Patient information: Endometrial cancer diagnosis and staging

ENDOMETRIAL CANCER OVERVIEW

Endometrial cancer is a type of uterine cancer that involves the lining of the uterus (the endometrium). In the United States, it is the most common cancer of the female reproductive system. Fortunately, most women are diagnosed at an early stage (before the has spread beyond the uterus) and the disease can be cured with surgery alone. The five-year survival rate among women with for early stage endometrial cancer is over 90 percent.

This topic review discusses the risk factors, symptoms, and diagnosis of adenocarcinoma of the most common type of endometrial cancer, called endometrioid endometrial cancer. A separate topic is available that discusses the treatment of this disease. (See "Patient information: Endometrial cancer treatment".)

THE UTERUS

To understand how endometrial cancer develops, it is helpful to understand the structure of the uterus. The uterus is a pear-shaped organ located between the bladder and the rectum. The inside of the uterus has two layers. The thin inner layer is called the endometrium. The thick outer layer is composed of muscle and is called the myometrium (myo = muscle) (picture 1).

In women who menstruate, the endometrium thickens every month in preparation for pregnancy. If the woman does not become pregnant, the endometrial lining is shed during the menstrual period. After menopause, when menstrual periods stop, the lining normally stops growing and shedding. In women who have endometrial cancer, the uterine lining is abnormal and may grow into the myometrium and adjacent organs (picture 2).

ENDOMETRIAL CANCER RISK FACTORS

There are two main types of endometrial cancer: type I (also called endometrioid endometrial cancer) and type II (called papillary or serous endometrial cancer). Type I endometrial cancers occur 80 percent of the time while type II cancers occur in the remaining 20 percent of patients. Type II cancers tend to be more aggressive.

The risk factors for type I are well known while type II risk factors are less clear. The risk factors for type I include the following:

• Older age — Endometrial cancer is most common in postmenopausal women, with the mean age of diagnosis in the early 60s. However, it can develop in premenopausal women as well, particularly in women who are obese or have polycystic ovary syndrome. (See "Patient information: Polycystic ovary syndrome (PCOS)".)

• Obesity — Obesity is a major risk factor for endometrial cancer. Obese women have higher levels of estrogen in their body, which stimulates the growth of the uterine lining (the endometrium). Women who are morbidly obese are at a significantly increased lifetime risk of developing endometrial cancer.
• Long-term estrogen exposure — Women who still have a uterus and who take estrogen replacement therapy alone (without a progestin) have a significant risk of endometrial cancer. Women who have a uterus and want to take hormone replacement therapy are advised to take estrogen plus progestin to reduce this risk. (See "Patient information: Postmenopausal hormone therapy".)

Other settings in which there might be long-term exposure to estrogen include:

• - Young age at the time of the first menstrual period
• - Older age at the time of the last menstrual period (menopause)
• - Never having given birth to a child

• Tamoxifen use — Women who take tamoxifen to prevent or treat breast cancer have an increased risk of endometrial cancer. In most cases, the risks of taking tamoxifen to treat breast cancer are outweighed by the benefits. There is controversy about the risks and benefits of taking tamoxifen to prevent breast cancer. (See "Patient information: Tamoxifen and raloxifene for the prevention of breast cancer".)

• Family predisposition and genetics — Women with a strong family history of colon cancer are at increased risk of developing endometrial cancer if they have the gene for an inherited condition known as hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch syndrome).

ENDOMETRIAL CANCER SYMPTOMS

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

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

• In a postmenopausal woman, any vaginal bleeding is considered abnormal, even if it is only one drop of blood, and especially if the woman is not taking hormone replacement therapy. Women who take hormone replacement therapy may experience bleeding in the first few months of treatment, although any vaginal bleeding should be reported to a healthcare provider.

ENDOMETRIAL CANCER DIAGNOSIS AND STAGING

Endometrial cancer is diagnosed by using a microscope to examine a sample of endometrial tissue. The tissue can be obtained with an office test (endometrial biopsy) or a day surgery procedure (hysteroscopy with dilation and curettage). These tests are described in detail in a separate topic review. (See "Patient information: Abnormal uterine bleeding".)

Once a diagnosis of endometrial cancer is established, two important questions must be answered:

• How extensive is the cancer involvement within the uterus?
• Has the tumor has spread outside of the uterus?

Although endometrial cancer starts within the uterus, cancer cells can break off from the endometrial tumor and spread to other areas of the body, typically through the bloodstream; this process is called metastasis. As a metastasis grows, it usually becomes visible on an x-ray or magnetic resonance imaging test (MRI). Tests to determine if the cancer has spread are often recommended during the evaluation, and may include a chest x-ray and/or MRI of the abdomen and pelvis.

If the endometrial cancer has spread to another organ (eg, the lung), the woman is said to have metastatic endometrial cancer, not lung cancer.

Tumor staging — Staging is a shorthand way of describing the local extent of the cancer (including its size and how deeply it has invaded the outer muscular layer of the uterus, the myometrium) and whether it has spread to other organs. While spread to other organs can be seen on x-ray studies, surgery (an exploratory laparotomy) is typically needed to determine the local tumor extent.

Exploratory laparotomy — Most women with endometrial cancer undergo a surgical procedure called exploratory laparotomy to define the local tumor extent. This surgery is done in an operating room after the woman is given general anesthesia. The surgeon usually makes a vertical (up and down) incision in the abdomen, then examines the organs within the pelvis and abdomen for signs of cancer.

In some women, surgery can be done laparoscopically, which uses a lighted telescope that is inserted into small incisions in the abdomen. The surgeon uses the scope to see inside the abdomen and remove tissues, as necessary. The choice between exploratory laparotomy and laparoscopy depends upon the woman's individual situation and the surgeon's preference. Given the importance of removing all cancerous tissue, the surgery is best performed by an experienced surgeon, such as a gynecologic oncologist.

During the surgery, the following procedures are performed:

• The uterus and ovaries are removed (called total abdominal hysterectomy and bilateral salpingo-oophorectomy). This procedure is described in detail in a separate topic review. (See "Patient information: Abdominal hysterectomy".)

• Fluid from the abdomen and any abnormal tissue in the pelvis or abdomen are evaluated to determine if the cancer has spread outside of the uterus.
• The lymph nodes surrounding the uterus are evaluated because they are one of the earliest sites of endometrial cancer spread. One of the most important factors in a woman's long-term prognosis is the presence of cancer outside the uterus. There is some debate about the best way to evaluate the lymph nodes; the options depend upon the extent of the woman's cancer.

If surgery is not possible — If surgery is thought to be too risky, such as in elderly women and those with serious underlying medical problems, radiation therapy alone may be recommended. This is described in full detail in a separate topic review. (See "Patient information: Endometrial cancer treatment", in the section on "Radiation therapy").

ENDOMETRIAL CANCER MANAGEMENT

The management of endometrial cancer depends upon the estimated risk that the disease will recur, which is based upon the following:

• The surgical stage of the cancer (table 1)
• The tumor grade (table 2)
• The histology

Depending on these characteristics, the risk that the endometrial cancer will recur after hysterectomy alone is considered to be low, intermediate, or high.

Stage — The stage of endometrial cancer is defined by a Roman numeral designation between I and IV, and subdivided by the letters A, B, and C. In general, the stages I, II, III, and IV refer to the location of tumor involvement, while the subdivisions A, B, and C define the extent of tumor involvement (eg, the size) (table 1). In general, a higher stage of disease indicates more extensive tumor involvement.

The tumor stage helps to guide treatment and provides important information about a woman's long-term prognosis. The criteria used to define these individual stages are used throughout the world.

Grade — The grade of a cancer is determined based upon how it appears under a microscope. Endometrial cancers are graded on a scale of 1 (low grade) to 3 (high grade). In general, grade refers to the aggressiveness of the tumor. Thus, high-grade tumors are usually faster growing and more likely to spread than low-grade tumors (table 2).

Histology — The appearance of the tumor cells under the microscope can also impact treatment. Some cell types, such as serous papillary or clear cell endometrial cancer, are associated with a higher risk of recurrence. These tumors grow and spread more rapidly than other types, and are usually treated more aggressively.

ENDOMETRIAL CANCER TREATMENT

The treatment and long-term prognosis of women with endometrial cancer is discussed in a separate topic review. (See "Patient information: Endometrial cancer treatment".)

PREGNANCY AND ENDOMETRIAL CANCER

Although cancer is more common in postmenopausal women, it can develop in younger women. A woman with endometrial cancer who would like to have a child in the future should discuss treatment options with her doctor; in women with low-risk disease, it is sometimes possible to have a "fertility preserving" treatment. (See "Patient information: Endometrial cancer treatment", in the section on "Women who want to preserve their fertility").

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Endometrial cancer treatment
Patient information: Polycystic ovary syndrome (PCOS)
Patient information: Postmenopausal hormone therapy
Patient information: Tamoxifen and raloxifene for the prevention of breast cancer
Patient information: Abnormal uterine bleeding
Patient information: Abdominal hysterectomy

Professional Level Information:
Endometrial cancer: Epidemiology, risk factors, clinical features, diagnosis, and screening
Endometrial cancer: Pretreatment evaluation, staging, and posttreatment surveillance
Endometrial hyperplasia
Evaluation of the endometrium for malignant or premalignant disease
Histopathology and pathogenesis of endometrial cancer
Treatment of locally recurrent or advanced endometrial cancer
Uterine papillary serous and clear cell cancer
Uterine sarcoma: Classification, clinical manifestations, and diagnosis
Uterine sarcoma: Staging and treatment

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• American Society of Clinical Oncology

       (www.cancer.net/portal/site/patient)

• The Women's Cancer Network

      (www.wcn.org)

• National Comprehensive Cancer Network

      (www.nccn.com/default.asp)

• Gynecologic Oncology Group

      (www.gog.org/gynecologiccancerinformation.html)

• National Cancer Institute

       1-800-4-CANCER
       (www.cancer.gov)

• American Cancer Society

       1-800-ACS-2345
      (www.cancer.org)

Patient Support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Cancer Forum

      (http://cancer.about.com/forum)

[1-4]