- Author: William T Creasman, MD; Chief Editor: Warner K Huh, MD more...
Endometrial cancer (also referred to as corpus uterine cancer or corpus cancer) is the most common female genital cancer in the developing world, with adenocarcinoma of the endometrium the most common type. In the United States, an estimated 2.8% of women will be diagnosed with this malignancy at some point in their lifetime.
Signs and symptoms
Approximately 75% of women with endometrial cancer are postmenopausal. Thus, the most common symptom is postmenopausal bleeding.
For the 25% of endometrial cancers in patients who are perimenopausal or premenopausal, the symptoms suggestive of cancer may be more subtle. The normal menstrual bleeding pattern during this period should become lighter and lighter and further and further apart. Heavy, frequent menstrual periods or intermenstrual bleeding must be evaluated.
See Clinical Presentation for more detail.
Examination in a woman with suspected endometrial carcinoma includes the following:
Pelvis and cervix: Findings may be normal, with no gross evidence of cervical disease and with a normal-sized uterus, because bleeding usually occurs from the endometrium
Endometrium: In vast majority of cases, no gross evidence of disease is noted
Once the diagnosis of endometrial cancer has been made, routine presurgical evaluation is performed to assess operability, including appropriate blood studies, electrocardiography, and chest radiography.
Some investigators believe vaginal ultrasonography to evaluate the endometrial stripe should be the first diagnostic procedure, because vaginal ultrasonography is less invasive than endometrial biopsy. However, limitations to using the endometrial stripe as a criterion for further diagnostic tests (eg, endometrial biopsy) include false readings in the presence of several conditions (eg, endometrial polyp, obesity, diabetes, receiving tamoxifen).
Hydroultrasonography is used to ensure that it is not a false-positive result when the endometrium is thickened.
The following procedures are used to determine the status of the endometrium:
Hysteroscopically directed biopsy (see the video below)
Dilatation and curettage: Limited current role
Examination with the patient under anesthesia: May be necessary in patients who are bleeding and have a cervical os that is very stenotic; anesthesia may be required to perform adequate dilatation for endometrial sampling
See Workup for more detail.
Treatment of endometrial cancer is dependent on the stage of the disease and the patient’s surgical candidacy. In general, surgery is recommended.
Operative procedures used for managing endometrial cancer include the following:
Total abdominal hysterectomy
Pelvic and para-aortic lymphadenectomy
Chemotherapeutic medications such as cisplatin can be used in the management of endometrial carcinoma.
Corpus cancer is the most frequently occurring female genital cancer. In developed countries, adenocarcinoma of the endometrium is the most common gynecological cancer; however, in developing countries, it is much less common than carcinoma of the cervix.
Approximately 54,870 new US cases of endometrial cancer are expected to have been diagnosed in 2015 (3.3% of all new US cancer cases); of these women, approximately 10,170 will die from this disease (1.7% of all cancer deaths). In the early part of the 20th century, cancer of the cervix killed more US women than any other cancer, but in the ensuing decades, the incidence for uterine cervical malignancy decreased precipitously. This decrease has been credited to the impact of screening with the Papanicolaou test (Pap smear). In less-developed countries, screening for cervical cancer is performed very infrequently, and therefore, cancer of the cervix is quite prevalent.
Multiple epidemiological risk factors have been identified in patients who have adenocarcinoma of the endometrium.
Obesity increases the risk for developing endometrial cancer, and some data suggest that a 2- to 3-fold increase in risk occurs if an individual is more than 50 lb heavier than the ideal weight for that person.
Nulliparity also increases risk 2- to 3-fold compared with parity.
An individual who has had a late menopause (aged >52 y) also appears to have an increased risk.
Unopposed estrogen, either as replacement therapy or endogenously produced (eg, granulosa cell tumor, polycystic ovarian disease), increases the risk of endometrial cancer several times.
Obesity is known to increase endogenous estrogen because the presence of fat appears to be responsible for the conversion of androstenedione to estrogen compounds at a much higher rate than if fat is not present.
Anovulation, which may be secondary to unopposed estrogen, also appears to contribute to this situation.
The most widely used anticancer drug is tamoxifen, and this drug has been suggested by some studies to cause an increased incidence of adenocarcinoma of the endometrium. These data were derived from retrospective analyses in which adenocarcinoma of the endometrium was not an end point in multiple prospective randomized studies evaluating the role of tamoxifen in patients with breast cancer. 
A case control study using the SEER database indicates that when confounding factors have been corrected, the risk of endometrial cancer does not appear to be increased in patients taking tamoxifen. This study is very reassuring because the potential for an increased number of women taking tamoxifen is becoming apparent, particularly as the prophylactic role of tamoxifen has been recommended for high-risk women.
Combination oral contraceptives
In contrast to tamoxifen, increasing data indicate that the use of combination oral contraceptives (OCs) decreases the risk of developing endometrial cancer.
Several studies have noted that women who use OCs at some time have a 0.5 relative risk of developing endometrial cancer compared with women who have never used OCs. This protection occurs in women who have used OCs for at least 12 months, and the protection continues for at least 10 years after OC use. Protection is most notable for nulliparous women.
Smoking apparently decreases the risk of developing endometrial cancer. The effects of smoking are related to body weight. Heavier women who smoke have the greatest reduction in risk.
Women who smoke are known to undergo menopause 1-2 years earlier than women who do not smoke.
Although smoking apparently reduces the risk of developing early stages of endometrial cancer, this advantage is strongly outweighed by the increased risk of lung cancer and other major health problems associated with smoking.
Associated medical conditions
Data suggest that women who have had breast cancer have a 2- to 3-fold increased risk of subsequently developing endometrial cancer.
Women who have hereditary nonpolyposis colon cancer (HNPCC) appear to have a markedly increased risk for developing endometrial cancer. Women with HNPCC account for only 2-10% of all female cases of colon cancer, but approximately 5% of all endometrial cancers occur in women with this risk factor. These women have a 22-50% lifetime risk of developing endometrial cancer, and the disease tends to occur at a younger age (approximately 15 y earlier). The greatest risk of developing endometrial cancer in women with HNPCC occurs from age 40-60 years, at which time the absolute risk is greater than 1% per y.
Currently, no data indicate that annual screening of women with HNPCC will detect endometrial cancer at a sufficiently early stage to improve survival compared with those whose diagnosis is made when symptoms appear. Nevertheless, because of the high risk of endometrial cancer in these individuals and because of the potential life-threatening nature of this disease, HNPCC patients should be so informed and screening is certainly suggested. According to American Cancer Society guidelines, women with HNPCC should be offered screening with an endometrial biopsy by age 35 years.
Bjorge et al found that metabolic syndrome is associated with an increased risk of endometrial carcinoma and fatal uterine corpus cancer. Particularly in women with a high body mass index, the association appears to go beyond the risk conferred by obesity alone.
Individuals with a family history of endometrial cancer appear to be at increased risk.
At one time, a classic phenotypic characteristic was thought to exist for a woman who would develop endometrial cancer. This phenotype included patients who were obese, nulliparous, and anovulatory in many instances. More recently, the existence of 2 pathogenic types of endometrial cancer was appreciated.
The first type occurs in women who fall into the classic category. These women are obese and have hyperlipidemia, signs of hyperestrogenism, uterine bleeding, infertility, and late onset of menopause. They may have hyperplasia of the ovary and endometrium. These patients tend to be white, obese, nulliparous, and have well-differentiated superficially invasive cancers that are sensitive to progesterone. They have a very favorable prognosis, and extrauterine disease is unusual in this group of patients. Fortunately, most women with endometrial cancer are in this category.
The second type occurs in women who have none of the disease states present in the classic presentation. These individuals tend to have poorly differentiated tumors, deep myometrial invasion, a high degree of metastasis to the lymph nodes and other sites, decreased sensitivity to progestins, and a poor prognosis. These patients tend to be thin, multiparous, and African American.
United States statistics
The most recent Surveillance, Epidemiology, and End Results (SEER) data are from 2008-2012 cases, which reveal a total age-adjusted incidence of 25.1 cases per 100,000 women. The incidence in white women is 25.8 cases per 100,000 compared to 24.0 cases per 100,000.
Race- and age-related demographics
Mortality is higher in black women (7.7 deaths per 100,000) than in white women (4.1 deaths per 100,000). Asian/Pacific Islander women have the lowest mortality (2.8% deaths per 100,000) among all races.
Endometrial adenocarcinoma occurs during the reproductive and menopausal years. The median age of women with this malignancy is 70 years; most patients are aged 65-74 years. Approximately 5% of women younger than 40 years have adenocarcinoma, and 20-25% of women are diagnosed before menopause.
Approximately 54,870 new US cases of endometrial cancer are expected to have been diagnosed in 2015 (3.3% of all new US cancer cases); of these women, approximately 10,170 will die from this disease (1.7% of all cancer deaths). On the basis of 2010-2012 data, an estimated 2.8% of women will be diagnosed with endometrial cancer in their lifetime.
Multiple prognostic factors exist for endometrial cancer. These prognostic factors generally are related to surgical pathologic findings. As in all cancers, the stage of the disease is the most important prognostic factor. Obviously, the surgical procedure helps determine the stage. Listed below are prognostic factors that may relate specifically to the stage of the disease and, thereby, may affect overall survival.
Prognostic factors - histopathologic subtypes
Most endometrial carcinomas are endometrioid adenocarcinomas. Adenoacanthomas (benign squamous components) and adenosquamous carcinoma (malignant squamous components) make up the next largest category.
Clear cell and papillary serous adenocarcinomas represent approximately 10% of all endometrial cancers and are considered to be poor histopathologic subtypes. These latter subtypes tend to have deeply invasive myometrial involvement, and they have a propensity for extrauterine spread, even though the myometrium may be superficially involved.
Previously, a patient with an adenosquamous carcinoma was thought to have a poor prognostic histotype because of the malignant squamous component.
Contemporary data suggest that irrespective of whether a squamous component is present (either benign or malignant), prognosis is related directly to the grade of the adeno component and not the fact that a squamous malignancy is present. If a malignant squamous component is present, a greater tendency exists for a more poorly differentiated adeno component to be present.
More recently, considerable evidence suggests that carcinosarcomas (CS) are not true sarcomas, as it appears they are derived from an epithelial origin. As a result CSs are now considered as a subset of endometrial cancers (type 2).
The degree of histologic differentiation of endometrial cancer has long been accepted as a sensitive indicator of prognosis. Patients with well-differentiated adenocarcinomas tend to have involvement of the endometrium or superficial myometrium, and extrauterine disease is unusual.
However, if a poorly differentiated lesion is present, these cancers tend to be much more aggressive, involving significant myometrial invasion, and often have extrauterine metastasis, either with positive peritoneal cytology, retroperitoneal spread, or involvement of the pelvic and/or para-aortic lymph nodes.
Because papillary and clear cell carcinomas are associated with a relatively poor prognosis, these subtypes are not usually graded but are considered in the same category as a poorly differentiated cancer.
The degree of myometrial invasion continues to be a consistent indication of tumor virulence. As the depth of myometrial invasion increases, the chance of having extrauterine disease is greater.
As noted above, grade and depth of invasion, as a generalization, are interrelated. As the grade of the tumor increases, an increase usually occurs in the depth of myometrial invasion; however, exceptions exist in that a grade 1 lesion can have deep myometrial invasion and a grade 3 lesion can be limited to the endometrium.
When grade and depth of invasion are evaluated separately, the depth of invasion appears to be a more important prognostic factor than the grade of the tumor.
Cytologic evaluation of the peritoneum appears to be an important prognostic factor. Although no universal agreement has been reached about the significance of cytologic evaluation findings, the vast majority of data in the literature suggest that they represent an independent prognostic factor.
Cytologic evaluation findings also appear to correlate with other prognostic factors, such as depth of myometrial invasion and lymph node metastasis.
The FIGO staging system states that positive cytology should be reported separately without changing the stage. If ascitic fluid is not present at the time of the exploratory laparotomy, a saline lavage of the pelvis and lower abdomen is performed and the specimen is submitted for cytologic evaluation.
Lymph node metastasis
A considerable number of patients who were thought to have clinical stage I endometrial cancer were, in fact, found to have lymph node metastasis when histopathologic evaluation was performed on the lymph nodes.
Again, a correlation among multiple prognostic factors has been shown to be present. Patients with poorly differentiated cancers, papillary serous and clear cell carcinomas, deep myometrial invasion, positive peritoneal cytology, or adnexal metastasis tend to have an increased risk of having lymph node metastasis.
Subsequent therapy after primary surgery depends on prognostic factors and spread of the disease. If the disease is limited to the uterus, surgery appears to be adequate treatment, with the possible exception of patients who have poorly differentiated deeply invasive myometrium. In these patients, data suggest that, possibly, postoperative irradiation may be of benefit. In patients who have disease outside of the uterus, radiation therapy may be effective; however, this has not been evaluated in a prospective randomized study. Most investigators irradiate the appropriate area if lymph node metastasis is present.
In patients with advanced disease (ie, intraperitoneal disease, disease outside of the peritoneal cavity), systemic chemotherapy may be of benefit. Studies suggest that carboplatin and paclitaxel are probably the drugs of choice when systemic chemotherapy is needed.
As previously noted, staging is the most important prognostic factor. Using the FIGO surgical staging classification from the recent annual report (worldwide data evaluation), 5-year survival rates of 87%, 76%, 63%, and 37% were noted for stages I, II, III, and IV of the disease, respectively. Because substages exist that take into consideration prognostic factors, 4 of the substages within stage I actually have better than 90% 5-year survival rates.
Increasingly, data suggest that lymphvascular space involvement in the myometrium predicts extant disease and a poor prognosis. Whether the poor prognosis remains when other prognostic factors are evaluated is less well defined.
A study found expression of the cell adhesion molecule L1CAM in early stage endometrial tumors to be a strong predictor of cancer recurrence. In a retrospective analysis of L1CAM expression in 1021 paraffin-embedded specimens of stage I, type I endometrial cancer, researchers found that 17.7% of the specimens were positive for L1CAM and that during a median follow-up of 5.3 years, recurrence rates were 51.4% among the L1CAM-positive cases, compared with just 2.9% among L1CAM-negative cases. Median overall survival was 8.9 years in patients with L1CAM-positve tumors, whereas median survival had not been reached in the L1CAM-negative patients.[7, 8]
In the study, L1CAM had sensitivities of 0.74 for recurrence and 0.77 for death, and specificities of 0.91 and 0.89, respectively. These data suggest that L1CAM is the best prognostic factor in stage I, type I endometrial cancer so far published.
Complications that may occur from therapy include complications that are normally expected from the surgical procedure itself. Because a lymphadenectomy is performed, increased bleeding could develop; however, unique complications from the procedure do not usually occur.
Postoperative complications can be expected, depending on the preoperative clinical condition of the patient. As noted previously (see Causes), many of these patients have comorbidities such as hypertension, obesity, diabetes, and increased age.
One postoperative complication that may be somewhat more common is thromboembolism because this is increased in patients who have cancer, are obese, and are older. In current practice, most physicians use some type of prophylaxis, either external pneumatic compression or low-dose heparin.
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