (GOG 99) showed that adjuvant pelvic RT improved locoregional control and relapse-free interval (ie, PFS), without OS benefit.181 Both the GOG 99 and PORTEC-1 trials revealed that most of the initial recurrences for patients with initial uterine-confined tumors were limited to the vagina, prompting the increasing use of vaginal brachytherapy alone as adjunctive treatment.181,185,186

To help select a patient population who may benefit from adjuvant RT, the GOG 99 and PORTEC trials defined risk factors for women at high-intermediate risk (HIR) for recurrence.178,181 These risk factors include age, in addition to deep myometrial invasion, grade, and LVSI. In GOG 99, women younger than 50 years had to have all 3 histologic risk factors to be considered HIR.181 If they were 50 to 70 years, they were considered HIR if they had 2 histologic risk factors. Women 70 years or older were defined as HIR if they also had one risk factor. In PORTEC-1, women had to have 2 of 3 risk factors (ie, age >60 years, deep myometrial invasion, grade 3 histology) to be considered at HIR for recurrence.178,185

Due to concerns about potential toxicity of external-beam pelvic RT, the role of vaginal brachytherapy alone in uterine-confined disease has been evaluated. PORTEC-2 randomly assigned patients to external-beam pelvic RT versus vaginal brachytherapy alone in uterine-confined disease. PORTEC-2 showed excellent and equivalent vaginal and pelvic control rates with both adjuvant radiation approaches and no difference in OS.187 Given that vaginal brachytherapy is associated with significantly less toxicity than pelvic RT, vaginal brachytherapy alone is a reasonable choice for most patients with uterine-confined endometrial cancer who are deemed candidates for adjuvant radiotherapy.185194 The use of vaginal brachytherapy and/or whole pelvic RT should be carefully tailored to a patient's pathologic findings. Both PORTEC-1 and PORTEC-2 specifically excluded patients with 1998 FIGO stage 1C and grade 3 endometrial carcinoma (2009 FIGO stage IB, grade 3);48 thus, the use of adjuvant brachytherapy alone in the highest risk subset remains undetermined.

A recent trial (GOG 249) examined vaginal cuff brachytherapy and carboplatin/paclitaxel therapy (brachy+chemo) versus pelvic EBRT only in patients with high-risk, uterine-confined endometrial carcinoma (n=601). Unlike PORTEC-2, GOG 249 reported significantly increased rates of nodal recurrence (primarily pelvic) in the brachy+chemo arm versus the pelvic EBRT arm. No significant between-group differences in vaginal or distant recurrence rates were observed. However there were more extravaginal pelvic failures in the brachy+chemo arm. At a median follow-up of 53 months, 3-year recurrence-free survival was 82% for both treatment arms; 3-year OS was 88% for the brachy+chemo cohort and 91% for the pelvic EBRT cohort. Acute toxicity was more common and severe for patients receiving brachytherapy with chemotherapy. No differences in late-onset toxicities were observed.195

Analysis of pooled data from PORTEC-1 and PORTEC-2 ranked the predictive power of multiple variables on patient outcomes examined in these trials. Patient age, tumor grade, and LVSI were highly predictive for locoregional relapse (LRR), distant relapse (DR), OS, and DFS, and treatment given (EBRT versus vaginal brachytherapy) was predictive for LRR and DFS.168 The benefit of adjuvant EBRT in the highest risk spectrum of uterine-confined disease remains controversial. Most NCCN Panel Members feel that patients with deeply invasive grade 3 tumors should receive adjuvant treatment. Two large retrospective SEER analyses of women with endometrial cancer found that adjuvant RT improved OS in those with high-risk disease.196,197 In a meta-analysis of randomized trials, a subset analysis found that adjuvant pelvic RT for stage I disease was associated with a trend towards a survival advantage in the highest-risk spectrum (eg, those with 1988 FIGO stage IC grade 3) but not in lower-risk patients; however, other reviews have shown conflicting results.189,198202

Recently, results were published from a long-term follow-up study (median, 20.5 years) of 568 patients with early-stage endometrial carcinoma who were enrolled in the Aalders trial. The study compared long-term outcomes in women who received vaginal brachytherapy plus EBRT versus vaginal brachytherapy alone. The findings suggested no statistical difference in OS between the study groups, and in this cohort, patients younger than 60 years of age who received EBRT had increased incidence of secondary cancers and subsequent higher mortality rates.189

Adjuvant Systemic Therapy: Carboplatin/paclitaxel is the preferred regimen in the adjuvant setting for high-risk uterine confined disease.205207 Patients with deeply invasive, grade 3, uterine-confined disease (2009 FIGO stage IB, grade 3 [formerly 1988 FIGO stage IC, grade 3]) have a relatively poor prognosis. Despite adjuvant therapy with pelvic RT, a significant number of patients continue to have an appreciable risk of distant metastases.181,182 Therefore, some clinicians suggested that adding systemic therapy to adjuvant RT may provide added therapeutic benefit (ie, decrease in distant metastases).170,203 Studies have evaluated the role of systemic therapy in highest-risk uterine-confined disease.203,204 PFS is improved with adjuvant sequential chemotherapy/RT.203 However, the NCCN panel feels that adjuvant systemic therapy is a category 2B recommendation in this setting because an OS advantage has not been shown.203 We await final results from GOG 249.

Individual Disclosures for Uterine Neoplasms Panel

T1

References

  • 1.

    SiegelRLMillerKDJemalA. Cancer Statistics, 2017. CA Cancer J Clin2017;67:730.

  • 2.

    D'AngeloEPratJ. Uterine sarcomas: a review. Gynecol Oncol2010;116:131139.

  • 3.

    SiegelRLMillerKDJemalA. Cancer statistics, 2016. CA Cancer J Clin2016;66:730.

  • 4.

    Van den BoschTCoosemansAMorinaM. Screening for uterine tumours. Best Pract Res Clin Obstet Gynaecol2012;26:257266.

  • 5.

    KitchenerHCTrimbleEL. Endometrial cancer state of the science meeting. Int J Gynecol Cancer2009;19:134140.

  • 6.

    DinkelspielHEWrightJDLewinSNHerzogTJ. Contemporary clinical management of endometrial cancer. Obstet Gynecol Int2013;2013:583891.

  • 7.

    ObermairAYouldenDRYoungJP. Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma. Int J Cancer2010;127:26782684.

    • Search Google Scholar
    • Export Citation
  • 8.

    UedaSMKappDSCheungMK. Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths. Am J Obstet Gynecol2008;198:218 e211e216.

    • Search Google Scholar
    • Export Citation
  • 9.

    ChanJKShermanAEKappDS. Influence of gynecologic oncologists on the survival of patients with endometrial cancer. J Clin Oncol2011;29:832838.

    • Search Google Scholar
    • Export Citation
  • 10.

    Benedetti PaniciPBasileSSalernoMG. Secondary analyses from a randomized clinical trial: age as the key prognostic factor in endometrial carcinoma. Am J Obstet Gynecol2014;210:363.e1363.e10.

    • Search Google Scholar
    • Export Citation
  • 11.

    DollKMTsengJDenslowSA. High-grade endometrial cancer: revisiting the impact of tumor size and location on outcomes. Gynecol Oncol2014;132:4449.

    • Search Google Scholar
    • Export Citation
  • 12.

    ResnickKEHampelHFishelRCohnDE. Current and emerging trends in Lynch syndrome identification in women with endometrial cancer. Gynecol Oncol2009;114:128134.

    • Search Google Scholar
    • Export Citation
  • 13.

    KwonJSScottJLGilksCB. Testing women with endometrial cancer to detect Lynch syndrome. J Clin Oncol2011;29:22472252.

  • 14.

    BuchananDDTanYYWalshMD. Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing. J Clin Oncol2014;32:90100.

    • Search Google Scholar
    • Export Citation
  • 15.

    FergusonSEAronsonMPollettA. Performance characteristics of screening strategies for Lynch syndrome in unselected women with newly diagnosed endometrial cancer who have undergone universal germline mutation testing. Cancer2014;120:39323939.

    • Search Google Scholar
    • Export Citation
  • 16.

    GoodfellowPJBillingsleyCCLankesHA. Combined Microsatellite Instability, MLH1 Methylation Analysis, and Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers From GOG210: An NRG Oncology and Gynecologic Oncology Group Study. J Clin Oncol2015;33:43014308.

    • Search Google Scholar
    • Export Citation
  • 17.

    WatkinsJCYangEJMutoMG. Universal screening for mismatch-repair deficiency in endometrial cancers to identify patients with Lynch syndrome and Lynch-like syndrome. Int J Gynecol Pathol2017;36:115127.

    • Search Google Scholar
    • Export Citation
  • 18.

    MillsAMLiouSFordJM. Lynch syndrome screening should be considered for all patients with newly diagnosed endometrial cancer. Am J Surg Pathol2014;38:15011509.

    • Search Google Scholar
    • Export Citation
  • 19.

    SmithRACokkinidesVBrawleyOW. Cancer screening in the United States, 2012: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin2012;62:129142.

    • Search Google Scholar
    • Export Citation
  • 20.

    CrispensMA. Endometrial and ovarian cancer in lynch syndrome. Clin Colon Rectal Surg2012;25:97102.

  • 21.

    ManchandaRSaridoganEAbdelraheimA. Annual outpatient hysteroscopy and endometrial sampling (OHES) in HNPCC/Lynch syndrome (LS). Arch Gynecol Obstet2012;286:15551562.

    • Search Google Scholar
    • Export Citation
  • 22.

    MeyerLABroaddusRRLuKH. Endometrial cancer and Lynch syndrome: clinical and pathologic considerations. Cancer Control2009;16:1422.

  • 23.

    JarvinenHJRenkonen-SinisaloLAktan-CollanK. Ten years after mutation testing for Lynch syndrome: cancer incidence and outcome in mutation-positive and mutation-negative family members. J Clin Oncol2009;27:47934797.

    • Search Google Scholar
    • Export Citation
  • 24.

    SchmelerKMLynchHTChenLM. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med2006;354:261269.

    • Search Google Scholar
    • Export Citation
  • 25.

    McCluggageWG. My approach to the interpretation of endometrial biopsies and curettings. J Clin Pathol2006;59:801812.

  • 26.

    McKenneyJKLongacreTA. Low-grade endometrial adenocarcinoma: a diagnostic algorithm for distinguishing atypical endometrial hyperplasia and other benign (and malignant) mimics. Adv Anat Pathol2009;16:122.

    • Search Google Scholar
    • Export Citation
  • 27.

    LeitaoMMJr.KehoeSBarakatRR. Comparison of D&C and office endometrial biopsy accuracy in patients with FIGO grade 1 endometrial adenocarcinoma. Gynecol Oncol2009;113:105108.

    • Search Google Scholar
    • Export Citation
  • 28.

    GimpelsonRJRappoldHO. A comparative study between panoramic hysteroscopy with directed biopsies and dilatation and curettage. a review of 276 cases. Am J Obstet Gynecol1988;158:489492.

    • Search Google Scholar
    • Export Citation
  • 29.

    LeeJHDubinskyTAndreottiRF. ACR appropriateness criteria(R) pretreatment evaluation and follow-up of endometrial cancer of the uterus. Ultrasound Q2011;27:139145.

    • Search Google Scholar
    • Export Citation
  • 30.

    OrtashiOJainSEmannuelO. Evaluation of the sensitivity, specificity, positive and negative predictive values of preoperative magnetic resonance imaging for staging endometrial cancer. A prospective study of 100 cases at the Dorset Cancer Centre. Eur J Obstet Gynecol Reprod Biol2008;137:232235.

    • Search Google Scholar
    • Export Citation
  • 31.

    CrivellaroCSignorelliMGuerraL. Tailoring systematic lymphadenectomy in high-risk clinical early stage endometrial cancer: the role of 18F-FDG PET/CT. Gynecol Oncol2013;130:306311.

    • Search Google Scholar
    • Export Citation
  • 32.

    KitajimaKSuzukiKSendaM. Preoperative nodal staging of uterine cancer: is contrast-enhanced PET/CT more accurate than non-enhanced PET/CT or enhanced CT alone?Ann Nucl Med2011;25:511519.

    • Search Google Scholar
    • Export Citation
  • 33.

    AntonsenSLJensenLNLoftA. MRI, PET/CT and ultrasound in the preoperative staging of endometrial cancer - a multicenter prospective comparative study. Gynecol Oncol2013;128:300308.

    • Search Google Scholar
    • Export Citation
  • 34.

    BollineniVRYtre-HaugeSBollineni-BalabayO. High diagnostic value of 18F-FDG PET/CT in endometrial cancer: systematic review and meta-analysis of the literature. J Nucl Med2016;57:879885.

    • Search Google Scholar
    • Export Citation
  • 35.

    DukJMAaldersJGFleurenGJde BruijnHW. CA 125: a useful marker in endometrial carcinoma. Am J Obstet Gynecol1986;155:10971102.

  • 36.

    DukJMAaldersJGFleurenGJ. Tumor markers CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen in patients with adenocarcinoma of the uterine cervix. Obstet Gynecol1989;73:661668.

    • Search Google Scholar
    • Export Citation
  • 37.

    PatsnerBOrrJWJr.MannWJJr.Use of serum CA 125 measurement in posttreatment surveillance of early-stage endometrial carcinoma. Am J Obstet Gynecol1990;162:427429.

    • Search Google Scholar
    • Export Citation
  • 38.

    RosePGSommersRMRealeFR. Serial serum CA 125 measurements for evaluation of recurrence in patients with endometrial carcinoma. Obstet Gynecol1994;84:1216.

    • Search Google Scholar
    • Export Citation
  • 39.

    PriceFVChambersSKCarcangiuML. CA 125 may not reflect disease status in patients with uterine serous carcinoma. Cancer1998;82:17201725.

    • Search Google Scholar
    • Export Citation
  • 40.

    LeslieKKThielKWGoodheartMJ. Endometrial cancer. Obstet Gynecol Clin North Am2012;39:255268.

  • 41.

    SmithRABrooksDCokkinidesV. Cancer screening in the United States, 2013: a review of current American Cancer Society guidelines, current issues in cancer screening, and new guidance on cervical cancer screening and lung cancer screening. CA Cancer J Clin2013;63:88105.

    • Search Google Scholar
    • Export Citation
  • 42.

    BoronowRCMorrowCPCreasmanWT. Surgical staging in endometrial cancer: clinical-pathologic findings of a prospective study. Obstet Gynecol1984;63:825832.

    • Search Google Scholar
    • Export Citation
  • 43.

    CowlesTAMagrinaJFMastersonBJCapenCV. Comparison of clinical and surgical-staging in patients with endometrial carcinoma. Obstet Gynecol1985;66:413416.

    • Search Google Scholar
    • Export Citation
  • 44.

    CreasmanWTMorrowCPBundyBN. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer1987;60:20352041.

    • Search Google Scholar
    • Export Citation
  • 45.

    BenedetJLBenderHJonesH. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet2000;70:209262.

    • Search Google Scholar
    • Export Citation
  • 46.

    WrightJDBarrena MedelNISehouliJ. Contemporary management of endometrial cancer. Lancet2012;379:13521360.

  • 47.

    PecorelliS. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet2009;105:103104.

  • 48.

    CreasmanW. Revised FIGO staging for carcinoma of the endometrium. Int J Gynaecol Obstet2009;105:109.

  • 49.

    MarianiADowdySCPodratzKC. New surgical staging of endometrial cancer: 20 years later. Int J Gynaecol Obstet2009;105:110111.

  • 50.

    AminMBEdgeSBGreeneFL. AJCC Cancer Staging Manual8th edition. New York: Springer; 2017.

  • 51.

    WethingtonSLBarrena MedelNIWrightJDHerzogTJ. Prognostic significance and treatment implications of positive peritoneal cytology in endometrial adenocarcinoma: Unraveling a mystery. Gynecol Oncol2009;115:1825.

    • Search Google Scholar
    • Export Citation
  • 52.

    TakeshimaNNishidaHTabataT. Positive peritoneal cytology in endometrial cancer: enhancement of other prognostic indicators. Gynecol Oncol2001;82:470473.

    • Search Google Scholar
    • Export Citation
  • 53.

    GoffBARiceLW. Assessment of depth of myometrial invasion in endometrial adenocarcinoma. Gynecol Oncol1990;38:4648.

  • 54.

    DanielAGPetersWA3rd. Accuracy of office and operating room curettage in the grading of endometrial carcinoma. Obstet Gynecol1988;71:612614.

    • Search Google Scholar
    • Export Citation
  • 55.

    SolimanPTFrumovitzMSpannuthW. Lymphadenectomy during endometrial cancer staging: practice patterns among gynecologic oncologists. Gynecol Oncol2010;119:291294.

    • Search Google Scholar
    • Export Citation
  • 56.

    KumarSMarianiABakkum-GamezJN. Risk factors that mitigate the role of paraaortic lymphadenectomy in uterine endometrioid cancer. Gynecol Oncol2013;130:441445.

    • Search Google Scholar
    • Export Citation
  • 57.

    KilgoreLCPartridgeEEAlvarezRD. Adenocarcinoma of the endometrium: survival comparisons of patients with and without pelvic node sampling. Gynecol Oncol1995;56:2933.

    • Search Google Scholar
    • Export Citation
  • 58.

    HavrileskyLJCragunJMCalingaertB. Resection of lymph node metastases influences survival in stage IIIC endometrial cancer. Gynecol Oncol2005;99:689695.

    • Search Google Scholar
    • Export Citation
  • 59.

    TodoYKatoHKaneuchiM. Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis. Lancet2010;375:11651172.

    • Search Google Scholar
    • Export Citation
  • 60.

    KitchenerHSwartAMQianQ. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet2009;373:125136.

    • Search Google Scholar
    • Export Citation
  • 61.

    Benedetti PaniciPBasileSManeschiF. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. J Natl Cancer Inst2008;100:17071716.

    • Search Google Scholar
    • Export Citation
  • 62.

    ACOG practice bulletin, clinical management guidelines for obstetrician-gynecologists, number 65, August 2005: management of endometrial cancer. Obstet Gynecol2005;106:413425.

    • Search Google Scholar
    • Export Citation
  • 63.

    SeamonLGFowlerJMCohnDE. Lymphadenectomy for endometrial cancer: the controversy. Gynecol Oncol2010;117:68.

  • 64.

    CreasmanWTMutchDEHerzogTJ. ASTEC lymphadenectomy and radiation therapy studies: are conclusions valid?Gynecol Oncol2010;116:293294.

  • 65.

    UccellaSPodratzKCAlettiGDMarianiA. Lymphadenectomy in endometrial cancer. Lancet2009;373:1170; author reply 1170–1171.

  • 66.

    UccellaSPodratzKCAlettiGDMarianiA. Re: Systematic pelvic lymphadenectomy vs no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. J Natl Cancer Inst2009;101:897898; author reply 898–899.

    • Search Google Scholar
    • Export Citation
  • 67.

    MilamMRJavaJWalkerJL. Nodal metastasis risk in endometrioid endometrial cancer. Obstet Gynecol2012;119:286292.

  • 68.

    NeubauerNLLurainJR. The role of lymphadenectomy in surgical staging of endometrial cancer. Int J Surg Oncol2011;2011:814649.

  • 69.

    MarianiADowdySCClibyWA. Prospective assessment of lymphatic dissemination in endometrial cancer: a paradigm shift in surgical staging. Gynecol Oncol2008;109:1118.

    • Search Google Scholar
    • Export Citation
  • 70.

    HirahatakeKHareyamaHSakuragiN. A clinical and pathologic study on para-aortic lymph node metastasis in endometrial carcinoma. J Surg Oncol1997;65:8287.

    • Search Google Scholar
    • Export Citation
  • 71.

    FrederickPJStraughnJMJr.The role of comprehensive surgical staging in patients with endometrial cancer. Cancer Control2009;16:2329.

  • 72.

    BarlinJNKhoury-ColladoFKimCH. The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes. Gynecol Oncol2012;125:531535.

    • Search Google Scholar
    • Export Citation
  • 73.

    BallesterMKoskasMCoutantC. Does the use of the 2009 FIGO classification of endometrial cancer impact on indications of the sentinel node biopsy?BMC Cancer2010;10:465.

    • Search Google Scholar
    • Export Citation
  • 74.

    HowJLauSPressJ. Accuracy of sentinel lymph node detection following intra-operative cervical injection for endometrial cancer: a prospective study. Gynecol Oncol2012;127:332337.

    • Search Google Scholar
    • Export Citation
  • 75.

    Khoury-ColladoFMurrayMPHensleyML. Sentinel lymph node mapping for endometrial cancer improves the detection of metastatic disease to regional lymph nodes. Gynecol Oncol2011;122:251254.

    • Search Google Scholar
    • Export Citation
  • 76.

    HollowayRWAbu-RustumNRBackesFJ. Sentinel lymph node mapping and staging in endometrial cancer: A Society of Gynecologic Oncology literature review with consensus recommendations. Gynecol Oncol2017;146:405415.

    • Search Google Scholar
    • Export Citation
  • 77.

    VidalFLeguevaquePMottonS. Evaluation of the sentinel lymph node algorithm with blue dye labeling for early-stage endometrial cancer in a multicentric setting. Int J Gynecol Cancer2013;23:12371243.

    • Search Google Scholar
    • Export Citation
  • 78.

    KimCHKhoury-ColladoFBarberEL. Sentinel lymph node mapping with pathologic ultrastaging: A valuable tool for assessing nodal metastasis in low-grade endometrial cancer with superficial myoinvasion. Gynecol Oncol2013.

    • Search Google Scholar
    • Export Citation
  • 79.

    Group SGOCPECWBurkeWMOrrJ. Endometrial cancer: a review and current management strategies: part I. Gynecol Oncol2014;134:385392.

  • 80.

    SolimanPTWestinSNDiounS. A prospective validation study of sentinel lymph node mapping for high-risk endometrial cancer. Gynecol Oncol2017;146:234239.

    • Search Google Scholar
    • Export Citation
  • 81.

    Abu-RustumNRKhoury-ColladoFPandit-TaskarN. Sentinel lymph node mapping for grade 1 endometrial cancer: is it the answer to the surgical staging dilemma?Gynecol Oncol2009;113:163169.

    • Search Google Scholar
    • Export Citation
  • 82.

    BallesterMDubernardGLecuruF. Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO). Lancet Oncol2011;12:469476.

    • Search Google Scholar
    • Export Citation
  • 83.

    PressJZGotliebWH. Controversies in the treatment of early stage endometrial carcinoma. Obstet Gynecol Int2012;2012:578490.

  • 84.

    TouhamiOTrinhXBGregoireJ. Predictors of non-sentinel lymph node (non-SLN) metastasis in patients with sentinel lymph node (SLN) metastasis in endometrial cancer. Gynecol Oncol2015;138:4145.

    • Search Google Scholar
    • Export Citation
  • 85.

    RossiECKowalskiLDScaliciJ. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol2017;18:384392.

    • Search Google Scholar
    • Export Citation
  • 86.

    PaleyPJVeljovichDSPressJZ. A prospective investigation of fluorescence imaging to detect sentinel lymph nodes at robotic-assisted endometrial cancer staging. Am J Obstet Gynecol2016;215:117 e111117.

    • Search Google Scholar
    • Export Citation
  • 87.

    SinnoAKFaderANRocheKL. A comparison of colorimetric versus fluorometric sentinel lymph node mapping during robotic surgery for endometrial cancer. Gynecol Oncol2014;134:281286.

    • Search Google Scholar
    • Export Citation
  • 88.

    RuscitoIGasparriMLBraicuEI. Sentinel node mapping in cervical and endometrial cancer: indocyanine green versus other conventional dyes—a meta-analysis. Ann Surg Oncol2016;23:37493756.

    • Search Google Scholar
    • Export Citation
  • 89.

    Bodurtha SmithAJFaderANTannerEJ. Sentinel lymph node assessment in endometrial cancer: a systematic review and meta-analysis. Am J Obstet Gynecol2016.

    • Search Google Scholar
    • Export Citation
  • 90.

    CormierBRozenholcATGotliebW. Sentinel lymph node procedure in endometrial cancer: a systematic review and proposal for standardization of future research. Gynecol Oncol2015;138:478485.

    • Search Google Scholar
    • Export Citation
  • 91.

    NaouraICanlorbeGBendifallahS. Relevance of sentinel lymph node procedure for patients with high-risk endometrial cancer. Gynecol Oncol2015;136:6064.

    • Search Google Scholar
    • Export Citation
  • 92.

    SchiavoneMBZivanovicOZhouQ. Survival of patients with uterine carcinosarcoma undergoing sentinel lymph node mapping. Ann Surg Oncol2016;23:196202.

    • Search Google Scholar
    • Export Citation
  • 93.

    HollowayRWGuptaSStavitzskiNM. Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis. Gynecol Oncol2016;141:206210.

    • Search Google Scholar
    • Export Citation
  • 94.

    DaraiEDubernardGBatsAS. Sentinel node biopsy for the management of early stage endometrial cancer: long-term results of the SENTI-ENDO study. Gynecol Oncol2015;136:5459.

    • Search Google Scholar
    • Export Citation
  • 95.

    KimCHSoslowRAParkKJ. Pathologic ultrastaging improves micrometastasis detection in sentinel lymph nodes during endometrial cancer staging. Int J Gynecol Cancer2013;23:964970.

    • Search Google Scholar
    • Export Citation
  • 96.

    RaimondEBallesterMHudryD. Impact of sentinel lymph node biopsy on the therapeutic management of early-stage endometrial cancer: results of a retrospective multicenter study. Gynecol Oncol2014;133:506511.

    • Search Google Scholar
    • Export Citation
  • 97.

    FrimerMKhoury-ColladoFMurrayMP. Micrometastasis of endometrial cancer to sentinel lymph nodes: is it an artifact of uterine manipulation?Gynecol Oncol2010;119:496499.

    • Search Google Scholar
    • Export Citation
  • 98.

    TouboulCBentivegnaEUzanC. Sentinel lymph node in endometrial cancer: a review. Curr Oncol Rep2013;15:559565.

  • 99.

    AmezcuaCAMacDonaldHRLumCA. Endometrial cancer patients have a significant risk of harboring isolated tumor cells in histologically negative lymph nodes. Int J Gynecol Cancer2006;16:13361341.

    • Search Google Scholar
    • Export Citation
  • 100.

    TodoYKatoHOkamotoK. Isolated tumor cells and micrometastases in regional lymph nodes in FIGO stage I to II endometrial cancer. J Gynecol Oncol2016;27:e1.

    • Search Google Scholar
    • Export Citation
  • 101.

    SmerageJBBarlowWEHortobagyiGN. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol2014;32:34833489.

    • Search Google Scholar
    • Export Citation
  • 102.

    St ClairCMErikssonAGDucieJA. Low-volume lymph node metastasis discovered during sentinel lymph node mapping for endometrial carcinoma. Ann Surg Oncol2016;23:16531659.

    • Search Google Scholar
    • Export Citation
  • 103.

    PlanteMStanleighJRenaudMC. Isolated tumor cells identified by sentinel lymph node mapping in endometrial cancer: does adjuvant treatment matter?Gynecol Oncol2017;146:240246.

    • Search Google Scholar
    • Export Citation
  • 104.

    ScaliciJLaughlinBBFinanMA. The trend towards minimally invasive surgery (MIS) for endometrial cancer: an ACS-NSQIP evaluation of surgical outcomes. Gynecol Oncol2015;136:512515.

    • Search Google Scholar
    • Export Citation
  • 105.

    JandaMGebskiVDaviesLC. Effect of total laparoscopic hysterectomy vs total abdominal hysterectomy on disease-free survival among women with stage I endometrial cancer: a randomized clinical trial. JAMA2017;317:12241233.

    • Search Google Scholar
    • Export Citation
  • 106.

    FaderANWeiseRMSinnoAK. Utilization of Minimally Invasive Surgery in Endometrial Cancer Care: A Quality and Cost Disparity. Obstet Gynecol2016;127:91100.

    • Search Google Scholar
    • Export Citation
  • 107.

    GalaalKBryantAFisherAD. Laparoscopy versus laparotomy for the management of early stage endometrial cancer. Cochrane Database Syst Rev2012:CD006655.

    • Search Google Scholar
    • Export Citation
  • 108.

    KornblithABHuangHQWalkerJL. Quality of life of patients with endometrial cancer undergoing laparoscopic international federation of gynecology and obstetrics staging compared with laparotomy: a Gynecologic Oncology Group study. J Clin Oncol2009;27:53375342.

    • Search Google Scholar
    • Export Citation
  • 109.

    WalkerJLPiedmonteMRSpirtosNM. Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2. J Clin Oncol2009;27:53315336.

    • Search Google Scholar
    • Export Citation
  • 110.

    MannschreckDMatsunoRKMoriartyJP. Disparities in surgical care among women with endometrial cancer. Obstet Gynecol2016;128:526534.

  • 111.

    WalkerJLPiedmonteMRSpirtosNM. Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol2012;30:695700.

    • Search Google Scholar
    • Export Citation
  • 112.

    KingLPMillerDS. Recent progress: gynecologic oncology group trials in uterine corpus tumors. Rev Recent Clin Trials2009;4:7074.

  • 113.

    VergoteIAmantFNevenP. Is it safe to treat endometrial carcinoma endoscopically?J Clin Oncol2009;27:53055307.

  • 114.

    MouritsMJBijenCBArtsHJ. Safety of laparoscopy versus laparotomy in early-stage endometrial cancer: a randomised trial. Lancet Oncol2010;11:763771.

    • Search Google Scholar
    • Export Citation
  • 115.

    HeHZengDOuH. Laparoscopic treatment of endometrial cancer: systematic review. J Minim Invasive Gynecol2013;20:413423.

  • 116.

    WangHLRenYFYangJ. Total laparoscopic hysterectomy versus total abdominal hysterectomy for endometrial cancer: a meta-analysis. Asian Pac J Cancer Prev2013;14:25152519.

    • Search Google Scholar
    • Export Citation
  • 117.

    MoriKMNeubauerNL. Minimally invasive surgery in gynecologic oncology. ISRN Obstet Gynecol2013;2013:312982.

  • 118.

    KrillLSBristowRE. Robotic surgery: gynecologic oncology. Cancer J2013;19:167176.

  • 119.

    ElSahwiKSHooperCDe LeonMC. Comparison between 155 cases of robotic vs. 150 cases of open surgical staging for endometrial cancer. Gynecol Oncol2012;124:260264.

    • Search Google Scholar
    • Export Citation
  • 120.

    ChanJKGardnerABTaylorK. Robotic versus laparoscopic versus open surgery in morbidly obese endometrial cancer patients—a comparative analysis of total charges and complication rates. Gynecol Oncol2015;139:300305.

    • Search Google Scholar
    • Export Citation
  • 121.

    CoronadoPJHerraizMAMagrinaJF. Comparison of perioperative outcomes and cost of robotic-assisted laparoscopy, laparoscopy and laparotomy for endometrial cancer. Eur J Obstet Gynecol Reprod Biol2012;165:289294.

    • Search Google Scholar
    • Export Citation
  • 122.

    SeamonLGCohnDEHenrettaMS. Minimally invasive comprehensive surgical staging for endometrial cancer: Robotics or laparoscopy?Gynecol Oncol2009;113:3641.

    • Search Google Scholar
    • Export Citation
  • 123.

    BellMCTorgersonJSeshadri-KreadenU. Comparison of outcomes and cost for endometrial cancer staging via traditional laparotomy, standard laparoscopy and robotic techniques. Gynecol Oncol2008;111:407411.

    • Search Google Scholar
    • Export Citation
  • 124.

    Cardenas-GoicoecheaJAdamsSBhatSBRandallTC. Surgical outcomes of robotic-assisted surgical staging for endometrial cancer are equivalent to traditional laparoscopic staging at a minimally invasive surgical center. Gynecol Oncol2010;117:224228.

    • Search Google Scholar
    • Export Citation
  • 125.

    BrudieLABackesFJAhmadS. Analysis of disease recurrence and survival for women with uterine malignancies undergoing robotic surgery. Gynecol Oncol2013;128:309315.

    • Search Google Scholar
    • Export Citation
  • 126.

    BackesFJBrudieLAFarrellMR. Short- and long-term morbidity and outcomes after robotic surgery for comprehensive endometrial cancer staging. Gynecol Oncol2012;125:546551.

    • Search Google Scholar
    • Export Citation
  • 127.

    FlemingNDRamirezPT. Robotic surgery in gynecologic oncology. Curr Opin Oncol2012;24:547553.

  • 128.

    SiestoGOrnaghiSIedaNVitobelloD. Robotic surgical staging for endometrial and cervical cancers in medically ill patients. Gynecol Oncol2013;129:593597.

    • Search Google Scholar
    • Export Citation
  • 129.

    van DamPHauspyJVerkinderenL. Are costs of robot-assisted surgery warranted for gynecological procedures?Obstet Gynecol Int2011;2011:973830.

    • Search Google Scholar
    • Export Citation
  • 130.

    WeinbergLRaoSEscobarPF. Robotic surgery in gynecology: an updated systematic review. Obstet Gynecol Int2011;2011:852061.

  • 131.

    RamirezPTAdamsSBoggessJF. Robotic-assisted surgery in gynecologic oncology: a Society of Gynecologic Oncology consensus statement. Developed by the Society of Gynecologic Oncology's Clinical Practice Robotics Task Force. Gynecol Oncol2012;124:180184.

    • Search Google Scholar
    • Export Citation
  • 132.

    AAGL. Guidelines for privileging for robotic-assisted gynecologic laparoscopy. J Minim Invasive Gynecol2014;21:157167.

  • 133.

    American Congress of Obstetricians and Gynecologists. Statement on Robotic Surgery by ACOG President James T. Breeden. 2013. Available at: http://www.acog.org/About-ACOG/News-Room/News-Releases/2013/Statement-on-Robotic-Surgery. Accessed March 182013.

    • Search Google Scholar
    • Export Citation
  • 134.

    SinnoAKFaderAN. Robotic-assisted surgery in gynecologic oncology. Fertil Steril2014;102:922932.

  • 135.

    GalaRBMarguliesRSteinbergA. Systematic review of robotic surgery in gynecology: robotic techniques compared with laparoscopy and laparotomy. J Minim Invasive Gynecol2014;21:353361.

    • Search Google Scholar
    • Export Citation
  • 136.

    SGO Position Statement: Morcellation. Society of Gynecologic Oncology; 2013. Available at: https://www.sgo.org/newsroom/position-statements-2/morcellation/. Accessed September 30 2014.

    • Search Google Scholar
    • Export Citation
  • 137.

    Power Morcellation and Occult Malignancy in Gynecologic Surgery. The American College of Obstetrics and Gynecologists; 2014. Available at: http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Power-Morcellation-and-Occult-Malignancy-in-Gynecologic-Surgery. Accessed September 30 2014.

    • Search Google Scholar
    • Export Citation
  • 138.

    U.S. Department of Health and Human Services. FDA discourages use of laparoscopic power morcellation for removal of uterus or uterine fibroidsFood and Drug Administration; 2014. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm393689.htm. Accessed September 30 2014.

    • Search Google Scholar
    • Export Citation
  • 139.

    BoganiGClibyWAAlettiGD. Impact of morcellation on survival outcomes of patients with unexpected uterine leiomyosarcoma: a systematic review and meta-analysis. Gynecol Oncol2015;137:167172.

    • Search Google Scholar
    • Export Citation
  • 140.

    WrightJDBuckAMShahM. Safety of ovarian preservation in premenopausal women with endometrial cancer. J Clin Oncol2009;27:12141219.

  • 141.

    KoskasMBendifallahSLutonD. Safety of uterine and/or ovarian preservation in young women with grade 1 intramucous endometrial adenocarcinoma: a comparison of survival according to the extent of surgery. Fertil Steril2012;98:12291235.

    • Search Google Scholar
    • Export Citation
  • 142.

    LeeTSLeeJYKimJW. Outcomes of ovarian preservation in a cohort of premenopausal women with early-stage endometrial cancer: A Korean Gynecologic Oncology Group study. Gynecol Oncol2013;131:289293.

    • Search Google Scholar
    • Export Citation
  • 143.

    ManfrediRMirkPMarescaG. Local-regional staging of endometrial carcinoma: role of MR imaging in surgical planning. Radiology2004;231:372378.

    • Search Google Scholar
    • Export Citation
  • 144.

    AkinOMironovSPandit-TaskarNHannLE. Imaging of uterine cancer. Radiol Clin North Am2007;45:167182.

  • 145.

    GundersonCCFaderANCarsonKABristowRE. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review. Gynecol Oncol2012;125:477482.

    • Search Google Scholar
    • Export Citation
  • 146.

    BakerJObermairAGebskiVJandaM. Efficacy of oral or intrauterine device-delivered progestin in patients with complex endometrial hyperplasia with atypia or early endometrial adenocarcinoma: a meta-analysis and systematic review of the literature. Gynecol Oncol2012;125:263270.

    • Search Google Scholar
    • Export Citation
  • 147.

    GraciaCRJerussJS. Lives in the balance: women with cancer and the right to fertility care. J Clin Oncol2013;31:668669.

  • 148.

    UshijimaKYahataHYoshikawaH. Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women. J Clin Oncol2007;25:27982803.

    • Search Google Scholar
    • Export Citation
  • 149.

    HubbsJLSaigRMAbaidLN. Systemic and local hormone therapy for endometrial hyperplasia and early adenocarcinoma. Obstet Gynecol2013;121:11721180.

    • Search Google Scholar
    • Export Citation
  • 150.

    TrimbleCLMethodMLeitaoM. Management of endometrial precancers. Obstet Gynecol2012;120:11601175.

  • 151.

    MehassebMKLatimerJA. Controversies in the management of endometrial carcinoma: an update. Obstet Gynecol Int2012;2012:676032.

  • 152.

    HahnHSYoonSGHongJS. Conservative treatment with progestin and pregnancy outcomes in endometrial cancer. Int J Gynecol Cancer2009;19:10681073.

    • Search Google Scholar
    • Export Citation
  • 153.

    ParkJYKimDYKimJH. Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer2013;49:868874.

    • Search Google Scholar
    • Export Citation
  • 154.

    ParkJYSeongSJKimTJ. Pregnancy outcomes after fertility-sparing management in young women with early endometrial cancer. Obstet Gynecol2013;121:136142.

    • Search Google Scholar
    • Export Citation
  • 155.

    BoenteMPYordanELJr.McIntoshDG. Prognostic factors and long-term survival in endometrial adenocarcinoma with cervical involvement. Gynecol Oncol1993;51:316322.

    • Search Google Scholar
    • Export Citation
  • 156.

    SartoriEGadducciALandoniF. Clinical behavior of 203 stage II endometrial cancer cases: the impact of primary surgical approach and of adjuvant radiation therapy. Int J Gynecol Cancer2001;11:430437.

    • Search Google Scholar
    • Export Citation
  • 157.

    GadducciACosioSGenazzaniAR. Old and new perspectives in the pharmacological treatment of advanced or recurrent endometrial cancer: hormonal therapy, chemotherapy and molecularly targeted therapies. Crit Rev Oncol Hematol2006;58:242256.

    • Search Google Scholar
    • Export Citation
  • 158.

    MountziosGPectasidesDBournakisE. Developments in the systemic treatment of endometrial cancer. Crit Rev Oncol Hematol2011;79:278292.

    • Search Google Scholar
    • Export Citation
  • 159.

    FioricaJVBrunettoVLHanjaniP. Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol2004;92:1014.

    • Search Google Scholar
    • Export Citation
  • 160.

    AltmanADThompsonJNelsonG. Use of aromatase inhibitors as first- and second-line medical therapy in patients with endometrial adenocarcinoma: a retrospective study. J Obstet Gynaecol Can2012;34:664672.

    • Search Google Scholar
    • Export Citation
  • 161.

    BarkerLCBrandIRCrawfordSM. Sustained effect of the aromatase inhibitors anastrozole and letrozole on endometrial thickness in patients with endometrial hyperplasia and endometrial carcinoma. Curr Med Res Opin2009;25:11051109.

    • Search Google Scholar
    • Export Citation
  • 162.

    RosePGBrunettoVLVanLeL. A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol2000;78:212216.

    • Search Google Scholar
    • Export Citation
  • 163.

    DecruzeSBGreenJA. Hormone therapy in advanced and recurrent endometrial cancer: a systematic review. Int J Gynecol Cancer2007;17:964978.

    • Search Google Scholar
    • Export Citation
  • 164.

    FishmanDARobertsKBChambersJT. Radiation therapy as exclusive treatment for medically inoperable patients with stage I and II endometrioid carcinoma with endometrium. Gynecol Oncol1996;61:189196.

    • Search Google Scholar
    • Export Citation
  • 165.

    CoonDBeriwalSHeronDE. High-dose-rate Rotte “Y” applicator brachytherapy for definitive treatment of medically inoperable endometrial cancer: 10-year results. Int J Radiat Oncol Biol Phys2008;71:779783.

    • Search Google Scholar
    • Export Citation
  • 166.

    NiaziTMSouhamiLPortelanceL. Long-term results of high-dose-rate brachytherapy in the primary treatment of medically inoperable stage I-II endometrial carcinoma. Int J Radiat Oncol Biol Phys2005;63:11081113.

    • Search Google Scholar
    • Export Citation
  • 167.

    van der Steen-BanasikEChristiaensMShashE. Systemic review: radiation therapy alone in medical non-operable endometrial carcinoma. Eur J Cancer2016;65:172181.

    • Search Google Scholar
    • Export Citation
  • 168.

    CreutzbergCLvan StiphoutRGNoutRA. Nomograms for prediction of outcome with or without adjuvant radiation therapy for patients with endometrial cancer: a pooled analysis of PORTEC-1 and PORTEC-2 trials. Int J Radiat Oncol Biol Phys2015;91:530539.

    • Search Google Scholar
    • Export Citation
  • 169.

    Group SGOCPECWBurkeWMOrrJ. Endometrial cancer: a review and current management strategies: part II. Gynecol Oncol2014;134:393402.

  • 170.

    CreutzbergCLNoutRA. The role of radiotherapy in endometrial cancer: current evidence and trends. Curr Oncol Rep2011;13:472478.

  • 171.

    KloppASmithBDAlektiarK. The role of postoperative radiation therapy for endometrial cancer: executive summary of an American Society for Radiation Oncology evidence-based guideline. Pract Radiat Oncol2014;4:137144.

    • Search Google Scholar
    • Export Citation
  • 172.

    MeyerLABohlkeKPowellMA. Postoperative radiation therapy for endometrial cancer: American Society of Clinical Oncology clinical practice guideline endorsement of the American Society for Radiation Oncology evidence-based guideline. J Clin Oncol2015;33:29082913.

    • Search Google Scholar
    • Export Citation
  • 173.

    MorrowCPBundyBNKurmanRJ. Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol1991;40:5565.

    • Search Google Scholar
    • Export Citation
  • 174.

    NeubauerNLHavrileskyLJCalingaertB. The role of lymphadenectomy in the management of preoperative grade 1 endometrial carcinoma. Gynecol Oncol2009;112:511516.

    • Search Google Scholar
    • Export Citation
  • 175.

    GretzHFrEconomosKHusainA. The practice of surgical staging and its impact on adjuvant treatment recommendations in patients with stage I endometrial carcinoma. Gynecol Oncol1996;61:409415.

    • Search Google Scholar
    • Export Citation
  • 176.

    Ben-ShacharIPavelkaJCohnDE. Surgical staging for patients presenting with grade 1 endometrial carcinoma. Obstet Gynecol2005;105:487493.

    • Search Google Scholar
    • Export Citation
  • 177.

    ElshaikhMAAl-WahabZMahdiH. Recurrence patterns and survival endpoints in women with stage II uterine endometrioid carcinoma: a multi-institution study. Gynecol Oncol2015;136:235239.

    • Search Google Scholar
    • Export Citation
  • 178.

    CreutzbergCLvan PuttenWLKoperPC. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet2000;355:14041411.

    • Search Google Scholar
    • Export Citation
  • 179.

    AaldersJAbelerVKolstadPOnsrudM. Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients. Obstet Gynecol1980;56:419427.

    • Search Google Scholar
    • Export Citation
  • 180.

    BlakePSwartAMOrtonJ. Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis. Lancet2009;373:137146.

    • Search Google Scholar
    • Export Citation
  • 181.

    KeysHMRobertsJABrunettoVL. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol2004;92:744751.

    • Search Google Scholar
    • Export Citation
  • 182.

    CreutzbergCLvan PuttenWLJWárlám-RodenhuisCC. Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial. J Clin Oncol2004;22:12341241.

    • Search Google Scholar
    • Export Citation
  • 183.

    ScholtenANvan PuttenWLJBeermanH. Postoperative radiotherapy for stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review. Int J Radiat Oncol Biol Phys2005;63:834838.

    • Search Google Scholar
    • Export Citation
  • 184.

    HockelMDornhoferN. Treatment of early endometrial carcinoma: is less more?Lancet2009;373:9799.

  • 185.

    CreutzbergCLNoutRALybeertML. Fifteen-year radiotherapy outcomes of the randomized PORTEC-1 trial for endometrial carcinoma. Int J Radiat Oncol Biol Phys2011;81:e631638.

    • Search Google Scholar
    • Export Citation
  • 186.

    AlektiarKMVenkatramanEChiDSBarakatRR. Intravaginal brachytherapy alone for intermediate-risk endometrial cancer. Int J Radiat Oncol Biol Phys2005;62:111117.

    • Search Google Scholar
    • Export Citation
  • 187.

    NoutRASmitVTPutterH. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet2010;375:816823.

    • Search Google Scholar
    • Export Citation
  • 188.

    SmallWJr.BeriwalSDemanesDJ. American Brachytherapy Society consensus guidelines for adjuvant vaginal cuff brachytherapy after hysterectomy. Brachytherapy2012;11:5867.

    • Search Google Scholar
    • Export Citation
  • 189.

    OnsrudMCvancarovaMHellebustTP. Long-term outcomes after pelvic radiation for early-stage endometrial cancer. J Clin Oncol2013;31:39513956.

    • Search Google Scholar
    • Export Citation
  • 190.

    NoutRAPutterHJurgenliemk-SchulzIM. Five-year quality of life of endometrial cancer patients treated in the randomised Post Operative Radiation Therapy in Endometrial Cancer (PORTEC-2) trial and comparison with norm data. Eur J Cancer2012;48:16381648.

    • Search Google Scholar
    • Export Citation
  • 191.

    RoperBAstnerSTHeydemann-ObradovicA. Ten-year data on 138 patients with endometrial carcinoma and postoperative vaginal brachytherapy alone: no need for external-beam radiotherapy in low and intermediate risk patients. Gynecol Oncol2007;107:541548.

    • Search Google Scholar
    • Export Citation
  • 192.

    NoutRAPutterHJurgenliemk-SchulzIM. Quality of life after pelvic radiotherapy or vaginal brachytherapy for endometrial cancer: first results of the randomized PORTEC-2 trial. J Clin Oncol2009;27:35473556.

    • Search Google Scholar
    • Export Citation
  • 193.

    McCloskeySATchaboNEMalhotraHK. Adjuvant vaginal brachytherapy alone for high risk localized endometrial cancer as defined by the three major randomized trials of adjuvant pelvic radiation. Gynecol Oncol2010;116:404407.

    • Search Google Scholar
    • Export Citation
  • 194.

    DunnEFGeyeHPlattaCS. Predictive factors of recurrence following adjuvant vaginal cuff brachytherapy alone for stage I endometrial cancer. Gynecol Oncol2014;133:494498.

    • Search Google Scholar
    • Export Citation
  • 195.

    RandallMEFiliaciVMcMeekinDS. A phase 3 trial of pelvic radiation therapy versus vaginal cuff brachytherapy followed by paclitaxel/carboplatin chemotherapy in patients with high-risk, early-stage endometrial cancer: a Gynecology Oncology Group study [abstract]. Int J Radiat Oncol Biol Phys2017.

    • Search Google Scholar
    • Export Citation
  • 196.

    ChinoJPJonesEBerchuckA. The influence of radiation modality and lymph node dissection on survival in early-stage endometrial cancer. Int J Radiat Oncol Biol Phys2012;82:18721879.

    • Search Google Scholar
    • Export Citation
  • 197.

    LeeCMSzaboAShrieveDC. Frequency and effect of adjuvant radiation therapy among women with stage I endometrial adenocarcinoma. JAMA2006;295:389397.

    • Search Google Scholar
    • Export Citation
  • 198.

    JohnsonNCornesP. Survival and recurrent disease after postoperative radiotherapy for early endometrial cancer: systematic review and meta-analysis. BJOG2007;114:13131320.

    • Search Google Scholar
    • Export Citation
  • 199.

    KongAJohnsonNCornesP. Adjuvant radiotherapy for stage I endometrial cancer. Cochrane Database Syst Rev2007.

  • 200.

    KongAJohnsonNKitchenerHCLawrieTA. Adjuvant radiotherapy for stage I endometrial cancer: an updated Cochrane systematic review and meta-analysis. J Natl Cancer Inst2012;104:16251634.

    • Search Google Scholar
    • Export Citation
  • 201.

    EifelPJ. The role of adjuvant radiation therapy for stage I endometrial cancer: does meta-analysis reveal the answer?J Natl Cancer Inst2012;104:16151616.

    • Search Google Scholar
    • Export Citation
  • 202.

    ParkHJNamEJKimS. The benefit of adjuvant chemotherapy combined with postoperative radiotherapy for endometrial cancer: a meta-analysis. Eur J Obstet Gynecol Reprod Biol2013;170:3944.

    • Search Google Scholar
    • Export Citation
  • 203.

    HogbergTSignorelliMde OliveiraCF. Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer—results from two randomised studies. Eur J Cancer2010;46:24222431.

    • Search Google Scholar
    • Export Citation
  • 204.

    JohnsonNBryantAMilesT. Adjuvant chemotherapy for endometrial cancer after hysterectomy. Cochrane Database Syst Rev2011:CD003175.

  • 205.

    MusteaAKoensgenDBelauA. Adjuvant sequential chemoradiation therapy in high-risk endometrial cancer: results of a prospective, multicenter phase-II study of the NOGGO (North-Eastern German Society of Gynaecological Oncology). Cancer Chemother Pharmacol2013;72:975983.

    • Search Google Scholar
    • Export Citation
  • 206.

    JutziLHoskinsPLimP. The importance of adjuvant chemotherapy and pelvic radiotherapy in high-risk early stage endometrial carcinoma. Gynecol Oncol2013;131:581585.

    • Search Google Scholar
    • Export Citation
  • 207.

    de BoerSMPowellMEMileshkinL. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol2016;17:11141126.

    • Search Google Scholar
    • Export Citation

If the inline PDF is not rendering correctly, you can download the PDF file here.

Article Sections

Figures

  • View in gallery

    NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 1.2018

    Version 1.2018, 10-13-17 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

  • View in gallery

    NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 1.2018

    Version 1.2018, 10-13-17 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

  • View in gallery

    NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 1.2018

    Version 1.2018, 10-13-17 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

  • View in gallery

    NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 1.2018

    Version 1.2018, 10-13-17 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

  • View in gallery

    NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 1.2018

    Version 1.2018, 10-13-17 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

  • View in gallery

    NCCN Clinical Practice Guidelines in Oncology: Uterine Neoplasms, Version 1.2018

    Version 1.2018, 10-13-17 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

References

  • 1.

    SiegelRLMillerKDJemalA. Cancer Statistics, 2017. CA Cancer J Clin2017;67:730.

  • 2.

    D'AngeloEPratJ. Uterine sarcomas: a review. Gynecol Oncol2010;116:131139.

  • 3.

    SiegelRLMillerKDJemalA. Cancer statistics, 2016. CA Cancer J Clin2016;66:730.

  • 4.

    Van den BoschTCoosemansAMorinaM. Screening for uterine tumours. Best Pract Res Clin Obstet Gynaecol2012;26:257266.

  • 5.

    KitchenerHCTrimbleEL. Endometrial cancer state of the science meeting. Int J Gynecol Cancer2009;19:134140.

  • 6.

    DinkelspielHEWrightJDLewinSNHerzogTJ. Contemporary clinical management of endometrial cancer. Obstet Gynecol Int2013;2013:583891.

  • 7.

    ObermairAYouldenDRYoungJP. Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma. Int J Cancer2010;127:26782684.

    • Search Google Scholar
    • Export Citation
  • 8.

    UedaSMKappDSCheungMK. Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths. Am J Obstet Gynecol2008;198:218 e211e216.

    • Search Google Scholar
    • Export Citation
  • 9.

    ChanJKShermanAEKappDS. Influence of gynecologic oncologists on the survival of patients with endometrial cancer. J Clin Oncol2011;29:832838.

    • Search Google Scholar
    • Export Citation
  • 10.

    Benedetti PaniciPBasileSSalernoMG. Secondary analyses from a randomized clinical trial: age as the key prognostic factor in endometrial carcinoma. Am J Obstet Gynecol2014;210:363.e1363.e10.

    • Search Google Scholar
    • Export Citation
  • 11.

    DollKMTsengJDenslowSA. High-grade endometrial cancer: revisiting the impact of tumor size and location on outcomes. Gynecol Oncol2014;132:4449.

    • Search Google Scholar
    • Export Citation
  • 12.

    ResnickKEHampelHFishelRCohnDE. Current and emerging trends in Lynch syndrome identification in women with endometrial cancer. Gynecol Oncol2009;114:128134.

    • Search Google Scholar
    • Export Citation
  • 13.

    KwonJSScottJLGilksCB. Testing women with endometrial cancer to detect Lynch syndrome. J Clin Oncol2011;29:22472252.

  • 14.

    BuchananDDTanYYWalshMD. Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing. J Clin Oncol2014;32:90100.

    • Search Google Scholar
    • Export Citation
  • 15.

    FergusonSEAronsonMPollettA. Performance characteristics of screening strategies for Lynch syndrome in unselected women with newly diagnosed endometrial cancer who have undergone universal germline mutation testing. Cancer2014;120:39323939.

    • Search Google Scholar
    • Export Citation
  • 16.

    GoodfellowPJBillingsleyCCLankesHA. Combined Microsatellite Instability, MLH1 Methylation Analysis, and Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers From GOG210: An NRG Oncology and Gynecologic Oncology Group Study. J Clin Oncol2015;33:43014308.

    • Search Google Scholar
    • Export Citation
  • 17.

    WatkinsJCYangEJMutoMG. Universal screening for mismatch-repair deficiency in endometrial cancers to identify patients with Lynch syndrome and Lynch-like syndrome. Int J Gynecol Pathol2017;36:115127.

    • Search Google Scholar
    • Export Citation
  • 18.

    MillsAMLiouSFordJM. Lynch syndrome screening should be considered for all patients with newly diagnosed endometrial cancer. Am J Surg Pathol2014;38:15011509.

    • Search Google Scholar
    • Export Citation
  • 19.

    SmithRACokkinidesVBrawleyOW. Cancer screening in the United States, 2012: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin2012;62:129142.

    • Search Google Scholar
    • Export Citation
  • 20.

    CrispensMA. Endometrial and ovarian cancer in lynch syndrome. Clin Colon Rectal Surg2012;25:97102.

  • 21.

    ManchandaRSaridoganEAbdelraheimA. Annual outpatient hysteroscopy and endometrial sampling (OHES) in HNPCC/Lynch syndrome (LS). Arch Gynecol Obstet2012;286:15551562.

    • Search Google Scholar
    • Export Citation
  • 22.

    MeyerLABroaddusRRLuKH. Endometrial cancer and Lynch syndrome: clinical and pathologic considerations. Cancer Control2009;16:1422.

  • 23.

    JarvinenHJRenkonen-SinisaloLAktan-CollanK. Ten years after mutation testing for Lynch syndrome: cancer incidence and outcome in mutation-positive and mutation-negative family members. J Clin Oncol2009;27:47934797.

    • Search Google Scholar
    • Export Citation
  • 24.

    SchmelerKMLynchHTChenLM. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med2006;354:261269.

    • Search Google Scholar
    • Export Citation
  • 25.

    McCluggageWG. My approach to the interpretation of endometrial biopsies and curettings. J Clin Pathol2006;59:801812.

  • 26.

    McKenneyJKLongacreTA. Low-grade endometrial adenocarcinoma: a diagnostic algorithm for distinguishing atypical endometrial hyperplasia and other benign (and malignant) mimics. Adv Anat Pathol2009;16:122.

    • Search Google Scholar
    • Export Citation
  • 27.

    LeitaoMMJr.KehoeSBarakatRR. Comparison of D&C and office endometrial biopsy accuracy in patients with FIGO grade 1 endometrial adenocarcinoma. Gynecol Oncol2009;113:105108.

    • Search Google Scholar
    • Export Citation
  • 28.

    GimpelsonRJRappoldHO. A comparative study between panoramic hysteroscopy with directed biopsies and dilatation and curettage. a review of 276 cases. Am J Obstet Gynecol1988;158:489492.

    • Search Google Scholar
    • Export Citation
  • 29.

    LeeJHDubinskyTAndreottiRF. ACR appropriateness criteria(R) pretreatment evaluation and follow-up of endometrial cancer of the uterus. Ultrasound Q2011;27:139145.

    • Search Google Scholar
    • Export Citation
  • 30.

    OrtashiOJainSEmannuelO. Evaluation of the sensitivity, specificity, positive and negative predictive values of preoperative magnetic resonance imaging for staging endometrial cancer. A prospective study of 100 cases at the Dorset Cancer Centre. Eur J Obstet Gynecol Reprod Biol2008;137:232235.

    • Search Google Scholar
    • Export Citation
  • 31.

    CrivellaroCSignorelliMGuerraL. Tailoring systematic lymphadenectomy in high-risk clinical early stage endometrial cancer: the role of 18F-FDG PET/CT. Gynecol Oncol2013;130:306311.

    • Search Google Scholar
    • Export Citation
  • 32.

    KitajimaKSuzukiKSendaM. Preoperative nodal staging of uterine cancer: is contrast-enhanced PET/CT more accurate than non-enhanced PET/CT or enhanced CT alone?Ann Nucl Med2011;25:511519.

    • Search Google Scholar
    • Export Citation
  • 33.

    AntonsenSLJensenLNLoftA. MRI, PET/CT and ultrasound in the preoperative staging of endometrial cancer - a multicenter prospective comparative study. Gynecol Oncol2013;128:300308.

    • Search Google Scholar
    • Export Citation
  • 34.

    BollineniVRYtre-HaugeSBollineni-BalabayO. High diagnostic value of 18F-FDG PET/CT in endometrial cancer: systematic review and meta-analysis of the literature. J Nucl Med2016;57:879885.

    • Search Google Scholar
    • Export Citation
  • 35.

    DukJMAaldersJGFleurenGJde BruijnHW. CA 125: a useful marker in endometrial carcinoma. Am J Obstet Gynecol1986;155:10971102.

  • 36.

    DukJMAaldersJGFleurenGJ. Tumor markers CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen in patients with adenocarcinoma of the uterine cervix. Obstet Gynecol1989;73:661668.

    • Search Google Scholar
    • Export Citation
  • 37.

    PatsnerBOrrJWJr.MannWJJr.Use of serum CA 125 measurement in posttreatment surveillance of early-stage endometrial carcinoma. Am J Obstet Gynecol1990;162:427429.

    • Search Google Scholar
    • Export Citation
  • 38.

    RosePGSommersRMRealeFR. Serial serum CA 125 measurements for evaluation of recurrence in patients with endometrial carcinoma. Obstet Gynecol1994;84:1216.

    • Search Google Scholar
    • Export Citation
  • 39.

    PriceFVChambersSKCarcangiuML. CA 125 may not reflect disease status in patients with uterine serous carcinoma. Cancer1998;82:17201725.

    • Search Google Scholar
    • Export Citation
  • 40.

    LeslieKKThielKWGoodheartMJ. Endometrial cancer. Obstet Gynecol Clin North Am2012;39:255268.

  • 41.

    SmithRABrooksDCokkinidesV. Cancer screening in the United States, 2013: a review of current American Cancer Society guidelines, current issues in cancer screening, and new guidance on cervical cancer screening and lung cancer screening. CA Cancer J Clin2013;63:88105.

    • Search Google Scholar
    • Export Citation
  • 42.

    BoronowRCMorrowCPCreasmanWT. Surgical staging in endometrial cancer: clinical-pathologic findings of a prospective study. Obstet Gynecol1984;63:825832.

    • Search Google Scholar
    • Export Citation
  • 43.

    CowlesTAMagrinaJFMastersonBJCapenCV. Comparison of clinical and surgical-staging in patients with endometrial carcinoma. Obstet Gynecol1985;66:413416.

    • Search Google Scholar
    • Export Citation
  • 44.

    CreasmanWTMorrowCPBundyBN. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer1987;60:20352041.

    • Search Google Scholar
    • Export Citation
  • 45.

    BenedetJLBenderHJonesH. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet2000;70:209262.

    • Search Google Scholar
    • Export Citation
  • 46.

    WrightJDBarrena MedelNISehouliJ. Contemporary management of endometrial cancer. Lancet2012;379:13521360.

  • 47.

    PecorelliS. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet2009;105:103104.

  • 48.

    CreasmanW. Revised FIGO staging for carcinoma of the endometrium. Int J Gynaecol Obstet2009;105:109.

  • 49.

    MarianiADowdySCPodratzKC. New surgical staging of endometrial cancer: 20 years later. Int J Gynaecol Obstet2009;105:110111.

  • 50.

    AminMBEdgeSBGreeneFL. AJCC Cancer Staging Manual8th edition. New York: Springer; 2017.

  • 51.

    WethingtonSLBarrena MedelNIWrightJDHerzogTJ. Prognostic significance and treatment implications of positive peritoneal cytology in endometrial adenocarcinoma: Unraveling a mystery. Gynecol Oncol2009;115:1825.

    • Search Google Scholar
    • Export Citation
  • 52.

    TakeshimaNNishidaHTabataT. Positive peritoneal cytology in endometrial cancer: enhancement of other prognostic indicators. Gynecol Oncol2001;82:470473.

    • Search Google Scholar
    • Export Citation
  • 53.

    GoffBARiceLW. Assessment of depth of myometrial invasion in endometrial adenocarcinoma. Gynecol Oncol1990;38:4648.

  • 54.

    DanielAGPetersWA3rd. Accuracy of office and operating room curettage in the grading of endometrial carcinoma. Obstet Gynecol1988;71:612614.

    • Search Google Scholar
    • Export Citation
  • 55.

    SolimanPTFrumovitzMSpannuthW. Lymphadenectomy during endometrial cancer staging: practice patterns among gynecologic oncologists. Gynecol Oncol2010;119:291294.

    • Search Google Scholar
    • Export Citation
  • 56.

    KumarSMarianiABakkum-GamezJN. Risk factors that mitigate the role of paraaortic lymphadenectomy in uterine endometrioid cancer. Gynecol Oncol2013;130:441445.

    • Search Google Scholar
    • Export Citation
  • 57.

    KilgoreLCPartridgeEEAlvarezRD. Adenocarcinoma of the endometrium: survival comparisons of patients with and without pelvic node sampling. Gynecol Oncol1995;56:2933.

    • Search Google Scholar
    • Export Citation
  • 58.

    HavrileskyLJCragunJMCalingaertB. Resection of lymph node metastases influences survival in stage IIIC endometrial cancer. Gynecol Oncol2005;99:689695.

    • Search Google Scholar
    • Export Citation
  • 59.

    TodoYKatoHKaneuchiM. Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis. Lancet2010;375:11651172.

    • Search Google Scholar
    • Export Citation
  • 60.

    KitchenerHSwartAMQianQ. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet2009;373:125136.

    • Search Google Scholar
    • Export Citation
  • 61.

    Benedetti PaniciPBasileSManeschiF. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. J Natl Cancer Inst2008;100:17071716.

    • Search Google Scholar
    • Export Citation
  • 62.

    ACOG practice bulletin, clinical management guidelines for obstetrician-gynecologists, number 65, August 2005: management of endometrial cancer. Obstet Gynecol2005;106:413425.

    • Search Google Scholar
    • Export Citation
  • 63.

    SeamonLGFowlerJMCohnDE. Lymphadenectomy for endometrial cancer: the controversy. Gynecol Oncol2010;117:68.

  • 64.

    CreasmanWTMutchDEHerzogTJ. ASTEC lymphadenectomy and radiation therapy studies: are conclusions valid?Gynecol Oncol2010;116:293294.

  • 65.

    UccellaSPodratzKCAlettiGDMarianiA. Lymphadenectomy in endometrial cancer. Lancet2009;373:1170; author reply 1170–1171.

  • 66.

    UccellaSPodratzKCAlettiGDMarianiA. Re: Systematic pelvic lymphadenectomy vs no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. J Natl Cancer Inst2009;101:897898; author reply 898–899.

    • Search Google Scholar
    • Export Citation
  • 67.

    MilamMRJavaJWalkerJL. Nodal metastasis risk in endometrioid endometrial cancer. Obstet Gynecol2012;119:286292.

  • 68.

    NeubauerNLLurainJR. The role of lymphadenectomy in surgical staging of endometrial cancer. Int J Surg Oncol2011;2011:814649.

  • 69.

    MarianiADowdySCClibyWA. Prospective assessment of lymphatic dissemination in endometrial cancer: a paradigm shift in surgical staging. Gynecol Oncol2008;109:1118.

    • Search Google Scholar
    • Export Citation
  • 70.

    HirahatakeKHareyamaHSakuragiN. A clinical and pathologic study on para-aortic lymph node metastasis in endometrial carcinoma. J Surg Oncol1997;65:8287.

    • Search Google Scholar
    • Export Citation
  • 71.

    FrederickPJStraughnJMJr.The role of comprehensive surgical staging in patients with endometrial cancer. Cancer Control2009;16:2329.

  • 72.

    BarlinJNKhoury-ColladoFKimCH. The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes. Gynecol Oncol2012;125:531535.

    • Search Google Scholar
    • Export Citation
  • 73.

    BallesterMKoskasMCoutantC. Does the use of the 2009 FIGO classification of endometrial cancer impact on indications of the sentinel node biopsy?BMC Cancer2010;10:465.

    • Search Google Scholar
    • Export Citation
  • 74.

    HowJLauSPressJ. Accuracy of sentinel lymph node detection following intra-operative cervical injection for endometrial cancer: a prospective study. Gynecol Oncol2012;127:332337.

    • Search Google Scholar
    • Export Citation
  • 75.

    Khoury-ColladoFMurrayMPHensleyML. Sentinel lymph node mapping for endometrial cancer improves the detection of metastatic disease to regional lymph nodes. Gynecol Oncol2011;122:251254.

    • Search Google Scholar
    • Export Citation
  • 76.

    HollowayRWAbu-RustumNRBackesFJ. Sentinel lymph node mapping and staging in endometrial cancer: A Society of Gynecologic Oncology literature review with consensus recommendations. Gynecol Oncol2017;146:405415.

    • Search Google Scholar
    • Export Citation
  • 77.

    VidalFLeguevaquePMottonS. Evaluation of the sentinel lymph node algorithm with blue dye labeling for early-stage endometrial cancer in a multicentric setting. Int J Gynecol Cancer2013;23:12371243.

    • Search Google Scholar
    • Export Citation
  • 78.

    KimCHKhoury-ColladoFBarberEL. Sentinel lymph node mapping with pathologic ultrastaging: A valuable tool for assessing nodal metastasis in low-grade endometrial cancer with superficial myoinvasion. Gynecol Oncol2013.

    • Search Google Scholar
    • Export Citation
  • 79.

    Group SGOCPECWBurkeWMOrrJ. Endometrial cancer: a review and current management strategies: part I. Gynecol Oncol2014;134:385392.

  • 80.

    SolimanPTWestinSNDiounS. A prospective validation study of sentinel lymph node mapping for high-risk endometrial cancer. Gynecol Oncol2017;146:234239.

    • Search Google Scholar
    • Export Citation
  • 81.

    Abu-RustumNRKhoury-ColladoFPandit-TaskarN. Sentinel lymph node mapping for grade 1 endometrial cancer: is it the answer to the surgical staging dilemma?Gynecol Oncol2009;113:163169.

    • Search Google Scholar
    • Export Citation
  • 82.

    BallesterMDubernardGLecuruF. Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO). Lancet Oncol2011;12:469476.

    • Search Google Scholar
    • Export Citation
  • 83.

    PressJZGotliebWH. Controversies in the treatment of early stage endometrial carcinoma. Obstet Gynecol Int2012;2012:578490.

  • 84.

    TouhamiOTrinhXBGregoireJ. Predictors of non-sentinel lymph node (non-SLN) metastasis in patients with sentinel lymph node (SLN) metastasis in endometrial cancer. Gynecol Oncol2015;138:4145.

    • Search Google Scholar
    • Export Citation
  • 85.

    RossiECKowalskiLDScaliciJ. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol2017;18:384392.

    • Search Google Scholar
    • Export Citation
  • 86.

    PaleyPJVeljovichDSPressJZ. A prospective investigation of fluorescence imaging to detect sentinel lymph nodes at robotic-assisted endometrial cancer staging. Am J Obstet Gynecol2016;215:117 e111117.

    • Search Google Scholar
    • Export Citation
  • 87.

    SinnoAKFaderANRocheKL. A comparison of colorimetric versus fluorometric sentinel lymph node mapping during robotic surgery for endometrial cancer. Gynecol Oncol2014;134:281286.

    • Search Google Scholar
    • Export Citation
  • 88.

    RuscitoIGasparriMLBraicuEI. Sentinel node mapping in cervical and endometrial cancer: indocyanine green versus other conventional dyes—a meta-analysis. Ann Surg Oncol2016;23:37493756.

    • Search Google Scholar
    • Export Citation
  • 89.

    Bodurtha SmithAJFaderANTannerEJ. Sentinel lymph node assessment in endometrial cancer: a systematic review and meta-analysis. Am J Obstet Gynecol2016.

    • Search Google Scholar
    • Export Citation
  • 90.

    CormierBRozenholcATGotliebW. Sentinel lymph node procedure in endometrial cancer: a systematic review and proposal for standardization of future research. Gynecol Oncol2015;138:478485.

    • Search Google Scholar
    • Export Citation
  • 91.

    NaouraICanlorbeGBendifallahS. Relevance of sentinel lymph node procedure for patients with high-risk endometrial cancer. Gynecol Oncol2015;136:6064.

    • Search Google Scholar
    • Export Citation
  • 92.

    SchiavoneMBZivanovicOZhouQ. Survival of patients with uterine carcinosarcoma undergoing sentinel lymph node mapping. Ann Surg Oncol2016;23:196202.

    • Search Google Scholar
    • Export Citation
  • 93.

    HollowayRWGuptaSStavitzskiNM. Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis. Gynecol Oncol2016;141:206210.

    • Search Google Scholar
    • Export Citation
  • 94.

    DaraiEDubernardGBatsAS. Sentinel node biopsy for the management of early stage endometrial cancer: long-term results of the SENTI-ENDO study. Gynecol Oncol2015;136:5459.

    • Search Google Scholar
    • Export Citation
  • 95.

    KimCHSoslowRAParkKJ. Pathologic ultrastaging improves micrometastasis detection in sentinel lymph nodes during endometrial cancer staging. Int J Gynecol Cancer2013;23:964970.

    • Search Google Scholar
    • Export Citation
  • 96.

    RaimondE<