Uterine cancer is the most common gynecological cancer in the United States, with a yearly new cancer case rate of 27.2 per 100,000 people and a yearly death rate of 5 per 100,000 people. Uterine cancer primarily refers to two types of cancer that affect the uterus: Endometrial carcinoma and uterine sarcoma. Uterine sarcoma is much less common than endometrial carcinoma.
While endometrial carcinoma is common and readily treated in the early stages, uterine sarcoma is rare and can be difficult to treat.
- Endometrial carcinoma: This cancer starts in the glandular tissues and/or connective tissues of the endometrium, which is the lining of the uterus. There are several subsets of this type of cancer:
- Endometrial adenocarcinoma (most common, affecting glandular tissues)
- Endometrial stromal carcinoma (less common, affecting connective tissues)
- Malignant mixed Müllerian tumors (rare, involving both carcinoma and sarcoma, also known as carcinosarcoma).
- Uterine Sarcoma: Uterine leiomyosarcoma (LMS) is the most common type of this cancer. LMS starts in the myometrium, which is the muscular layer of the uterus.
Uterine cancer may not cause symptoms, particularly in the early stages. When they occur, symptoms can include abnormal vaginal bleeding and pelvic pain.
Because they affect different areas of the uterus, symptoms of endometrial cancer can differ from symptoms of uterine sarcoma.
Bleeding that’s unrelated to menstruation
Unusual vaginal discharge without any visible blood
Difficult or painful urination
Pain during intercourse
Pain and/or mass in the pelvic area
Unintentional weight loss
Unusual vaginal bleeding or spotting
Unusual vaginal discharge without any visible blood
Pain in the abdomen
A mass (lump or growth) in the vagina
Feeling full at all times
Loss of appetite and changes in bowel and bladder habits can occur as the malignancy invades nearby organs.
While scientists don’t fully understand what causes uterine cancer, hormonal imbalances are believed to play a role. Estrogen can cause the cells and tissue of the endometrium to multiply faster than usual, which can lead to endometrial hyperplasia (abnormal enlargement of the endometrium).
Risk factors for uterine cancer include:
- Age: Endometrial cancer mainly affects postmenopausal people, with an average age at diagnosis of 60. It is uncommon in people under age 45.
- Race: White people are slightly more likely to be diagnosed with endometrial cancer, but Black people are more likely to die from it. It is important to consider the role of systemic racism in medicine when examining information by race.
- A high number of menstrual cycles: This refers to the number of menstrual cycles in a person’s lifetime and includes people who experienced their first menstrual period before age 12 or who went through menopause after age 50.
- No prior pregnancies: Uterine cancer is more common among people who have not been pregnant. One possible explanation for this link is that the body produces more progesterone and less estrogen during pregnancy. Another possibility is that infertility is associated with an imbalance between progesterone and estrogen, which could also contribute to uterine cancer.
- Age at time of giving birth: There is a possible link between the age at which a person gives birth for the first time and uterine cancer, but more studies are necessary to draw conclusions.
- Estrogen replacement therapy (ERT): During menopause, the body produces less estrogen. ERT is used after menopause to treat symptoms such as vaginal dryness, severe hot flashes, and sleeplessness. It may also be prescribed if someone is at risk for osteoporosis. ERT is associated with an increased risk of uterine cancer, particularly when the endometrium is exposed to estrogen without progesterone. To reduce this risk, your healthcare provider may prescribe low doses of estrogen combined with progesterone.
- Tamoxifen: There is a low risk of developing endometrial cancer from tamoxifen (less than 1% per year). This drug is used to prevent and treat breast cancer. It acts as an anti-estrogen in the breast but acts like an estrogen in the uterus. In people who have gone through menopause, this treatment can cause the uterine lining to grow, which may increase the risk of endometrial cancer. If you are taking tamoxifen, your healthcare provider will check for signs of cancer with yearly gynecologic exams, and you should watch for symptoms of endometrial cancer—such as abnormal bleeding. If symptoms appear, consult your healthcare provider.
- Lynch syndrome: This is a hereditary syndrome linked to a higher risk of some cancers including endometrial, colorectal, and ovarian cancer. The estimated lifetime risk of endometrial cancer in the general population is 2.6%, and Lynch syndrome increases the estimated endometrial cancer risk to 42 to 54%.
- Genetics: While more research needs to be done, a study strongly suggests a link between the BRCA1 genetic mutation and a slightly increased risk of an uncommon but aggressive uterine cancer, serous or serous-like endometrial cancer. People who carry the BRCA1 (or BRCA2) genetic mutation are sometimes advised to have a mastectomy to reduce the chances of breast cancer associated with this gene mutation. Sometimes the uterus is removed at the same time as the ovaries if surgery for ovary removal is already scheduled.
- Obesity: More than 50% of endometrial cancers are linked with obesity. Adipose tissue (fat) converts androgen to estrogen, which can lead to an increase in unopposed estrogen exposure. This increases the risk of uterine cancer. Other conditions that can lead to this increase include metabolic syndrome and diabetes mellitus type II.
A Key Difference Between Endometrial Cancer and Uterine Sarcoma
Unlike endometrial carcinoma, uterine sarcoma is linked to prior radiation exposure anywhere from five to 25 years earlier. Women with retinoblastoma, a type of eye cancer, are also more likely to get this rare and severe form of uterine cancer.
If you are experiencing symptoms of uterine cancer, be sure to make an appointment to see your healthcare provider. In addition to asking about your symptoms, your provider will use several tests to make a diagnosis.
- Physical exam: Your healthcare provider will check for pallor (abnormally pale skin), or a rapid pulse, which can occur due to blood loss. During your physical exam, your provider will feel your uterus and abdomen to check for enlargement or tenderness. During your pelvic examination, your practitioner will look for signs, such as bloody discharge or blood clots.
- Transvaginal ultrasound: A transvaginal ultrasound is used to examine the uterine lining. In postmenopausal people, lining over four millimeters thick is considered abnormal, and may prompt further testing, such as a biopsy.
- Hysteroscopy: During a hysteroscopy, your healthcare provider inserts a thin, lighted tube into your vagina to observe your cervix and uterus. The uterus is filled with saline to facilitate visualization. This can help determine the cause for abnormal bleeding, and in some cases, biopsy or removal of a lesion might be done during the procedure.
- Endometrial biopsy: During this procedure, a small amount of uterine lining is removed through the cervix. This tissue is then examined under a microscope.
- Dilation and curettage (D&C): If the results of the endometrial biopsy are not diagnostic, a D&C might be performed. Generally done as outpatient surgery, endometrial tissue is scraped out of the uterus with a special tool through the medically dilated cervix during this procedure. The tissue sample is then examined with a microscope.
Your signs and symptoms might also prompt your healthcare provider to consider the possibility of other conditions, including endometriosis, fibroids, adenomyosis, atrophic vaginitis, endometrial atrophy, endometrial hyperplasia, and endometrial/cervical polyps. You might need to have one or more tests to rule out another condition during your diagnostic evaluation.
If you are diagnosed with cancer, your cancer will be staged. Staging defines the size and extent of metastasis (spread) of cancer. Staging is an important step because it helps determine how cancer should be treated and how successful the treatment might be.
Staging is determined by the TNM system.
Tumor. How big is it? How far has cancer grown into the uterus and has it reached nearby organs or structures?
Nodes. Has cancer spread to the para-aortic lymph nodes (the lymph nodes in the pelvis or around the aorta, which is the main artery that runs from the heart down the back of the abdomen and pelvis)?
Metastasis. Has cancer spread to distant lymph nodes or distant organs in other parts of the body?
A letter or number is added after the T, N, or M to give more specific information. This information is combined in a process called stage grouping. Higher numbers and letters after the T, N, or M indicate the cancer is more advanced.
Tests used to determine staging include:
- Physical exam Depending on the location of the tumor, a physical exam may help determine size.
- Imaging tests Tests such as x-rays, CT scans, MRIs, ultrasound, and PET scans help with visualization of the tumor and metastases.
- Blood tests A CA 125 test measures the amount of cancer antigen 125 in the blood, and may be used to monitor some cancers during and after treatment.
- Advanced genomic testing The DNA from the cancer cells taken from a biopsy of a tumor is sequenced. Specific genetic abnormalities often guide targeted cancer therapy.
Endometrial cancer is classified by numerical stages and lettered substages, with lower numbers and early letters indicating less advanced cancer.
|The Stages and What They Mean|
|I||The cancer is growing in the uterus. It has not spread to lymph nodes.|
|IA||The cancer is in the endometrium and may have grown less than halfway through the myometrium. It has not spread to lymph nodes.|
|IB||The cancer has grown more than halfway through the myometrium, but has not spread beyond the body of the uterus. It has not spread to the lymph nodes.|
|II||The cancer has spread from the body of the uterus and is growing into the supporting connective tissue of the cervix (cervical stroma). It has not spread outside the uterus or to lymph nodes.|
|III||The cancer has spread outside the uterus, but has not spread to the inner lining of the rectum or urinary bladder. It has not spread to lymph nodes.|
|IIIA||The cancer has spread to the outer surface of the uterus (serosa) and/or to the fallopian tubes or ovaries (the adnexa). It has not spread to lymph nodes.|
|IIIB||The cancer has spread to the vagina or to the tissues around the uterus (parametrium). It has not spread to lymph nodes.|
|IIIC1||The cancer is growing in the body of the uterus. It may have spread to some nearby tissues, but is not growing into the inside of the bladder or rectum. It has spread to pelvic lymph nodes, but not to lymph nodes around the aorta or distant sites.|
|IIIC2||The cancer is growing in the body of the uterus. It may have spread to some nearby tissues, but is not growing into the inside of the bladder or rectum. It has spread to lymph nodes around the aorta (para-aortic lymph nodes).|
|IVA||The cancer has spread to the inner lining of the rectum or urinary bladder (the mucosa). It may or may not have spread to nearby lymph nodes, but has not spread to distant sites.|
|IVB||The cancer has spread to inguinal (groin) lymph nodes, the upper abdomen, the omentum (fatty tissue that hangs down from the stomach and liver and wraps around the intestines), or to organs away from the uterus, such as the lungs, liver, or bones. The cancer can be any size and it might or might not have spread to other lymph nodes.|
Most Uterine Cancer Is Caught Early
Because vaginal bleeding in women ages 50 to 60 is readily recognized as being abnormal, around 70% of women with uterine cancer are diagnosed at stage I.
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.
Why Are Staging and Grading Important?
Staging and grading help direct the appropriate course of treatment and help with prognosis (estimating the likely outcome of treatment), including survival times.
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.
Treatment Can Differ Between Endometrial Cancer and Uterine Sarcoma
Endometrial cancer and uterine sarcoma are both treated similarly. With that said, uterine sarcoma is far more aggressive and typically requires chemotherapy in early-stage disease, while endometrial cancer might not.
Several treatment options are available.
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 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 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.
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 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.
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 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.
What Is a Prognosis?
Prognosis is a prediction or estimate of the chance of recovery or survival from a disease.
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.
|5-Year Relative Survival Rate For Endometrial Cancer Based on SEER Stage|
|Localized||No sign that the cancer has spread outside of the uterus.||95%|
|Regional||The cancer has spread from the uterus to nearby structures or lymph nodes.||69%|
|Distant||The cancer has spread to distant parts of the body such as the lungs, liver or bones.||17%|
Facing treatment for uterine cancer can be overwhelming. It can help to break down your needs into smaller categories that are easier to tackle.
- Support: Enlist the help of friends and family. Loved ones often want to help, but don’t know where to start. They often give a blanket, “Let me know if you need anything.” Tell them specifically what you need, be that rides to appointments, meals prepared, or a comforting shoulder.
- Support groups: Friends and family are great for support, but sometimes talking to someone who knows what you are going through can make a huge difference. Cancer support groups can be a good place to find people who you can relate to. You can find them through sources like Cancer Support Community, Gynecologic Cancers Patients Support Group, and Foundation For Women’s Cancer.
- Managing side effects: Side effects like nausea, pain, vaginal dryness, lack of appetite, and others can be managed with medications prescribed by your healthcare provider. Practical measures such as wearing loose, comfortable clothing to your radiation treatments can also go a long way to managing your comfort levels.
- Sexuality: It’s natural to worry about how cancer and cancer treatment could affect your sex life. What sexual activities are safe is best decided with the guidance of your healthcare provider. You might ask your provider questions about safety, medication, comfort, or anything else that’s on your mind.
- Stress reduction: Dealing with cancer is stressful for you and your loved ones. Some ways to help reduce stress include healthy eating, exercise, mediation, seeking support, accessing social services, and doing activities that you find enjoyable and relaxing. If the stress becomes unmanageable or intrusive, speak with your healthcare provider about how to find mental health support, such as counseling or medication.
- Financial assistance: Financial stress can be part of cancer treatment. The Cancer Financial Assistance Coalition (CFAC) offers financial resources for people with cancer.
A Word From Get Meds Info
The word cancer is always fear-inducing, and cancer treatment can be daunting. If you have received a diagnosis of uterine cancer, don’t panic. Stop, breathe, and remember that there are effective treatments available, and remission is possible.
Early diagnosis usually means better outcomes. Whatever your age, if you notice unusual vaginal bleeding or pelvic pain, don’t ignore it. These symptoms may not signal cancer, but they should always be taken seriously and checked by a healthcare provider.
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University of Alabama Family Medicine Clinic. Estrogen replacement therapy.
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