Basics
Description
- Endometrial cancer is the most common gynecologic malignancy in the US, arising from the epithelial lining of the uterine corpus. It is divided into 2 categories: Type I (endometrial cancer related to hormonal stimulation: 80%) and type II (unrelated to hormonal stimulation: 20%).
- Pathology: Endometrioid adenocarcinoma (75-80%), serous carcinoma (1-5%), clear-cell carcinoma (5-10%), mixed-pattern carcinomas, and rare subtypes including mucinous, squamous cell, transitional cell, and small cell carcinomas.
- Serous carcinoma and clear-cell carcinoma are highly aggressive, usually found in advanced stage in older women.
Epidemiology
- Usually seen in postmenopausal women (mean age 60-65 years), although 25% of cases occur in premenopausal women.
- Higher incidence in Western countries
Incidence
42,160 newly diagnosed cases/year; 7,780 deaths/year
Risk Factors
For type I endometrial carcinoma:
- Unopposed estrogen: Hormone replacement therapy [relative risk (RR): 3.0-15]
- Functional ovarian tumors
- Obesity (RR: 1.59)
- High-fat diet
- Chronic anovulation: Polycystic ovary syndrome
- Tamoxifen therapy
- Nulliparity (infertility)
- Diabetes mellitus
- Hypertension
- Endometrial hyperplasia
- History of breast cancer (BRCA), Lynch syndrome (hereditary nonpolyposis colorectal cancer)
- Family history of endometrial cancer
General Prevention
Screening is not generally warranted except in women with Lynch syndrome.
Etiology
Thought to be caused by a combination of genetic mutations and hormonal factors
Diagnosis
History
- Protective factors in history include oral contraceptive use and smoking (only in postmenopausal women).
- Signs and symptoms:
- Postmenopausal women:
- Abnormal vaginal bleeding (90%) (1)[A]
- Approximately 5-20% of women who present with abnormal bleeding will be found to have endometrial cancer.
- Premenopausal women:
- Diagnosis may be difficult.
- Should be suspected in women with prolonged, heavy menstruation or mid-cycle bleeding, particularly if they have risk factors.
Physical Exam
- Most often pelvic exam will be normal
- May feel mass if advanced
Tests
Lab
Serum CA-125 to predict extrauterine spread of the disease
Imaging
- Transvaginal ultrasonography to evaluate the endometrial thickness in postmenopausal women:
- <5 mm; low risk
- ≥20 mm; high risk
- Chest x-ray to evaluate for lung metastasis
- An abdominal CT scan is not routinely necessary unless extrapelvic disease is suspected.
- Sonohysterography to identify women with focal endometrial abnormalities (focused biopsies needed)
Surgery
- Endometrial biopsy for diagnosis; can be performed in the office setting, no anesthesia required. The post-test probability of endometrial cancer:
- After a positive test: 82% (95% CI: 60-93%)
- After a negative test: 0.9% (95% CI: 0.4-2.4%)
- Dilation and curettage with hysteroscopy: Gold standard, requires anesthesia
- Surgical staging (see "Surgery"¯ in "Treatment"¯)
Differential Diagnosis
- Sarcoma of uterus
- Polyps
- Endometrial/vaginal atrophy
- Hormone replacement therapy
- Endometrial hyperplasia
Treatment
Additional Treatment
General Measures
- Adjuvant chemotherapy should be considered in women with high-intermediate and high-risk disease. In stage III-IV disease, adjuvant chemotherapy results in improved outcome compared to whole-abdominal radiotherapy (2)[A].
- The most effective regimen and duration of therapy are unclear: Anthracyclines, platinums, with or without taxanes, are preferred.
Radiotherapy
- Adjuvant pelvic radiation after complete surgical staging in women with early stage intermediate risk decreases the local recurrence, but does not prolong survival (3)[A].
- For high-risk women, pelvic and whole-abdominal irradiation reduces the risk of local recurrence and may prolong survival.
Surgery
- Surgical staging includes hysterectomy with bilateral salpingo-oophorectomy, peritoneal cytology, and pelvic, paraaortic lymph nodes sampling or removal, and cytoreduction in advanced stage disease (4)[A].
- Based on the results of surgical staging and pathological examination, the risk of recurrence is estimated by an experienced oncologist.
- Low risk: Surgical staging alone is an adequate treatment.
- Intermediate risk: Surgical staging + adjuvant radiation with or without chemotherapy
- High risk: Surgical staging + extent of surgery + adjuvant radiation and/or chemotherapy
Ongoing Care
Follow-Up Recommendations
Patient Monitoring
- Periodic evaluation by a gynecological oncologist, including history, physical examination, and pelvic examination every 3-6 months for 2 years and then every 6 months or yearly up to 5 years
- Vaginal cytology: Every 6 months for 2 years and then yearly
- Chest x-ray: Yearly
- CA-125 measurement (optional): Every visit
Prognosis
The 5-year survival rates for stage I, II, III, and IV disease are 85-91%, 74-83%, 57-66%, and 20-25%, respectively.
Complications
Recurrence: 75-95% of recurrence occurs within the first 3 years of diagnosis.
- Most local recurrence occurs in vagina; potentially curative surgery is often possible.
- The major sites of metastasis are the abdominal cavity, liver, and lungs.
References
1 ACOG practice bulletin, clinical management guidelines for obstetrician-gynecologists, number 65, August 2005: Management of endometrial cancer. Obstet Gynecol. 2005;106:413-425. [View Abstract]2Randall ME, Filiaci VL, Muss H. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: A Gynecologic Oncology Group Study. J Clin Oncol. 2006;24:36-44. [View Abstract]3 Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomized trials): Pooled trial results, systematic review, and meta-analysis. Lancet. 2009;373:137-146.4Pecorelli S. Endometrial cancer: Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet. 2009;105:103-104. [View Abstract]
Additional Reading
1Jemal A, Siegel R, Ward E. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225-249. [View Abstract]
Codes
ICD9
182.0 Malignant neoplasm of corpus uteri, except isthmus
ICD10
C54.1 Malignant neoplasm of endometrium
SNOMED
- 93781006 primary malignant neoplasm of endometrium (disorder)
- 188192002 malignant neoplasm of endometrium of corpus uteri (disorder)
- 123845008 adenocarcinoma of endometrium (disorder)
- 254878006 endometrial carcinoma (disorder)
Clinical Pearls
- The most common gynecologic malignancy in the US
- Primarily a disease of postmenopausal women presenting with abnormal uterine bleeding
- There is an increased risk in women exposed to unopposed estrogen, those who have received tamoxifen therapy for breast cancer, and those who are at risk of hereditary nonpolyposis colorectal cancer.
- Most cases are diagnosed at an early stage when surgery alone may be curative.
- Diagnosis can be made with office-based endometrial biopsy, although a hysteroscopy with dilation and curettage remains the gold standard.