Endometrial Cancer

Endometrial cancer is a type of cancer that begins in the lining of the uterus and is the most common gynecologic cancer affecting women in the United States. While it can be a serious diagnosis, it’s often found early because it causes noticeable symptoms like unusual vaginal bleeding, which allows for timely treatment.

Table of contents

• What Is Endometrial Cancer?
• Associated Anatomy
• Types of Endometrial Cancer
• How Common Is Endometrial Cancer?
• Signs and Symptoms
• Risk Factors
• Diagnosis and Testing
• Stages of Endometrial Cancer
• Treatment Options
• Living With Endometrial Cancer

What Is Endometrial Cancer?

Endometrial cancer is a disease in which malignant (cancer) cells form in the tissues of the endometrium, which is the lining of the uterus^[1][2]. The uterus, also called the womb, is a hollow, pear-shaped organ in a woman’s pelvis where a baby grows during pregnancy^[1][2].

In most nonpregnant women, the uterus is about 3 inches long^[2]. The lower, narrow end of the uterus is called the cervix, which leads to the vagina^[2]. The top part of your uterus is called the body or corpus^[5].

Endometrial cancer is different from cancer of the muscle of the uterus, which is called uterine sarcoma. Uterine sarcomas develop in the myometrium, the muscle wall of the uterus, and are very rare^[2][5]. Because endometrial cancer makes up about 95% of all cases of uterine cancer, people often use the terms “endometrial cancer” and “uterine cancer” to mean the same thing^[5].

• Uterus
• Endometrium (uterine lining)
• Cervix
• Vagina
• Ovaries
• Fallopian tubes

Types of Endometrial Cancer

Endometrial cancer has historically been classified into two main types based on how the cells look under a microscope and how they behave^[4][6].

Type 1 endometrial cancers are more common, accounting for about 80% of all endometrial cancers^[4]. These are primarily of endometrioid origin and tend to grow slowly. They are most often found only inside the uterus and usually have a better outlook^[6].

Type 2 endometrial cancers are less common but more aggressive. These include serous and clear cell carcinomas^[4]. Serous and papillary serous carcinomas make up 4% to 6% of endometrial cancers, while clear cell carcinomas account for 1% to 2%^[4]. Type 2 cancers grow more quickly and often spread to other parts of the body^[6].

Recent studies have begun classifying endometrial cancers according to a current molecular subgrouping system, which looks at the genetic makeup of the cancer cells^[4][13]. This newer approach helps doctors determine the best treatment for each person’s cancer.

How Common Is Endometrial Cancer?

Endometrial cancer is the most common type of cancer affecting the female reproductive organs in the United States^[4][5][6]. In 2023 alone, over 66,000 new cases were expected, and over 13,000 deaths were due to this cancer^[4]. Globally, it is the sixth most common cancer, with 417,000 new cases and 97,000 deaths in 2020^[13].

About 3% of women will receive a diagnosis of uterine cancer at some point during their lives^[5]. Endometrial cancer mainly develops after menopause, with most cases diagnosed in women in their mid-60s^[5][6].

Despite recent advances and novel treatments, survival for endometrial cancer has decreased in the past 10 years. Uterine cancer is one of the few cancers with an increase in overall mortality, with a rise of 1.7% over the past 10 years^[13].

Signs and Symptoms

The most common symptom of endometrial cancer is abnormal bleeding from the vagina^[1][2][9]. Endometrial cancer is often found at an early stage because it causes symptoms that prompt women to see their doctors^[1].

Symptoms of endometrial cancer may include^[1][2][5]:

• Vaginal bleeding after menopause
• Vaginal bleeding or spotting between periods before menopause
• Bleeding between periods
• Extremely prolonged, heavy, or frequent vaginal bleeding if you’re older than 40
• Vaginal discharge not related to menstruation
• Thin white or clear vaginal discharge if you’re postmenopausal
• Lower abdominal pain or cramping in your pelvis, just below your belly
• Pelvic pain
• Difficult or painful urination
• Pain during sexual intercourse

Symptoms of advanced endometrial cancer include abdominal or pelvic pain, bloating, feeling full quickly when eating, and changes in bowel or bladder habits^[6].

These signs and symptoms may be caused by endometrial cancer or by other conditions. If you notice unusual pain or irregular vaginal bleeding, talk to your healthcare provider^[1][2][5]. An accurate diagnosis is important so you can get the proper treatment.

Risk Factors

A risk factor is anything that increases your chance of getting a disease. Having a risk factor does not mean that you will get cancer, and not having risk factors doesn’t mean that you will not get cancer^[2].

Several factors can increase the chances you’ll develop uterine cancer. If you’re at high risk, talk to your healthcare provider about steps you can take to protect your health^[5].

Hormonal Factors

Many risk factors for endometrial cancer relate to the balance between estrogen and progesterone, two hormones that affect the endometrium^[5]. The levels of estrogen and progesterone in your body can affect your risk of endometrial cancer. When estrogen is present without enough progesterone, it can cause the endometrium to become too thick^[6].

Exposure of endometrial tissue to estrogen made by the body can be caused by^[2]:

• Never giving birth
• Menstruating at an early age
• Starting menopause at a later age
• Having irregular menstrual periods
• Being in perimenopause or menopause

Medical Conditions

Certain medical conditions increase the risk of endometrial cancer^[2][5][6]:

• Obesity or being overweight (having a body mass index of 25 or greater is a major risk factor; as BMI increases, so does the risk of cancer)
• Having metabolic syndrome
• Having type 2 diabetes
• Having polycystic ovary syndrome (PCOS)
• Having endometrial hyperplasia (a condition where the endometrium becomes too thick)

Medications

Taking certain medications can affect endometrial cancer risk:

Taking estrogen-only hormone replacement therapy (HRT) after menopause increases the risk of endometrial cancer^[2][6]. Women taking estrogen alone also have an increased risk of endometrial cancer. Taking estrogen combined with progesterone does not increase a woman’s risk of endometrial cancer^[2]. If you have a uterus, estrogen-only therapy can cause the endometrium to thicken. Because of this, your doctor may recommend that you take estrogen along with a form of progesterone called progestin to keep the endometrium from getting too thick^[6].

Taking tamoxifen to prevent or treat breast cancer can increase the risk of endometrial cancer^[2]. A patient who takes this drug and has abnormal vaginal bleeding should have a follow-up exam and a biopsy of the endometrial lining if needed^[2].

Genetic and Family Factors

Having certain genetic conditions and family history can increase risk^[2][6]:

• Having a family history of endometrial cancer in a first-degree relative (mother, sister, or daughter)
• Having certain genetic conditions, such as Lynch syndrome
• Personal history of breast, ovarian, or colon cancer

Age

Older age is the main risk factor for most cancers. The chance of getting cancer increases as you get older^[2]. Most cases of endometrial cancer are diagnosed after menopause, in women in their mid-60s^[6].

Diagnosis and Testing

If you have symptoms that could be due to endometrial cancer, you usually start by seeing your doctor, who will then decide whether to do tests or refer you to a specialist^[9].

Tests and procedures used to diagnose endometrial cancer include^[10]:

Pelvic Exam

A pelvic exam checks the reproductive organs. During the exam, a healthcare professional carefully inspects the outer genitals. Two fingers of one hand are inserted into the vagina and the other hand presses on the abdomen to feel the uterus and ovaries. A device called a speculum is inserted into the vagina to open the vaginal canal so the health professional can look for signs of cancer or other problems^[10].

Imaging Tests

Imaging tests make pictures of the inside of the body. They can tell your healthcare team about your cancer’s location and size^[10].

One imaging test might be a transvaginal ultrasound. In this procedure, a wandlike device called a transducer is inserted into the vagina. The transducer emits sound waves that generate images of your pelvic organs^[10].

Endometrial Biopsy

An endometrial biopsy is a procedure to remove a small piece of tissue from the endometrium for examination under a microscope. This helps determine if cancer cells are present and what type they are^[10].

Hysteroscopy

Hysteroscopy is a procedure that allows the doctor to look inside the uterus using a thin, lighted instrument called a hysteroscope. This instrument is inserted through the vagina and cervix into the uterus to examine the endometrium and take tissue samples if needed^[10].

Additional Tests

Tests that examine the endometrium are used to diagnose endometrial cancer^[2]. If cancer is found, additional tests may be done to determine if the cancer has spread to other parts of the body.

Stages of Endometrial Cancer

The stage of a cancer tells you about its size and whether it has spread^[9]. If you receive an endometrial cancer diagnosis, your provider may also tell you what stage of cancer you have. Uterine cancers are staged on a scale from I to IV^[19].

In some cases, your provider may not be able to tell what stage of cancer you have until surgery to remove the cancer has been performed^[19].

The stages are defined as follows^[19]:

Stage I: Cancer hasn’t spread beyond your uterus

Stage II: Cancer has spread to your cervix

Stage III: Cancer has spread to your vagina, ovaries, and/or lymph nodes

Stage IV: Cancer has spread to your bladder or other organs far away from your uterus

Stages I and II are sometimes called early stage, while Stages III and IV are also referred to as advanced, late-stage or, for Stage IV, metastatic^[19].

Treatment Options

Treatment for endometrial cancer depends on several factors, including the stage and type of cancer, whether it has spread, and your general health^[9]. The treatment plan can be complex, and some patients require care from more than one doctor. An endometrial cancer patient’s plan for care should be coordinated by a gynecologic oncologist, a doctor who specializes in both cancer diagnosis and treatment and has special training in operating on cancers of the uterus and other reproductive organs^[12][19].

Surgery

Surgery is the most common treatment for endometrial cancer^[11][12]. Surgery both removes the cancer in the uterus and determines the stage^[12].

The minimum surgical procedure is hysterectomy (removal of the uterus and cervix) with removal of both fallopian tubes and ovaries^[12]. Often surgery also includes the removal of lymph nodes in the pelvis and abdomen. This procedure can be performed through a traditional incision in the skin of the abdomen or with minimally invasive surgery^[12].

Minimally invasive techniques, which include standard laparoscopy or robotic surgery, may allow for a quicker recovery and less pain after surgery and fewer wound complications than open surgery^[12].

If endometrial cancer is found early, surgically removing the uterus often cures it^[1].

Radiation Therapy

Radiation therapy uses high-energy rays or particles to destroy cancer cells. It may be used after surgery to kill any remaining cancer cells, or as a main treatment for women who cannot have surgery^[11].

Chemotherapy

Chemotherapy uses drugs to destroy cancer cells. It is usually used for advanced or recurrent endometrial cancer. Chemotherapy may be combined with other treatments^[11][12].

Hormone Therapy

Hormone therapy uses hormones or hormone-blocking drugs to fight cancer. Some endometrial cancers grow in response to hormones. Hormone therapy may be an option for some women, especially those with cancer that has spread beyond the uterus or has come back after treatment^[11][12].

Immunotherapy

Immunotherapy helps your immune system fight cancer. Immune checkpoint inhibitors are a type of immunotherapy that work by blocking proteins that prevent the immune system from attacking cancer cells^[16][17].

In 2024, the United States Food and Drug Administration approved three immune checkpoint inhibitors to treat advanced endometrial cancer: dostarlimab-gxly (Jemperli), durvalumab (Imfinzi), and pembrolizumab (Keytruda)^[16]. These drugs are usually combined with chemotherapy but can also be used on their own. You may need additional testing to see if these medications could help treat your cancer^[16].

Targeted Therapy

Targeted therapies are drugs that target specific proteins in cancer cells^[16]. As of 2024, lenvatinib (Lenvima) is the only targeted therapy that’s been approved by the FDA to treat endometrial cancer. Lenvatinib is a type of targeted therapy called a kinase inhibitor. It works by blocking proteins that cancer cells use to grow and form new blood vessels. Lenvatinib is usually used with an immune checkpoint inhibitor, like pembrolizumab^[16].

Living With Endometrial Cancer

Living with endometrial cancer can be challenging, whether during treatment or in remission. There are steps you can take to try to bring more brightness to your days^[20].

Making Healthy Choices

When living with advanced endometrial cancer, it’s vital to take care of your body as it recovers. Healthy eating is a critical step in managing cancer treatment side effects as you heal. You’ll also have more energy from eating nutrient-dense meals^[22].

A healthy diet includes foods that are packed with vitamins, minerals, and antioxidants. Doctors recommend eating plenty of fruits, vegetables, legumes, and healthy fats. Some studies have shown that eating fruits and vegetables can lower the risk of endometrial cancer by 50 percent to 60 percent^[22].

Moving your body, maintaining a healthy diet, staying hydrated, and getting rest is important. Work with your doctor to determine what’s appropriate for you^[20].

Building a Support System

You don’t have to go through this experience alone. Develop a support team that can help you along the way by reaching out to^[20]:

• Professional help (such as a counselor or therapist)
• Family and friends
• Other people with cancer (through online forums, gynecologic cancer events, etc.)
• Endometrial or gynecologic cancer advocacy groups, which can provide emotional support, education, financial assistance, and connection to other people living with gynecologic cancer

Your Healthcare Team

Several healthcare professionals may be involved in your care^[19]:

• Gynecologic oncologists specialize in both cancer diagnosis and treatment and have special training in operating on cancers of the reproductive organs
• Medical oncologists are experts in treating cancer using different medical approaches, like chemotherapy or pharmaceutical drugs
• Oncology nurses specialize in cancer care and may work with you throughout diagnosis and treatment
• Radiation oncologists are experts in using radiation to treat cancer
• Social workers have training in counseling and practical support
• Patient navigators can help educate you about cancer and facilitate conversations with providers
• Registered dietitians can help you cope with treatment side effects and help you maintain healthy eating habits
• Genetic counselors can help determine your risk of getting certain types of cancer based on your personal and family medical history

Follow-up Care

After treatment, regular screening is recommended to detect recurrence. Talk to your healthcare team about routine gynecologic care and pelvic exams^[20][21].

The possibility of your endometrial cancer returning can be scary. Understanding what recurrent endometrial cancer means is an important step in choosing the right treatment plan with your healthcare team and managing the emotions that come along with it^[20].

Honoring Your Feelings

Living with endometrial cancer can make you feel a variety of emotions: frustration, sadness, guilt, and exhaustion, to name a few. Give yourself permission to feel your emotions. Remember that feelings don’t define who you are^[20].

Stay in close contact with your support group, caregivers, and doctor and let them know how you’re feeling. Creating connections is a great way to keep yourself in the moment^[20].