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Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017
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Image courtesy of Wikimedia Commons /Prokopyuk Vladimir Yurievich.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Cancer of the corpus uteri (upper uterus, body of the uterus) or uterine cancer is also generally referred to as endometrial cancer, because approximately 92% of cases affect the inner lining of the uterus.[1] (Another main type of uterine malignancy, uterine sarcomas, affect the muscle layer or supporting connective tissue of the uterus, comprise about 3%-8% of all uterine neoplasms, and are more aggressive than endometrial cancers.[2,3] Uterine sarcomas will not be discussed in this slideshow.)
Worldwide, endometrial cancer is the sixth most common neoplasm in women and the 14th most common malignancy overall.[4] In the United States, it is the most common cancer of the female genital tract,[2,5,6] accounting for 6% of all malignancies in women,[6] and the 10th most common cancer overall.[7] Note that although endometrial carcinoma is the most common gynecological cancer in developed nations,[8] cervical cancer is more common in developing countries.[4] Fortunately, endometrial cancer is often identified at an early, localized, and treatable stage.[2,5,6]
The most common endometrial cancer cell type is endometrioid adenocarcinoma, which is composed of malignant glandular epithelial elements (although an admixture of squamous metaplasia also occurs),[6,9] followed by adenoacanthomas (benign squamous components) and adenosquamous carcinomas (malignant squamous components).[9] Other uterine tumor cell types include the following[6,9]:
Papillary serous (5%-10%)
Clear cell (1%-4%)
Mucinous (1%)
Squamous cell (<1%)
Mixed (10%)
Undifferentiated
Images courtesy of Jayakrishnan K, Anupama R, Koshy A, Raju R. J Hum Reprod Sci. 2010;3(1):38-41. [Open access.] PMID: 20607008, PMCID: PMC2890909.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Etiopathophysiology and Risk Factors
Although the exact etiology for most cases of endometrial cancer remains to be elucidated,[5] sporadic mutations appear to cause the majority and about 5% result from inherited mutations.[2] Known risk factors include the following[1,2,5,10]:
Increased estrogen levels (as occurs in those who are obese and/or have abdominal fat, diabetes, and/or high-fat diets)
Use of tamoxifen therapy or hormone replacement therapy (HRT)
Early age at menarche (<12 years)
Late age at menopause
Nulliparity
History of polycystic ovarian syndrome (PCOS)
Personal and/or family history of Lynch syndrome/hereditary nonpolyposis colorectal cancer (HNPCC); breast, ovarian, and/or colorectal cancer; and/or endometrial hyperplasia
Older age (≥55 years)
The images were obtained from a subfertile 31-year-old woman with PCOS. The transvaginal sonograms show endometrial thickness (23 mm) (top left) and increased vascularity on Doppler evaluation (top right). An endometrial biopsy sample obtained from the same patient revealed well-differentiated endometrial adenocarcinoma (bottom center).
Adapted image courtesy of SEER Program at the National Cancer Institute (NCI).
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Incidence and Mortality
Since 1988, the overall annual US incidence of endometrial cancer has been increasing by 1.3% among women younger than 50 years; since 2005, the annual increase has been 1.9% among women aged 50 years and older.[1] Between 2005 and 2014, associated mortality rose by 1.4% each year.[7]
In 2017, the Surveillance, Epidemiology, and End Results (SEER) Program and the American Cancer Society (ACS) estimate there will be approximately 61,380 new US cases of cancer of the uterine corpus—representing approximately 3.6% of all new US cancer cases—with about 10,920 deaths (1.8% of all cancer deaths) from this disease.[5,7] Age-adjusted 2010-2014 data indicate there were 25.7 new cases per 100,000 women per year, with 4.6 deaths per 100.000 women annually.[7]
Data from 2012 to 2014 indicate about 2.8% of women will be diagnosed with endometrial cancer in their lifetime.[7] This disease predominantly occurs in middle-aged and older women (aged 55-64 years [34.5%] and 65-74 years [25.8%], followed by those aged 45-54 years [16.7%] and 75-84 years [11.7%]).[7] The median age at diagnosis is 62 years.
White, black, and non-Hispanic women are affected slightly more than those of Hispanic, American Indian/Alaska Native, and Asian/Pacific Islander descent; however, mortality is higher in black women (8.1 deaths per 100,000) than in non-Hispanic women (4.6 deaths per 100,000) and white women (4.2 deaths per 100,000).[7] Among all races/ethnicities, Asian/Pacific Islander women have the lowest mortality (2.9 deaths per 100,000).
Adapted anterior view of the anatomy and physiology of the female reproductive system courtesy of OpenStax; micrographs courtesy of the Regents of University of Michigan Medical School via OpenStax.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Presentation
Unusual or irregular vaginal bleeding, spotting, or discharge is the presenting sign in 90% of patients with endometrial cancer.[1,5,6,10] In most cases, this is postmenopausal bleeding. In younger women, signs/symptoms may be more subtle; therefore, any abrupt change in the pattern of menstrual bleeding should be evaluated.[5,10]
Common symptoms of endometrial cancer include the following[1,5,6]:
Dysuria
Pelvic pain
Pain during intercourse
The anatomic portion of the image shows the relationship of the ovaries, oviducts, and uterus. The normal histologic appearance of selected regions of the endometrium, myometrium (right light micrograph, ×20 magnification), and an ovary (left light micrograph, ×400 magnification) is also depicted.
Tables courtesy of Medscape. * = The FIGO system no longer includes stage 0 (Tis); ** = Endocervical glandular involvement should only be considered as stage I and no longer as stage II.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Classification, Staging, and Grading
The International Federation of Obstetricians and Gynecologists (FIGO) and the American Joint Committee on Cancer (AJCC) have similar staging systems to define endometrial cancer (shown); both systems classify the extent of the tumor, the involvement of any lymph nodes, and whether metastasis has occurred.[2,5,6,10,11] In general, the FIGO system has been the standard staging system.
FIGO stages are further sub-classified into two main clinicopathologic types, as follows:
Type 1: Estrogen-dependent endometrioid carcinoma[11]; may arise from complex atypical hyperplasia and is pathogenically linked to unopposed estrogenic stimulation[6]; typically not very aggressive[5]
Type 2: Estrogen-independent non-endometrioid carcinoma[11]; develops from atrophic endometrium and is not associated with hormone stimulation[6]; usually more likely to grow and metastasize outside the uterus[5]
Carcinosarcomas of the uterus (malignant mixed mesodermal tumors, malignant mixed mullerian tumors [MMMTs]) begin in the endometrium and demonstrate histologic features of both endometrial carcinoma and sarcoma[5,12]; they are considered, and staged as, type 2 endometrial carcinomas.[5,6] At least four subtypes of endometrial carcinomas have also been identified on the basis of integrated genomic characterization,[13] which may aid in refining their classification and have potential prognostic and therapeutic implications.[6]
Diagrams courtesy of Cancer Research UK (CRUK) via Wikimedia Commons.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Endometrial cancers are also graded on the basis of how much the tumor cells form glands with an appearance similar to those of the healthy endometrium, as follows[5,10,11]:
Grade 1 (low grade, type 1): Well differentiated; 95% or more of the tumor cells form glands
Grade 2 (low grade, type 1): Moderately differentiated; 50%-94% of the tumor cells form glands
Grade 3 (high grade, type 2): Poorly differentiated; less than 50% of the tumor cells form glands
The images illustrate different stages of endometrial cancer. Top left: Stages 1A and 1B. Top right: Stage 2. Bottom left: Stages 3A to 3C. Bottom right: Stages 4A and 4B.
Adapted images courtesy of Flickr/Ed Uthman.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Currently, no standard or routine screening test exists for asymptomatic women at average risk of endometrial cancer.[1,5] Fortunately, the majority of affected women are diagnosed in the early stages owing to the most common presenting sign, postmenopausal bleeding.[1,2,11]
The National Comprehensive Cancer Network (NCCN) recommends that clinicians consider using immunohistochemistry and/or microsatellite instability (MSI) to screen the tumor for defective DNA mismatch repair (eg, MLH1, MSH2, MSH6), which may help to identify which women should undergo mutation testing for Lynch syndrome.[2] For women with known or suspected Lynch syndrome, the ACS recommends annual screening beginning at age 35 years with endometrial biopsy and/or transvaginal ultrasonography (TVUS).[1,5]
Women with Lynch syndrome who have completed childbearing may consider prophylactic hysterectomy/bilateral salpingo-oophorectomy (BSO).[2,5]
Clinicians should also consider screening for genetic mutations—as well as consider obtaining genetic testing and providing genetic counseling—in all patients with endometrial and/or colorectal cancer, particularly in women younger than 50 years and those with a family history of endometrial and/or colorectal cancer.[2,5]
The left gross specimen shows a FIGO grade III endometrioid adenocarcinoma that invades slightly more than half the thickness of the myometrium. The right specimen is a longitudinal section through the full length of the uterus (corpus is at the top; the elongate cervix trails off to the bottom). It demonstrates a FIGO grade I endometrioid adenocarcinoma that is limited to the corpus uteri and does not grossly invade the underlying myometrium.
Image of hysteroscopy courtesy of Bruce Blaus of Blausen Medical via Wikimedia Commons. Hysteroscopy may be used to evaluate the endometrium for lesions (eg, polyp[s]) and/or other abnormalities.[2,5]
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Workup
A detailed history and physical examination, including a thorough pelvic examination, should be performed in women with suspected endometrial carcinoma.
Laboratory studies
Routine laboratory testing includes a complete blood cell (CBC) count and platelets.[2] The NCCN guidelines indicate that hepatic and renal function tests and chemistry profiles are optional studies, which should be obtained as indicated on the basis of clinical findings. A serum CA-125 assay may be useful for monitoring clinical response in patients with extrauterine disease.[2,5]
Patients with known or suspected Lynch syndrome and those with a personal and/or family history of endometrial or colorectal cancer should be considered for screening for defective DNA mismatch repair and/or genetic testing (and counseling).[2,5]
Procedures
To detect the presence of endometrial hyperplasia or endometrial cancer and/or to confirm the diagnosis, a technique that allows direct sampling of the endometrial tissue is required[5,6]; this typically involves endometrial biopsy (with or without endocervical curettage, with or without hysteroscopy).[2,5,6] Owing to a 10% false-negative rate in office endometrial biopsies,[2] a symptomatic woman with a negative or equivocal endometrial biopsy must undergo fractional dilation and curettage (D&C) under anesthesia.[2,5]
Surgical staging to assess disease status is obtained on the basis of preoperative and intraoperative findings.[2] It is generally recommended for intermediate- to high-risk endometrioid cancer (stage IA G3 and IB).[11]
Image courtesy of Wikimedia Commons/Nephron.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
This very high–magnification micrograph shows endometrioid endometrial adenocarcinoma (hematoxylin and eosin [H&E] stain). Malignant endometrial glands and squamous metaplasia are present.
Image courtesy of Wikimedia Commons/Mikael Häggström.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
TVUS is typically the initial imaging modality of choice for evaluating women with suspected endometrial cancer.[5,11,14,15] This study may be used to measure the endometrial thickness (endometrial stripe) and evaluate the endometrium for any abnormality. In general, an endometrial thickness of 4-5 mm or less has a very high negative predictive value for excluding endometrial cancer in women with postmenopausal bleeding.[14,15]
Note that false-positive results can occur in obese and/or diabetic patients,[16] as well as in the presence of the following[15]:
Adenomatous hyperplasia
Endometrial polyp(s)
Tamoxifen-related endometrial changes
Endometrial extension of cervical cancer
Degenerating submucosal leiomyoma
Blood clots
Hydroultrasonography (saline infusion sonogram, hysterosonogram) may be used to increase the accuracy of TVUS findings if the endometrium is found to be abnormally thickened.[5,16] This study involves inserting a small volume of saline into the endometrial cavity and then repeating TVUS.
The transvaginal sonogram was obtained from a postmenopausal woman who presented with intermittent vaginal fluid discharge. Uterine fluid accumulation is seen. Biopsy results revealed endometrioid adenocarcinoma.
Images courtesy of Arif A, Abideen ZU, Zia N, Khan MA, Nawaz T, Malik AZ. BMC Res Notes. 2013;6:476. [Open access.] PMID: 24252257, PMCID: PMC3874625.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Other imaging studies are generally reserved for evaluating patients with suspected extrauterine disease, as follows[2,5,11]:
Chest radiography: To assess for pulmonary metastasis
Abdominal computed tomography (CT) scanning (shown): To detect any extrapelvic disease
Dynamic contrast-enhanced magnetic resonance imaging (MRI): To gauge cervical involvement and/or determine depth of myometrial invasion
F-18 (18F) fluorodeoxyglucose positron emission tomography (FDG-PET) scanning: To assess for distant metastases
The different views of the abdominal CT scans demonstrate rare metastatic involvement of the spleen in a patient with endometrial adenocarcinoma. (A gross specimen of the spleen and histology from the same patient can be seen in slide 16.)
Image courtesy of Zamani F, Goodarzi S, Hallaji F, et al. Iran J Radiol. 2012;9(4):202-8. [Open access.] PMID: 23407805, PMCID: PMC3569552.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
This sagittal T2-weighted MRI shows a large mass within the endometrial cavity invading the deep myometrium and cervical stroma. The patient was a middle-aged woman with biopsy-proven stage II endometrial carcinoma.
Image courtesy of Wikimedia Commons/Hic et nunc.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Treatment
Standard management of endometrial cancer involves surgery, with or without radiation therapy, hormone therapy, or chemotherapy.[5,6,10,11,16]
Patients of childbearing age who have low-risk disease and wish to maintain fertility may choose conservative management with hormone therapy (typically with continuous progestin-based therapy, megestrol and/or tamoxifen, or aromatase inhibitors).[2,5] For postmenopausal patients, however, surgery is recommended.
Clinicians must discuss the various treatment options and risks with their patients on an individualized basis, and provide counseling on treatment decisions.
The image is an intraoperative photograph showing a laparoscopic view of female reproductive organs.
Perioperative images courtesy of Wikimedia Commons/Hic et nunc.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Surgery
The following surgical procedures are usually used for endometrial cancer[2,5,10,11]:
Total abdominal hysterectomy (TAH), via laparotomy, laparoscopy, or robotics (stage I-II disease; radical hysterectomy may be necessary for stage II-IV disease)
BSO (stage I-IV disease)
Pelvic and para-aortic lymphadenectomy (stage I-II disease; selected cases with high-risk disease)
Surgical staging
Peritoneal cytology
Debulking (for resectable stage III-IV disease and good performance status)
The role of sentinel node sampling for early-stage disease continues to evolve.[2,5,10,11]
Localized endometrial carcinoma is usually curable with hysterectomy and BSO alone.[2,5,6] Optimal results may be obtained with either of two standard treatments: hysterectomy or hysterectomy and adjuvant radiation therapy (in the presence of deep invasion of the myometrial muscle [50% of the depth] or a grade 3 tumor with myometrial invasion).[6]
Top left image: A prehysterectomy uterus with a posterior wall fibroid. Top right and bottom left images: Laparoscopic hysterectomy in progress and at completion, respectively. Bottom right image: Cervical stump following removal of the uterine corpus at laparoscopic hysterectomy.
Image courtesy of Wikimedia Commons/Tdvorak.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Radiotherapy and/or chemotherapy
Adjuvant external-beam radiation therapy (EBRT) in patients with stage I disease has not been associated with improved survival but appears to decrease locoregional recurrence.[6,11] Vaginal cuff brachytherapy appears to be equivalent to EBRT in the adjuvant setting for stage I disease, but it has less radiation-associated morbidity.[6,11] In stage III-IV disease, EBRT with or without brachytherapy may be used for patients who are not surgical candidates or whose tumors are unresectable.[2,11]
Platinum-based chemotherapy with or without radiotherapy may be used in patients with stage I G3 disease and adverse risk factors, as well as in those with stage II-IV tumors.[2,11]
The image shows an example of a postoperative anteroposterior radiation treatment field for stage I-II endometrial cancer. L5-S1 may be used as the superior border of the field if pelvic lymph node dissection results are negative, or it may be at L4-L5 if no pelvic lymph node dissection was performed or positive lymph nodes were found; the inferior border is the inferior edge of the pubic ramus, and the lateral borders are about 2 cm lateral to the bony pelvis (to ensure adequate lymph node coverage).
The brown shading delineates the rectum. The orange shading overlies the common iliac lymph nodes; the yellow shading, the external iliac lymph nodes; the light-green shading, the obturator lymph nodes; the purple shading, the internal iliac lymph nodes; and the dark-green shading, the presacral lymph nodes.
Images courtesy of Arif A, Abideen ZU, Zia N, Khan MA, Nawaz T, Malik AZ. BMC Res Notes. 2013;6:476. [Open access.] PMID: 24252257, PMCID: PMC3874625.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Metastasis and Recurrent Disease
Regional and distant metastases are important concerns in patients with endometrial cancer. Predictive models have been established to identify those at high risk for lymph node metastases by using features such as histologic grade, tumor diameter, depth of myometrial invasion, and status of lymphovascular space involvement (LVSI).[17] Lymphadenectomy in patients with high-risk early or advanced disease should include dissection of pelvic and para-aortic areas up to the renal vessels to ensure accuracy in the evaluation of all potential positive nodes.[18]
There is no standard management of metastatic disease. Treatment options for low-grade, asymptomatic, and hormone receptor–positive disseminated metastasis include hormone therapy and chemotherapy.[2] For higher-grade, symptomatic, or large-volume metastases, consider chemotherapy with or without palliative radiation treatment. The NCCN recommends supportive measures or enrollment in a clinical trial for patients with persistent progression of disseminated metastases.[2]
For local recurrent disease, surgery with or without radiation therapy may be curative.[2,5] For women who aren't surgical candidates, radiation therapy with or without hormone therapy may be used. For distant recurrences, surgery and/or focused radiotherapy may be directed at small, isolated regions, with or without hormone therapy and/or chemotherapy. For widespread recurrences, treatment is generally the same as that for stage IV disease. Palliative radiation therapy and enrollment in a clinical trial are also options.[2,5]
The gross specimen of a spleen (left image) was obtained from the same patient as in slide 11 with endometrial adenocarcinoma and metastasis to the spleen. There is a mass in the center of the spleen that extends to the margins of the specimen as well as diffuse parenchymal infiltration. In the micrograph (right image), the black arrow on the left shows the endometrial tissue comprising neoplastic glands, with increased mitosis and nucleocytoplasmic ratio. Formation of glands, nests, and sheets are present along with necrosis. The white arrow shows the normal splenic tissue, and the black arrow on the bottom right shows the tumor-spleen parenchyma interface.
Adapted image courtesy of Flickr/Ed Uthman.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Prognosis, Prognostic Factors, and Survival
The prognosis in patients with endometrial carcinoma principally depends on the tumor type, stage, grade, histologic subtype, and depth/extent of invasion (generally related to surgical pathologic findings).[2,6,11] In general, endometrial carcinoma carries a good prognosis, with increased survival in younger patients and those who have early-stage and/or lower-grade disease.[2,6,11]
Poor prognostic factors include the following[2,6]:
Advanced stage of disease
High-grade histology (eg, ≥8 mitoses per 10 high-power fields)
Myometrial invasion and/or LVSI
Older age
Absence of progesterone receptors
Tumor involvement of lower uterine segment
The image shows a longitudinal section through a hysterectomy specimen. The lower uterine segment is at the left (excludes the cervix); the fundus is at the right.
Adapted image courtesy of SEER Program at the NCI.
Endometrial Cancer: Common but Predominantly Curable
Ali Ahmad, MD | September 27, 2017 | Contributor Information
Endometrial clear cell and papillary serous adenocarcinomas are histologically similar to those of the ovary and the fallopian tube and have a worse prognosis (5-year survival: 62% and 53%, respectively) than endometrioid adenocarcinomas (5-year survival: 83%),[6,9] as these subtypes have a tendency to invade deeply into the myometrium and to spread outside the uterus.[5,9,11]
Approximately 25% of endometrial cancers involve LVSI. The 5-year overall survival is 64% in the presence of LVSI but 88% the absence of LVSI.[11]
Data from 2010 to 2014 indicate that death predominantly occurs in women aged 65-74 years (29.4%), followed by those aged 55-64 years (23.4%), 75-84 years (22.9%), older than 84 years (14.3%), and 45-54 years (7.7%).[7] The median age at death is 70 years.
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Clinicians must know the different types of ovarian cysts, treatment options, and indications for referral to a gynecologic oncologist. Do you know how to best manage this condition in your patients?Slideshows, May 2016
Corpus cancer is the most frequently occurring female genital cancer. Approximately 47,100 cases of corpus cancer were predicted to occur in the United States in 2012, making it the fourth most common cancer among women; of these women, approximately 8,000 will die from the disease.Diseases/Conditions, September 2016
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Contributor Information
Author
Ali Ahmad, MD
Complex General Surgical Oncology Fellow
Roger Williams Medical Center
Providence, Rhode Island
Disclosure: Ali Ahmad, MD, has disclosed no relevant financial relationships.
Contributor
Vera Ruvinskaya, MS
Disclosure: Vera Ruvinskaya, MS, has disclosed no relevant financial relationships.
Editor
John Heinegg, RN
Section Editor
Medscape Drugs & Diseases
New York, New York
Disclosure: John Heinegg, RN, has disclosed no relevant financial relationships.
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN guidelines). Uterine neoplasms. Version 3.2017—July 18, 2017. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed: September 14, 2017.
World Health Organization, International Agency for Research on Cancer. GLOBOCAN 2012: Estimated cancer incidence, mortality, and prevalence worldwide in 2012. Population fact sheets. Available at: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed September 14, 2017.
National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. SEER stat fact sheets: endometrial cancer. Available at: http://seer.cancer.gov/statfacts/html/corp.html. Accessed September 14, 2017.
de Haydu C, Black JD, Schwab CL, English DP, Santin AD. An update on the current pharmacotherapy for endometrial cancer. Expert Opin Pharmacother. 2016 Mar;17(4):489-99. PMID: 26629895
Plataniotis G, Castiglione M, for the ESMO Guidelines Working Group. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010 May;21 suppl 5:v41-5. PMID: 20555100
Colombo N, Preti E, Landoni F, et al, for the ESMO Guidelines Working Group. Endometrial cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct;24 suppl 6:vi33-8. PMID: 24078661
Kandoth C, Schultz N, Cherniack AD, et al, for the Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature. 2013 May 2;497(7447):67-73. PMID: 23636398
American College of Obstetricians and Gynecologists. ACOG Committee opinion no. 440: the role of transvaginal ultrasonography in the evaluation of postmenopausal bleeding. (Reaffirmed in 2015.) Obstet Gynecol. 2009 Aug;114(2 pt 1):409-11. PMID: 19623006
Bendifallah S, Canlorbe G, Laas E, et al. A predictive model using histopathologic characteristics of early-stage type 1 endometrial cancer to identify patients at high risk for lymph node metastasis. Ann Surg Oncol. 2015 Dec;22(13):4224-32. PMID: 25869227
Fotopoulou C, El-Balat A, du Bois A, et al. Systematic pelvic and paraaortic lymphadenectomy in early high-risk or advanced endometrial cancer. Arch Gynecol Obstet. 2015 Dec;292(6):1321-7. PMID: 25990476
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