What Is Uterine Cancer?

Grading

Grade refers to the appearance of the cancerous cells, specifically how much they look like healthy cells when viewed under a microscope.

A low-grade tumor appears similar to healthy tissue and has organized cell groupings. Well-differentiated cancer tissue resembles healthy tissue and would be described as low-grade.

Cancerous tissue that appears very different from healthy tissue is considered poorly differentiated and classified as a high-grade tumor.

• Grade X (GX): The grade cannot be evaluated.
• Grade 1 (G1): The cells are well differentiated.
• Grade 2 (G2): The cells are moderately differentiated.
• Grade 3 (G3): The cells are poorly differentiated.

Treatment

Treatment is determined based on the type of cancer, stage, grade, patient age and overall health, and the desire to bear children. Cancer cells are also examined to determine whether certain treatments, like hormone therapy, might work.

Treatment decisions about targeted drugs may also be based on the genetic characteristics of the cells.

Another factor in planning your treatment is your performance status, which is how well you can carry on ordinary activities and how much you are expected to tolerate treatments.

Several treatment options are available.

Surgery

Typically, surgery is the first-line of treatment for uterine cancer. The goal of surgery is to remove the tumor and some of the healthy surrounding tissue (known as a margin).

Surgeries that may be done for treatment of uterine cancer include:

• Simple hysterectomy: Removal of the uterus and cervix.
• Radical hysterectomy: Removal of the uterus, cervix, the upper part of the vagina, and nearby tissues.
• Bilateral salpingo-oophorectomy: For people who have been through menopause, both fallopian tubes and both ovaries are removed at the same time as the hysterectomy.
• Lymphadenectomy (lymph node removal): To determine if cancer has spread beyond the uterus, your surgeon may remove lymph nodes near the tumor during your hysterectomy.

The most common short-term side effects of surgery include pain and tiredness. Other side effects may include nausea, vomiting, difficulty emptying your bladder, and difficulty having bowel movements. These problems are usually temporary. You will begin with a liquid diet right after surgery, gradually returning to solid food.

If you are premenopausal and have your ovaries removed, you will experience menopausal symptoms due to changes in hormone production.

Lymphedema (swelling in the legs) is a possible side effect of a lymphadenectomy.

Radiation

Radiation therapy uses high-energy x-rays or other particles to destroy cancer cells. Radiation therapy can be delivered externally (external-beam radiation therapy, known as EBRT) or internally (brachytherapy) and usually involves a number of treatments scheduled over a period of time.

Radiation therapy is usually administered after surgery to destroy remaining cancer cells, but it is sometimes administered before surgery to shrink the tumor. Sometimes it is used if someone is unable to have surgery.

Side effects of radiation vary, often depending on the amount of radiation therapy. Side effects may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. These effects usually resolve within months after treatment is completed. Long-term side effects can occur, but are less common.

Chemotherapy

Chemotherapy is a type of medication that destroys cancer cells, usually by keeping the cells from dividing to make more cells. For the treatment of uterine cancer, chemotherapy is started after surgery, or if cancer returns after initial treatment.

Chemotherapy typically consists of either one drug or a combination of drugs given in cycles over a period of time.

It can be administered on its own or in combination with other therapies, such as radiation. The treatment is delivered either intravenously or swallowed in pill form.

Side effects can include fatigue, risk of infection, nausea and vomiting, hair loss, peripheral neuropathy (numbness/tingling in the arms and/or legs), loss of appetite, and diarrhea. Side effects usually go away several months after chemotherapy is complete, and treatments are available to combat these side effects.

Hormone Therapy

Hormones or hormone-blocking drugs can be used to treat cancer, especially endometrial cancer that’s advanced (stage III or IV) or has come back after treatment.

Hormone treatment for endometrial cancer can include:

• Progestins: This is the main hormone treatment used for endometrial cancer. These drugs slow the growth of endometrial cancer cells and may help preserve fertility in certain cases. The two most common progestins are Provera (medroxyprogesterone acetate), given by injection or as a pill) and Megace (megestrol acetate), given by pill or liquid. Side effects can include: hot flashes; night sweats; weight gain (from fluid retention and an increased appetite); worsening of depression; increased blood sugar levels in people with diabetes; and rarely, serious blood clots.
• Tamoxifen: Often used to treat breast cancer, Tamoxifen is an anti-estrogen drug that might also be used to treat advanced or recurrent endometrial cancer. Tamoxifen is sometimes alternated with progesterone, which seems to work well and be better tolerated than progesterone alone. Potential side effects include hot flashes and vaginal dryness. People taking tamoxifen also are at higher risk for serious blood clots in the legs.
• Luteinizing hormone-releasing hormone agonists (LHRH agonists): These drugs lower estrogen levels in premenopausal people who still have functional ovaries by “turning off” the ovaries so they don’t produce estrogen. Also known as gonadotropin-releasing hormone (GNRH) agonists, Zoladex (goserelin) and Lupron (leuprolide) are drugs that might be used to treat endometrial cancer. They’re given as a shot every 1 to 3 months. Side effects can include hot flashes, vaginal dryness, and other symptoms of menopause. They can also cause muscle and joint aches. If taken long-term, these drugs can weaken bones, sometimes leading to osteoporosis.
• Aromatase inhibitors (AIs): Without functional ovaries, fat tissue becomes the body’s main source of estrogen. Drugs such as Femara (letrozole), Arimidex (anastrozole), and Aromasin (exemestane) can stop estrogen production to reduce estrogen levels even further. They are currently most commonly used in people who can’t have surgery. They are usually used to treat breast cancer but are being studied for how they can be best used for endometrial cancer as well. Side effects can include headaches, joint and muscle pain, and hot flashes. If taken long-term, these drugs can weaken bones, sometimes leading to osteoporosis

Targeted Therapy

Targeted therapy targets the specific genes, proteins, or tissue environment that contributes to cancer growth and survival, blocking the growth and spread of cancer cells with a limited impact on healthy cells.

Targeted therapy is typically reserved for stage IV cancer when other treatments fail to slow progression. It is available for uterine cancer in clinical trials and, in some instances, as part of standard-of-care treatment regimens.

Targeted therapy for uterine cancer includes:

• Anti-angiogenesis therapy: This focuses on stopping angiogenesis (the process of making new blood vessels) in order to “starve” the tumor. Avastin (bevacizumab) is a type of anti-angiogenesis therapy used to treat uterine cancer.
• Mammalian target of rapamycin (mTOR) inhibitors: People with advanced or recurrent uterine cancer may be treated with a drug such as Afinitor (everolimus) that blocks the mTOR pathway, where mutations are common with endometrial cancer. Other drugs that target this pathway include ridaforolimus and Torisel (temsirolimus), currently approved to treat other types of cancer.
• Targeted therapy to treat a rare type of uterine cancer: Uterine serous carcinoma is a rare but aggressive type of endometrial cancer. About 30% of these tumors express the HER2 gene. Herceptin (trastuzumab) is a HER2 targeted therapy mostly used to treat HER2-positive breast cancer; however, in a phase II clinical trial, researchers found that combined with chemotherapy, trastuzumab was effective in treating these kinds of tumors.

Side effects of targeted therapy vary based on the type of treatment, so it’s best to discuss potential side effects with your healthcare provider before beginning treatment.

Immunotherapy

Also called biologic therapy, the goal of immunotherapy is to boost the body’s natural defenses to fight the cancer using materials made either by the body or in a laboratory to improve, target, or restore immune system function.

The immunotherapy drug Keyruda (pembrolizumab) has been approved to treat some uterine cancer tumors. It is sometimes used in combination with Levinma (lenvatinib), a targeted therapy drug.

Immunotherapy is typically used for advanced uterine cancer or when other treatments have been ineffective.

Side effects vary depending on the type of treatment and can include skin reactions, flu-like symptoms, diarrhea, and weight changes. Lenvima may cause high blood pressure.

Palliative Care

Palliative care focuses on the physical, social, and emotional effects of cancer. The goal is to provide symptom support and non-medical support for patients and their loved ones. It can begin at any time during treatment and can have greater benefits when started right after a cancer diagnosis. Palliative care is associated with less severe symptoms, a better quality of life, and higher satisfaction with treatment.

Prognosis

Survival estimates are based on the Surveillance, Epidemiology, and End Results (SEER) database—which classifies cancer by how much or little it has spread throughout the body.

This is, of course, an estimate—some people live much longer than estimated.