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.
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| 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. Refer to the
PDQ summary on Uterine Sarcoma Treatment for more information.
Taking tamoxifen for breast cancer or taking estrogen alone
(without progesterone) can affect the risk of developing endometrial cancer.
Endometrial cancer may develop in breast cancer patients who have
been treated with tamoxifen. A
patient taking this drug should have a pelvic 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 developing endometrial cancer.
Taking estrogen in combination with progesterone (another hormone) does not increase a
woman’s risk of this cancer.
Possible signs of endometrial cancer include unusual vaginal
discharge or pain in the pelvis.
These and other symptoms may be caused by endometrial cancer. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:
- 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 examined
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: Surgery to remove samples of tissue or the inner lining of the uterus. The cervix is dilated and a curette (spoon-shaped instrument) is inserted into the uterus to remove tissue. Tissue samples may be taken and checked under a microscope for signs of disease. This procedure is also called a D&C.
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.
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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.
There are three ways that cancer spreads in the body.
The three ways that cancer spreads in the body are:
- Through tissue. Cancer invades the surrounding normal tissue.
- Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
- Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.
When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.
The following stages are used for endometrial
cancer:
Stage I
In stage I, cancer is
found in the uterus only. Stage I is divided
into stages IA, IB, and IC, based on how far the cancer has spread.
- Stage IA: Cancer is in the endometrium only.
- Stage IB: Cancer has spread into the inner half of the myometrium (muscle layer of the uterus).
- Stage IC: Cancer has spread into the outer half of the myometrium.
Stage II
In stage II, cancer
has spread from the uterus to the cervix, but has not spread outside the uterus. Stage II
is divided into stages IIA and IIB, based on how far the cancer has spread
into the cervix.
- Stage IIA: Cancer has spread to the glands where the cervix and uterus meet.
- Stage IIB: Cancer has spread into the connective tissue of the cervix.
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 one or more of the following:
- the outermost layer of the uterus; or
- tissue just beyond the uterus; or
- the peritoneum.
- Stage IIIB: Cancer has spread beyond the uterus and cervix, into the vagina.
- Stage IIIC: Cancer has spread to lymph nodes near the uterus.
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 IVB: Cancer has spread to other parts of the body beyond the pelvis, including lymph nodes in the abdomen and/or groin.
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Recurrent Endometrial Cancer
Recurrentendometrial
cancer is cancer that has recurred
(come back) after it has been treated. The cancer may come back in the
pelvis, in
lymph nodes in the
abdomen, or in other parts of the
body.
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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.
Three 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. 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.
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 are 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.
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 spinal column, 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.
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 clinical trials database.
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.
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Treatment Options by Stage
A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.
Stage I Endometrial Cancer
Treatment of stage I endometrial
cancer may include the following:
- Surgery (total abdominalhysterectomy and bilateral salpingo-oophorectomy). Lymph nodes in the
pelvis and
abdomen may also be removed for
examination under a microscope to check for cancercells.
- Surgery (total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or
without removal of lymph nodes in the pelvis and abdomen) followed by
internal radiation
therapy 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
radiation therapy and/or chemotherapy.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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. General information about clinical trials is available from the NCI Web site.
Stage II Endometrial Cancer
Treatment of stage IIA endometrial
cancer is usually a combination of therapies, including internal
and external radiation therapy and surgery.
Stage IIA
Treatment of stage IIA endometrial cancer may include the
following:
- Surgery (total abdominalhysterectomy and bilateral salpingo-oophorectomy). Lymph nodes in the pelvis and abdomen may also be removed for examination under
a microscope to check for cancercells.
- Surgery (total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or
without removal of lymph nodes in the pelvis and abdomen) followed by internal radiation therapy
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 radiation therapy and/or chemotherapy.
Stage IIB
Treatment of stage IIB endometrial
cancer may include the following:
- Surgery (total abdominalhysterectomy, bilateral salpingo-oophorectomy, and removal of lymph nodes in the pelvis and abdomen for examination under a
microscope to check for cancercells) followed by radiation therapy.
- Internal radiation therapy and external radiation therapy, followed by surgery (hysterectomy and bilateral salpingo-oophorectomy, and
removal of lymph nodes in the pelvis and abdomen for examination under a
microscope to check for cancer cells).
- Surgery (radical hysterectomy with or without removal of
lymph nodes in the pelvis for examination under a microscope to check for
cancer cells).
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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. 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 for examination under a microscope to check for cancercells)
followed by internal radiation therapy and external radiation therapy.
- Radiation therapy alone for patients who cannot have
surgery.
- Hormone
therapy for patients who cannot have surgery
or radiation therapy.
- Clinical trials of chemotherapy.
- Clinical trials of new therapies.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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. 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:
- Internal radiation therapy and external radiation therapy.
- Hormone therapy.
- Clinical trials of chemotherapy.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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. General information about clinical trials is available from the NCI Web site.
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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 PDQ Cancer Clinical Trials Registry 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. General information about clinical trials is available from the NCI Web site.
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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:
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This information is provided by the National Cancer Institute.
This information was last updated on October 12, 2009.
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of endometrial cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Prognostic factors.
- Cellular classification.
- Staging.
- Treatment options by cancer stage.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
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General Information
Note: Separate PDQ summaries on Uterine Sarcoma Treatment, Endometrial Cancer Screening, and
Endometrial Cancer Prevention are also available.
Note: Estimated new cases and deaths from endometrial (uterine corpus) cancer in the United States in 2009:[1]
- New cases: 42,160.
- Deaths: 7,780.
Cancer of the endometrium is the most common gynecologic malignancy and
accounts for 6% of all cancers in women. It is a highly curable tumor. 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, though 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), perhaps 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. Distant metastases can
occur and most commonly involve the lungs, inguinal and supraclavicular nodes,
liver, bones, brain, and 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 or positive washings) 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 four
statistically significant adverse prognostic factors: myometrial invasion,
vascular invasion, eight or more mitoses per ten high-power fields, and an absence
of progesterone receptors.[14]
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] The preponderance of evidence,
however, would suggest that 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. Oncogene expression, DNA ploidy, and the fraction of cells in
S-phase have also been found to be prognostic indicators of clinical
outcome.[28] 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]
References:
American Cancer Society.: Cancer Facts and Figures 2009. Atlanta, Ga: American Cancer Society, 2009. Also available online. Last accessed January 6, 2010.
DuBeshter B, Warshal DP, Angel C, et al.: Endometrial carcinoma: the relevance of cervical cytology. Obstet Gynecol 77 (3): 458-62, 1991.
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.
Ziel HK, Finkle WD: Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med 293 (23): 1167-70, 1975.
Jick SS, Walker AM, Jick H: Estrogens, progesterone, and endometrial cancer. Epidemiology 4 (1): 20-4, 1993.
Jick SS: Combined estrogen and progesterone use and endometrial cancer. Epidemiology 4 (4): 384, 1993.
Bilezikian JP: Major issues regarding estrogen replacement therapy in postmenopausal women. J Womens Health 3(4): 273-282, 1994.
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.
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.
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.
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.
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.
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.
Tornos C, Silva EG, el-Naggar A, et al.: Aggressive stage I grade 1 endometrial carcinoma. Cancer 70 (4): 790-8, 1992.
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.
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.
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.
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.
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.
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.
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.
Lurain JR: The significance of positive peritoneal cytology in endometrial cancer. Gynecol Oncol 46 (2): 143-4, 1992.
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.
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.
Creasman WT: Prognostic significance of hormone receptors in endometrial cancer. Cancer 71 (4 Suppl): 1467-70, 1993.
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.
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.
Gurpide E: Endometrial cancer: biochemical and clinical correlates. J Natl Cancer Inst 83 (6): 405-16, 1991.
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.
Homesley HD, Zaino R: Endometrial cancer: prognostic factors. Semin Oncol 21 (1): 71-8, 1994.
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Cellular Classification
The most common endometrial cancer cell type is endometrioid adenocarcinoma,
which is composed of malignant glandular epithelial elements; an admixture of
squamous metaplasia is not uncommon. Adenosquamous tumors contain malignant
elements of both glandular and squamous epithelium;[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:
- Endometrioid (75%–80%)
- Ciliated adenocarcinoma.
- Secretory adenocarcinoma.
- Papillary or villoglandular.
- Adenocarcinoma with squamous differentiation.
- Adenoacanthoma.
- Adenosquamous.
- Uterine papillary serous (<10%).
- Mucinous (1%).
- Clear cell (4%).
- Squamous cell (<1%).
- Mixed (10%).
- Undifferentiated.
References:
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.
Gusberg SB: Virulence factors in endometrial cancer. Cancer 71 (4 Suppl): 1464-6, 1993.
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Stage Information
A hysterectomy is required to determine the degree of myometrial invasion. The
following surgical staging has been adopted by the International Federation of
Gynecology and Obstetrics (FIGO) and by the American Joint Committee on Cancer:[1][2][3]
Stage I
Stage I endometrial cancer is carcinoma confined to the corpus uteri.
- Stage IA: tumor limited to endometrium.
- Stage IB: invasion to less than 50% of the myometrium.
- Stage IC: invasion to greater than 50% of the myometrium.
Stage II
Stage II endometrial cancer involves the corpus and the cervix but has not
extended outside the uterus.
- Stage IIA: endocervical glandular involvement only.
- Stage IIB: cervical stromal invasion.
Stage III
Stage III endometrial cancer extends outside of the uterus but is confined to
the true pelvis.
- Stage IIIA: tumor invades serosa and/or adnexa and/or positive peritoneal
cytology.
- Stage IIIB: vaginal metastases.
- Stage IIIC: metastases to pelvic and/or para-aortic lymph nodes.
Stage IV
Stage IV endometrial cancer involves the bladder or bowel mucosa or has
metastasized to distant sites.
- Stage IVA: tumor invasion of bladder and/or bowel mucosa.
- Stage IVB: distant metastases, including intra-abdominal and/or inguinal
lymph nodes.
Endometrial cancer can be grouped with regard to the degree of differentiation
of the adenocarcinoma, as follows:
- G1: no more than 5% of a nonsquamous or nonmorular solid growth pattern.
- G2: 6% to 50% of a nonsquamous or nonmorular solid growth pattern.
- G3: greater than 50% of a nonsquamous or nonmorular solid growth pattern.
FIGO staging for endometrial cancer:
- Stage IA G123: tumor limited to endometrium.
- Stage IB G123: invasion to less than 50% of the myometrium.
- Stage IC G123: invasion to greater than 50% of the myometrium.
- Stage IIA G123: endocervical glandular involvement only.
- Stage IIB G123: cervical stromal invasion.
- Stage IIIA G123: tumor invades serosa and/or adnexa and/or positive
peritoneal cytology.
- Stage IIIB G123: vaginal metastases.
- Stage IIIC G123: metastases of pelvic and/or para-aortic lymph nodes.
- Stage IVA G123: tumor invasion of bladder and/or bowel mucosa.
- Stage IVB: distant metastases including intra-abdominal and/or inguinal
lymph nodes.
References:
Shepherd JH: Revised FIGO staging for gynaecological cancer. Br J Obstet Gynaecol 96 (8): 889-92, 1989.
FIGO staging for corpus cancer [Erratum]. Br J Obstet Gynaecol 99 (5): 440, 1992.
Corpus uteri. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 267-73.
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Treatment Option Overview
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
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 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.[1][2][3][Level of evidence: 1iiDii]
Vaginal cuff brachytherapy may be associated with less radiation-related morbidity than pelvic radiation. It has been shown to reduce the risk of vaginal cuff recurrence without an
effect on survival.
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:
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.
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.
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.
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Stage I Endometrial Cancer
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
Standard treatment options:
If the tumor is well or moderately differentiated, involves the upper 66% of the corpus, has negative peritoneal cytology, is without vascular
space invasion, and has less than a 50% myometrial invasion, a total abdominal
hysterectomy and bilateral salpingo-oophorectomy should be done. Selected
pelvic lymph nodes may be removed. If they are negative, no postoperative
treatment is indicated. Postoperative treatment with a vaginal cylinder is
advocated by some clinicians.[1]
For all other cases and cell types, a periaortic and selective pelvic node
sampling should be combined with the total abdominal hysterectomy and bilateral
salpingo-oophorectomy, if there are no medical or technical contraindications.
One study found that node dissection per se did not significantly add to the
overall morbidity from hysterectomy.[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]
If the pelvic nodes are positive and the periaortic nodes are negative, total
pelvic radiation therapy, including the common iliac nodes, should be given. The
incidence of bowel complications is approximately 4%, and it can be even higher
if the radiation therapy is given after pelvic lymphadenectomy.[9] If the surgery is
done using a retroperitoneal approach, the toxic effects are lessened. If the
periaortic nodes are positive, the patient is a candidate for clinical trials
that could include radiation therapy and/or chemotherapy. Patients who have medical
contraindications to surgery should be treated with radiation therapy alone,
but inferior cure rates below those attained with surgery may occur.[1][10][11]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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:
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.
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.
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.
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.
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.
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.
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.
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.
Greven KM, Lanciano RM, Herbert SH, et al.: Analysis of complications in patients with endometrial carcinoma receiving adjuvant irradiation. Int J Radiat Oncol Biol Phys 21 (4): 919-23, 1991.
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.
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.
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Stage II Endometrial Cancer
Many combinations of preoperative intracavitary and external-beam radiation
therapy (EBRT) with hysterectomy and bilateral salpingo-oophorectomy are used for
treatment of stage II endometrial cancer, with careful biopsy of the
para-aortic nodes at the time of surgery. When microscopic cervical stromal
involvement is found, postoperative radiation therapy (EBRT and vaginal
radiation therapy) should be used.
Stage IIA
Stage IIA (endocervical glandular involvement only) should be treated the same
as stage I disease.
Stage IIB
Standard treatment options:
- Hysterectomy, bilateral salpingo-oophorectomy, and node sampling followed by
postoperative radiation therapy.
- Preoperative intracavitary and EBRT followed by
hysterectomy and bilateral salpingo-oophorectomy. (A biopsy of the para-aortic
nodes should be done at the time of surgery.)
- Radical hysterectomy and pelvic lymphadenectomy in selected cases.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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.
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Stage III Endometrial Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Standard treatment options:
In general, patients with stage III endometrial cancer are treated with surgery and radiation therapy.
Patients with inoperable disease, caused by the tumor that extends to the pelvic wall, may be treated with radiation therapy. The usual
approach is to use a combination of intracavitary and external-beam radiation
therapy.
Patients who are not candidates for either surgery or radiation therapy may
be treated with progestational agents. Postoperative radiation therapy is used
in patients who were thought to have had more localized disease (clinical stage
I or stage II) but are found during a hysterectomy to have positive lymph nodes or
adnexa. Studies of patterns of failure have found a high rate of distant
metastases in the upper abdominal and extra-abdominal sites. For this reason,
patients with stage III disease may be candidates for innovative clinical
trials.[1]
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).[2] 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 to 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%).[3][Level of evidence: 1iiA] In a subsequent trial, paclitaxel with doxorubicin had a similar outcome to cisplatin with doxorubicin.[4][5] 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. [4][5][Level of evidence: 1iiDiv]
Treatment options under clinical evaluation:
- Clinical trials such as GOG 94.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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:
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.
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.
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.
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.
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.
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Stage IV Endometrial Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
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.
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
(Delalutin), medroxyprogesterone (Provera), and megestrol (Megace).[1]
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).[2] 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 to 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%).[3][Level of evidence: 1iiA] In a subsequent trial, paclitaxel with doxorubicin had a similar outcome to cisplatin with doxorubicin.[4][5] 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.[4][5][Level of evidence: 1iiDiv]
Treatment options under clinical evaluation:
No standard chemotherapy program is available for patients with metastatic uterine
cancer, though doxorubicin has activity. Some studies have demonstrated
activity of doxorubicin-containing combinations, though no
prospective comparison of single-agent versus combination chemotherapy is available that has
demonstrated superiority of the combinations.[6][7]
Paclitaxel has demonstrated antitumor activity and has been evaluated.[8]
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 PDQ Cancer Clinical Trials Registry 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:
Lentz SS: Advanced and recurrent endometrial carcinoma: hormonal therapy. Semin Oncol 21 (1): 100-6, 1994.
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.
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.
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.
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.
Hancock KC, Freedman RS, Edwards CL, et al.: Use of cisplatin, doxorubicin, and cyclophosphamide to treat advanced and recurrent adenocarcinoma of the endometrium. Cancer Treat Rep 70 (6): 789-91, 1986.
Seski JC, Edwards CL, Herson J, et al.: Cisplatin chemotherapy for disseminated endometrial cancer. Obstet Gynecol 59 (2): 225-8, 1982.
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.
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Recurrent Endometrial Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
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 to 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 to 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 also has significant activity.[9]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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:
Kauppila A: Oestrogen and progestin receptors as prognostic indicators in endometrial cancer. A review of the literature. Acta Oncol 28 (4): 561-6, 1989.
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.
Quinn MA, Campbell JJ: Tamoxifen therapy in advanced/recurrent endometrial carcinoma. Gynecol Oncol 32 (1): 1-3, 1989.
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.
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.
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.
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.
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.
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.
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Important:
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
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This information is provided by the National Cancer Institute.
This information was last updated on May 22, 2009.