Metastatic Endometrial Cancer

Written by Keri Wiginton
Medically Reviewed by Laura J. Martin, MD on March 27, 2025
11 min read

Metastatic endometrial cancer is when cancer that starts in the lining of the uterus (endometrium) spreads to other parts of the body. Your doctor may call it stage IV endometrial cancer or advanced metastatic uterine cancer.

Doctors divide stage IV endometrial cancer into subtypes based on where it has spread: 

  • Stage IVA  – Cancer in your bladder or colon 
  • Stage IVB – Cancer in distant organs like the lungs, liver, or lymph nodes outside the pelvis

Around 10% to 15% of people with endometrial cancer are diagnosed after it has already spread to distant body parts. While metastatic endometrial cancer isn't considered curable, newer treatments can slow its growth, ease symptoms, and help you live longer. 

Who treats metastatic endometrial cancer? 

Your regular doctor or obstetrician/gynecologist (OB/GYN) may be the first to suspect cancer, but a gynecologic oncologist should confirm the diagnosis and create a treatment plan. These are specialists who focus on cancers of the female reproductive system and know about the latest treatment options.  

"Patients should seek out the highest level of care available to them because it's hard to go back and redo things," says Rebecca Stone, MD, a gynecologic oncologist with Johns Hopkins Medicine. "There's no replacement for expertise in getting it right the first time." 

A muscle layer called the myometrium surrounds the uterine lining. It acts like a gate that holds cancer in, but sometimes cancer cells find a way out. 

Endometrial cancer spreads in three main ways:

Direct invasion. This is when cancer cells detach from the original tumor and invade nearby tissues. In endometrial cancer, cells are most likely to spread from the uterus directly to the cervix, bladder, vagina, ovaries, fallopian tubes, or rectum. 

Lymphatic spread. This happens when cancer cells travel through your lymphatic system, a network that helps move germ-fighting fluid through the body. These tubes act like highways for immune cells, which is a good thing. But when cancer cells hitch a ride, they can reach other organs. 

Hematogenous (bloodstream). Cancer cells sometimes travel to faraway organs (like the lungs or liver) by entering the bloodstream. This is more common with aggressive endometrial cancers like serous and clear cell adenocarcinomas.

Endometrial cancer common metastatic sites

When endometrial cancer spreads, it often moves into the cervix, bladder, vagina, ovaries, fallopian tubes, rectum or nearby lymph nodes first. But given the chance, it can show up in distant organs.

A study of nearly 4,000 people with metastatic endometrial cancer found that common distant organs sites where the cancer spreads include:

  • Lungs – 29.4%
  • Liver – 14.9%
  • Bones – 10.5%
  • Brain – 3.1% 

Other studies report lower rates of brain involvement. One study reported brain metastasis in about 0.3% to 1.4% of people with endometrial cancer, most often in those with advanced, high-grade tumors. 

Abnormal vaginal bleeding is the most common sign of endometrial cancer at any stage. This includes bleeding between periods or after menopause (going a full year without a period). Even light spotting after menopause is cause for concern and should be checked by a doctor. 

Other metastatic endometrial cancer symptoms may include: 

  • Unusual or bad-smelling discharge
  • Very heavy periods (especially after age 40)
  • Constant pelvic pain or pressure
  • Pain when you pee
  • Pain during sex

You may also have: 

  • Anemia (a low red blood cell count)
  • Serious fatigue or weakness 
  • Weight loss without trying
  • Night sweats

When endometrial cancer spreads beyond the uterus, your symptoms depend on where the cancer is. For more context, here's a breakdown by organ: 

Lungs: 

  • Shortness of breath
  • Ongoing cough
  • Chest pain or pressure
  • Coughing up blood

Liver: 

  • Belly pain, especially in the upper right side
  • Yellowing of the skin and eyes (jaundice) 
  • Belly swelling due to fluid buildup
  • Feeling full quickly
  • Loss of appetite

Bones:

  • Pain in the spine, hips, or other bones
  • Bones that break easily
  • Stiffness or other problems getting around

Brain: 

  • Headache
  • Dizziness or balance problems
  • Seizures or loss of consciousness
  • Memory or speech problems

Can you have metastatic endometrial cancer without obvious symptoms?

It's rare, but possible. For example, if you have a physical barrier in your cervix, such as scar tissue from a previous surgery, it could block blood from leaving your uterus. This might prevent you from noticing early signs of cancer, such as abnormal bleeding. 

Doctors use several tests to find out how far endometrial cancer has spread. You may need one or more of the following: 

Imaging. Scans help doctors see inside your body to find out exactly where the cancer has spread. Common imaging tests for metastatic endometrial cancer include:  

  • Ultrasound 
  • Computed tomography (CT) scan 
  • Chest X-ray 
  • Magnetic resonance imaging (MRI) 
  • Positron emission tomography (PET) scan

Biopsy. If imaging suggests you have cancer outside your uterus, doctors will take a small tissue sample (biopsy) from the tumor and look at it under a microscope. This is the best way to confirm a metastatic endometrial cancer diagnosis. 

Molecular subtyping. Your doctor may test your tumor for genetic mutations. This helps guide your treatment plan. Common molecular subtypes and what they mean include: 

  • Copy number high/low – Measures cancer cell instability
  • TP53 mutation – Signals more aggressive cancer
  • Mismatch repair (MMR) protein – Helps decide if immunotherapy might work
  • Microsatellite instability (MSI) – Another way to know if you're eligible for immunotherapy
  • POLE mutation – Linked to better treatment response
  • HER2 amplification – May respond better to certain kinds of targeted therapy

Blood tests. Doctors may check your blood for signs that cancer has spread or that your treatment isn't working, including: 

  • Complete blood count (CBC) 
  • Complete metabolic panel (CMP) 

CA-125 is sometimes checked since some endometrial cancers – particularly advanced-stage cancers – release this protein. But it's more commonly used to monitor ovarian cancer.

Your treatment plan depends on where the cancer has spread, how aggressive it is, what symptoms you have, and how your body responds to therapy. 

You may get one or more of the following: 

Surgery

Your doctor might suggest surgery to remove your uterus, ovaries, and fallopian tubes (hysterectomy). If your tumor is large or has spread to other areas of the abdomen (belly area), a debulking procedure may be done to remove as much of the tumor as possible to help ease symptoms and make other treatments (like chemo and radiation) work better.

If the cancer has spread far beyond your pelvis, surgery may not be very helpful. Your doctor will let you know what's right for you. 

Chemo and radiation therapy

Chemotherapy is a standard treatment for advanced endometrial cancer. It helps slow the growth of fast-dividing cancer cells throughout the body. Doctors often combine it with radiation therapy, which uses high-energy beams to target and destroy cancer cells.  

Common chemotherapy drugs include: 

  • Carboplatin and paclitaxel

Other chemo drugs that may be used:

  • Cisplatin
  • Doxorubicin
  • Ifosfamide

Chemotherapy is given in cycles to allow your body time to recover. In some cases, radiation therapy is used between cycles. 

How does radiation therapy treat metastatic endometrial cancer?

Radiation therapy is used to shrink tumors in specific areas. This can ease pain and other symptoms. External beam radiation therapy (EBRT) is the most common type. That's when a machine directs high-energy rays at tumors from outside your body. 

Other types of radiation therapy include: 

  • Internal radiation (brachytherapy)
  • Stereotactic body radiation therapy (SBRT) 

Hormone therapy

Also called endocrine therapy, progestins are a synthetic form of the hormone progesterone that can slow the growth of endometrial cancer cells. Other types of hormone therapy slow cancer growth by blocking or lowering estrogen. It's often used alongside chemotherapy or other treatments. 

Hormone therapy for endometrial cancer may include: 

  • Aromatase inhibitors
  • CDK 4/6 inhibitors
  • Fulvestrant (Faslodex)
  • Gonadotropin-releasing hormone (GnRH) agonists
  • Progestins
  • Tamoxifen 

Your doctor will tailor hormone therapy based on your cancer type and hormone sensitivity. It's important to note that hormone therapy for endometrial cancer isn't the same as the kind used to manage menopause systems, which is called hormone replacement therapy (HRT). 

Targeted therapy

This treatment targets specific receptors on cancer cells. It typically causes fewer side effects than chemotherapy, since it spares healthy cells, but doctors often combine it with other treatments. 

One type of targeted therapy for endometrial cancer targets the HER2 protein. If you block this protein, cancer cells can't grow and divide as fast. 

Targeted therapy for HER2-positive endometrial cancer includes:

  • Fam-trastuzumab deruxtecan (Enhertu)
  • Trastuzumab (Herceptin) 

Doctors sometimes use a type of drug called an mTOR inhibitor. These block a protein called mTOR, which also helps cancer cells survive.

Common mTOR inhibitors include: 

  • Everolimus (Afinitor)
  • Temsirolimus (Torisel)

Other targeted therapies include kinase inhibitors and angiogenesis inhibitors that block tumors from forming new blood vessels and target certain proteins in cancer cells helping to slow their growth.

Immunotherapy

This is a type of treatment that helps your body fight cancer. One type of immunotherapy called immune checkpoint inhibitors trigger parts of your immune system to better identify and attack cancer cells. They work particularly well for endometrial cancer with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). 

"The discovery of mismatch repair deficient endometrial cancer has been a game changer," Stone says. "People with those tumors tend to be exquisitely sensitive to immunotherapy."  

Immunotherapy drugs approved for advanced endometrial cancer include: 

  • Dostarlimab (Jemperli)
  • Durvalumab (Imfinzi)
  • Pembrolizumab (Keytruda)

Combined with chemotherapy, treatment with immune checkpoint inhibitors may help you live longer without your endometrial cancer getting worse. Your doctor can check your tumor cells for genetic changes to find out which type of immunotherapy might be right for you. 

Palliative care

This is a type of supportive treatment. The goal is to help manage side effects and symptoms of cancer or its treatment. Unlike end-of-life care (hospice), you can get it at any time after your diagnosis.

Palliative care for endometrial cancer may help with things like:

  • Pain 
  • Fatigue and nausea
  • Emotional or psychological support

If you want supportive care but don't want to leave your house to get it, there's good news: Studies show that virtual palliative care works just as well as in-person visits to improve the lives of people with cancer. 

In general, the five-year survival rate for stage IV endometrial cancer is about 19%. This means that about 2 out of 10 people diagnosed at this advanced stage are expected to be alive five years after diagnosis. 

But there've been a lot of advances in endometrial cancer treatment, so you may live longer than that. Your outlook depends on several things, including: 

  • Where the cancer has spread
  • Your overall health
  • Treatment options
  • Genetic changes in your tumor
  • How your cancer responds to treatment

Your doctor can help you understand what to expect based on your specific situation. 

What to do if metastatic endometrial cancer has advanced

If your cancer isn't responding to treatment anymore, you and your doctor should talk about what comes next. That isn't about giving up – it's about making sure you live as well as possible for as long as possible. 

"I always tell people, we'll take it one step at a time. At each step, we'll gather new information, regroup, discuss what it means, and make the best decision for you," Stone says.

Here are some questions to ask your doctor: 

  • Do I qualify for clinical trials or experimental treatments?
  • How can palliative care help me feel better and make the most out of life?
  • When is it time for hospice care? How will it help?
  • What end-of-life decisions do I need to make?   

Talk to your doctor about your goals and priorities. Ask if a social worker can explain things like advance directives, a health care proxy, and a living will. If you make these legal decisions early on, you can trust that your care will align with your wishes, even if you're unable to make choices later. 

Remember, you're not alone. Medical professionals, family, friends, and cancer groups can help you navigate this journey every step of the way. Here are some tips to find support: 

Work with your care team. Check in with your doctor regularly. They'll help you tailor treatments to manage pain, fatigue, emotional issues, and other symptoms that keep you from feeling your best. 

Find your cancer community. Connect with other people who know what you're going through. You may find in-person or virtual groups through: 

  • Cancer Support Community
  • SHARE Cancer Support
  • CancerCare
  • Cancer Survivors Network  

Take advantage of resources. Groups that provide free counseling, financial assistance, and patient education include: 

  • American Cancer Society: 800-227-2345
  • CancerCare: 800-813-4673
  • National Comprehensive Cancer Network (NCCN) treatment guidelines 

If you need help with medical bills and treatment costs, reach out to groups such as the Patient Advocate Foundation and Patient Access Network (PAN) Foundation.

Metastatic endometrial cancer happens when cancer that starts in your uterine lining spreads to other parts of your body. While doctors are still searching for a cure, treatment can help you feel better and manage symptoms. 

Your doctor may suggest surgery, chemotherapy, radiation, hormone therapy, targeted therapy, or immunotherapy, depending on your cancer stage and type.

Talk to your medical team about the best way to manage symptoms and meet your goals. Work with a gynecologic oncologist for best results, as expert care can improve outcomes and ensure you get the latest treatment options. 

How fast does endometrial cancer spread?

It depends on the type and stage at diagnosis. Most people are diagnosed with type 1. This is a slow-growing type of endometrial cancer that's usually found only in the uterus. It can stay there for months or years. Type 2 cancers are less common, but they're more aggressive and can spread quickly. 

Can metastatic endometrial cancer spread to the brain?

Yes, but it's rare. Most studies show brain metastasis happens in around 1% or less of endometrial cancer cases. Your odds of getting it are higher if you have a fast-growing (high-grade) advanced disease. 

How often is endometrial cancer metastatic? 

Around 10%-15% of people with endometrial cancer are diagnosed with an advanced disease. This is more likely to happen if you have an aggressive cancer type or are diagnosed late.

Is metastatic endometrial cancer curable?

Not usually, but that may change as treatment advances. For now, hormone therapy, chemotherapy, immunotherapy, and targeted drugs are used to help slow the disease and improve your life.