Uterine Corpus Cancer

Published on 10/03/2015 by admin

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Chapter 41 Uterine Corpus Cancer

Cancer of the endometrium is the most common gynecologic malignancy in the United States. For 2007, it is estimated that there will be more than 39,000 new cases and 7400 deaths. It is the fourth most common malignancy found in American women after breast, colorectal, and lung cancer and is predominantly a disease of affluent, obese, postmenopausal women of low parity.

image Epidemiology and Etiology

The median age for endometrial cancer is about 58 years. The risk factors associated with the development of carcinoma of the endometrium are listed in Box 41-1. Any factor that increases the exposure to unopposed estrogen increases the risk for endometrial cancer. If the proliferative effects of estrogen are not counteracted by a progestin, endometrial hyperplasia and possibly adenocarcinoma can result.

Obesity results in an increased extraovarian aromatization of androstenedione to estrone. Androstenedione is secreted by the adrenal glands, whereas the increased peripheral conversion occurs predominantly in fat depots but also in the liver, kidneys, and skeletal muscles. Granulosa-theca cell tumors of the ovary produce estrogen, and up to 15% of patients with these tumors have an associated endometrial cancer.

Unopposed estrogenic stimulation from anovulatory cycles occurs in patients who have polycystic ovarian syndrome (Stein-Leventhal syndrome) and in patients with a late menopause. In postmenopausal women taking estrogen replacement without a progestin for menopausal symptoms, the risk for cancer developing appears to be both dose and duration dependent. This increased risk varies from 2-fold to 14-fold compared with nonusers. The addition of progestin in a cyclic fashion for 10 to 14 days of the month or in a continuous fashion daily throughout the month eliminates this increased risk. Women taking tamoxifen for breast cancer have a twofold to threefold increased risk for endometrial cancer. Young women who use oral contraceptives have been shown to have a lower incidence of subsequent endometrial cancer.

About 5% of endometrial cancers occur in women with the hereditary nonpolyposis colon cancer syndrome (HNPCC), which is caused by germ line mutations in the DNA repair genes. Women with the HNPCC syndrome have about a 40% risk for developing endometrial cancer, usually before the menopause.

image Symptoms

The most common symptom of endometrial cancer is abnormal vaginal bleeding, which is present in 90% of patients. Postmenopausal bleeding is always abnormal and must be investigated. The most common conditions associated with postmenopausal bleeding are listed in Table 41-1. In the premenopausal patient, especially after age 35 years, menorrhagia or intermenstrual bleeding may signal an endometrial malignancy.

TABLE 41-1 ETIOLOGY OF POSTMENOPAUSAL BLEEDING

Factor Approximate Percentage
Exogenous estrogens 30
Atrophic endometritis, vaginitis 30
Endometrial cancer 15
Endometrial or cervical polyps 10
Endometrial hyperplasia 5
Miscellaneous (e.g., cervical cancer, uterine sarcoma, urethral caruncle, trauma) 10

image Diagnosis

Any woman who presents with postmenopausal bleeding should have a transvaginal ultrasound. If the endometrial thickness is greater than 5 mm, endometrial evaluation is necessary. Outpatient techniques for endometrial sampling include the use of the Kevorkian curette, Vabra aspirator, Gravlee jet washer, and Pipelle cannula. These techniques have a diagnostic accuracy of about 90%. If the endometrial biopsy reveals endometrial cancer, definitive treatment can be arranged. If the endometrial biopsy is negative for cancer or reveals endometrial hyperplasia, a hysteroscopy and fractional dilation and curettage should be performed under general anesthesia. Specimens from the endometrium and endocervix should be submitted separately for histologic evaluation to determine whether the tumor has extended to the endocervix.

In a premenopausal patient with high-risk factors and abnormal uterine bleeding, the endometrium must be sampled. Failure to respond to medical management or a suspicious transvaginal ultrasound is another indication for hysteroscopy and uterine curettage. A grossly obvious lesion of the cervix or vagina should be biopsied directly.

STAGING

The International Federation of Gynecology and Obstetrics (FIGO) changed from a clinical to a surgical staging system for endometrial cancer in 1988. The new surgical staging, based on pathologic confirmation of the extent of spread, is shown in Table 41-2.

TABLE 41-2 International Federation of Gynecology and Obstetrics (FIGO) STAGING OF ENDOMETRIAL CARCINOMA (1988)

Stage Ia Tumor limited to endometrium
Stage Ib Invasion through less than half of the myometrium
Stage Ic Invasion equal to or more than half of the myometrium
Stage IIa Endocervical glandular involvement only
Stage IIb Cervical stroma invasion
Stage IIIa Tumor invades serosa or adnexa or both, or positive peritoneal cytologic findings, or both
Stage IIIb Vaginal metastases
Stage IIIc Metastases to pelvic or para-aortic lymph nodes, or both
Stage IVa Tumor invasion of bladder or bowel mucosa, or both
Stage IVb Distant metastases including intraabdominal or inguinal lymph nodes, or both
Histologic grade does not change the stage
Grade 1 Well differentiated
Grade 2 Moderately differentiated
Grade 3 Poorly differentiated

image Treatment

STAGE I

Surgery

An exploratory laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy is performed on all patients, unless there are absolute medical contraindications (Figure 41-3). On opening the abdomen, peritoneal washings are taken with normal saline for cytologic evaluation. About 15% of patients with disease confined to the corpus have positive peritoneal cytology. Retroperitoneal spaces should be opened and evaluated, and any enlarged pelvic or para-aortic lymph nodes should be resected. Formal surgical staging, including at least pelvic lymphadenectomy, should be performed on high-risk patients, including those with serous, clear cell, or grade 3 histology; outer-half myometrial invasion; or cervical extension. Laparoscopic surgery, including laparoscopic-assisted vaginal hysterectomy and bilateral salpingo-oophorectomy, with or without laparoscopic lymph node dissection, is being increasingly used, particularly for obese patients, and those with grade 1 or 2 cancers.

RECURRENT DISEASE

Seventy-five percent of recurrences develop within 2 years of treatment. If recurrent disease is detected, the patient should undergo a complete physical examination and metastatic workup. Careful follow-up is particularly important for patients treated without adjuvant therapy. Most recurrences in these patients are at the vaginal vault, and 70% to 80% of isolated vault recurrences can be salvaged by radiation therapy.

Metastases in other sites, such as the upper abdomen, lungs, or liver, are treated initially with high-dose progestins or antiestrogens. About one third of recurrent endometrial carcinomas contain estrogen and progesterone receptors, with the more well-differentiated tumors more likely to contain such receptors. As with breast cancer, the likelihood of a patient responding to progestin treatment is increased in patients whose tumor contains estrogen and progesterone receptors. About 80% of such patients respond to progestin therapy, compared with fewer than 10% of patients whose tumor is receptor negative.

Medroxyprogesterone acetate (Provera, 50 mg 3 times daily; Depo-Provera, 400 mg intramuscularly weekly) or megestrol acetate (Megace), 80 mg twice daily, may be given. If disease progresses while the patient is receiving progestins, chemotherapy may be offered. The combination of carboplatin and paclitaxel (Taxol) gives a response rate of about 50%.

ENDOMETRIAL STROMAL TUMORS

The three types of stromal tumors are (1) endometrial stromal nodule; (2) endometrial stromal sarcoma, previously known as endolymphatic stromal myosis; and (3) high-grade endometrial sarcoma. The first of these, the stromal nodule, is a rare benign condition. There are typically three or fewer mitoses per 10 high-power fields. A hysterectomy is curative.

Endometrial stromal sarcoma is a low-grade lesion. Histologically, there is minimal to no cellular atypia, with usually fewer than five mitoses per 10 high-power fields. There is always evidence of vascular channel invasion. These patients usually present with abnormal vaginal bleeding and often with pelvic pain.

Most patients are cured with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Local and distant recurrences may occur even 10 to 20 years later and require reexploration and resection of disease. Prolonged survival is possible after resection of recurrent disease, and response to progestins is good. Pelvic disease may respond to radiation therapy.

High-grade endometrial sarcoma generally causes abnormal uterine bleeding, and more than half of patients are premenopausal. The diagnosis can often be made by endometrial biopsy or uterine curettage. Histologically, there are 10 or more mitoses per 10 high-power fields, and the lesion is composed of very poorly differentiated cells. Aggressive myometrial invasion occurs, and hematogenous spread is common at the time of diagnosis.

The treatment of high-grade endometrial sarcoma is total abdominal hysterectomy and bilateral salpingo-oophorectomy. A thorough exploration of the peritoneal cavity and retroperitoneum should be made for evidence of metastases. Postoperative pelvic irradiation improves local control but does not improve survival. In patients with metastatic disease, progestogens or chemotherapy may be offered. The best chemotherapeutic agents are cisplatin, doxorubicin, and ifosfamide, but the prognosis is poor.