Different Types of Uterine Cancer: Risk Factors, Diagnosis and Treatment

Uterine cancer is the most commonly diagnosed cancer affecting the female reproductive system and can cause both emotional and physical side effects. More women are diagnosed with uterine cancer (also known as endometrial cancer) than cervical, ovarian, vulvar, vaginal and fallopian tube cancer.

According to the National Cancer Institute, uterine cancer accounts for 3.6% of all cancer cases. In 2020 alone, there will be an estimated 65,620 new cases of uterine cancer diagnosed. The NCI projects uterine cancer will claim the lives of 12,590 women this year, which is about 2.1% of all cancer deaths. This article will cover the risk factors, diagnoses and treatment of the different types of uterine cancer.

What is uterine cancer?

The uterus is the hollow, inverted pear-shaped, reproductive organ in the pelvis. The uterus connects at the top to the fallopian tubes, which connect to the ovaries, allowing for eggs (ovum) to implant in the uterus. The lower portion of the uterus narrows to the cervix where it connects the vaginal canal. When not pregnant, the lining of the uterus, called the endometrium, sheds and causes a woman’s menstrual cycle each month.

Unfortunately, cancer can develop when cells in the uterus begin to grow out of control. The most common type of uterine cancer is endometrial cancer. Endometrial cancer starts when cells in the endometrium proliferate. Uterine sarcoma, a rare form of uterine cancer, is also a type of cancer that grows within the uterine muscles or other tissues that support the uterus.

What are the leading causes of uterine cancer?

Risk factors for uterine cancer include:

• Endometrial overgrowth (hyperplasia)
• Obesity
• Polycystic ovarian syndrome (PCOS)
• Having never been pregnant
• Early menses
• Menopause after age 55
• Estrogen hormone therapy without progesterone
• Tamoxifen use (a drug used to treat cancer)
• Radiation to the pelvis
• Family history of uterine cancer
• Older age
• Lynch syndrome

Obesity and PCOS can alter the body’s hormones and cause an increase in estrogen. Taking estrogen hormone therapy without progesterone causes the body to act the same way.

Exposure to elevated levels of estrogen in any of these cases without also increasing progesterone levels can lead to endometrial cancer.

The longer a woman menstruates also increases her risk of developing uterine cancer. Women who start menstruating before age 12 or who enter menopause later have more periods than others. During pregnancy, the menstrual cycle stops. The increased number of menstrual cycles exposes the endometrium to more estrogen.

Lynch syndrome is a hereditary condition that increases the risk of endometrial cancer and other cancers because of a genetic mutation. As you age, the risk of many diseases also increases. Endometrial cancer is most likely to occur after menopause. Finally, the benefits of using tamoxifen to treat cancer outweigh the very small risk it may pose in developing uterine cancer.

The chief symptom of uterine cancer is typically abnormal vaginal bleeding. Many women become alarmed and seek medical care. It is important to make an appointment with a healthcare provider if any of the following occur:

• Bleeding after menopause
• Vaginal discharge with an odor
• Spotting between menstrual cycles
• Abnormal bleeding
• Change in urination
• Abdominal pain
• Painful sexual intercourse
• Vaginal mass
• Pelvic mass
• Weight loss
• Feeling full

What are the different types of uterine cancer?

There are 2 different types of uterine cancer: endometrial cancer and uterine sarcoma.

• Together, they account for more than 90% of uterine cancer cases and occur in the uterine lining.
• Uterine sarcoma occurs less frequently and forms in the muscles and other supportive tissues of the uterus
• Cervical cancer is not a type of uterine cancer

Endometrial cancer (also known as endometrial adenocarcinoma): More than 80% of all endometrial cancers are adenocarcinomas of the endometrium.

• Serous adenocarcinoma: Cancer is more likely to spread to the lymph nodes and elsewhere in the body.
• Adenosquamous carcinoma: A rare cancer, much like endometrial adenocarcinoma, that lines the outer layer of the uterus.
• Uterine carcinosarcoma: Cancer cells resemble endometrial cancer and sarcoma but pose a high risk of spreading to the lymph nodes and throughout the body.

Uterine sarcoma: A rare cancer that forms in the uterine muscle wall, and makes up less than 4% of all cancers. The following are types of uterine sarcoma:

• Uterine leiomyosarcoma: The most common kind of uterine sarcoma in the uterine myometrium, the muscular wall, that makes up 2% of uterine cancers.
• Endometrial stromal sarcomas: This cancer develops in connective tissue that supports the uterus and represents less than 1% of all uterine cancers. However, this type of cancer is typically slow growing.
• Undifferentiated sarcoma: Comprises less than 1% of all uterine cancers, undifferentiated sarcoma is like endometrial stromal sarcoma but grows and spreads more quickly.

Primary pure squamous cell carcinoma of the endometrium is a very rare form of uterine cancer. It’s so rare that its frequency is unknown, and the World Health Organization has reported only 70 cases. SCC is a primary carcinoma of the uterine lining in which squamous cells are differentiated to varying degrees.

While the specific cause of endometrial cancer is unknown, experts believe a genetic mutation in the DNA causes changes to the cells in the uterine lining. Typically, when healthy cells become abnormal, they stop multiplying and die at a set rate. When there are DNA changes, the endometrial cancer cells grow and divide uncontrollably forming a mass or tumor.

Who is at risk for endometrial cancer?

The main causes of endometrial cancer include:

• Taking tamoxifen for breast cancer. See your provider for a pelvic exam annually and report any abnormal vaginal bleeding immediately.
• Having radiation therapy to any pelvic organs.
• Having had more menstrual cycles.
• Having increased exposure to estrogen without added progesterone.

What causes uterine sarcoma?

Risk factors for uterine sarcoma differ from those for endometrial cancer and include:

• Radiation therapy to the pelvic area (cancer can occur 5-25 years following treatment)
• Being African American, which makes you twice as likely to develop uterine sarcoma as white or Asian women
• History of retinoblastoma

What are the symptoms of uterine sarcoma?

The most common types of uterine cancer have the following symptoms:

• Unusual vaginal bleeding
• Spotting
• Postmenopausal bleeding
• Abnormal vaginal discharge
• Urinating frequently
• Abdominal pain
• Vaginal mass or lump
• Feeling full

Different forms of uterine cancer diagnoses

While symptoms may indicate what’s happening, it is important to get an accurate diagnosis. Endometrial cancer and uterine sarcoma are diagnosed by specific tests that help doctors determine more about the health of your uterus. Testing may include:

• Pelvic ultrasound: Performed by placing an ultrasound probe covered in gel on your abdomen to examine the uterus, ovaries and other pelvic organs. If this view does not provide enough information, the next step is inserting an ultrasound wand into the vagina.
• Endometrial biopsy: Performed by inserting a small flexible tube through the cervix to the uterus and removing a small piece of uterine tissue. The test can be performed during a pelvic exam. The biopsy is sent to the laboratory to determine whether cancer cells are present.

Uterine cancer treatment options

Hysterectomy

A hysterectomy is the most common surgical procedure to treat endometrial cancer. Surgery removes the uterus and cervix, and lymph nodes, ovaries and fallopian tubes may be removed as well. Surgical cancer treatment has side effects like bleeding and infection.

Radiation therapy

Radiation therapy uses high-energy rays to kill endometrial cancer cells. Radiation can be given as follows:

• Vaginal brachytherapy: A tube with radioactive seeds is placed in the vagina following surgery. It does not affect the bladder or rectum to the extent of external radiation.
• External radiation: Similar to having an X-ray. However, the overall radiation treatment time is short and is given 5 days a week for 4-6 weeks.

Side effects for radiation therapy may include skin changes and fatigue.

• Chemotherapy: Systemic treatment used to kill cancer cells. Chemo can be taken by tablet or infused into your veins to circulate throughout the body. The treatment is given in cycles or rounds, followed by breaks in treatment. To ensure the best outcome, several chemo drugs may be used in combination. Side effects include nausea, fatigue and hair loss. These symptoms typically disappear following treatment.
• Hormone therapy: Different from menopausal hormone therapy, the treatment uses hormones or hormone-blocking drugs to fight cancer.
• Targeted drugs: Drugs affect cancer cells only, not healthy cells, and can have fewer side effects than chemo.
• Immunotherapy: Boosts your existing immune system to attack cancer cells, particularly advanced endometrial cancer.

Clinical trials test new drugs or treatments by comparing standard treatments with others.

Uterine papillary serous carcinoma is a rare form of endometrial cancer that comprises about 5% of all cases. It spreads faster and is more likely to recur following treatment than all other types of cancer, even when detected early. Risk factors include:

• Uterine papillary serous carcinoma (UPSC) is a rare form of endometrial cancer that comprises about 5% of all cases.
• It spreads faster and is more likely to recur following treatment than all other types of cancer, even when detected early.
• Women who are African American and postmenopausal are at higher risk for UPSC. UPSC may also be associated with genetic mutation.
• Women who develop UPSC are more likely to have relatives with ovarian, endometrial and pancreatic cancer.
• The symptoms and tests for diagnosis are like other types of uterine cancer.
• UPSC treatments include laparotomy (abdominal surgery to determine if the cancer has spread), hysterectomy, radiation, targeted therapy and chemotherapy.

How can you detect uterine cancer early?

Endometrial cancer can be detected at an earlier stage when symptoms like abnormal vaginal bleeding are reported early. Almost 70% of women are diagnosed early, when the cancer is confined to the uterus. Unfortunately, 20% of women are diagnosed after the cancer has spread to nearby organs. About 10% are diagnosed after cancer has spread elsewhere in the body.

Seeing your clinician regularly can help keep you safe. If discovered early, the prognosis is much better. There are no screening tests for uterine cancer. However, during your annual pelvic exam, your gynecologist will check your uterus to feel for any masses or lumps.

If you have symptoms, or your healthcare provider detects something suspicious, he or she will perform further tests.

Can you fully recover from uterine cancer?

Yes, women can fully recover from uterine cancer after aggressive treatment, like surgery and radiation. Many women feel better about 1-2 weeks following surgery and can resume normal activities after 1-2 months.

Recovery from uterine cancer is more challenging if the cancer cells have metastasized to other parts of the body. The 5-year survival rate for all uterine cancer is 81.2%. The survival data are broken down further depending on how advanced the cancer is.

SEER Stage 5-year survival rate

Leiomyosarcoma, local: 64%

Leiomyosarcoma, regional: 36%

Leiomyosarcoma, distant: 14%

Leiomyosarcoma, all stages: 42%

Undifferentiated sarcoma, local: 64%

Undifferentiated sarcoma, regional: 42%

Undifferentiated sarcoma, distant: 21%

Undifferentiated sarcoma, all stages: 42%

Endometrial stromal sarcoma, local: 98%

Endometrial stromal sarcoma, regional: 92%

Endometrial stromal sarcoma, distant: 76%

Endometrial cancer, local: 95%

Endometrial cancer, regional: 69%

Endometrial cancer, distant: 17%

Endometrial cancer, all levels: 81%

Receiving a diagnosis of uterine cancer is overwhelming, which is why it is critical to seek nationally recognized cancer care. Our cancer specialists provide comprehensive and compassionate care, resulting in excellent patient outcomes. The doctors at The University of Kansas Cancer Center are at the forefront of leading-edge research and treatment.

The University of Kansas Cancer Center provides the Kansas City region and the state of Kansas with leading-edge cancer treatment. It is the only National Cancer Institute-designated cancer center in the region.