Endometrial Cancer (Uterine Cancer)

Endometrial cancer is the most common gynecologic cancer. It develops from the inner lining of the uterus, and is commonly referred to as uterine cancer.

What is Endometrial Cancer?

In order to better understand endometrial cancer, it can be helpful to learn about the different layers that make up the uterus.

The uterus is a hollow organ that is approximately the size and shape of a pear. The upper part of the uterus is the body, and is called the corpus. The lower part of the uterus, which rests just above the vagina, is the cervix.

The body (corpus) of the uterus consists of 3 layers, including:

  • Endometrium, the inner layer or lining of the uterus
  • Myometrium, the thick layer of muscle that makes up the bulk of the outer layer of the uterus.
  • Serosa, a thinner layer of tissue coating the outside of the uterus

Screening for Endometrial Cancer

There is no screening test for endometrial cancer.  Fortunately, many women are diagnosed at early stages because they have symptoms that lead to an evaluation.

Endometrial cancer may be associated with some hereditary genetic syndromes such as Lynch syndrome (also called hereditary non-polyposis colon cancer syndrome HNPCC), Cowden syndrome, or BRCA1 mutations. People with these genetic disorders may consider yearly testing for endometrial cancer with a pelvic ultrasound and endometrial biopsy starting at age 35. The effectiveness of screening in these cases has not been established.

Common Symptoms of Endometrial Cancer

  • Abnormal uterine bleeding, such as bleeding after menopause or between periods
  • Difficult or painful urination
  • Changes in bowel or bladder habits
  • Lower abdominal pain or pelvic cramping
  • Pain during intercourse

The most common symptom of endometrial cancer is abnormal bleeding. It is important to be seen by a doctor if you experience abnormal bleeding, because an earlier diagnosis can improve the chances of successful treatment.

Endometrial Cancer Risk Factors

Several factors are linked to increased risk for endometrial cancer, including:

  • Obesity
  • Increased exposure to the hormone estrogen. This may include exposure to medications, such as some forms of hormone replacement therapy or tamoxifen, or by conditions associated with high levels of estrogen production, such as polycystic ovarian syndrome (PCOS) or hormone-producing granulosa cell tumors.  
  • Increased age
  • A high-fat diet, and low exercise, is linked to increased risk, though this may be due to an overlap in obesity as a risk factor
  • Diabetes is linked to increased risk, which may also be due to its link with obesity, a known risk factor
  • Family history of endometrial or colon cancer, typically connected to a genetic disorder called hereditary nonpolyposis colon cancer (HNPCC), also called Lynch Syndrome. Lynch Syndrome is usually caused by a defect in in genes MLH1, MSH2, MLH3, MSH6, TGBR2, PMS1, or PMS2.
  • Family history of breast or ovarian cancer linked with BRCA1 gene mutations may also increase the risk of some kinds of endometrial cancer
  • Pelvic radiation therapy

Several other factors are linked to decreased risk of developing endometrial cancer, including:

  • Low number of lifetime menstrual cycles, whether due to starting menstruation late, or starting menopause early
  • Pregnancy, which increases progesterone levels
  • Intrauterine device (IUD) use. Initial studies identifying a protective effect of IUDs evaluated IUDs that did not contain hormones. Recent studies indicate that IUDs that release progesterone may have additional protective effects and can also be used as a component of treatment for atypical hyperplasia or low grade endometrial cancer.

Types of Endometrial Cancer

Endometrial cancer, also called endometrial carcinoma, is cancer that starts in the endometrium, the inner lining of the uterus. Most endometrial cancers are adenocarcinomas, which means they arise from glandular cells that line the uterine cavity. These cancers are subdivided into Type I and Type II tumors.  

Type I tumors include endometrioid adenocarcinoma. These cancers often develop in response to high levels of estrogen and are typically diagnosed at early stages.

Type II tumors include less common subtypes such as serous adenocarcinoma or papillary serous adenocarcinoma. Clear cell carcinoma, carcinosarcoma, and undifferentiated carcinomas are included in this subset. Type II tumors classically do not develop in response to hormone signaling. These cancers may be more aggressive and are diagnosed at later stages.

Endometrial Cancer Diagnosis

If you experience symptoms commonly associated with endometrial cancer, you should see your doctor, preferably a gynecologist. The gynecologist will perform a physical and a pelvic exam, and will talk through your symptoms, risk factors, and medical history.

A gynecologist may then perform an ultrasound to get a more detailed view of the uterus, ovaries, and fallopian tubes. Different types of ultrasounds may be performed. A pelvic ultrasound is a noninvasive procedure that can provide a clear picture of the abdomen; while a transvaginal ultrasound (TVUS) involves insertion of a probe into the vagina, which can provide a clearer view of the uterus. A TVUS can reveal if tumors are present, or if the endometrium is thicker than normal, which can be a sign of endometrial cancer.

Tissue Sampling

If an ultrasound reveals cause for concern, a doctor will then need to collect a tissue sample from the endometrium, for closer inspection in the lab. A tissue sample, viewed under a microscope, is the only way to definitively diagnose endometrial cancer. 

In most cases, a doctor will begin with an endometrial biopsy. This procedure, which is especially accurate in post-menopausal patients, involves inserting a thin tube through the vagina into the uterus, which uses suction to collect a tissue sample. As part of the procedure, a doctor may also perform a hysteroscopy — insertion of a small telescope to help identify and draw tissue samples from any abnormalities. A doctor may use local anesthetic to help with discomfort from the procedures.

If an endometrial biopsy does not provide a definitive result, a doctor may perform a dilation and curettage (D&C). This is an outpatient procedure which is typically performed in a surgical center, so that additional anesthesia or sedation can be administered, which takes less than one hour to complete. In a D&C, a doctor will dilate the cervix and use an instrument to scrape tissue from inside the uterus, for further analysis. A D&C may also include a hysteroscopy. Patients may experience cramping or spotting after a D&C.

Tissue Testing

Once endometrial tissue is collected, it is examined under a microscope to confirm or rule out cancer. If cancer cells are found, further analysis will determine more detailed information such as the specific cancer type, and the grade of disease. Some patients may benefit from genetic testing, which can reveal changes in genes or proteins that can help guide recommendations for the most effective treatments.

Stages of Endometrial Cancer

Endometrial cancer stage can vary from stage 1 (I) to stage 4 (IV), and is determined, for the most part, by how far the cancer has spread. This is often determined at the time of surgery. Lower stage disease means the cancer is only found in the uterus, whereas a higher stage means the cancer has spread. 

Staging can be complicated to understand, but it is an important factor in guiding treatment. Patients should not hesitate to ask their medical team for clarification as to cancer stage, and what that means for treatment and prognosis. Read more about endometrial cancer staging from the American Cancer Society.

How is Endometrial Cancer Treated?

Surgery

The main treatment for endometrial cancer is typically surgery, which should be performed by a gynecologic oncologist. In this surgery, called a total hysterectomy, the doctor will remove the uterus and cervix. In most cases the uterus will be removed through an incision in the abdomen, in what is called a simple hysterectomy, though in some cases a doctor may recommend a vaginal hysterectomy instead, which means the uterus will be removed through the vagina. If cancer has spread, the doctor may perform a radical hysterectomy, removing the entire uterus as well as tissue around the uterus, and the upper part of the vagina.

Doctors may also perform a bilateral salpingo-oophorectomy (BSO), which involves removing the fallopian tubes and both ovaries. In a pre-menopausal patient, removing both ovaries will result in surgical menopause. Patients age 45 and under may wish to discuss the possibility of keeping one or both ovaries intact in order to delay menopause if this is a safe option based on the findings at the time of surgery. 

In addition, surgery may involve removing lymph nodes, which will then be tested to better determine the cancer’s surgical stage and spread. 

For early stage endometrioid adenocarcinoma, surgery and close monitoring may be the only treatment needed. Depending on the stage, and specific type of cancer, additional treatments may be needed after surgery, which may include:

  • Radiation may be delivered internally using an insert that is placed in the vagina, or externally, using an instrument that is similar to an X-ray machine. Radiation treatment will typically begin 4 – 6 weeks after surgery to allow time for healing.
  • Chemotherapy may be delivered orally or through the veins.  Chemotherapy is commonly used for Type II tumors and for some advanced stage, recurrent, or high grade Type I tumors.
  • Hormone therapy, which may include oral regimens or progesterone-releasing IUDs, can be used as primary treatment for people with early stage low grade disease who wish to preserve their fertility.  Hormone therapy is also used in people who may be unable to undergo surgery because of other medical conditions. Hormone therapy is also used as a component of treatment for recurrent endometrial cancer.
  • Immune therapy, which is a treatment strategy that boosts a person’s immune response to cancer, has been very effective in some forms of endometrial cancer. Immune therapy may be given in combination with other treatments, including radiation or targeted therapy.
  • Targeted therapy is different from chemotherapy in that it more pointedly targets specific features of cancer cells. Drugs targeting pathways that regulate angiogenesis, or blood vessel growth, have been approved for endometrial cancer treatment. It may be possible for some patients to participate in clinical trials for targeted therapies that show promise.

There is no single best treatment for endometrial cancer, as the most effective regimen will vary by the cancer’s type, stage and spread, as well as a patient’s overall health. Determining the right treatment plan can be complicated, so patients should be sure to discuss with their medical team, and should not be afraid to ask questions. Learn more about treating endometrial cancer.

Endometrial Cancer Recurrence

If cancer returns after successful treatment, it is called a recurrence. Even after being declared NED (no evidence of disease), many patients still feel nervous about the cancer coming back. If a patient does experience a recurrence, it will often be within a few years of completing their treatment. The most common site of endometrial cancer recurrence is at the top of the vagina – where the uterus was previously.  Fortunately, this site can be evaluated during a speculum exam. Because of this, it is important for patients to commit to regular appointments with their doctor for follow-up care, and to immediately contact their medical team if they experience vaginal bleeding or other symptoms of a possible recurrence. 

Treatment for patients with recurrent endometrial cancer will depend on whether the cancer is localized or has spread, as well as the patient’s initial treatment. 

Survival Rates and Incidence of Endometrial and Uterine Cancers

The overall 5-year relative survival rate for endometrial cancer is 84%. Survival rates vary depending on how far the cancer has spread when it is initially detected and treated. The 5-year relative survival rate for endometrial cancer that is localized to the uterus is 96%. The 5-year relative survival rate for endometrial cancer that has regional spread to nearby structures or lymph nodes is 71%. The 5-year relative survival rate for endometrial cancer that has spread to distant parts of the body is 20%.

The American Cancer Society estimates that in 2022 about 65,950 new cases of cancer of the body of the uterus will be diagnosed, and about 12,550 women will die from cancers of the uterine body.

These estimates include both endometrial cancers and uterine sarcomas.

Up to 10% of uterine cancers are sarcomas, so the actual numbers for endometrial cancer cases and deaths are slightly lower than these estimates.

For detailed information about endometrial cancer, visit the American Cancer Society.

Support with Endometrial Cancer

OCRA has several support programs available for those with endometrial cancer.

Patients can find peer support through Woman to Woman, where they are matched with trained survivor mentors to lend a listening ear and emotional support in a way that only other gynecologic cancer survivors can. Woman to Woman is offered at program sites across the U.S., and through our virtual national mentoring program. Request a peer mentor through OCRA’s Woman to Woman program.

Those with endometrial cancer and all gynecologic cancers are also invited to take part in OCRA’s virtual support series, Staying Connected. Sessions are offered weekly and monthly, and cover a variety of topics. Registration is required. View the support series schedule and register today.

OCRA’s online support forum through Inspire offers a place for patients, survivors and loved ones to connect about life with endometrial cancer.