Endometrial Adenocarcinoma

Endometrial adenocarcinoma is a type of cancer that begins in the inner lining of the uterus and represents the most common gynecologic malignancy affecting women in the United States.

Table of contents

• What is Endometrial Adenocarcinoma?
• The Uterus and Endometrium
• Types of Endometrial Adenocarcinoma
• Other Names
• How Common Is This Cancer?
• Signs and Symptoms
• Risk Factors
• Diagnosis and Testing
• Stages of the Disease
• Treatment Options
• Outlook and Survival
• Living With Endometrial Cancer

What is Endometrial Adenocarcinoma?

Endometrial adenocarcinoma is a type of cancer that begins as a growth of cells in the uterus, which is the hollow, pear-shaped organ in the pelvis where a baby develops during pregnancy. This cancer specifically starts in the layer of cells that form the lining of the uterus, called the endometrium^[1].

The term “adenocarcinoma” means that the cancerous cells are found in the glandular tissue of the womb lining. This type of cancer is sometimes called uterine cancer or endometrial cancer. While other types of cancer can form in the uterus, including uterine sarcoma (which develops in the muscle wall), these are much less common than endometrial adenocarcinoma^[1][4].

Metastatic Endometrioid Adenocarcinoma, Metastatic Endometrioid Cancer, Metastatic Endometrioid Carcinoma, Metastatic Uterine Adenocarcinoma, Metastatic Uterine Cancer, Metastatic Uterine Carcinoma, Endometrioid Adenocarcinoma, Uterine Cancer

C54.1

The Uterus and Endometrium

• Uterus
• Endometrium
• Cervix
• Vagina
• Ovaries
• Fallopian tubes

The uterus is part of the reproductive system in women. The top part of the uterus is called the body or corpus. At the end of the uterus is the cervix, which connects the uterus to the vagina. Cancer in the cervix is a different type of cancer than cancer in the body of the uterus^[4].

The endometrium is the inner layer of the uterus. It changes during the menstrual cycle in response to hormones. Hormones called estrogen and progesterone cause the endometrium to thicken in case of pregnancy. If no pregnancy occurs, the body produces less progesterone, which causes the endometrial lining to shed. That’s when menstrual periods take place^[4].

Types of Endometrial Adenocarcinoma

Most womb cancers start in specific cells in the womb lining and are adenocarcinomas. There are several types of endometrial adenocarcinoma^[6].

Endometrioid adenocarcinoma is the most common type. This includes several subtypes such as adenocarcinoma not otherwise specified, adenocarcinoma with squamous differentiation, secretory adenocarcinoma, ciliated carcinoma, and villoglandular types. These cancers are often diagnosed at an early stage and are usually treated successfully^[6].

Serous carcinoma is much less common than endometrioid cancers. It also develops from the lining of the womb and is considered a type 2 endometrial cancer^[6].

Clear cell carcinoma of the womb lining is very rare. These cells get their name from looking clear under a microscope. This is also called a non-endometrioid cancer and is a type 2 endometrial cancer^[6].

Doctors sometimes divide endometrial cancers into two main types. Type 1 cancers are the most common type. They are usually endometrioid adenocarcinomas and are linked to excess estrogen in the body. They are generally slow growing and less likely to spread. Type 2 cancers are not linked to excess estrogen. They are generally faster growing and more likely to spread. They include uterine serous carcinomas and clear cell carcinomas^[6].

Other Names

This condition has historically been classified into type 1 and type 2 endometrial cancer based on characteristics seen under a microscope. More than 80% of all endometrial cancers are of endometrioid origin, making them type 1 cancers. Type 2 endometrial cancers are primarily of serous or clear cell origin^[3].

How Common Is This Cancer?

Endometrial cancer is the most prevalent gynecologic malignancy in the United States and a significant cause of illness and death in women. In 2023 alone, over 66,000 new cases were expected^[3]. Endometrial carcinomas account for a significant number of these cases, as fewer than 10% of uterine corpus cancers are sarcomas. Endometrioid adenocarcinomas comprise more than 83% of the uterine corpus cancers reported^[3].

In the United States, endometrial cancer is the most common cancer affecting the reproductive system of women. About 3% of women will receive a diagnosis of uterine cancer at some point during their lives. Each year, about 65,000 women receive a diagnosis^[4]. Endometrial cancer mainly develops after menopause (the time when menstrual periods stop)^[4].

Signs and Symptoms

Endometrial cancer is often found at an early stage because it causes symptoms. Often the first symptom is irregular vaginal bleeding^[1].

Symptoms of endometrial adenocarcinoma may include^[1]:

• Vaginal bleeding after menopause
• Bleeding between periods
• Pelvic pain

Signs of uterine cancer can resemble those of many other conditions, especially conditions affecting reproductive organs. Other symptoms may include^[4]:

• Vaginal bleeding or spotting after menopause, even a slight amount
• Lower abdominal pain or cramping in the pelvis, just below the belly
• Thin white or clear vaginal discharge if you’re postmenopausal
• Extremely prolonged, heavy, or frequent vaginal bleeding if you’re older than 40

If you notice unusual pain or irregular vaginal bleeding, talk to your healthcare provider. An accurate diagnosis is important so you can get the proper treatment^[4].

Risk Factors

Researchers aren’t sure of the exact cause of uterine cancer. Something happens to create changes in cells in the uterus. The changed cells grow and multiply out of control, which can form a mass called a tumor^[4].

Certain risk factors can increase the chances you’ll develop uterine cancer. Many of them relate to the balance between estrogen and progesterone^[4]. Risk factors for endometrial cancer include^[10]:

• Taking estrogen-only hormone replacement therapy after menopause
• Taking tamoxifen to prevent or treat breast cancer
• Obesity (having excess body weight)
• Having metabolic syndrome (a group of conditions that increase health risks)
• Having type 2 diabetes
• Never giving birth
• Menstruating at an early age
• Starting menopause at a later age
• Having polycystic ovary syndrome
• Having a family history of endometrial cancer in a first-degree relative (mother, sister, or daughter)
• Having certain genetic conditions, such as Lynch syndrome
• Having endometrial hyperplasia (a condition where the uterine lining becomes too thick)
• Older age

Endometrial cancer may develop in breast cancer patients who have been treated with tamoxifen. 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^[10].

Women taking estrogen (a hormone that can affect the growth of some cancers) alone also have an increased risk of endometrial cancer. Taking estrogen combined with progesterone does not increase a woman’s risk of endometrial cancer^[10].

Diagnosis and Testing

Tests and procedures used to diagnose endometrial cancer include^[8]:

Examining the pelvis: 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. The device opens the vaginal canal so the health professional can look for signs of cancer or other problems^[8].

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. 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 the pelvic organs^[8].

The diagnosis and staging of endometrial adenocarcinoma can also be made by^[7]:

• Chest x-ray
• Computed tomography (CT) scan
• Dilation and curettage (D&C)
• Endometrial biopsy
• Hysteroscopy (a thin, lighted instrument provides a view of the inside of the uterus)
• Lymph node dissection
• Magnetic resonance imaging (MRI)
• Positron emission tomography (PET) scan
• Physical exam and health history

Stages of the Disease

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. 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^[20].

The stages are defined as follows^[20]:

• Stage I: Cancer is found only in the uterus or womb, and it has not spread to other parts of the body
• Stage II: The tumor has spread from the uterus to the cervical stroma but not to other parts of the body
• Stage III: The cancer has spread beyond the uterus, but it is still only in the pelvic area
• Stage IV: The cancer has spread (metastasized) to the rectum, bladder, and/or distant organs

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^[20].

Endometrial cancer can recur (come back) after it has been treated. The cancer may come back in the uterus, the pelvis, in lymph nodes in the abdomen, or in other parts of the body^[7].

Treatment Options

Treatment options for endometrial cancer include surgery, radiation, chemotherapy, hormone therapy, or some combination of these. The final treatment recommendation is based on several factors, the most important of which are the stage of the cancer, how healthy the woman is, and whether she wishes to have children in the future^[11].

Surgery is the most common treatment for endometrial cancer. Surgery both removes the cancer in the uterus and determines the stage. The minimum surgical procedure is hysterectomy (removal of the uterus and cervix) with removal of both fallopian tubes and ovaries. Often surgery also includes the removal of lymph nodes in the pelvis and abdomen^[11].

This procedure can be performed through a traditional incision in the skin of the abdomen or with minimally invasive surgery. Patients treated with minimally invasive techniques, which include standard laparoscopy or robotic surgery, may have a quicker recovery and experience less pain after surgery and fewer wound complications than patients treated with open surgery^[11].

Surgery is the cornerstone of treatment for endometrial carcinoma except for select premenopausal patients desiring fertility and patients with significant medical problems. In patients with stage 1a, grade 1 disease, no further therapy is indicated^[12].

The other treatment methods include^[7]:

• Radiation therapy: Using high-energy rays to kill cancer cells
• Chemotherapy: Using drugs to kill cancer cells
• Hormone therapy: Using hormones or hormone-blocking drugs to fight cancer
• Targeted therapy: Using drugs that target specific features of cancer cells

Young women who desire future fertility may be candidates for medical management via oral progestin therapy or progestin intrauterine device. Potential candidates should have low-risk disease (grade 1 or 2, limited to the uterus), be willing to adhere to progestin therapy and monitoring, and understand the risk of progressive disease^[12].

Radiation therapy alone can be used as primary therapy in patients with significant medical problems that make surgery too risky. Progestin therapy may be considered in patients who are not able to tolerate either surgery or radiation therapy^[12].

Outlook and Survival

If endometrial cancer is found early, surgically removing the uterus often cures it^[1]. Most cases are diagnosed at an early stage and are treatable with surgery alone^[3].

However, women with features predictive of a high rate of relapse and women with cancer spread beyond the uterus at diagnosis have a high rate of relapse despite additional therapy. While several treatment methods are now available to treat women who present with metastatic endometrial cancer, overall outlook remains poor^[7].

The most common cause of death in patients with endometrial cancer is cardiovascular disease because of related metabolic risk factors^[13].

Living With Endometrial Cancer

Living with endometrial cancer can be challenging, but taking time to reflect on your needs and set personal goals may help provide motivation. By focusing on what inspires you, you may be able to bring more positivity and strength to your daily life^[17].

Make healthy choices: 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^[17].

Maintaining a healthy diet is crucial for people living with advanced endometrial cancer, as proper nutrition helps manage treatment side effects and supports healing. Doctors recommend eating healthy and nutritious foods. Some research suggests that following the Mediterranean diet lowers the risk of endometrial cancer. This involves eating plenty of fruits, vegetables, legumes, and healthy fats^[18].

Reach out: 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 professional help (such as a counselor or therapist), family and friends, other people with cancer (through online forums or events), and endometrial or gynecologic cancer advocacy groups^[17].

Honor 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^[17].

After treatment, regular screening is recommended to detect recurrence. Talk to your healthcare team about routine gynecologic care and pelvic exams. 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^[17].