Uterine (endometrial) cancer: Full guide

What is uterine (endometrial) cancer?

Endometrial cancer starts in the endometrium. This is the inner lining of the uterus (womb). It is the most common cancer of the female reproductive organs in the US.

The most common early sign is bleeding after menopause. Bleeding between periods or very heavy periods can also be a sign. Because bleeding shows up early, many people are diagnosed when the cancer is still only in the uterus.

Too much estrogen without progesterone raises the risk. This can come from extra body weight, some hormone pills, or the breast cancer medicine tamoxifen. Diabetes, never being pregnant, and older age also raise the risk.

Some families carry Lynch syndrome. This inherited condition raises the risk of uterine, colon, and other cancers. Every uterine cancer should be tested for signs of it.

A rare group of uterine cancers called uterine sarcomas starts in the muscle or support tissue of the uterus. They act differently and are treated differently. Your care team will tell you which kind you have.

Types

Endometrioid carcinoma

The most common type, about 8 in 10 cases. It is often linked to extra estrogen. It is usually low grade, grows slowly, and is often found early.

Serous carcinoma

A less common type that grows and spreads faster. It is often found in older people. It acts more like ovarian cancer and usually needs more treatment.

Clear cell carcinoma

A rare, fast-growing type. It usually needs more treatment after surgery.

Carcinosarcoma

An aggressive cancer with features of both carcinoma and sarcoma. Even though the name sounds like a sarcoma, it is treated like a high-risk endometrial cancer.

Uterine leiomyosarcoma

The most common uterine sarcoma. It starts in the muscle wall of the uterus. It is sometimes found after surgery for what was thought to be a fibroid.

Endometrial stromal sarcoma

A rare sarcoma that starts in the support tissue of the lining. The low-grade kind grows slowly and is fueled by hormones, so hormone-blocking medicines help.

Other uterine sarcomas

Rare types include high-grade stromal sarcoma, undifferentiated sarcoma, adenosarcoma, and PEComa. They need care from an expert team.

Tests you may have

Transvaginal ultrasound

A small wand in the vagina uses sound waves to measure the thickness of the uterine lining. A thick lining after menopause needs more testing.

Endometrial biopsy

A thin tube takes a small sample of the uterine lining. It is often done in the office. It is the main way to diagnose this cancer.

Hysteroscopy and D&C

A thin camera looks inside the uterus, and tissue is gently scraped out. This is done if an office biopsy is not clear.

Pelvic MRI

A scan that uses magnets to show how deep the cancer has grown into the uterine wall.

CT or PET-CT scan

Scans of the chest, belly, and pelvis to see if the cancer has spread.

Sentinel lymph node biopsy

During surgery, a dye shows the first lymph nodes the cancer would reach. Only those are removed and checked. This causes less leg swelling than removing many nodes.

MMR testing

A test on the tumor for a DNA repair problem. It is done for every uterine cancer. It guides treatment and checks for possible Lynch syndrome.

Molecular testing

Tests for POLE, p53, hormone receptors, and HER2. They help sort the cancer into groups that predict how it may behave.

Genetic counseling

If tumor tests suggest Lynch syndrome, you will be offered a blood test for inherited gene changes. Results may also help your family.

What the stage means

The stage tells how far the cancer has spread. It is usually set after surgery, when the uterus and lymph nodes are checked.

Uterine cancer uses stages 1 to 4. Newer staging also looks at the tumor type and molecular group. Your team may use both the stage and these results to plan care.

Stage 1

The cancer is only in the uterus. This is the most common stage at diagnosis. Surgery alone may be enough, or radiation may be added.

Stage 2

The cancer has spread to the cervix but not beyond the uterus. Surgery is usually followed by radiation.

Stage 3

The cancer has spread outside the uterus to the ovaries, tubes, vagina, pelvic tissue, or lymph nodes. Chemotherapy is usually given, sometimes with radiation or immunotherapy.

Stage 4

The cancer has spread to the bladder or bowel lining, inside the belly, or to distant organs. Treatment uses medicines that travel through the whole body, often chemotherapy with immunotherapy.

Tumor markers and gene tests

Tumor tests now play a big role in uterine cancer. They help predict how the cancer will act. They also help decide who needs more treatment and which medicines may work best.

Doctors sort most uterine cancers into four molecular groups: POLE, MMR deficient, p53 abnormal, and no specific molecular profile.

MMR deficient (dMMR) or MSI-high

About 1 in 4 uterine cancers have a DNA repair problem. These cancers often respond very well to immunotherapy. Some are caused by Lynch syndrome.

MMR proficient (pMMR)

Most uterine cancers have normal DNA repair. Immunotherapy can still help some, often combined with chemotherapy or other medicines.

POLE mutation

A gene change that, surprisingly, means a very good outlook. Some people with POLE cancers may need less treatment after surgery.

p53 abnormal

A gene change linked to faster-growing cancers like serous carcinoma. These cancers usually need stronger treatment, even at early stages.

No specific molecular profile

Cancers with none of the above changes. They are often hormone-driven, and the outlook depends on other features like grade and stage.

HER2

A protein that is high in some serous cancers and carcinosarcomas. If positive, HER2-targeted medicines like trastuzumab may be added.

Estrogen and progesterone receptors

If the cancer has these, hormone medicines may help control it, especially low-grade cancers that come back.

Lynch syndrome genes

MLH1, MSH2, MSH6, PMS2, and EPCAM. An inherited change raises cancer risk for you and your relatives. Uterine cancer is often the first cancer in people with Lynch syndrome.

Main treatments

Surgery

Removing the uterus, cervix, ovaries, and fallopian tubes, plus sentinel lymph nodes. It is often done through small cuts with a camera or robot. It treats the cancer and sets the stage.

Watchful follow-up

For many low-risk stage 1 cancers, surgery is all that is needed. You will then have regular checkups.

Vaginal brachytherapy

Internal radiation placed inside the vagina for a few short visits. It lowers the chance the cancer comes back at the top of the vagina.

External beam radiation

Radiation aimed at the pelvis from a machine. It is used when there is a higher chance the cancer could come back in the pelvis.

Chemotherapy

Carboplatin and paclitaxel are the main chemotherapy medicines. They are given by IV for higher-risk or advanced cancers, sometimes with radiation.

Immunotherapy with chemotherapy

For advanced or recurrent cancer, medicines like dostarlimab, pembrolizumab, or durvalumab are added to chemotherapy and then continued. The benefit is largest in MMR deficient cancers.

Lenvatinib plus pembrolizumab

A targeted pill combined with immunotherapy. It is used for some cancers that come back after chemotherapy, mainly MMR proficient cancers.

Hormone therapy

Progestins or estrogen-blocking pills. They can control some low-grade, hormone-driven cancers. They may also be used to save fertility in very early cancer in carefully chosen people.

HER2-targeted therapy

Trastuzumab can be added to chemotherapy for advanced HER2-positive serous cancer. Trastuzumab deruxtecan, an antibody-drug conjugate, is an option later for HER2-high tumors.

Uterine sarcoma treatment

Surgery is the main treatment. If sarcoma is suspected, the uterus is removed whole, not cut into pieces (morcellation). Leiomyosarcoma that has spread is treated with chemotherapy. Low-grade stromal sarcoma is treated with hormone-blocking pills. Care at a sarcoma center is best.

Common side effects and what helps

Recovery after surgery

Most people go home in a day or two after surgery with small cuts. Walk a little each day and avoid heavy lifting for a few weeks.

Early menopause

Removing the ovaries before natural menopause causes hot flashes and dryness. Ask your team which treatments are safe for you.

Vaginal dryness and narrowing

Radiation can cause dryness and narrowing. Moisturizers, lubricants, and a vaginal dilator can help.

Bowel and bladder changes

Pelvic radiation can cause diarrhea or a frequent need to pee. Drink fluids, and ask about diet changes and medicines.

Fatigue

Feeling very tired is common. Short walks and light activity help. Rest when you need to.

Low blood counts and infection

Chemotherapy lowers blood counts. Wash your hands often and avoid sick people. Call right away if you have a fever.

Numbness and hair loss

Paclitaxel can cause numb hands and feet and hair loss. Tell your team about numbness early. Hair usually grows back.

Immune side effects

Immunotherapy can inflame healthy organs, including the bowels, lungs, liver, skin, and hormone glands. Report new diarrhea, cough, rash, or feeling very tired. Early treatment helps.

High blood pressure and hand-foot changes

Common with lenvatinib. Check your blood pressure at home if asked. Use lotion and soft shoes, and tell your team about sore hands or feet.

Leg swelling (lymphedema)

Removing lymph nodes or radiation can cause leg swelling. Sentinel node biopsy lowers this risk. A lymphedema therapist can help.

Living with and after uterine cancer

Most people with early uterine cancer are cured with treatment. You will have regular checkups with exams, usually more often in the first few years.

Report any new vaginal bleeding, pelvic pain, cough, or weight loss. These can be signs the cancer has come back.

Staying active, eating well, and keeping a healthy weight help your overall health. They may also help your heart, which matters for long-term health after uterine cancer.

Early menopause and radiation can affect your sex life and comfort. Moisturizers, dilators, and pelvic floor therapy can help. Your team wants to hear about these concerns.

If you have Lynch syndrome, you will need regular colon checks and other screening. Your relatives can be tested too. This can help them find cancer early or prevent it.

If you have low-grade stromal sarcoma, do not take estrogen without talking to your team. Estrogen can make these tumors grow.

It is normal to feel worried or sad. Support groups, counselors, and social workers can help you and your family.