Uterine/Endometrial Cancer

WHAT IS UTERINE / ENDOMETRIAL CANCER?

Endometrial cancer is a disease in which malignant (cancer) cells form in the tissues of the endometrium.

The endometrium is the lining of the uterus. The uterus is a hollow, muscular organ in a woman’s pelvis. The uterus is where a fetus grows. In most nonpregnant women, the uterus is about 3 inches long.

Cancer of the endometrium is different from cancer of the muscle of the uterus, which is called sarcoma of the uterus. Cancer of the endometrium is the most common gynecologic malignancy and accounts for 6% of all cancers in women. It is a highly curable tumor.

Cellular Classification

The most common endometrial cancer cell type is endometrioid adenocarcinoma, which is composed of malignant glandular epithelial elements; an admixture of squamous metaplasia is not uncommon. Adenosquamous tumors contain malignant elements of both glandular and squamous epithelium; clear cell and papillary serous carcinoma of the endometrium are tumors that are histologically similar to those noted in the ovary and the fallopian tube, and the prognosis is worse for these tumors. Mucinous, squamous, and undifferentiated tumors are rarely encountered. Frequency of endometrial cancer cell types is as follows:

Endometrioid (75%-80%)
Ciliated adenocarcinoma.
Secretory adenocarcinoma.
Papillary or villoglandular.
Adenocarcinoma with squamous differentiation.
Adenoacanthoma.
Adenosquamous.
Uterine papillary serous (<10%).
Mucinous (1%).
Clear cell (4%).
Squamous cell (< 1%).
Mixed (10%).
Undifferentiated.


WHAT ARE THE RISK FACTORS OF UTERINE / ENDOMETRIAL CANCER?

Taking tamoxifen for breast cancer or taking estrogen alone (without progesterone) can affect the risk of developing endometrial cancer.

Endometrial cancer may develop in breast cancer patients who have been treated with tamoxifen. A patient taking this drug should have a pelvic examination every year and report any vaginal bleeding (other than menstrual bleeding) as soon as possible. Women taking estrogen (a hormone that can affect the growth of some cancers) alone have an increased risk of developing endometrial cancer. Taking estrogen in combination with progesterone (another hormone) does not increase a woman’s risk of this cancer.



HOW TO DETECT UTERINE / ENDOMETRIAL CANCER?

Possible signs of endometrial cancer include unusual vaginal discharge or pain in the pelvis.

Bleeding or discharge not related to menstruation (periods).
Difficult or painful urination.
Pain during sexual intercourse.
Pain in the pelvic area.
Tests that examine the endometrium are used to detect (find) and diagnose endometrial cancer.

One of the following procedures may be used to diagnose:

Endometrial biopsy: The removal of tissue from the endometrium (inner lining of the uterus) by inserting a thin, flexible tube through the cervix and into the uterus. The tube is used to gently scrape a small amount of tissue from the endometrium and then remove the tissue samples. A pathologist views the tissue under a microscope to look for cancer cells.
Dilatation and curettage: A surgical procedure to remove samples of tissue or the inner lining of the uterus. The cervix is dilated and a curette (spoon-shaped instrument) is inserted into the uterus to remove tissue. Tissue samples may be taken for biopsy. This procedure is also called a D&C.
Stage Information

A hysterectomy is required to determine the degree of myometrial invasion.

Stage I:carcinoma confined to the corpus uteri.

Stage IA: tumor limited to endometrium.
Stage IB: invasion to less than one half of the myometrium.
Stage IC: invasion to greater than one half of the myometrium.
Stage II: cancer involves the corpus and the cervix, but has not extended outside the uterus.

Stage IIA: endocervical glandular involvement only.
Stage IIB: cervical stromal invasion.
Stage III:cancer extends outside of the uterus but is confined to the true pelvis.

Stage IIIA: tumor invades serosa and/or adnexa and/or positive peritoneal cytology.
Stage IIIB: vaginal metastases.
Stage IIIC: metastases to pelvic and/or para-aortic lymph nodes.
Stage IV:cancer involves the bladder or bowel mucosa or has metastasized to distant sites.

Stage IVA: tumor invasion of bladder and/or bowel mucosa.
Stage IVB: distant metastases, including intra-abdominal and/or inguinal lymph nodes.


HOW TO TREAT UTERINE / ENDOMETRIAL CANCER?

Patients with endometrial cancer who have localized disease are usually curable by hysterectomy and bilateral salpingo-oophorectomy. Best results are obtained with either of 2 standard treatments: hysterectomy or hysterectomy and adjuvant radiation therapy (when deep invasion of the myometrial muscle [one half the depth] or grade 3 tumor with myometrial invasion is present). Results of a randomized trial on the use of adjuvant radiation therapy in patients with stage I disease did not show improved survival, but did show a significant increase in morbidity. Vaginal cuff brachytherapy, however, does not increase morbidity and reduces the risk of vaginal cuff recurrence without an effect on survival. Some patients have regional and distant metastases that, although occasionally responsive to standard hormone therapy, are rarely curable. For these patients, standard therapy is inadequate.

Progestational agents have been evaluated as adjuvant therapy in a randomized clinical trial of stage I disease and have been shown to be of no benefit. These studies, however, were not stratified according to level of progesterone receptor in the primary tumor. No trials of adjuvant progestins in more advanced disease are reported. Determination of progesterone receptors in the primary tumor is encouraged, and entry onto an appropriate adjuvant trial (if receptor levels are high) should be considered. If no trial is available, data from receptors on the primary tumor may help guide therapy for recurrent disease, should it occur.

Stage I Endometrial Cancer

Standard treatment options

If the tumor is well or moderately differentiated, involves the upper two thirds of the corpus, has negative peritoneal cytology, is without vascular space invasion, and has less than 50% myometrial invasion, a total abdominal hysterectomy and bilateral salpingo-oophorectomy should be done. Selected pelvic lymph nodes may be removed. If they are negative, no postoperative treatment is indicated. Postoperative treatment with a vaginal cylinder is advocated by some.

For all other cases and cell types, a periaortic and selective pelvic node sampling should be combined with the total abdominal hysterectomy and bilateral salpingo-oophorectomy if there are no medical or technical contraindications. One study found that node dissection per se did not significantly add to the overall morbidity from hysterectomy. While the irradiation will reduce the incidence of local and regional recurrence, improved survival has not been proven and toxic effects are worse.

If the pelvic nodes are positive and the periaortic nodes are negative, total pelvic irradiation, including the common iliac nodes, should be given. The incidence of bowel complications is approximately 4%, and it can be even higher if the radiation is given after pelvic lymphadenectomy. If the surgery is done using a retroperitoneal approach, the toxic effects are lessened. If the periaortic nodes are positive, the patient is a candidate for clinical trials that could include radiation and/or chemotherapy. Patients who have medical contraindications to surgery should be treated with radiation therapy alone, but inferior cure rates below those attained with surgery may occur.

Stage II Endometrial Cancer

Many combinations of preoperative intracavitary and external-beam radiation therapy with hysterectomy and bilateral salpingo-oophorectomy are used for treatment of stage II endometrial cancer, with careful biopsy of the para-aortic nodes at the time of surgery. When microscopic cervical stromal involvement is found, postoperative irradiation (external-beam and vaginal irradiation) should be used.

Stage IIA

Stage IIA (endocervical glandular involvement only) should be treated the same as stage I disease.

Stage IIB

Standard treatment options:

Hysterectomy, bilateral salpingo-oophorectomy, and node sampling followed by postoperative irradiation.
Preoperative intracavitary and external-beam radiation therapy followed by hysterectomy and bilateral salpingo-oophorectomy. (A biopsy of the para-aortic nodes should be done at the time of surgery.)
Radical hysterectomy and pelvic lymphadenectomy in selected cases.
Stage III Endometrial Cancer

Standard treatment options:

In general, these patients are treated with surgery and radiation therapy. These patients may be inoperable if the tumor extends to the pelvic wall, and in this case, they should be treated with radiation therapy. The usual approach is to use a combination of intracavitary and external-beam radiation therapy. Patients who are not candidates for either surgery or irradiation may be treated with progestational agents. Postoperative radiation therapy is used in patients who were thought to have had more localized disease (clinical stage I or II) but are found during hysterectomy to have positive lymph nodes or adnexa. Studies of patterns of failure have found a high rate of distant metastases in the upper abdominal and extra-abdominal sites. For this reason, patients with stage III disease may be candidates for innovative clinical trials.

Stage IV Endometrial Cancer

Standard treatment options

Treatment of stage IV endometrial cancer is dictated by the site of metastatic disease and symptoms related to disease sites. For bulky pelvic disease, radiation therapy consisting of a combination of intracavitary and external- beam irradiation is used. When distant metastases, especially pulmonary metastases, are present, hormonal therapy is indicated and useful.

The most common hormonal treatment has been progestational agents, which produce good antitumor responses in up to 15% to 30% of patients. These responses are associated with significant improvement in survival. Progesterone and estrogen hormone receptors have been identified in endometrial carcinoma tissues. Responses to hormones are correlated with the presence and level of hormone receptors and the degree of tumor differentiation. Standard progestational agents include hydroxyprogesterone (Delalutin), medroxyprogesterone (Provera), and megestrol (Megace).[1]

Recurrent Endometrial Cancer

For localized recurrences (pelvis and periaortic lymph nodes) or distant metastases in selected sites, irradiation may be an effective palliative therapy. In rare instances, pelvic irradiation may be curative in pure vaginal recurrence when no prior radiation has been used. Patients positive for estrogen and progesterone receptors respond best to progestin therapy. Among 115 patients with advanced endometrial cancer who were treated with progestins, 75% (42 of 56) of those with detectable progesterone receptors in their tumors before treatment responded, compared to only 7% without detectable progesterone receptors (4 of 59). A receptor-poor status may predict not only poor response to progestins, but also a better response to cytotoxic chemotherapy. There is evidence to suggest that tamoxifen (20 milligrams twice a day) will give a response rate of 20% in those who do not respond to standard progesterone therapy. Clinical trials are appropriate for patients whose disease recurs with distant metastases and who are unresponsive to hormonal therapy.[4] Doxorubicin is the most active anticancer agent employed, with useful but temporary responses obtained in up to one third of patients with metastatic disease. Paclitaxel also has significant activity.[5]



HOW TO DETECT THE PROGNOSIS OF UTERINE / ENDOMETRIAL CANCER?

Certain factors affect prognosis (chance of recovery) and treatment options,as the following:

The stage of the cancer (whether it is in the endometrium only, involves the whole uterus, or has spread to other places in the body).
How the cancer cells look under a microscope.
Whether the cancer cells are affected by progesterone.
Endometrial cancer is highly curable.