In the USA, endometrial cancer is the most common gynecologic malignancy and the fourth most common malignancy in women after breast, colorectal, and lung cancer. About 34,000 new cases of endometrial cancer were diagnosed in 1996. It affects mainly postmenopausal women, with incidence peaking between ages 50 and 60; < 5% of cases occur among women < 40 yr.

Etiology and Pathology
Endometrial cancer is more common in industrialized countries in which dietary fat intake is high. The most significant risk factor is obesity, which increases risk by 3 to 10 times. Endometrial cancer is more common in women with conditions that tend to result in unopposed estrogen (high circulating levels of estrogen with no or low levels of progesterone), such as unopposed estrogen replacement therapy, obesity, polycystic ovarian syndrome, nulliparity, late menopause, estrogen-producing tumors, anovulation, or oligo-ovulation. Women with a history of pelvic radiation therapy or with a personal or family history of breast or ovarian cancer are at increased risk. A small percentage of cases may be hereditary.
Endometrial hyperplasia usually precedes endometrial cancer and is classified by the degree of cytologic atypia. Its treatment consists of progestins or surgery, depending on the complexity of the lesion and the patient’s desire to avoid hysterectomy.

Endometrial cancer may spread from the surface of the uterine cavity to the cervical canal; through the myometrium to the serosa and into the peritoneal cavity; via the lumen of the fallopian tube to the ovary, broad ligament, and peritoneal surfaces; via the bloodstream, leading to distant metastases; or via the lymphatics. The higher (more undifferentiated) the grade of the tumor, the greater likelihood of deep myometrial invasion, pelvic or para-aortic lymph node metastases, or extrauterine spread.

Adenocarcinoma accounts for > 80% of cases of endometrial cancer. Sarcomas account for about 5% of all uterine malignancies and include mixed mesodermal tumors, leiomyosarcomas, and endometrial stromal sarcomas. Sarcomas tend to be more aggressive, are more likely to produce local, regional, and distant metastases, and have a worse prognosis.

Symptoms, Signs, and Diagnosis
More than 90% of patients with endometrial cancer have abnormal uterine bleeding (eg, postmenopausal bleeding, premenopausal recurrent metrorrhagia). About 1/3 of women with postmenopausal bleeding have endometrial carcinoma. In postmenopausal women, a vaginal discharge may precede bleeding by several weeks or months.

If a Papanicolaou (Pap) smear shows endometrial cells in a postmenopausal woman or atypical endometrial cells in a woman of any age, further evaluation is indicated. However, a Pap smear does not accurately detect endometrial malignancies.

Tissue sampling from the endometrium, usually performed in the physician’s office, is the definitive diagnostic procedure. This procedure is > 90% accurate, compared with a fractional dilation and curettage with hysteroscopy, performed in the operating room. The latter is used when outpatient sampling is not diagnostic. Transvaginal ultrasonography may also be useful.

Once a histologic diagnosis of endometrial cancer is made, pretreatment evaluation includes serum chemistry studies, liver function tests, a CBC, chest x-ray, and ECG. Additional endoscopic and radiologic studies are not routinely necessary. Pelvic and abdominal CT may help if extrauterine or metastatic disease is suspected.

Staging, Prognosis, and Treatment
Staging is based on histologic differentiation (grade) of the tumor and findings during surgery, including depth of invasion, cervical involvement (glandular involvement vs. stromal invasion), and extrauterine metastases, such as those to the adnexa, lymph nodes, and peritoneal cavity (

see Table 241-1). An adequate abdominal incision is made, allowing sampling of peritoneal fluid for cytologic evaluation and exploration of the abdomen and pelvis, with biopsy or excision of suspicious extrauterine lesions. Pelvic and para-aortic lymph nodes should be sampled in high-risk situations and, if suspicious, removed. A radical hysterectomy with pelvic and para-aortic lymph node dissection is indicated if cervical involvement is suspected.

Prognosis is influenced by the tumor’s histologic appearance and grading, the patient’s age (older women have a poorer prognosis), and metastatic spread. Overall, 63% of patients are cancer-free >= 5 yr after treatment. For patients with stage I disease, the reported 5-yr survival rate is 70 to 95%; the 5-yr survival rate for those with stage III or IV disease is 10 to 60%.

Stage I, grade 1 endometrial cancer without deep myometrial invasion is usually localized; the probability of lymph node metastasis is < 2%. Surgery can usually be limited to a total hysterectomy, bilateral salpingo-oophorectomy, and peritoneal cytologic examination. For grades 2 and 3 and for grade 1 with deep myometrial invasion, a pelvic and para-aortic lymphadenectomy may be added.

Very few patients with cancer confined to the uterus have recurrences. Accurate surgical staging enables 50 to 75% of patients with stage I disease to forego postoperative radiation therapy. Extrapelvic cancer, depending on the site and extent, is treated with extended-field radiation, systemic chemotherapy, or hormone therapy. Most patients with stage IV disease are best treated with systemic chemotherapy.

Progesterone therapy, used for advanced or recurrent disease, leads to regression in 35 to 40% of patients. Progesterone can induce regression of pulmonary, vaginal, and mediastinal metastases. Treatment continues indefinitely if the response is favorable. The duration of remission varies but may last 2 to 3 yr.

Several cytotoxic drugs (especially doxorubicin and cisplatin) are active against metastatic and recurrent endometrial cancer. Monthly regimens combining doxorubicin 60 mg/m2 and cisplatin 75 mg/m2 IV may have overall response rates of >= 50%. Paclitaxel shows activity against this cancer.