Article: Endometrial cancer

Endometrial cancer involves cancerous growth of the endometrium (lining of the uterus). It mainly occurs after menopause, and presents with vaginal bleeding. A hysterectomy (surgical removal of the uterus) is generally performed.

It is the most common gynecologic cancer in the United States, with over 35,000 women being diagnosed each year in the U.S. Because of effective screening, it is only the third most common cause of gynecologic cancer deaths (behind ovarian and cervical cancer).

The same risk factors for endometrial cancer predisposes women to endometrial hyperplasia, which is a precursor lesion for endometrial cancer. An atypical complex hyperplasia carries a 30% risk of developing endometrial cancer while a typical simple hyperplasia only carries a 2-3% risk.

Epidemiology

Endometrial cancer occurs in both premenopausal (25%) and postmenopausal women (75%). The most commonly affected age group is between 50 and 59 years of age. Most tumors are caught early and thus prognosis is good and mortality is declining.

Risk Factors

Most women with endometrial cancer have a history of unopposed and increased levels of estrogen. One of estrogen's normal functions is to stimulate the buildup of the endometrial lining of the uterus. Excess estrogen administered to laboratory animals can produce endometrial hyperplasia, which is a precursor for cancer.

Increased estrogen may be due to:

• obesity (> 30 lb or 14 kg overweight)
• exogenous (medication)

The incidence of endometrial cancer in women in the U.S. is 1 % to 2 %. The incidence peaks between the ages of 60 and 70 years, but 2 % to 5 % of cases may occur before the age of 40 years. Increased risk of developing endometrial cancer has been noted in women with increased levels of natural estrogen.

Associated conditions include the following:

• obesity
• hypertension
• polycystic ovary syndrome

Increased risk is also associated with the following:

• nulliparity (never having carried a pregnancy)
• infertility (inability to become pregnant)
• early menarche (onset of menstruation)
• late menopause (cessation of menstruation)

Women who have a history of endometrial polyps or other benign growths of the uterine lining, postmenopausal women who use estrogen-replacement therapy (specifically if not given in conjunction with periodic progestin) and those with diabetes are also at increased risk.

Tamoxifen, a drug used to treat breast cancer, can also increase the risk of developing endometrial cancer.

Symptoms

• abnormal uterine bleeding, abnormal menstrual periods
• bleeding between normal periods in premenopausal women
• vaginal bleeding and/or spotting in postmenopausal women

in women older than 40: extremely long, heavy, or frequent episodes of bleeding (may indicate premalignant changes)

• lower abdominal pain or pelvic cramping

thin white or clear vaginal discharge in postmenopausal women

Diagnosis

Results from a pelvic examination are frequently normal, especially in the early stages of disease. Changes in the size, shape or consistency of the uterus and/or its surrounding, supporting structures may exist when the disease is more advanced.

• Endometrial curettage is the diagnostic test of choice. Both endometrial and endocervical material should be sampled.
• If endometrial curettage does not yield sufficient diagnostic material, a dilation and curettage (D&C) is necessary for diagnosing the cancer.
• Endometrial aspiration or biopsy may assist the diagnosis.
• A Pap smear may be either normal or show abnormal cellular changes.
• Transvaginal ultrasound to evaluate the endometrial thickness in women with postmenopausal bleeding is increasingly being used to evaluate for endometrial cancer.
• Routine screening of asymptomatic women is not indicated since the disease is highly-curable in those patients who are likely to have the disease detected by screening.

Pathology

Histopathology is usually an endometrioid adenocarcinoma.

Endometrial adenocarcinoma

It appears on a background of endometrial hyperplasia. Tumor cells are atypical and form irregular glands, with multiple lumens, pluristratification. The stroma is reduced, producing the "back to back" aspect. With evolution of the disease, the myometrium is infiltrated.

Evaluation

Patients with newly-diagnosed endometrial cancer do not routinely undergo imaging studies, such as CT scans to evaluate for extent of disease, since this is of low yield. Preoperative evaluation should include a complete medical history and physical examination, pelvic examination and rectal examination with stool guaiac test, chest X-ray, complete blood count, and blood chemistry tests, including liver function tests. Colonoscopy is recommended if the stool is guaiac positive or the women has symptoms, due to the etiologic factors common to both endometrial cancer and colon cancer. The tumor marker CA-125 is sometimes checked, since this can predict advanced stage disease.^[1]

Stages of endometrial cancer

Endometrial carcinoma is surgically staged using the FIGO cancer staging system.

• Stage IA: tumor is limited to the endometrium
• Stage IB: invasion of less than half the myometrium
• Stage IC: invasion of more than half the myometrium
• Stage IIA: endocervical glandular involvement only
• Stage IIB: cervical stromal invasion
• Stage IIIA: tumor invades serosa or adnexa, or malignant peritoneal cytology
• Stage IIIB: vaginal metastasis
• Stage IIIC: metastasis to pelvic or para-aortic lymph nodes
• Stage IVA: invasion of the bladder or bowel
• Stage IVB: distant metastasis, including intraabdominal or inguinal lymph nodes

Treatment

The primary treatment is surgical. Surgical treatment should consist of, at least, cytologic sampling of the peritoneal fluid, abdominal exploration, palpation and biopsy of suspicious lymph nodes, abdominal hysterectomy, and removal of both ovaries (bilateral salpingo-oophorectomy). Lymphadenectomy, or removal of pelvic and para-aortic lymph nodes, is sometimes performed for tumors that have high risk features, such as pathologic grade 3 serous or clear-cell tumors, invasion of more than 1/2 the myometrium, or extension to the cervix or adnexa. Sometimes, removal of the omentum is also performed.

Abdominal hysterectomy is recommended over vaginal hysterectomy because it affords the opportunity to examine and obtain washings of the abdominal cavity to detect any further evidence of cancer.

Women with stage 1 disease who are at increased risk for recurrence and those with stage 2 disease are often offered surgery in combination with radiation therapy. Chemotherapy may be considered in some cases, especially for those with stage 3 and 4 disease.

Support Groups

The stress of illness can often be helped by joining a support group where members share common experiences and problems.

Expectations

Because endometrial cancer is usually diagnosed in the early stages (70 % to 75 % of cases are in stage 1 at diagnosis; 10 % to 15 % of cases are in stage 2; 10 % to 15 % of cases are in stage 3 or 4), there is a better probable outcome associated with it than with other types of gynecological cancers such as cervical or ovarian cancer.

Survival rates

The 5-year survival rate for endometrial cancer following appropriate treatment is:

• 75% to 95% for stage 1
• 50% for stage 2
• 30% for stage 3
• less than 5% for stage 4

Complications

• Anemia may result, caused by chronic loss of blood. (This may occur if the woman has ignored symptoms of prolonged or frequent abnormal menstrual bleeding.)
• A perforation (hole) of the uterus may occur during a D and C or an endometrial biopsy.