Carcinoma of the endometrium

Definition Endometrial cancer arises from the glandular tissue within the uterine lining. Prevalence Endometrial cancer is the most common of the gynecologic malignancies. Approximately 2% to 3% of women in the United States will develop cancer of the endometrium at some point during their lives. With an estimated 37,000 new cases last year, it is the fourth most common malignancy among women. It predominantly affects older women, with 75% of cases occurring in the postmenopausal years. Pathophysiology Endometrial cancer is a heterogeneous disease that is believed to have two biologically different subtypes, implying two different mechanisms for its origin.
Low-Risk Subtype

The most common subtype is a well-differentiated carcinoma (grade 1 or 2 endometrioid histology) that behaves in an indolent fashion, causes bleeding symptoms in its early stages, and is curable in most cases. Risk factors for this low-risk subtype are well known and are related to an increase in circulating estrogens: obesity, chronic anovulation and nulliparity, estrogen replacement therapy (unopposed by progesterone), and tamoxifen use.
High-Risk Subtype

The high-risk subtype accounts for a minority of endometrial malignancies. These poorly differentiated tumors (grade 3 endometrioid, clear cell, and papillary serous carcinoma) are not associated with increased circulating estrogens. Rather, they appear to occur spontaneously in postmenopausal women without clearly defined risk factors. These tumors metastasize early and account for a disproportionate number of mortalities from endometrial malignancy. Modes of spread include local invasion and lymphatic and vascular embolization. The most common metastatic sites include the cervix, adnexa, and retroperitoneal lymph nodes. Signs and Symptoms Endometrial cancer usually manifests with abnormal uterine bleeding. It should be suspected in any postmenopausal woman with bleeding symptoms. Pre- or perimenopausal women might have bleeding abnormalities such as menorrhagia or metrorrhagia. Less commonly, asymptomatic women can present with an abnormal Papanicolaou (Pap) smear revealing atypical or malignant endometrial cells. A normal Pap smear in a symptomatic woman, however, must never be relied on to exclude endometrial pathology.

Diagnosis A complete physical examination is the first step in the evaluation of a woman with suspected endometrial cancer. Inspection of the vulva, anus, vagina, and cervix is necessary to evaluate for metastatic lesions. A biopsy should be done for any suspicious genital tract lesions detected on examination. Bimanual and rectovaginal examination to evaluate the uterus, cervix, adnexa, parametria, and rectum is essential. Palpation of the inguinal and supraclavicular nodes may reveal enlargement in advanced cases with metastatic disease. Histologic evaluation of endometrial tissue is necessary. An endometrial biopsy can be performed safely and easily in the office setting in most symptomatic patients. The sensitivity for detecting endometrial carcinoma approaches that of a dilation and curettage (D&C) and avoids the expense and morbidity of an operative procedure. Several biopsy instruments are available for use, including the Pipelle sampler and Novak curette. Occasionally, D&C is necessary to obtain tissue for histologic evaluation. Cervical stenosis and patient discomfort are common indications for D&C. This outpatient surgical procedure may be performed using a paracervical block with sedation; however, in some cases, general or regional anesthesia may be preferred. Hysteroscopy and saline infusion sonography visualize endometrial lesions, such as polyps, within the uterine cavity and can be useful adjuncts to endometrial sampling techniques. If endometrial cancer is confirmed, further studies are needed to optimize treatment planning, including a chest x-ray to rule out metastatic disease. Other studies may be performed based on a patient's risk factors and symptoms at presentation. These include computed tomography (CT) scans of the abdomen and pelvis with oral and intravenous contrast (for preoperative assessment of extrauterine tumor spread in high-grade endometrial malignancies); sigmoidoscopy, colonoscopy, or barium enema; intravenous pyelogram; and serum cancer antigen 125 (CA 125) assay for papillary serous carcinoma. Treatment Treatment is based on the surgically determined disease stage and on assessment of prognostic features.1 Staging of endometrial cancer is defined by the International Federation of Gynecology and Obstetrics (FIGO) criteria outlined in Table 1. Surgical staging by exploratory laparotomy requires a peritoneal cytology assessment, intraoperative inspection of the abdominal and pelvic organs (diaphragm, liver, omentum, pelvic and aortic lymph nodes, peritoneal surfaces) for evaluation of metastatic disease, hysterectomy with bilateral salpingo-oophorectomy, and retroperitoneal lymph node sampling.2
Table 1: FIGO Staging for Endometrial Carcinoma

Stag e I II III

Definition Carcinoma confined to the corpus uteri Carcinoma that involves the corpus and the cervix but has not extended outside the uterus Carcinoma that extends outside the uterus but is confined to the true pelvis and/or

IV

retroperitoneal lymph nodes Carcinoma that involves the bladder or bowel mucosa or that has metastasized to distant sites

FIGO, International Federation of Gynecology and Obstetrics.

Surgery

Although endometrial cancer is traditionally managed by laparotomy, increasing evidence supports the safety and efficacy of laparoscopic hysterectomy in appropriately selected patients at low risk for extrauterine tumor spread.
Adjuvant Treatment

The need for adjuvant therapy is based on disease stage and on risk factors for tumor recurrence.
Stage I Disease

For disease confined to the uterus, patients are placed in low-, intermediate-, and high-risk categories, and adjuvant therapies are based on pathologic features. In general, stage I tumors that are higher grade and more deeply invasive into the myometrium have a greater risk for recurrence and benefit from adjuvant therapy postoperatively. Whole-pelvis radiotherapy, with or without vaginal cuff brachytherapy, is the most commonly used adjuvant postoperative treatment modality. Patients with the histologic variant papillary serous carcinoma, an aggressive endometrial lesion with a high risk for extrapelvic recurrence, are generally offered chemotherapy to reduce postoperative recurrence risk, although this treatment is controversial.
Stage II Disease

For disease involving the uterine cervix, there are several treatment options. When unsuspected cervical stromal involvement is found during surgery, postoperative external-beam radiotherapy with vaginal cuff brachytherapy is indicated. If cervical involvement is known preoperatively, various combinations of surgery and radiotherapy have been used:

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 Radical hysterectomy and pelvic lymphadenectomy

Unfortunately, there is no standard treatment for stage II endometrial cancer, and the equivalence of these strategies has not been assessed in comparative randomized trials.
Stage III Disease

In general, postoperative whole-pelvis radiotherapy (vaginal cuff brachytherapy) is indicated when disease involves adnexal structures or retroperitoneal nodes. Patients with para-aortic involvement might benefit from extended-field radiotherapy.
Stage IV Disease

The site of metastatic disease and associated symptoms dictate the appropriate treatment of stage IV endometrial cancer. For bulky pelvic disease, radiation therapy consisting of a combination of intracavitary and external beam irradiation is used. When distant metastases are present, systemic therapy is indicated. Satisfactory tumor responses to hormonal treatment with progestational agents can often be achieved in well-differentiated (grades 1 and 2) tumors. Useful chemotherapeutic agents include doxorubicin and paclitaxel. Outcomes Endometrial cancer is one of the most curable of the gynecologic cancers because most patients have well-differentiated tumors and present with symptoms early in the disease process (Table 2). Five-year survival rates are much poorer in patients with the less common and poorly differentiated tumor histologies. These patients often present with metastatic disease and account for a disproportionate number of endometrial cancer deaths.
Table 2: Endometrial Carcinoma: Stage at Presentation and 5-year Relative Survival Rate

Disease Extent All stages Localized Regional Distant Unstaged

Stage Distribution (%) 73 13 9 4

Survival (%) 84 96 66 27 53

Adapted from Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics Review, 1973-1995. Bethesda, National Cancer Institute, 1998. INTRODUCTION Endometrial cancer is a type of uterine cancer that involves the lining of the uterus (the endometrium). Treatment for endometrial cancer usually includes surgical removal of the uterus, cervix, ovaries, and fallopian tubes; it may also involve sampling or removal of the surrounding lymph nodes. There are two types of endometrial cancer, which are classified by their relationship to estrogen stimulation: More information on the epidemiology, diagnosis, staging, and treatment of endometrial cancer is available by subscription. This topic will discuss the medical and radiation approaches for endometrial cancer following surgical treatment. (See "Patient information: Uterine cancer (The Basics)" and "Patient information: Endometrial cancer diagnosis and staging".) SURGICAL APPROACH TO ENDOMETRIAL CANCER

For women who are good candidates for surgery, hysterectomy, removal of both ovaries and both fallopian tubes (called a bilateral salpingo-oophorectomy, or BSO) and sampling or removal of surrounding lymph nodes is generally performed. The hysterectomy can be done through an incision in the lower abdomen (a total abdominal hysterectomy, or TAH), through the vagina with the help of a laparoscope (total laparoscopic hysterectomy (TLH)), or using a surgical robot (robot-assisted hysterectomy). The results at surgery will help your doctor determine if further treatment is necessary. (See "Patient information: Vaginal hysterectomy" and "Patient information: Abdominal hysterectomy".) DEFINING RISK IN ENDOMETRIAL CANCER There are several recognized pathologic and clinical factors that can identify if you are at an increased risk of relapse after surgery, which can help your doctor determine an appropriate treatment pathway. These factors include: aggressively appearing cancer cells when viewed under the microscope (also called high grade); cancer that invades through the uterine muscle (invades the myometrium); tumor extending outside of the uterus (into the cervix, lower uterine segment, pelvis, or ovaries); papillary serous or clear cell histology (type of endometrial cancer); involvement of the lymphatic or blood vessels (lymphovascular invasion); and older age.

If your cancer is confined to the endometrium (subset of stage IA) it is considered to be low risk. If the cancer has invaded the myometrium (subset of stage IA and all of stage IB) or has microscopic involvement of the cervix (subset of stage II), then it is considered to be of intermediate risk. Some doctors further refine this risk group to include the presence of other factors: lymphovascular invasion, outer-third myometrial invasion, and high tumor grade. However, women of any age with all three risk factors described above; women between 50 and 69 years with two of the risk factors; or women 70 years or older with one risk factor would be considered to have intermediate-high risk disease. Women without these risk factors are considered to have low-intermediate risk disease. Your cancer is considered high risk if it has obvious involvement of the cervix at the time of surgery (a more advanced subset of stage II), has involvement of the pelvis (stage III), involves tissue outside the pelvis (stage IV), or is of papillary serous or clear cell type.

TREATMENT OPTIONS IN ENDOMETRIAL CANCER Treatment for endometrial cancer depends on the risk for persistent or recurrent disease after surgical therapy: Low-risk disease The risk of relapse after surgery for low-risk endometrial cancer is very low with estimates placed at 5 percent or less. Given this, no further treatment is generally recommended. Intermediate-risk disease Women with low-intermediate risk disease can be observed without further treatment since their risk of relapse after surgery alone is low (5 percent or less). Women with high-intermediate risk endometrial cancer benefit from adjuvant therapy to help reduce the chances of the cancer coming back in the pelvis (also known as a local recurrence). For most

women with intermediate-risk disease, adjuvant vaginal or external beam radiation therapy is given. Of the two ways to give radiation, vaginal brachytherapy seems to be as effective as external beam radiation therapy with fewer gastrointestinal side effects. These modes of radiation therapy are described below. High-risk disease Women with high risk endometrial cancer are treated with adjuvant chemotherapy, especially if the disease is located outside of the uterus. Some clinicians recommend adjuvant radiation with or without chemotherapy if high-risk disease is confined to the uterus. TYPES OF ADJUVANT TREATMENT Radiation therapy Radiation therapy refers to the use of high-energy x-rays to slow or stop the growth of cancer cells. Exposure to x-rays damages cells. Unlike normal cells, cancer cells cannot repair the damage caused by exposure to x-rays over several days. This prevents the cancer cells from growing further and causes them to eventually die. For patients with endometrial cancer, adjuvant radiation is given to decrease the risk of the cancer coming back in the pelvis (this is called locoregional recurrence). Radiation is usually given as external beam radiation, meaning that the radiation beam is generated by a machine that is outside the patient. Exposure to the beam typically takes only a few seconds (similar to having an x-ray). The main benefit of adjuvant radiation therapy for endometrial cancer is that it reduces the risk of a locoregional recurrence (ie, that the cancer will come back in the pelvis or vagina). There are two ways to deliver radiation therapy (RT): vaginal brachytherapy (VB) and external beam radiation therapy (EBRT). Vaginal brachytherapy Brachytherapy delivers radiation from a device that is temporarily placed inside the vagina. This device delivers a high dose of radiation directly to the area where cancer cells are most likely to be found, and this helps to minimize the effects of radiation on healthy tissues. There are two types of vaginal brachytherapy: low-dose rate and high-dose rate.

Low-dose rate brachytherapy uses a device that delivers radiation through the vagina continuously for two or three days, 24 hours per day. Patients stay in the hospital during this treatment. High-dose rate brachytherapy also uses a device that delivers radiation through the vagina. However, the device is placed in the vagina for only a few minutes at a time once a day, and treatment is generally repeated three to five times. This treatment is generally given as an outpatient, and women who get high-dose rate brachytherapy do not have to stay in the hospital overnight. They can usually continue their normal daily activities during treatment.

External beam radiation therapy With external beam radiation therapy (EBRT), the source of the radiation is outside the body, and the area to be treated (referred to as the radiation "field") is designed carefully to limit the amount of radiation directed at healthy tissue. During EBRT, your body is positioned beneath the X-ray machine in the same way every day, and the radiation field is exposed to the radiation beam for a few seconds (similar to having an X-ray) once per day,

five days per week, for five to six weeks. This is done as an outpatient, and you can usually continue your normal daily activities during treatment. Side effects of radiation therapy Radiation can cause both short-term and long term side effects. The short term side effects may include:

Feeling tired Needing to empty your bladder frequently Discomfort with urination Loose stools and feeling the need to have a bowel movement frequently Temporary loss of pubic hair

In addition to the short-term side effects, which usually resolve after treatment is completed, there are long-term side effects that may not appear until months after treatment is completed and they may become more chronic problems. These include:

Urine leakage Pain or bleeding with bowel movements Narrowing or scarring of the vagina

Chemotherapy Chemotherapy is a treatment given to stop the growth of cancer cells. It aims to destroy any remaining cancer cells to increase the chance of cure. This type of chemotherapy is called "adjuvant", which means that it is given after surgery with curative intent. For women with high-risk endometrial cancer, a combination of agents (called a regimen) is usually recommended. This typically consists of two drugs, carboplatin and paclitaxel. However, some clinicians may prescribe the three-drug combination of cisplatin, doxorubicin, and paclitaxel (TAP). How is chemotherapy given? Chemotherapy is not given every day but instead is given in cycles. A cycle of chemotherapy (which is typically 21 or 28 days) refers to the time it takes to give the treatment and then allow the body to recover from the side effects of the medicines. This treatment usually involves a combination of several chemotherapy drugs (called regimens). Following surgery, it is usually started within four to six weeks postoperatively, and precedes radiation therapy, if this too has been recommended. Since different combinations of chemotherapy can be used, your doctor will describe which specific chemotherapy drugs will be needed, how long treatment will last, and what side effects are expected from your treatment. Side effects of chemotherapy It is important to understand that while chemotherapy can cause side effects, some of which can be quite serious, not all patients who are getting chemotherapy will develop all of these side effects. The most common side effects of chemotherapy include:

Feeling tired Temporary hair loss Nausea and vomiting Diarrhea Low blood counts

Menopausal symptoms, like hot flashes, night sweats, and vaginal dryness Numbness and tingling of the fingers and toes (this is called neuropathy)

SPECIAL CONSIDERATIONS FOR WOMEN WITH NEWLY DIAGNOSED ENDOMETRIAL CANCER While most women with newly diagnosed endometrial cancer should undergo surgical treatment and adjuvant treatment tailored to risk, there are several situations in which the above discussion may not necessarily apply. These include the following scenarios: Endometrial cancer in the young woman Young premenopausal women are sometimes diagnosed with endometrial cancer at a time when they are considering or desire to have children. For young women with a low risk of relapse, surgery (hysterectomy) may be delayed. This is not an option for women with intermediate- or high-risk endometrial cancer. However, women should know of options to preserve fertility and alternate means of becoming a parent before beginning any form of treatment. If surgical treatment is delayed, progestin treatment is used to suppress the growth of the endometrial cancer. Women who are able to delay immediate surgery for family planning still require definitive surgical treatment. Without surgery there is a significant risk that the cancer will come back later. Cancer in the obese patient or medically inoperable woman For women who are obese or who have other serious medical problems, surgery with nodal sampling or removal may not be a treatment option. For these women, treatment options may include a more limited surgical procedure to remove the uterus or non-surgical treatment such as the use of radiation therapy. Incompletely staged patients As described above, the treatment of endometrial cancer requires information on the tumor and whether lymph nodes are involved. However, for some women, surgery may not have included comprehensive staging (ie, evaluation of nodes). Most clinicians will not give adjuvant therapy to women with low-risk endometrial cancer who have not had lymph node sampling. However, options for women with intermediate- or high- risk disease, include further surgical evaluation or the use of adjuvant chemotherapy or radiation. Your doctor can help you decide which of these options may be best for you. (See 'Defining risk in endometrial cancer' above.) FOLLOW-UP AFTER ENDOMETRIAL CANCER TREATMENT Most women and families affected by endometrial cancer worry about their short-term and longterm health and the risk of the cancer coming back. It is important for women to talk openly and honestly with their family and healthcare team. Many women benefit from bringing a family member or friend to visits with their doctor; this person can help you to understand your options, ask important questions, take notes, and provide emotional support. A variety of support options are available both during and after treatment, including individual counseling, support groups, and Internet-based discussion groups. A list of reputable groups is available as well. (See 'Patient support' below.)

Cancer surveillance Experts recommend close follow-up after the completion of treatment for endometrial cancer, particularly in the first three years after diagnosis when the risk of recurrence is highest. This usually includes an exam and Pap smear every three to six months for several years. Other tests, like blood tests and computed tomography (CT) scans or other radiology tests should be done only if a recurrence is suspected. If the cancer does not come back after five years, women can usually stop seeing the oncologist and return to their primary care provider or women's healthcare provider. Women should call their doctor if they develop any symptoms of vaginal bleeding, pain in the belly or pelvis, a cough that will not go away, or unintentional weight loss. These could be signs that the cancer has come back. Treating menopausal symptoms Premenopausal woman who have had their ovaries removed as part of treatment usually experience symptoms of menopause. This may include hot flashes, night sweats, and vaginal dryness. The most effective treatment for these symptoms is the female hormone estrogen. Most experts think that estrogen is a reasonable option for women with endometrial cancer. You should discuss the potential risks and benefits of estrogen with your doctor. For women receiving adjuvant treatment (eg, radiation therapy or chemotherapy), some experts recommend waiting 6 to 12 months after finishing treatment before beginning estrogen therapy. Other non-hormonal treatments for menopausal symptoms are available; these are discussed separately. (See "Patient information: Nonhormonal treatments for menopausal symptoms".) Sexual issues after treatment Changes in the vagina are common after endometrial cancer treatment. Pelvic or vaginal radiation can cause the vagina to shorten, narrow, and feel dry. These changes can cause pain with sex (also called dyspareunia). Many of these problems are treatable:

Ask your doctor or nurse about using vaginal dilators to prevent and treat narrowing of the vagina. Use a vaginal moisturizer or lubricant during sex to treat dryness. Women with endometrial cancer may be able to use a vaginal estrogen (a cream, vaginal ring, or pill) to treat dryness. More information about vaginal estrogen is available in a separate article. (See "Patient information: Vaginal dryness".) Pelvic physical therapy and counseling for sexual or psychological difficulties can be helpful. (See "Patient information: Sexual problems in women".)

ENDOMETRIAL CANCER SYMPTOMS The most common sign of endometrial cancer is abnormal vaginal bleeding.

In a woman who is still having menstrual periods, abnormal bleeding is defined as bleeding between menstrual periods or heavy menstrual bleeding. (See "Patient information: Abnormal uterine bleeding".)

In a postmenopausal woman, any vaginal bleeding is considered abnormal, even if it is only one drop of blood. This is especially true in women who are not taking postmenopausal hormone therapy.

Women who take postmenopausal hormone therapy often have some vaginal bleeding in the first few months of treatment. However, if you are taking postmenopausal hormone therapy and you have bleeding, you should check with your doctor or nurse. ENDOMETRIAL CANCER DIAGNOSIS AND STAGING Your doctor or nurse might recommend testing for endometrial cancer if you have abnormal bleeding. The most commonly used tests include:

A test that is done in the office, called endometrial biopsy. A test that is done as a day surgery, called hysteroscopy with dilation and curettage. (See "Patient information: Dilation and curettage (D and C)".)

These tests take a sample of tissue from the lining of the uterus, called the endometrium. A doctor will examine the tissue with a microscope to see if there are signs of cancer. Tumor staging Once endometrial cancer is diagnosed, the next step is to determine its stage. Staging is a system used to describe the spread of a cancer. Endometrial cancer's stage is based on:

How deeply the cancer has invaded the muscle wall of the uterus Whether there are signs that the cancer has spread to other organs on a physical exam, MRI of the abdomen and pelvis, chest X-ray, or other imaging tests

Endometrial cancer stages range from stage I (cancer has not invaded beyond the lining of the uterus) to stage IV (the cancer has spread to distant organs, such as the liver). In general, lowerstage cancers are less aggressive and require less treatment than do higher-stage cancers. Surgery Surgery is usually done to determine how deeply the cancer has invaded the muscle wall of the uterus. At the same time, the cancer can be treated by removing the uterus, ovaries, and fallopian tubes. Surgery is done in an operating room with general anesthesia, and most women stay in the hospital for several days after the surgery. Surgery can be done by making a vertical (up-and-down) or horizontal (left-to-right) incision in the abdomen, then examining the organs within the pelvis and abdomen for signs of cancer. This is called a laparotomy. In other cases, surgery can be done laparoscopically, which is done through small incisions in the abdomen. The surgeon uses a thin, lighted instrument with a camera (a laparoscope) to see inside the abdomen and remove tissues.

The choice between laparotomy and laparoscopy depends on your situation and your surgeon's preference. During the surgery, the following procedures are performed:

The uterus and ovaries are removed (called total abdominal hysterectomy and bilateral salpingo-oophorectomy). This procedure is described in detail in a separate article. (See "Patient information: Abdominal hysterectomy".) Fluid from the abdomen and any abnormal tissue in the pelvis or abdomen are evaluated to determine whether the cancer has spread outside of the uterus The lymph nodes surrounding the uterus are examined. One of the first places that endometrial cancer spreads to is the lymph nodes. Swelling of the legs (lymphedema) affects approximately five to 40 percent of women with endometrial cancer following removal of lymph nodes.

If surgery is not possible If surgery is too risky, such as in elderly women and women with serious medical problems, radiation therapy alone may be recommended. ENDOMETRIAL CANCER TREATMENT The treatment of endometrial cancer depends on how likely it is that the cancer will come back after treatment. This risk is based on:

The stage of the cancer, which is based on what is found during surgery (see 'Tumor staging' above) How aggressive the tumor appears (called the tumor grade) when the tissue is examined under a microscope. High-grade tumors are usually faster growing and more likely to spread than low-grade tumors. What type of cells make up the tumor (called cell histology). Some cell types have a higher risk of coming back after treatment.

Depending on these characteristics, the cancer is said to have a low, intermediate, or high risk of coming back after surgery. These designations are used to decide which treatments, if any, are needed after surgery to decrease the risk of the cancer coming back. Endometrial cancer treatment is discussed in a separate article. (See "Patient information: Endometrial cancer treatment after surgery".) PREGNANCY AND ENDOMETRIAL CANCER Although cancer is more common in postmenopausal women, it can develop in younger women. A woman with endometrial cancer who would like to have a child in the future should discuss treatment options with her doctor. (See "Patient information: Endometrial cancer treatment after surgery", section on 'Endometrial cancer in the young woman'.)

Staging

If uterine cancer is diagnosed, your doctor needs to learn the extent (stage) of the disease to help you choose the best treatment. The stage is based on whether the cancer has invaded nearby tissues or spread to other parts of the body. When cancer spreads from its original place to another part of the body, the new tumor has the same kind of abnormal cells and the same name as the primary (original) tumor. For example, if uterine cancer spreads to the lung, the cancer cells in the lung are actually uterine cancer cells. The disease is metastatic uterine cancer, not lung cancer. It's treated as uterine cancer, not as lung cancer. Doctors sometimes call the new tumor "distant" disease. To learn whether uterine cancer has spread, your doctor may order one or more tests:

Lab tests: A Pap test can show whether cancer cells have spread to the cervix, and blood tests can show how well the liver and kidneys are working. Also, your doctor may order a blood test for a substance known as CA-125. Cancer may cause a high level of CA-125.

Chest x-ray: An x-ray of the chest can show a tumor in the lung.

CT scan: An x-ray machine linked to a computer takes a series of detailed pictures of your pelvis, abdomen, or chest. You may receive an injection of contrast material so your lymph nodes and other tissues show up clearly in the pictures. A CT scan can show cancer in the uterus, lymph nodes, lungs, or elsewhere.

MRI: A large machine with a strong magnet linked to a computer is used to make detailed pictures of your uterus and lymph nodes. You may receive an injection of contrast material. MRI can show cancer in the uterus, lymph nodes, or other tissues in the abdomen.

In most cases, surgery is needed to learn the stage of uterine cancer. The surgeon removes the uterus and may take tissue samples from the pelvis and abdomen. After the uterus is removed, it is checked to see how deeply the tumor has grown. Also, the other tissue samples are checked for cancer cells. These are the stages of uterine cancer:

Stage 0: The abnormal cells are found only on the surface of the inner lining of the uterus. The doctor may call this carcinoma in situ.

Stage I: The tumor has grown through the inner lining of the uterus to the endometrium. It may have invaded the myometrium.

Stage II: The tumor has invaded the cervix.

Stage III: The tumor has grown through the uterus to reach nearby tissues, such as the vagina or a lymph node.

Stage IV: The tumor has invaded the bladder or intestine. Or, cancer cells have spread to parts of the body far away from the uterus, such as the liver, lungs, or bones.

Treatment
Treatment options for people with uterine cancer are surgery, radiation therapy, chemotherapy, and hormone therapy. You may receive more than one type of treatment. The treatment that's right for you depends mainly on the following:

Whether the tumor has invaded the muscle layer of the uterus

Whether the tumor has invaded tissues outside the uterus

Whether the tumor has spread to other parts of the body

The grade of the tumor

Your age and general health

You may have a team of specialists to help plan your treatment. Your doctor may refer you to a specialist, or you may ask for a referral. Specialists who treat uterine cancer include gynecologists, gynecologic oncologists (doctors who specialize in treating female cancers),

medical oncologists, and radiation oncologists. Your health care team may also include an oncology nurse and a registered dietitian. Your health care team can describe your treatment choices, the expected results of each, and the possible side effects. Because cancer therapy often damages healthy cells and tissues, side effects are common. Before treatment starts, ask your health care team about possible side effects and how treatment may change your normal activities. You and your health care team can work together to develop a treatment plan that meets your needs. At any stage of disease, supportive care is available to control pain and other symptoms, to relieve the side effects of treatment, and to ease emotional concerns. Information about such care is available on NCI's Web site at http://www.cancer.gov/cancertopics/coping. Also, NCI's Cancer Information Service can answer your questions about supportive care. Call 1800-4-CANCER (1-800-422-6237). Or chat using LiveHelp, NCI's instant messaging service, at http://www.cancer.gov/livehelp. You may want to talk with your doctor about taking part in a clinical trial. Clinical trials are research studies testing new treatments. They are an important option for people with all stages of uterine cancer. See the Taking Part in Cancer Research section. You may want to ask your doctor these questions before you begin treatment:

What is the grade of the tumor? What is the stage of the disease? Has the tumor invaded the muscle layer of the uterus or spread to other organs?

What are my treatment choices? Which do you suggest for me? Why?

What are the expected benefits of each kind of treatment?

What can I do to prepare for treatment?

Will I need to stay in the hospital? If so, for how long?

What are the risks and possible side effects of each treatment? How can side effects be

managed?

What is the treatment likely to cost? Will my insurance cover it?

How will treatment affect my normal activities?

Would a research study (clinical trial) be a good choice for me?

Can you recommend other doctors who could give me a second opinion about my treatment options?

How often should I have checkups?

Surgery
Surgery is the most common treatment for women with uterine cancer. You and your surgeon can talk about the types of surgery (hysterectomy) and which may be right for you. The surgeon usually removes the uterus, cervix, and nearby tissues. The nearby tissues may include:

Ovaries

Fallopian tubes

Nearby lymph nodes

Part of the vagina

The time it takes to heal after surgery is different for each woman. After a hysterectomy, most women go home in a couple days, but some women leave the hospital the same day. You'll probably return to your normal activities within 4 to 8 weeks after surgery. You may have pain or discomfort for the first few days. Medicine can help control your pain. Before surgery, you should discuss the plan for pain relief with your doctor or nurse. After surgery, your doctor can adjust the plan if you need more pain control. It's common to feel tired or weak for a while. You may have nausea and vomiting. Some women are constipated after surgery or lose control of their bladder. These effects are usually temporary. If you haven't gone through menopause yet, you'll stop having menstrual periods after surgery, and you won't be able to become pregnant. Also, you may have hot flashes, vaginal dryness, and night sweats. These symptoms are caused by the sudden loss of female hormones. Talk with your doctor or nurse about your symptoms so that you can develop a treatment plan together. There are drugs and lifestyle changes that can help, and most symptoms go away or lessen with time. Surgery to remove lymph nodes may cause lymphedema (swelling) in one or both legs. Your health care team can tell you how to prevent or relieve lymphedema. For some women, a hysterectomy can affect sexual intimacy. You may have feelings of loss that make intimacy difficult. Sharing these feelings with your partner may be helpful. Sometimes couples talk with a counselor to help them express their concerns.

Radiation Therapy
Radiation therapy is an option for women with all stages of uterine cancer. It may be used before or after surgery. For women who can't have surgery for other medical reasons, radiation therapy may be used instead to destroy cancer cells in the uterus. Women with cancer that invades tissue beyond the uterus may have radiation therapy and chemotherapy. Radiation therapy uses high-energy rays to kill cancer cells. It affects cells in the treated area only. Doctors use two types of radiation therapy to treat uterine cancer. Some women receive both types:

External radiation therapy: A large machine directs radiation at your pelvis or other areas with cancer. The treatment is usually given in a hospital or clinic. You may receive external radiation 5 days a week for several weeks. Each session takes only a few minutes.

Internal radiation therapy (also called brachytherapy): A narrow cylinder is placed inside your vagina, and a radioactive substance is loaded into the cylinder. Usually, a

treatment session lasts only a few minutes and you can go home afterward. This common method of brachytherapy may be repeated two or more times over several weeks. Once the radioactive substance is removed, no radioactivity is left in the body. Side effects depend mainly on which type of radiation therapy is used, how much radiation is given, and which part of your body is treated. External radiation to the abdomen and pelvis may cause nausea, vomiting, diarrhea, or urinary problems. You may lose hair in your genital area. Also, your skin in the treated area may become red, dry, and tender. You are likely to become tired during external radiation therapy, especially in the later weeks of treatment. Resting is important, but doctors usually advise patients to try to stay as active as they can. For women who have not had surgery to remove the ovaries, external radiation aimed at the pelvic area can harm the ovaries. Menstrual periods usually stop, and women may have hot flashes and other symptoms of menopause. Menstrual periods are more likely to return for younger women. After either type of radiation therapy, you may have dryness, itching, or burning in your vagina. Your doctor may advise you to wait to have sex until a few weeks after radiation therapy ends. Also, radiation therapy may make the vagina narrower. A narrow vagina can make sex or followup exams difficult. There are ways to prevent this problem. If it does occur, however, your health care team can tell you about ways to expand the vagina. Although the side effects of radiation therapy can be upsetting, they can usually be treated or controlled. Talk with your doctor or nurse about ways to relieve discomfort.

Chemotherapy
Chemotherapy uses drugs to kill cancer cells. It may be used after surgery to treat uterine cancer that has an increased risk of returning after treatment. For example, uterine cancer that is a high grade or is Stage II, III, or IV may be more likely to return. Also, chemotherapy may be given to women whose uterine cancer can't be completely removed by surgery. For advanced cancer, it may be used alone or with radiation therapy. Chemotherapy for uterine cancer is usually given by vein (intravenous). It's usually given in cycles. Each cycle has a treatment period followed by a rest period. You may have your treatment in an outpatient part of the hospital, at the doctor's office, or at home. Some women may need to stay in the hospital during treatment. The side effects depend mainly on which drugs are given and how much. Chemotherapy kills fast-growing cancer cells, but the drugs can also harm normal cells that divide rapidly:

Blood cells: When drugs lower the levels of healthy blood cells, you're more likely to get infections, bruise or bleed easily, and feel very weak and tired. Your health care team will check for low levels of blood cells. If your levels are low, your health care team may stop the chemotherapy for a while or reduce the dose of the drug. There are also medicines that can help your body make new blood cells.

Cells in hair roots: Chemotherapy may cause hair loss. If you lose your hair, it will grow back after treatment, but the color and texture may be changed.

Cells that line the digestive system: Chemotherapy can cause a poor appetite, nausea and vomiting, diarrhea, or mouth and lip sores. Your health care team can give you medicines and suggest other ways to help with these problems. They usually go away when treatment ends.

Other possible side effects include skin rash, tingling or numbness in your hands and feet, hearing problems, loss of balance, joint pain, or swollen legs and feet. Your health care team can suggest ways to control many of these problems. Most go away when treatment ends.
Uterine Cancer (Cancer of the Uterus, Endometrial Cancer) At A Glance

Cancer of the uterus occurs most often in women between the ages of 55 and 70 years. Risk factors (factors that increase chances of developing the disease) have been identified. Abnormal bleeding after menopause is the most common symptom of cancer of the uterus. Cancer of the uterus is diagnosed based on the results of the pelvic examination, pap smear, biopsy of the uterus, and D and C procedure. Treatment of cancer of the uterus depends on the stage of the disease, the growth rate of the cancer, as well as the age and health of the woman.