• Endometrial cancer may return, most often within the first three years after treatment.
• Advanced endometrial cancer is when the cancer has spread beyond the uterus, either within the pelvis or to distant parts of the body.
• The outlook for people with advanced or recurrent endometrial cancer is improving due to new treatment options.

Whether you're living with a new endometrial cancer diagnosis or a survivor who’s completed treatment, it can feel like you’re waiting for the other shoe to drop. Of the million questions running through your head, one may be, “What happens if my cancer returns or continues to spread?”

This article covers what to expect if your endometrial cancer recurs (returns) or if you’ve been diagnosed with advanced-stage disease. We’ll go over the risks for recurrence and progression, what treatments are available, and what your prognosis (outlook) is.

What Is Recurrent Endometrial Cancer?

Once you finish endometrial cancer treatment, your oncologist will conduct regular monitoring tests to see whether there’s any cancer remaining. You’re in remission if you have no signs of cancer in your body. Unfortunately, there’s a risk of your cancer returning, even if your treatment was successful.

Recurrent endometrial cancer is diagnosed when your cancer comes back after you’ve been in remission. Studies show your cancer is more likely to return within three years of your first treatment. Your cancer may return to the same area as before, or it may have metastasized (spread to other areas).

The likelihood of endometrial cancer returning can vary depending on the stage at which it was diagnosed. For example, in a study of 209 people with endometrial cancer, the risk of recurrence increased with stage:

• Stage 1 — 6.5 percent
• Stage 2 — 20 percent
• Stage 3 — 37.5 percent
• Stage 4 — 66.7 percent

Other factors that may raise the risk of your endometrial cancer coming back include older age and if the initial cancer has spread to your cervix or ovaries.

The grade of your cancer can also help predict recurrence. High-grade tumors that are more aggressive and spread quickly are more likely to return than low-grade tumors. The grade of cancer refers to details about the way cancer cells look when viewed under a microscope: Low-grade tumors appear as healthy, organized-looking cells, and higher-grade tumors appear abnormal and disorganized. These details provide clues about the way cancer is likely to grow or spread.

What Is Advanced Endometrial Cancer?

Endometrial cancer is a form of uterine cancer. Advanced endometrial cancer is diagnosed when it’s found outside of the uterus. There are two types of advanced cancer — locally advanced and metastatic.

Locally advanced or stage 3 endometrial cancer is diagnosed when the cancer is found in the tissues near your uterus, including the vagina and pelvic area. Metastatic or stage 4 endometrial cancer has spread to distant parts of your body, such as the liver, lungs, or brain.

Around 90 percent of people with endometrial cancer are originally diagnosed with stage 1 or stage 2 disease. Many people notice unusual signs early, like vaginal bleeding, that lead to a quick diagnosis. This finding means that only 10 percent of endometrial cancer cases are diagnosed at advanced stages.

Treatment for Advanced or Recurrent Endometrial Cancer

If you’ve been diagnosed with recurrent or advanced endometrial cancer, your oncologist will work with you to create a new treatment plan. Your treatment options depend on many factors, including:

• Where your cancer is located
• Previous treatments you’ve had
• Your overall health

Your oncologist will also use biomarkers to help make choices about your treatment. Biomarkers are proteins or mutations (genetic variations) in your endometrial cancer. If you have a certain biomarker, your cancer might respond better to a specific, more targeted treatment.

For example, your oncologist will likely test for mismatch repair deficiency (dMMR) and microsatellite instability (MSI). These biomarkers are found in cancer cells that can’t repair damaged DNA correctly. They create even more mutations that can be treated with certain drugs.

Chemotherapy and Radiation Therapy

The most common treatment for advanced or recurrent endometrial cancer is chemotherapy with carboplatin and paclitaxel. Depending on your case, you may also have surgery to help remove any tumors.

Recurrent endometrial cancer can be harder to treat because cancer cells are likely resistant to previously used chemotherapy drugs. This means your oncologist has to choose new treatments. If you were treated with carboplatin and paclitaxel before, they may use other chemotherapy drugs like:

• Doxorubicin
• Cisplatin
• Docetaxel

Locally advanced endometrial cancer can also be treated with radiotherapy (radiation therapy). This treatment uses high-powered X-rays to damage and kill cancer cells. Brachytherapy is an option for people whose cancer has spread or returned to the vagina. This technique uses an applicator made with radioactive materials that’s roughly the shape and size of a tampon. It’s inserted into the vagina to kill any nearby cancer cells.

Immunotherapy

Immunotherapy is a new treatment that helps your immune system recognize and destroy cancer cells. Recent clinical trials (large studies) have looked at pembrolizumab (Keytruda) and dostarlimab-gxly (Jemperli) for treating advanced or recurrent endometrial cancer.

Dostarlimab-gxly is approved for treating endometrial cancer in people with dMMR. To qualify for this treatment, they need to have taken a platinum-based treatment before and not be eligible for curative surgery or radiation.

Pembrolizumab is approved for treating any cancer with dMMR. Your oncologist must check that you have dMMR with a test approved by the U.S. Food and Drug Administration (FDA).

Hormonal Therapy

Some types of endometrial cancer rely on the hormones estrogen and progesterone to grow. There may be more estrogen receptors (ERs) or progesterone receptors (PRs) on the outside walls of the cancer cells. Blocking these receptors can help treat cancer that’s returned or spread.

If your endometrial cancer is positive for ER, PR, or both, your oncologist can give you hormonal therapy. These treatments are typically used for breast cancer, but they’ve also been shown to help treat endometrial cancer. Examples include:

• Megestrol acetate (Megace)
• Medroxyprogesterone acetate (Provera)
• Tamoxifen
• Anastrozole (Arimidex)
• Letrozole (Femara)
• Exemestane (Aromasin)
• Fulvestrant (Faslodex)

Targeted Therapy

As doctors and researchers continue to learn more about endometrial cancer, they find new ways to target tumors. Targeted therapy for endometrial cancer is a type of treatment that focuses on attacking specific features of cancer cells, leaving healthy cells mostly unharmed. It blocks the growth and spread of cancer by targeting specific molecules or pathways involved in cancer development. This approach offers a more precise and effective way to treat endometrial cancer with fewer side effects compared to traditional treatments like chemotherapy.

Bevacizumab (Avastin) and lenvatinib (Lenvima) block tumors from making new blood vessels. These medications prevent the tumor from getting more oxygen and nutrients. As a result, the cancer cells grow more slowly and stop spreading.

Bevacizumab can be prescribed on its own or along with chemotherapy. Lenvatinib is typically prescribed along with pembrolizumab for advanced endometrial cancer.

Another type of medication used to treat advanced or recurrent endometrial cancer are mTOR inhibitors. They block the mTOR protein, which plays a role in cell growth and division. Examples include everolimus (Afinitor) and temsirolimus (Torisel).

Prognosis for Advanced or Recurrent Endometrial Cancer

If you’ve been told your endometrial cancer has returned, or if you’ve been diagnosed with advanced disease, you’re likely wondering how it affects your outlook. Studies show that the median survival is 12 to 15 months. This means that after 12 to 15 months, half of people with advanced or recurrent endometrial cancer are still alive.

Where your cancer returns can affect your prognosis with endometrial cancer. For example, a study published in the British Journal of Cancer found that women whose cancer returned in the pelvis had a 73.4 percent chance of living for three years. If their cancer had spread to other parts of their body, they had a 38.1 percent chance of living for three years.

New Treatments Are Improving Outlook for Endometrial Cancer

New treatment options are helping people with advanced or recurrent endometrial cancer live longer, healthier lives. This is especially true for new immunotherapies. Two clinical trials have reported that adding immunotherapy to standard chemotherapy treatments helps stop cancer from growing and spreading.

Make sure to have honest and informative conversations with your oncologist to understand your situation while living with advanced or recurrent endometrial cancer. They will explain your risk factors, available treatments, and other essential information to help you make informed decisions about your health care journey.

Talk With Others Who Understand

On MyEndometrialCancerCenter, the site for people with endometrial cancer and their loved ones, people come together to gain a new understanding of endometrial cancer and connect with others who understand life with this condition.

Are you living with advanced or recurrent endometrial cancer? Share your experience in the comments below.