Endometrial Cancer Treatment (PDQ®)


Information for: Patients | Healthcare Professionals

General Information About 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, 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. The lower, narrow end of the uterus is the cervix, which leads to the vagina.

Anatomy of the female reproductive system; drawing shows the uterus, myometrium (muscular outer layer of the uterus), endometrium (inner lining of the uterus), ovaries, fallopian tubes, cervix, and vagina. 
Anatomy of the female reproductive system. The organs in the female reproductive system include the uterus, ovaries, fallopian tubes, cervix, and vagina. The uterus has a muscular outer layer called the myometrium and an inner lining called the endometrium.

Cancer of the endometrium is different from cancer of the muscle of the uterus, which is called sarcoma of the uterus. See the PDQ summary on Uterine Sarcoma Treatment for more information.

Taking tamoxifen for breast cancer or taking estrogen alone (without progesterone) can increase the risk of 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 exam 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 endometrial cancer. Taking estrogen combined with progesterone (another hormone) does not increase a woman’s risk of this cancer.

Signs and symptoms of endometrial cancer include unusual vaginal discharge or pain in the pelvis.

These and other signs and symptoms may be caused by endometrial cancer or by other conditions. Check with your doctor if you have any of the following:

  • 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.

Because endometrial cancer begins inside the uterus, it does not usually show up in the results of a Pap test. For this reason, a sample of endometrial tissue must be removed and checked under a microscope to look for cancer cells. One of the following procedures may be used:

  • 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 procedure to remove samples of tissue from the inner lining of the uterus. The cervix is dilated and a curette (spoon-shaped instrument) is inserted into the uterus to remove tissue. The tissue samples are checked under a microscope for signs of disease. This procedure is also called a D&C.
    Dilatation and curettage (D and C). Three-panel drawing showing a side view of the female reproductive anatomy during a D and C procedure. The first panel shows a speculum widening the opening of the vagina. The cervix, uterus with abnormal tissue, bladder, and rectum are also shown; an inset shows the lower half of a woman covered by a drape on an exam table with her legs apart  and her feet in stirrups. The middle panel shows the uterus and a dilator inserted through the vagina into the cervix. The third panel shows a curette scraping out abnormal tissue from the uterus; an inset shows a close up of the curette with the abnormal tissue in it. 
    Dilatation and curettage (D and C). A speculum is inserted into the vagina to widen it in order to look at the cervix (first panel). A dilator is used to widen the cervix (middle panel). A curette is put through the cervix into the uterus to scrape out abnormal tissue (last panel).

Other tests and procedures used to diagnose endometrial cancer include the following:

  • Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
  • Transvaginal ultrasound exam: A procedure used to examine the vagina, uterus, fallopian tubes, and bladder. An ultrasound transducer (probe) is inserted into the vagina and used to bounce high-energy sound waves (ultrasound) off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. The doctor can identify tumors by looking at the sonogram.
    Transvaginal ultrasound; drawing shows a side view of the female reproductive anatomy during a transvaginal ultrasound procedure. An ultrasound probe (a device that makes sound waves that bounce off tissues inside the body) is shown inserted into the vagina. The bladder, uterus, right fallopian tube, and right ovary are also shown. The inset shows the diagnostic sonographer (a person trained to perform ultrasound procedures) examining a woman on a table, and a computer screen shows an image of the patient’s internal tissues. 
    Transvaginal ultrasound. An ultrasound probe connected to a computer is inserted into the vagina and is gently moved to show different organs. The probe bounces sound waves off internal organs and tissues to make echoes that form a sonogram (computer picture).
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on 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.

Stages of Endometrial Cancer

After endometrial cancer has been diagnosed, tests are done to find out if cancer cells have spread within the uterus or to other parts of the body.

The process used to find out whether the cancer has spread within the uterus or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. Certain tests and procedures are used in the staging process. A hysterectomy (an operation in which the uterus is removed) will usually be done to help find out how far the cancer has spread.

The following procedures may be used in the staging process:

  • Pelvic exam: An exam of the vagina, cervix, uterus, fallopian tubes, ovaries, and rectum. The doctor or nurse inserts one or two lubricated, gloved fingers of one hand into the vagina and the other hand is placed over the lower abdomen to feel the size, shape, and position of the uterus and ovaries. A speculum is also inserted into the vagina and the doctor or nurse looks at the vagina and cervix for signs of disease. A Pap test or Pap smear of the cervix is usually done. The doctor or nurse also inserts a lubricated, gloved finger into the rectum to feel for lumps or abnormal areas.
    Pelvic exam; drawing shows a side view of the female reproductive anatomy during a pelvic exam. The uterus, left fallopian tube, left ovary, cervix, vagina, bladder, and rectum are shown. Two gloved fingers of one hand of the doctor or nurse are shown inserted into the vagina, while the other hand is shown pressing on the lower abdomen. The inset shows a woman covered by a drape on an exam table with her legs apart and her feet in stirrups.  
    Pelvic exam. A doctor or nurse inserts one or two lubricated, gloved fingers of one hand into the vagina and presses on the lower abdomen with the other hand. This is done to feel the size, shape, and position of the uterus and ovaries. The vagina, cervix, fallopian tubes, and rectum are also checked.
  • Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • PET scan (positron emission tomography scan): A procedure to find malignanttumorcells in the body. A small amount of radioactiveglucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

  • Tissue. The cancer spreads from where it began by growing into nearby areas.
  • Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
  • Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

  • Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
  • Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if endometrial cancer spreads to the lung, the cancer cells in the lung are actually endometrial cancer cells. The disease is metastatic endometrial cancer, not lung cancer.

The following stages are used for endometrial cancer:

Stage I

Stage IA and stage IB endometrial cancer shown in two cross-section drawings of the uterus and cervix. Drawing on the left shows stage IA, with cancer in the endometrium and myometrium of the uterus. Drawing on the right shows stage IB, with cancer more than halfway through the myometrium. Also shown are the fallopian tubes, ovaries, and vagina. 
Stage IA and stage IB endometrial cancer. In stage IA, cancer is in the endometrium only or less than halfway through the myometrium (the muscle layer of the uterus). In stage IB, cancer has spread halfway or more into the myometrium.

In stage I, cancer is found in the uterus only. Stage I is divided into stages IA and IB, based on how far the cancer has spread.

  • Stage IA: Cancer is in the endometrium only or less than halfway through the myometrium (muscle layer of the uterus).
  • Stage IB: Cancer has spread halfway or more into the myometrium.

Stage II

Stage II endometrial cancer shown in a cross-section drawing of the uterus, cervix, fallopian tubes, ovaries, and vagina. Cancer is shown in the endometrium and myometrium of the uterus and in the cervix. 
Stage II endometrial cancer. Cancer has spread into connective tissue of the cervix, but has not spread outside the uterus.

In stage II, cancer has spread into connective tissue of the cervix, but has not spread outside the uterus.

Stage III

In stage III, cancer has spread beyond the uterus and cervix, but has not spread beyond the pelvis. Stage III is divided into stages IIIA, IIIB, and IIIC, based on how far the cancer has spread within the pelvis.

  • Stage IIIA: Cancer has spread to the outer layer of the uterus and/or to the fallopian tubes, ovaries, and ligaments of the uterus.
    Stage IIIA endometrial cancer shown in a cross-section drawing of the uterus, ligaments of the uterus, cervix, fallopian tubes, ovaries, and vagina. Cancer is shown in the endometrium of the uterus, the outer layer of the uterus, a fallopian tube, an ovary, and a ligament of the uterus. 
    Stage IIIA endometrial cancer. Cancer has spread to the outer layer of the uterus and/or to the fallopian tubes, ovaries, or ligaments of the uterus.
  • Stage IIIB: Cancer has spread to the vagina or to the parametrium (connective tissue and fat around the uterus).
    Stage IIIB endometrial cancer shown in a cross-section drawing of the uterus, cervix, fallopian tubes, ovaries, and vagina.  Cancer is shown in the endometrium of the uterus, the parametrium, the cervix, and the vagina. 
    Stage IIIB endometrial cancer. Cancer has spread to the vagina and/or to the parametrium (connective tissue and fat around the uterus and cervix).
  • Stage IIIC: Cancer has spread to lymph nodes in the pelvis and/or around the aorta (largest artery in the body, which carries blood away from the heart).
    Stage IIIC endometrial cancer shown in a cross-section drawing of the uterus, cervix, fallopian tubes, ovaries, and vagina. Also shown are the lymph nodes in the pelvis and the aorta with nearby lymph nodes. Cancer is shown in the endometrium and myometrium of the uterus and in lymph nodes in the pelvis and near the aorta. 
    Stage IIIC endometrial cancer. Cancer has spread to lymph nodes in the pelvis and/or around the aorta (the largest artery in the body, which carries blood away from the heart).

Stage IV

In stage IV, cancer has spread beyond the pelvis. Stage IV is divided into stages IVA and IVB, based on how far the cancer has spread.

  • Stage IVA: Cancer has spread to the bladder and/or bowel wall.
    Stage IVA endometrial cancer shown in a side-view cross-section drawing of the uterus, bladder, cervix, vagina, small intestine, and large intestine. Cancer is shown in the bladder, uterus, and bowel. 
    Stage IVA endometrial cancer. Cancer has spread into the bladder and/or bowel.
  • Stage IVB: Cancer has spread to other parts of the body beyond the pelvis, including the abdomen and/or lymph nodes in the groin.
    Stage IVB endometrial cancer; drawing shows cancer has spread beyond the pelvis to lymph nodes in the abdomen. Inset shows cancer spreading through the blood and lymph nodes to other parts of the body. 
    Stage IVB endometrial cancer. Cancer has spread beyond the pelvis to other parts of the body, such as the abdomen and/or lymph nodes in the groin.

Recurrent Endometrial Cancer

Recurrentendometrial cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the uterus, the pelvis, in lymph nodes in the abdomen, or in other parts of the body.

Treatment Option Overview

There are different types of treatment for patients with endometrial cancer.

Different types of treatment are available for patients with endometrial cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Four types of standard treatment are used:

Surgery

Surgery (removing the cancer in an operation) is the most common treatment for endometrial cancer. The following surgical procedures may be used:

  • Total hysterectomy: Surgery to remove the uterus, including the cervix. If the uterus and cervix are taken out through the vagina, the operation is called a vaginalhysterectomy. If the uterus and cervix are taken out through a large incision (cut) in the abdomen, the operation is called a total abdominal hysterectomy. If the uterus and cervix are taken out through a small incision (cut) in the abdomen using a laparoscope, the operation is called a total laparoscopic hysterectomy.
    Hysterectomy; drawing shows the female reproductive anatomy, including the ovaries, uterus, vagina, fallopian tubes, and cervix. Dotted lines show which organs and tissues are removed in a total hysterectomy, a total hysterectomy with salpingo-oophorectomy, and a radical hysterectomy. An inset shows the location of two possible incisions on the abdomen: a low transverse incision is just above the pubic area and a vertical incision is between the navel and the pubic area. 
    Hysterectomy. The uterus is surgically removed with or without other organs or tissues. In a total hysterectomy, the uterus and cervix are removed. In a total hysterectomy with salpingo-oophorectomy, (a) the uterus plus one (unilateral) ovary and fallopian tube are removed; or (b) the uterus plus both (bilateral) ovaries and fallopian tubes are removed. In a radical hysterectomy, the uterus, cervix, both ovaries, both fallopian tubes, and nearby tissue are removed. These procedures are done using a low transverse incision or a vertical incision.
  • Bilateral salpingo-oophorectomy: Surgery to remove both ovaries and both fallopian tubes.
  • Radical hysterectomy: Surgery to remove the uterus, cervix, and part of the vagina. The ovaries, fallopian tubes, or nearby lymph nodes may also be removed.

Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given radiation therapy or hormone treatment after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Hormone therapy

Hormone therapy is a cancer treatment that removes hormones or blocks their action and stops cancer cells from growing. Hormones are substances made by glands in the body and circulated in the bloodstream. Some hormones can cause certain cancers to grow. If tests show that the cancer cells have places where hormones can attach (receptors), drugs, surgery, or radiation therapy is used to reduce the production of hormones or block them from working.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.

Biologic therapy

Biologic therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options by Stage

Stage I Endometrial Cancer

Treatment of stage I endometrial cancer may include the following:

  • Surgery (total hysterectomy and bilateral salpingo-oophorectomy). Lymph nodes in the pelvis and abdomen may also be removed and viewed under a microscope to check for cancercells.
  • Surgery (total hysterectomy and bilateral salpingo-oophorectomy, with or without removal of lymph nodes in the pelvis and abdomen) followed by internal or external radiation therapy to the pelvis. After surgery, a plastic cylinder containing a source of radiation may be placed in the vagina to kill any remaining cancer cells.
  • Radiation therapy alone for patients who cannot have surgery.
  • Clinical trials of new types of treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I endometrial carcinoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage II Endometrial Cancer

Treatment of stage II endometrial cancer is usually surgery (radical hysterectomy and bilateral salpingo-oophorectomy). Lymph nodes in the pelvis and abdomen may also be removed and viewed under a microscope to check for cancercells. Radiation therapy may follow surgery.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II endometrial carcinoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage III Endometrial Cancer

Treatment of stage III endometrial cancer may include the following:

  • Surgery (radical hysterectomy and removal of lymph nodes in the pelvis so they can be viewed under a microscope to check for cancercells) followed by adjuvantchemotherapy and/or radiation therapy.
  • Chemotherapy combined with internal and external radiation therapy for patients who cannot have surgery.
  • Hormone therapy for patients who cannot have surgery or radiation therapy.
  • A clinical trial of biologic therapy with or without chemotherapy.
  • Clinical trials of new types of treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III endometrial carcinoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage IV Endometrial Cancer

Treatment of stage IV endometrial cancer may include the following:

  • Surgery followed by chemotherapy and/or radiation therapy.
  • Internal and external radiation therapy for patients who cannot have surgery.
  • Hormone therapy for patients whose cancer has spread to distant parts of the body (such as the lungs).
  • Clinical trials of chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV endometrial carcinoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Treatment Options for Recurrent Endometrial Cancer

Treatment of recurrentendometrial cancer may include the following:

  • Radiation therapy as palliative therapy to relieve symptoms and improve the patient’s quality of life.
  • Hormone therapy.
  • Clinical trials of chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent endometrial carcinoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

To Learn More About Endometrial Cancer

For more information from the National Cancer Institute about endometrial cancer, see the following:

For general cancer information and other resources from the National Cancer Institute, see the following:


This information is provided by the National Cancer Institute.

This information was last updated on November 22, 2013.


General Information About Endometrial Cancer

Incidence and Mortality

Estimated new cases and deaths from endometrial (uterine corpus) cancer in the United States in 2013:[1]

  • New cases: 49,560.
  • Deaths: 8,190.

Cancer of the endometrium is the most common gynecologic malignancy in the United States and accounts for 6% of all cancers in women. Irregular vaginal bleeding is an early sign and foremost symptom of the highly curable endometrial tumor To detect endometrial cancer, a technique that directly samples the endometrial tissue is mandatory. The Pap smear is not reliable as a screening procedure in endometrial cancer, although a retrospective study found a strong correlation between positive cervical cytology and high-risk disease (i.e., high-grade tumor and deep myometrial invasion) [2] as well as an increased risk of nodal disease.[3] The degree of tumor differentiation has an important impact on the natural history of this disease and on treatment selection. An increased incidence of endometrial cancer has been found in association with prolonged, unopposed estrogen exposure.[4][5] In contrast, combined estrogen and progesterone therapy prevents the increase in risk of endometrial cancer associated with unopposed estrogen use.[6][7] In some patients, an antecedent history of complex hyperplasia with atypia can be demonstrated. An increased incidence of endometrial cancer has also been found in association with tamoxifen treatment of breast cancer (NSABP-B-14), related to the estrogenic effect of tamoxifen on the endometrium.[8][9] Because of this increase, patients on tamoxifen should have follow-up pelvic examinations and should be examined if there is any abnormal uterine bleeding.

The pattern of spread is partially dependent on the degree of cellular differentiation. Well-differentiated tumors tend to limit their spread to the surface of the endometrium; myometrial extension is less common. In patients with poorly differentiated tumors, myometrial invasion occurs much more frequently. Myometrial invasion is frequently a harbinger of lymph node involvement and distant metastases and is often independent of the degree of differentiation.[10][11] Metastatic spread occurs in a characteristic pattern. Spread to the pelvic and para-aortic nodes is common. When distant metastasis occurs, it most commonly involves the following:

  • Lungs.
  • Inguinal and supraclavicular nodes.
  • Liver.
  • Bones.
  • Brain.
  • Vagina.

Another factor found to correlate with extrauterine and nodal spread of tumor is involvement of the capillary-lymphatic space on histopathologic examination.[12] Three prognostic groupings of clinical stage I disease become possible by careful operative staging. Patients with grade 1 tumors involving only endometrium and no evidence of intraperitoneal disease (i.e., adnexal spread) have a low risk (<5%) of nodal involvement.[13] Patients with grade 2 or 3 tumors and invasion of less than 50% of the myometrium and no intraperitoneal disease have a 5% to 9% incidence of pelvic node involvement and a 4% incidence of positive para-aortic nodes. Patients with deep muscle invasion and high-grade tumors and/or intraperitoneal disease have a significant risk of nodal spread, 20% to 60% to pelvic nodes and 10% to 30% to para-aortic nodes. One study was directed specifically at stage I, grade 1 carcinomas of favorable histologic type. The authors identified the following four statistically significant adverse prognostic factors:[14]

  • Myometrial invasion.
  • Vascular invasion.
  • Eight or more mitoses per ten high-power fields.
  • An absence of progesterone receptors.

Another group identified aneuploidy and a high S-phase fraction as predictive of poor prognosis.[15] A Gynecologic Oncology Group study related surgical-pathologic parameters and postoperative treatment to recurrence-free interval and recurrence site. For patients without extrauterine spread, the greatest determinants of recurrence were grade 3 histology and deep myometrial invasion. In this study, the frequency of recurrence was greatly increased with positive pelvic nodes, adnexal metastasis, positive peritoneal cytology, capillary space involvement, involvement of the isthmus or cervix, and, particularly, positive para-aortic nodes (includes all grades and depth of invasion). Of the cases with aortic node metastases, 98% were in patients with positive pelvic nodes, intra-abdominal metastases, or tumor invasion of the outer 33% of the myometrium.[16][17]

When the only evidence of extrauterine spread is positive peritoneal cytology, the influence on outcome is unclear. The value of therapy directed at this cytologic finding is not well founded.[18][19][20][21][22][23] As a result, although the collection of cytology specimens is still suggested, a positive result does not upstage the disease. Other extrauterine disease must be present before additional postoperative therapy is considered.

One report found progesterone receptor levels to be the single most important prognostic indicator of 3-year survival in clinical stage I and II disease. Patients with progesterone receptor levels higher than 100 had a 3-year disease-free survival of 93% compared with 36% for a level lower than 100. Only cervical involvement and peritoneal cytology were significant prognostic variables after adjusting for progesterone receptor levels.[24] Other reports confirm the importance of hormone receptor status as an independent prognostic factor.[25] Additionally, immunohistochemical staining of paraffin-embedded tissue for both estrogen and progesterone receptors has been shown to correlate with International Federation of Gynecology and Obstetrics grade as well as survival.[26][27][28] On the basis of these data, progesterone and estrogen receptors, assessed either by biochemical or immunohistochemical methods, should be included, when possible, in the evaluation of stage I and II patients. The following have also been found to be prognostic indicators of clinical outcome:[28]

  • Oncogene expression.
  • DNA ploidy.
  • The fraction of cells in S-phase.

For example, overexpression of the Her-2/neu oncogene has been associated with a poor overall prognosis.[29] A general review of prognostic factors has been published.[30]

Related Summaries

Other PDQ summaries containing information related to endometrial (uterine corpus) cancer include the following:

  • Endometrial Cancer Prevention
  • Endometrial Cancer Screening
  • Uterine Sarcoma Treatment

References:

  1. American Cancer Society.: Cancer Facts and Figures 2013. Atlanta, Ga: American Cancer Society, 2013. Available online. Last accessed January 10, 2014.

  2. DuBeshter B, Warshal DP, Angel C, et al.: Endometrial carcinoma: the relevance of cervical cytology. Obstet Gynecol 77 (3): 458-62, 1991.

  3. Larson DM, Johnson KK, Reyes CN Jr, et al.: Prognostic significance of malignant cervical cytology in patients with endometrial cancer. Obstet Gynecol 84 (3): 399-403, 1994.

  4. Ziel HK, Finkle WD: Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med 293 (23): 1167-70, 1975.

  5. Jick SS, Walker AM, Jick H: Estrogens, progesterone, and endometrial cancer. Epidemiology 4 (1): 20-4, 1993.

  6. Jick SS: Combined estrogen and progesterone use and endometrial cancer. Epidemiology 4 (4): 384, 1993.

  7. Bilezikian JP: Major issues regarding estrogen replacement therapy in postmenopausal women. J Womens Health 3 (4): 273-82, 1994.

  8. van Leeuwen FE, Benraadt J, Coebergh JW, et al.: Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet 343 (8895): 448-52, 1994.

  9. Fisher B, Costantino JP, Redmond CK, et al.: Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst 86 (7): 527-37, 1994.

  10. Hendrickson M, Ross J, Eifel PJ, et al.: Adenocarcinoma of the endometrium: analysis of 256 cases with carcinoma limited to the uterine corpus. Pathology review and analysis of prognostic variables. Gynecol Oncol 13 (3): 373-92, 1982.

  11. Nori D, Hilaris BS, Tome M, et al.: Combined surgery and radiation in endometrial carcinoma: an analysis of prognostic factors. Int J Radiat Oncol Biol Phys 13 (4): 489-97, 1987.

  12. Hanson MB, van Nagell JR Jr, Powell DE, et al.: The prognostic significance of lymph-vascular space invasion in stage I endometrial cancer. Cancer 55 (8): 1753-7, 1985.

  13. Takeshima N, Hirai Y, Tanaka N, et al.: Pelvic lymph node metastasis in endometrial cancer with no myometrial invasion. Obstet Gynecol 88 (2): 280-2, 1996.

  14. Tornos C, Silva EG, el-Naggar A, et al.: Aggressive stage I grade 1 endometrial carcinoma. Cancer 70 (4): 790-8, 1992.

  15. Friberg LG, Norén H, Delle U: Prognostic value of DNA ploidy and S-phase fraction in endometrial cancer stage I and II: a prospective 5-year survival study. Gynecol Oncol 53 (1): 64-9, 1994.

  16. Morrow CP, Bundy BN, Kurman RJ, et al.: Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol 40 (1): 55-65, 1991.

  17. Lanciano RM, Corn BW, Schultz DJ, et al.: The justification for a surgical staging system in endometrial carcinoma. Radiother Oncol 28 (3): 189-96, 1993.

  18. Ambros RA, Kurman RJ: Combined assessment of vascular and myometrial invasion as a model to predict prognosis in stage I endometrioid adenocarcinoma of the uterine corpus. Cancer 69 (6): 1424-31, 1992.

  19. Turner DA, Gershenson DM, Atkinson N, et al.: The prognostic significance of peritoneal cytology for stage I endometrial cancer. Obstet Gynecol 74 (5): 775-80, 1989.

  20. Piver MS, Recio FO, Baker TR, et al.: A prospective trial of progesterone therapy for malignant peritoneal cytology in patients with endometrial carcinoma. Gynecol Oncol 47 (3): 373-6, 1992.

  21. Kadar N, Homesley HD, Malfetano JH: Positive peritoneal cytology is an adverse factor in endometrial carcinoma only if there is other evidence of extrauterine disease. Gynecol Oncol 46 (2): 145-9, 1992.

  22. Lurain JR: The significance of positive peritoneal cytology in endometrial cancer. Gynecol Oncol 46 (2): 143-4, 1992.

  23. Lurain JR, Rice BL, Rademaker AW, et al.: Prognostic factors associated with recurrence in clinical stage I adenocarcinoma of the endometrium. Obstet Gynecol 78 (1): 63-9, 1991.

  24. Ingram SS, Rosenman J, Heath R, et al.: The predictive value of progesterone receptor levels in endometrial cancer. Int J Radiat Oncol Biol Phys 17 (1): 21-7, 1989.

  25. Creasman WT: Prognostic significance of hormone receptors in endometrial cancer. Cancer 71 (4 Suppl): 1467-70, 1993.

  26. Carcangiu ML, Chambers JT, Voynick IM, et al.: Immunohistochemical evaluation of estrogen and progesterone receptor content in 183 patients with endometrial carcinoma. Part I: Clinical and histologic correlations. Am J Clin Pathol 94 (3): 247-54, 1990.

  27. Chambers JT, Carcangiu ML, Voynick IM, et al.: Immunohistochemical evaluation of estrogen and progesterone receptor content in 183 patients with endometrial carcinoma. Part II: Correlation between biochemical and immunohistochemical methods and survival. Am J Clin Pathol 94 (3): 255-60, 1990.

  28. Gurpide E: Endometrial cancer: biochemical and clinical correlates. J Natl Cancer Inst 83 (6): 405-16, 1991.

  29. Hetzel DJ, Wilson TO, Keeney GL, et al.: HER-2/neu expression: a major prognostic factor in endometrial cancer. Gynecol Oncol 47 (2): 179-85, 1992.

  30. Homesley HD, Zaino R: Endometrial cancer: prognostic factors. Semin Oncol 21 (1): 71-8, 1994.

Cellular Classification of Endometrial Cancer

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;[1] 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.[2] Mucinous, squamous, and undifferentiated tumors are rarely encountered. Frequency of endometrial cancer cell types is as follows:

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

References:

  1. Zaino RJ, Kurman R, Herbold D, et al.: The significance of squamous differentiation in endometrial carcinoma. Data from a Gynecologic Oncology Group study. Cancer 68 (10): 2293-302, 1991.

  2. Gusberg SB: Virulence factors in endometrial cancer. Cancer 71 (4 Suppl): 1464-6, 1993.

Stage Information for Endometrial Cancer

Definitions: FIGO

The Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) and the American Joint Committee on Cancer (AJCC) have designated staging to define endometrial cancer; the FIGO system is most commonly used.[1][2]

Carcinosarcomas should be staged as carcinoma.[2] FIGO stages are further subdivided by the histologic grade of the tumor, for example, stage IC G2.

Table 1. Carcinoma of the Endometriuma

Stage

 

Ib 

Tumor confined to the corpus uteri.

IAb 

No or less than half myometrial invasion.

IBb 

Invasion equal to or more than half of the myometrium.

IIb 

Tumor invades cervical stroma but does not extend beyond the uterus.c 

IIIb 

Local and/or regional spread of the tumor.

IIIAb 

Tumor invades the serosa of the corpus uteri and/or adnexae.d 

IIIBb 

Vaginal and/or parametrial involvement.d 

IIICb 

Metastases to pelvic and/or para-aortic lymph nodes.d 

IIIC1b 

Positive pelvic nodes.

IIIC2b 

Positive para-aortic lymph nodes with or without positive pelvic lymph nodes.

IVb 

Tumor invades bladder and/or bowel mucosa, and/or distant metastases.

IVAb 

Tumor invasion of bladder and/or bowel mucosa.

IVBb 

Distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes.

aAdapted from FIGO Committee on Gynecologic Oncology.[1]

bEither G1, G2, or G3 (G = grade).

cEndocervical glandular involvement only should be considered as stage I and no longer as stage II.

dPositive cytology has to be reported separately without changing the stage.

References:

  1. Pecorelli S: Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 105 (2): 103-4, 2009.

  2. Corpus uteri. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 403-18.

Treatment Option Overview

Patients with endometrial cancer who have localized disease are usually curable by hysterectomy and bilateral salpingo-oophorectomy. Best results are obtained with either of two standard treatments: hysterectomy or hysterectomy and adjuvant radiation therapy (when deep invasion of the myometrial muscle [50% of the depth] or grade 3 tumor with myometrial invasion is present). Results of two randomized trials on the use of external-beam radiation therapy (EBRT) in patients with stage I disease did not show improved survival but did show reduced locoregional recurrence (3%–4% vs. 12%–14% after 5–6 years' median follow-up, P <.001) with an increase in side effects.[1][2][3][Level of evidence: 1iiDii] Results of a study by the Danish Endometrial Cancer Group also suggest that the absence of radiation does not improve the survival of patients with stage I, intermediate-risk disease (grade 1 and 2 with >50% myometrial invasion or grade 3 with <50% myometrial invasion).[4]

Vaginal cuff brachytherapy is associated with less radiation-related morbidity than is EBRT and has been shown to be equivalent to EBRT in the adjuvant setting for patients with stage I disease.[5] A subset of patients with stage I disease are at a high risk of recurrence and are eligible for adjuvant therapy. Most patients will do well with surgery alone.

Some patients have regional and distant metastases that, though 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.

References:

  1. Creutzberg CL, van Putten WL, Koper PC, et al.: Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet 355 (9213): 1404-11, 2000.

  2. Keys HM, Roberts JA, Brunetto VL, et al.: A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 92 (3): 744-51, 2004.

  3. Scholten AN, van Putten WL, Beerman H, et al.: Postoperative radiotherapy for Stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review. Int J Radiat Oncol Biol Phys 63 (3): 834-8, 2005.

  4. Bertelsen K, Ortoft G, Hansen ES: Survival of Danish patients with endometrial cancer in the intermediate-risk group not given postoperative radiotherapy: the Danish Endometrial Cancer Study (DEMCA). Int J Gynecol Cancer 21 (7): 1191-9, 2011.

  5. Nout RA, Smit VT, Putter H, et al.: Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet 375 (9717): 816-23, 2010.

Stage I Endometrial Cancer

Standard treatment options:  

A total hysterectomy and bilateral salpingo-oophorectomy should be done if the tumor:

  • Is well or moderately differentiated.
  • Involves the upper 66% of the corpus.
  • Has negative peritoneal cytology.
  • Is without vascular space invasion.
  • Has less than a 50% myometrial invasion.

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 clinicians.[1]

For all other cases and cell types, a pelvic and selective periaortic node sampling should be combined with the total 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.[2] While the radiation therapy will reduce the incidence of local and regional recurrence, improved survival has not been proven and toxic effects are worse.[3][4][5][6] Results of two randomized trials on the use of adjuvant radiation therapy in patients with stage I disease did not show improved survival but did show reduced locoregional recurrence (3%–4% vs. 12%–14% after 5–6 years' median follow-up, P <.001) with an increase in side effects.[6][7][8][Level of evidence: 1iiDii] Results of a study by the Danish Endometrial Cancer Group also suggest that the absence of radiation does not improve the survival of patients with stage I, intermediate-risk disease (grade 1 and 2 with >50% myometrial invasion or grade 3 with <50% myometrial invasion).[9]

The PORTEC-2 trial randomly assigned patients with stage I endometrial cancer who did not undergo lymph node dissection to undergo vaginal brachytherapy (VBT) or external-beam radiation therapy (EBRT), with prevention of vaginal recurrence as the primary outcome.[10] At 5 years, there was no difference in the rates of vaginal recurrence, locoregional recurrence, progression-free survival or overall survival (OS) (84.8% [95% confidence interval—CI—, 79.3–90.3] vs. 79.6% [95% CI, 71.2–88.0] for VBT and EBRT, respectively; P = .57). There were significantly fewer gastrointestinal toxic effects in the VBT group, making VBT the preferred option for adjuvant treatment of patients with stage I disease.[10][Level of evidence: 1iA]

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.[1][11][12]

Several randomized trials have compared total laparoscopic hysterectomy (TLH) with the standard open procedure, total abdominal hysterectomy (TAH), for patients with early-stage endometrial cancer. Thus far, these reports have been limited to the feasibility of the procedure and quality of life. Feasibility of the laparoscopic approach has been confirmed, although TLH is associated with a longer operative time.[13][14][15] TLH had an improved [13][14] or similar [15] adverse event profile and a shorter hospital stay [13][14][15] when compared with TAH. TLH was associated with less pain and quicker resumption of daily activities,[15][16] although one study found that most of the gains in quality of life favoring laparoscopy at the 6-week postsurgical period were no longer significant at 6 months.[15][16] Questions remain regarding the efficacy of TLH compared with TAH for endometrial cancer [17] and are awaiting the reports of disease-free survival and OS from these phase III studies.

The completed GOG-LAP2 trial included 2,616 patients with clinical stage I to IIA disease and randomly assigned them two-to-one to comprehensive surgical staging via laparoscopy or laparotomy.[18] Time to recurrence was the primary endpoint, with noninferiority defined as a difference in recurrence rate of less than 5.3% between the two groups at 3 years. The recurrence rate at 3 years was 10.24% for patients in the laparotomy arm, compared with 11.39% for patients in the laparoscopy arm, with an estimated difference between groups of 1.14% (90% lower bound, -1.278; 95% upper bound, 3.996). Although this difference was lower than the prespecified limit, the statistical requirements for noninferiority were not met because of a lower-than-expected number of recurrences in both groups. The OS at 5 years was 89.8% in both groups. Future analyses may determine whether there are subgroups of patients for whom there is a clinically significant decrement when laparoscopic staging is utilized.[18][Level of evidence: 1iiDiii]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I endometrial carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Eltabbakh GH, Piver MS, Hempling RE, et al.: Excellent long-term survival and absence of vaginal recurrences in 332 patients with low-risk stage I endometrial adenocarcinoma treated with hysterectomy and vaginal brachytherapy without formal staging lymph node sampling: report of a prospective trial. Int J Radiat Oncol Biol Phys 38 (2): 373-80, 1997.

  2. Homesley HD, Kadar N, Barrett RJ, et al.: Selective pelvic and periaortic lymphadenectomy does not increase morbidity in surgical staging of endometrial carcinoma. Am J Obstet Gynecol 167 (5): 1225-30, 1992.

  3. Aalders J, Abeler V, Kolstad P, et al.: Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients. Obstet Gynecol 56 (4): 419-27, 1980.

  4. Morrow CP, Bundy BN, Kurman RJ, et al.: Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol 40 (1): 55-65, 1991.

  5. Marchetti DL, Caglar H, Driscoll DL, et al.: Pelvic radiation in stage I endometrial adenocarcinoma with high-risk attributes. Gynecol Oncol 37 (1): 51-4, 1990.

  6. Creutzberg CL, van Putten WL, Koper PC, et al.: Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet 355 (9213): 1404-11, 2000.

  7. Keys HM, Roberts JA, Brunetto VL, et al.: A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 92 (3): 744-51, 2004.

  8. Scholten AN, van Putten WL, Beerman H, et al.: Postoperative radiotherapy for Stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review. Int J Radiat Oncol Biol Phys 63 (3): 834-8, 2005.

  9. Bertelsen K, Ortoft G, Hansen ES: Survival of Danish patients with endometrial cancer in the intermediate-risk group not given postoperative radiotherapy: the Danish Endometrial Cancer Study (DEMCA). Int J Gynecol Cancer 21 (7): 1191-9, 2011.

  10. Nout RA, Smit VT, Putter H, et al.: Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet 375 (9717): 816-23, 2010.

  11. Stokes S, Bedwinek J, Kao MS, et al.: Treatment of stage I adenocarcinoma of the endometrium by hysterectomy and adjuvant irradiation: a retrospective analysis of 304 patients. Int J Radiat Oncol Biol Phys 12 (3): 339-44, 1986.

  12. Grigsby PW, Kuske RR, Perez CA, et al.: Medically inoperable stage I adenocarcinoma of the endometrium treated with radiotherapy alone. Int J Radiat Oncol Biol Phys 13 (4): 483-8, 1987.

  13. Janda M, Gebski V, Brand A, et al.: Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE): a randomised trial. Lancet Oncol 11 (8): 772-80, 2010.

  14. Walker JL, Piedmonte MR, Spirtos NM, et al.: Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2. J Clin Oncol 27 (32): 5331-6, 2009.

  15. Mourits MJ, Bijen CB, Arts HJ, et al.: Safety of laparoscopy versus laparotomy in early-stage endometrial cancer: a randomised trial. Lancet Oncol 11 (8): 763-71, 2010.

  16. Kornblith AB, Huang HQ, Walker JL, et al.: Quality of life of patients with endometrial cancer undergoing laparoscopic international federation of gynecology and obstetrics staging compared with laparotomy: a Gynecologic Oncology Group study. J Clin Oncol 27 (32): 5337-42, 2009.

  17. Vergote I, Amant F, Neven P: Is it safe to treat endometrial carcinoma endoscopically? J Clin Oncol 27 (32): 5305-7, 2009.

  18. Walker JL, Piedmonte MR, Spirtos NM, et al.: Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol 30 (7): 695-700, 2012.

Stage II Endometrial Cancer

Standard treatment options:  

  1. If cervical involvement is documented, options include radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymph node dissection.
  2. If the cervix is clinically uninvolved but extension to the cervix is documented on postoperative pathology, radiation therapy should be considered.

The completed GOG-LAP2 trial included 2,616 patients with clinical stage I to IIA disease and randomly assigned them two-to-one to comprehensive surgical staging via laparoscopy or laparotomy.[1] Time to recurrence was the primary endpoint, with noninferiority defined as a difference in recurrence rate of less than 5.3% between the two groups at 3 years. The recurrence rate at 3 years was 10.24% for patients in the laparotomy arm, compared with 11.39% for patients in the laparoscopy arm, with an estimated difference between groups of 1.14% (90% lower bound, -1.278; 95% upper bound, 3.996). Although this difference was lower than the prespecified limit, the statistical requirements for noninferiority were not met because of a lower-than-expected number of recurrences in both groups. The OS at 5 years was 89.8% in both groups. Future analyses may determine whether there are subgroups of patients for whom there is a clinically significant decrement when laparoscopic staging is utilized.[1][Level of evidence: 1iiDiii]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II endometrial carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Walker JL, Piedmonte MR, Spirtos NM, et al.: Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol 30 (7): 695-700, 2012.

Stage III Endometrial Cancer

Standard treatment options:  

In general, patients with stage III endometrial cancer are treated with surgery, followed by chemotherapy, or radiation therapy, or both. For many years, radiation therapy was the standard adjuvant treatment for patients with endometrial cancer. However, several randomized trials have confirmed improved survival when adjuvant chemotherapy is used instead of radiation therapy. In a trial conducted in a subset of patients with stage III or IV disease with residual tumors smaller than 2 cm and no parenchymal organ involvement, the use of the combination of cisplatin and doxorubicin resulted in improved overall survival (OS) compared with whole-abdominal radiation therapy (adjusted hazard ratio, 0.68; 95% confidence interval limits, 0.52–0.89; P = .02; 5-year survival rates of 55% vs. 42%).[1][Level of evidence: 1iiA]

In a subsequent trial, paclitaxel with doxorubicin had an outcome similar to that of cisplatin with doxorubicin.[2][3] The three-drug regimen (doxorubicin, cisplatin, and paclitaxel) with granulocyte colony-stimulating factor (G-CSF), however, was significantly superior to cisplatin plus doxorubicin: response rates were 57% versus 34%; progression-free survival was 8.3 months versus 5.3 months; and OS was 15.3 months versus 12.3 months, respectively. The superior regimen was associated with a 12% grade 3 and a 27% grade 2 peripheral neuropathy.[2][3][Level of evidence: 1iiDiv]

Given the toxicity and limited efficacy of these regimens, other treatment options have been widely sought. Several observational studies [4][5] and phase II studies [6][7][8][9] suggested clinical activity with the combination of platinums and paclitaxel in endometrial cancer patients with measurable disease either following primary surgery or at recurrence. As a result, the Gynecologic Oncology Group (GOG) opened protocol GOG-0209, a noninferiority trial comparing the combination of doxorubicin, cisplatin, and paclitaxel (TAP) with G-CSF to carboplatin and paclitaxel. The interim results, currently available in abstract form, showing that carboplatin and paclitaxel is not inferior to TAP have lent credence to the use of carboplatin and paclitaxel as the standard for adjuvant treatment of stage III and IV disease.

Patients with inoperable disease caused by tumor that extends to the pelvic wall may be treated with a combination of chemotherapy and radiation therapy. The usual approach is to use a combination of intracavitary radiation therapy and external-beam radiation therapy.

Patients who are not candidates for either surgery or radiation therapy may be treated with progestational agents. 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.[10]

Treatment options under clinical evaluation:  

  • The use of biological agents alone, or in combination with chemotherapy, is being investigated in multiple clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III endometrial carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Randall ME, Filiaci VL, Muss H, et al.: Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 24 (1): 36-44, 2006.

  2. Fleming GF, Brunetto VL, Cella D, et al.: Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 22 (11): 2159-66, 2004.

  3. Fleming GF, Filiaci VL, Bentley RC, et al.: Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study. Ann Oncol 15 (8): 1173-8, 2004.

  4. Arimoto T, Nakagawa S, Yasugi T, et al.: Treatment with paclitaxel plus carboplatin, alone or with irradiation, of advanced or recurrent endometrial carcinoma. Gynecol Oncol 104 (1): 32-5, 2007.

  5. Sovak MA, Hensley ML, Dupont J, et al.: Paclitaxel and carboplatin in the adjuvant treatment of patients with high-risk stage III and IV endometrial cancer: a retrospective study. Gynecol Oncol 103 (2): 451-7, 2006.

  6. Hoskins PJ, Swenerton KD, Pike JA, et al.: Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study. J Clin Oncol 19 (20): 4048-53, 2001.

  7. Pectasides D, Xiros N, Papaxoinis G, et al.: Carboplatin and paclitaxel in advanced or metastatic endometrial cancer. Gynecol Oncol 109 (2): 250-4, 2008.

  8. Nomura H, Aoki D, Takahashi F, et al.: Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin in patients with advanced or recurrent endometrial carcinoma: a Japanese Gynecologic Oncology Group study (JGOG2041). Ann Oncol 22 (3): 636-42, 2011.

  9. Dimopoulos MA, Papadimitriou CA, Georgoulias V, et al.: Paclitaxel and cisplatin in advanced or recurrent carcinoma of the endometrium: long-term results of a phase II multicenter study. Gynecol Oncol 78 (1): 52-7, 2000.

  10. Greven KM, Curran WJ Jr, Whittington R, et al.: Analysis of failure patterns in stage III endometrial carcinoma and therapeutic implications. Int J Radiat Oncol Biol Phys 17 (1): 35-9, 1989.

Stage IV Endometrial Cancer

Standard treatment options:  

Treatment of patients with 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 radiation therapy is used. When distant metastases, especially pulmonary metastases, are present, hormonal therapy is indicated and useful. Observational studies support maximal cytoreductive surgery for patients with stage IV disease, although these conclusions need to be interpreted with care because of the small number of cases and likely selection bias.

When possible, patients with stage IV endometrial cancer are treated with surgery, followed by chemotherapy, or radiation therapy, or both. For many years, radiation therapy was the standard adjuvant treatment for patients with endometrial cancer. However, several randomized trials have confirmed improved survival when adjuvant chemotherapy is used instead of radiation therapy. In a trial conducted in a subset of patients with stage III or IV disease with residual tumors smaller than 2 cm and no parenchymal organ involvement, the use of the combination of cisplatin and doxorubicin resulted in improved overall survival (OS) compared with whole-abdominal radiation therapy (adjusted hazard ratio, 0.68; 95% confidence interval limits, 0.52–0.89; P = .02; 5-year survival rates of 55% vs. 42%).[1][Level of evidence: 1iiA]

In a subsequent trial, paclitaxel with doxorubicin had an outcome similar to that of cisplatin with doxorubicin.[2][3] The three-drug regimen (doxorubicin, cisplatin, and paclitaxel) with granulocyte colony-stimulating factor (G-CSF), however, was significantly superior to cisplatin plus doxorubicin: response rates were 57% versus 34%; progression-free survival was 8.3 months versus 5.3 months; and OS was 15.3 months versus 12.3 months, respectively. The superior regimen was associated with a 12% grade 3 and a 27% grade 2 peripheral neuropathy.[2][3][Level of evidence: 1iiDiv]

Given the toxicity and limited efficacy of these regimens, other treatment options have been widely sought. Several observational studies [4][5] and phase II studies [6][7][8][9] suggested clinical activity with the combination of platinums and paclitaxel in endometrial cancer patients with measurable disease either following primary surgery or at recurrence. As a result, the Gynecologic Oncology Group (GOG) opened protocol GOG-0209, a noninferiority trial comparing the combination of doxorubicin, cisplatin, and paclitaxel (TAP) and G-CSF with carboplatin and paclitaxel. The interim results, currently available in abstract form, showing that carboplatin and paclitaxel is not inferior to TAP have lent credence to the use of carboplatin and paclitaxel as the standard for adjuvant treatment in stage III and IV disease.

The most common hormonal treatment has been progestational agents, which produce good antitumor responses in as many as 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, medroxyprogesterone, and megestrol.[10]

Treatment options under clinical evaluation:  

All patients with advanced disease should be considered for clinical trials that evaluate single-agent or combination therapy for this disease.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV endometrial carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Randall ME, Filiaci VL, Muss H, et al.: Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 24 (1): 36-44, 2006.

  2. Fleming GF, Brunetto VL, Cella D, et al.: Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 22 (11): 2159-66, 2004.

  3. Fleming GF, Filiaci VL, Bentley RC, et al.: Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study. Ann Oncol 15 (8): 1173-8, 2004.

  4. Arimoto T, Nakagawa S, Yasugi T, et al.: Treatment with paclitaxel plus carboplatin, alone or with irradiation, of advanced or recurrent endometrial carcinoma. Gynecol Oncol 104 (1): 32-5, 2007.

  5. Sovak MA, Hensley ML, Dupont J, et al.: Paclitaxel and carboplatin in the adjuvant treatment of patients with high-risk stage III and IV endometrial cancer: a retrospective study. Gynecol Oncol 103 (2): 451-7, 2006.

  6. Hoskins PJ, Swenerton KD, Pike JA, et al.: Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study. J Clin Oncol 19 (20): 4048-53, 2001.

  7. Pectasides D, Xiros N, Papaxoinis G, et al.: Carboplatin and paclitaxel in advanced or metastatic endometrial cancer. Gynecol Oncol 109 (2): 250-4, 2008.

  8. Nomura H, Aoki D, Takahashi F, et al.: Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin in patients with advanced or recurrent endometrial carcinoma: a Japanese Gynecologic Oncology Group study (JGOG2041). Ann Oncol 22 (3): 636-42, 2011.

  9. Dimopoulos MA, Papadimitriou CA, Georgoulias V, et al.: Paclitaxel and cisplatin in advanced or recurrent carcinoma of the endometrium: long-term results of a phase II multicenter study. Gynecol Oncol 78 (1): 52-7, 2000.

  10. Lentz SS: Advanced and recurrent endometrial carcinoma: hormonal therapy. Semin Oncol 21 (1): 100-6, 1994.

Recurrent Endometrial Cancer

For patients with localized recurrences (pelvis and periaortic lymph nodes) or distant metastases in selected sites, radiation therapy may be an effective palliative therapy. In rare instances, pelvic radiation therapy may be curative in pure vaginal recurrence when no prior radiation therapy 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 patients) of those with detectable progesterone receptors in their tumors before treatment responded, compared with only 7% without detectable progesterone receptors (4 of 59 patients).[1] A receptor-poor status may predict not only poor response to progestins but also a better response to cytotoxic chemotherapy.[2] Evidence suggests that tamoxifen (20 mg twice a day) will give a response rate of 20% in those who do not respond to standard progesterone therapy.[3]

Several randomized trials by the Gynecologic Oncology Group have utilized the known antitumor activity of doxorubicin. The addition of cisplatin to doxorubicin increased response rates and progression-free survival (PFS) over doxorubicin alone but without an effect on overall survival (OS).[4] However, in a trial conducted in a subset of patients with stage III or IV disease with residual tumors smaller than 2 cm and no parenchymal organ involvement, the use of the combination of cisplatin and doxorubicin resulted in improved OS compared with whole-abdominal radiation therapy (adjusted hazard ratio, 0.68; 95% confidence interval limits, 0.52–0.89; P = .02; 5-year survival rate of 55% vs. 42%).[5][Level of evidence: 1iiA] In a subsequent trial, paclitaxel with doxorubicin had a similar outcome to cisplatin with doxorubicin.[6][7] The three-drug regimen (doxorubicin, cisplatin, and paclitaxel) with granulocyte colony-stimulating factor, however, was significantly superior to cisplatin plus doxorubicin: response rates were 57% versus 34%, PFS was 8.3 months versus 5.3 months, and OS was 15.3 months versus 12.3 months, respectively. The superior regimen was associated with a 12% grade 3 and a 27% grade 2 peripheral neuropathy.[6][7][Level of evidence: 1iiDiv]

Clinical trials are appropriate for patients whose disease recurs with distant metastases and who are unresponsive to hormonal therapy.[8] Doxorubicin is the most active anticancer agent employed, with useful but temporary responses obtained in as many as 33% of patients with metastatic disease. Paclitaxel, in combination with platinums or as a single agent, also has significant activity.[9]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent endometrial carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Kauppila A: Oestrogen and progestin receptors as prognostic indicators in endometrial cancer. A review of the literature. Acta Oncol 28 (4): 561-6, 1989.

  2. Kauppila A, Friberg LG: Hormonal and cytotoxic chemotherapy for endometrial carcinoma. Steroid receptors in the selection of appropriate therapy. Acta Obstet Gynecol Scand Suppl 101: 59-64, 1981.

  3. Quinn MA, Campbell JJ: Tamoxifen therapy in advanced/recurrent endometrial carcinoma. Gynecol Oncol 32 (1): 1-3, 1989.

  4. Thigpen JT, Brady MF, Homesley HD, et al.: Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 22 (19): 3902-8, 2004.

  5. Randall ME, Filiaci VL, Muss H, et al.: Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 24 (1): 36-44, 2006.

  6. Fleming GF, Brunetto VL, Cella D, et al.: Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 22 (11): 2159-66, 2004.

  7. Fleming GF, Filiaci VL, Bentley RC, et al.: Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study. Ann Oncol 15 (8): 1173-8, 2004.

  8. Cornelison TL, Baker TR, Piver MS, et al.: Cisplatin, adriamycin, etoposide, megestrol acetate versus melphalan, 5-fluorouracil, medroxyprogesterone acetate in the treatment of endometrial carcinoma. Gynecol Oncol 59 (2): 243-8, 1995.

  9. Ball HG, Blessing JA, Lentz SS, et al.: A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol 62 (2): 278-81, 1996.


This information is provided by the National Cancer Institute.

This information was last updated on June 14, 2013.


 
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