Whether you're newly diagnosed with endometrial cancer or a survivor who’s completed treatment, it can feel like you’re waiting for the other shoe to drop. These may be among the million questions running through your head: “What happens if my cancer returns? How will it be treated? What will my outlook be?”

This article covers what to expect if your endometrial cancer recurs, or returns. 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 recommend follow-ups and regular testing to look for any remaining cancer. 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. Endometrial cancer may return to the same area as before or may have metastasized (spread to other areas).

The likelihood of endometrial cancer returning depends on several factors related to the disease and to the person’s overall health. Recent studies have found key factors that can increase the risk of the cancer returning, including the stage of the disease, tumor grade and size, and myometrial invasion, as well as the type of endometrial cancer.

Disease Stage

The stage at which endometrial cancer is diagnosed greatly affects the chances of recurrence:

• Stage 1 — 4.8 percent
• Stage 2 — 17.6 percent
• Stage 3 — 20 percent to 50 percent
• Stage 4 — 66.7 percent

Tumor Grade

Tumor grade describes how cancer cells look under a microscope. Low-grade tumors resemble normal cells and are less likely to spread. High-grade tumors look more abnormal, are more aggressive, and are more likely to come back after treatment.

Tumor Size

Tumors larger than 2 centimeters (about the size of a grape) have a higher chance of recurring.

Myometrial Invasion

Cancer that invades deeper into the myometrium (the muscular wall of the uterus) is more likely to come back, especially if the cancer cells are more aggressive. Researchers have found that the risk of recurrence becomes about twice as high when cancer spreads deeply into this area.

Endometrial Cancer Type

Endometrial cancer can also be classified into two types. Type 1 endometrial cancers are linked to high levels of the hormone estrogen. These cancers tend to be less aggressive, and studies show that around 20 percent of cases recur, according to the journal Cancers. Type 2 cancers, including clear cell and serous carcinomas, don’t rely on estrogen, tend to grow faster, and are more aggressive. Around half of type 2 endometrial cancer cases recur.

Treatment for Recurrent Endometrial Cancer

If you’ve been diagnosed with recurrent 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
• Your previous treatments
• Your overall health

Your oncologist will also use biomarkers to help guide your treatment plan. Biomarkers are proteins or mutations (genetic variations) found in your endometrial cancer. Certain biomarkers can predict how well your cancer might respond to a specific treatment. For example, your oncologist will likely test for:

• Mismatch repair deficiency (dMMR)
• 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.

Surgery

Surgery can be very effective when the cancer is confined to one area and hasn't spread to other parts of the body. The goal of surgery is to remove as much of the cancer as possible to help keep it from growing or spreading more. Research shows that surgeons can completely remove tumors in about 56 percent to 71 percent of cases.

Chemotherapy and Radiation Therapy

The most common treatment for recurrent endometrial cancer is chemotherapy. Oncologists usually combine the drugs carboplatin and paclitaxel. Recurrent disease can be harder to treat because cancer cells are likely to resist chemotherapy you’ve already tried. Your oncologist will have to choose new treatments. If you received carboplatin and paclitaxel before, they may use other drugs like:

• Cisplatin
• Docetaxel (Taxotere)
• Doxorubicin

Radiotherapy

Some people with recurrent endometrial cancer can also be given radiotherapy (radiation therapy). This treatment uses high-powered X-rays to damage and destroy cancer cells. Your oncologist may recommend radiation therapy if you didn’t receive it during your first round of treatment. It’s also preferred for those who've been treated only with surgery.

Brachytherapy is an option when cancer has returned to the vagina. This technique uses an applicator that’s roughly the shape and size of a tampon and made with radioactive materials. The applicator is inserted into the vagina to kill any nearby cancer cells.

Immunotherapy

Immunotherapy is a newer treatment designed to help the immune system identify and destroy cancer cells. The U.S. Food and Drug Administration (FDA) has approved a few immunotherapy options for treating recurrent endometrial cancer.

Cancer cells can sometimes evade the immune system, making it harder for the body to fight them. Immunotherapy works by blocking proteins that cancer cells use to hide from the immune system. For example, pembrolizumab (Keytruda) and dostarlimab-gxly (Jemperli) inhibit a protein called PD-1, whereas durvalumab (Imfinzi) interferes with PD-L1. Inhibiting these proteins allows the immune system to recognize and attack the cancer cells more effectively.

These drugs can also be combined with chemotherapy. Pembrolizumab and dostarlimab-gxly are approved for anyone with recurrent endometrial cancer. Durvalumab is specifically for people who have the dMMR biomarker. Your oncologist can check for this biomarker using an FDA-approved test.

Hormonal Therapy

Endometrial cancers that rely on the hormones estrogen and progesterone to grow may have more estrogen receptors or progesterone receptors on their cells. Blocking these hormone receptors can help treat cancer that has returned.

If your endometrial cancer tests positive for estrogen or progesterone receptors or both, your oncologist may recommend hormonal therapy. These treatments are commonly used for breast cancer, but research shows they can also help manage endometrial cancer. Examples include:

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

Targeted Therapy

Targeted therapy for endometrial cancer works by attacking specific features of cancer cells, leaving healthy cells mostly unharmed. Targeted therapy blocks the growth and spread of cancer by aiming at specific changes found only in endometrial cancer cells. This approach has fewer side effects compared with traditional treatments like chemotherapy.

Bevacizumab (Avastin) and lenvatinib (Lenvima) work by preventing tumors from making new blood vessels. By cutting off the tumors’ supply of oxygen and nutrients, these medications can slow the growth of cancer cells and keep them from spreading.

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

Prognosis for Recurrent Endometrial Cancer

If you’ve been told your endometrial cancer has returned, you’re likely wondering how this recurrence 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 recurrent or advanced endometrial cancer are still alive.

The site of your cancer’s return 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, such as to the lungs, they had a 38.1 percent chance of living for three years.

Read more about survival rates for advanced endometrial cancer.

New Treatments Are Improving the Outlook for Endometrial Cancer

Clinical trials are helping researchers find new treatment options to help people with recurrent endometrial cancer live longer, healthier lives. This is especially true for new immunotherapies and targeted therapies. Clinical trials may offer access to emerging treatments that aren’t yet widely available but could be effective for your specific case. You can ask your oncologist if you may be eligible to participate in any of these research studies.

Make sure you have honest conversations with your oncologist about recurrent endometrial cancer. They’ll explain your risk factors, available treatments, and other essential information. Together, this information will help you make informed decisions about your health care journey.

Talk With Others Who Understand

On MyEndometrialCancerTeam, the site for people with endometrial cancer and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with the condition.

Are you living with recurrent endometrial cancer? How long after treatment did it return, and how are you treating it? Share your experience in the comments below, or start a conversation on your Activities page.