In recent years, researchers and scientists have actively researched endometrial cancer — especially advanced or recurrent endometrial cancer. Discoveries about different subtypes of endometrial cancer now help doctors to determine the best treatment for each person’s cancer. This means if you or a loved one are living with the condition, you may now have access to promising new options.

Understanding the newer treatments now available will help you make informed decisions. This article will cover recent advances in endometrial cancer treatment and five questions to ask your doctor to make sure you get the best care for your endometrial cancer.

Recent Advances in the Treatment of Endometrial Cancer

In 2021, the U.S. Food and Drug Administration (FDA) approved a combination of lenvatinib (Lenvima) and pembrolizumab (Keytruda) to treat endometrial cancer. Researchers found that compared to chemotherapy, this combination significantly extended progression-free survival (the length of time you live with cancer, without it getting worse) and overall survival.

Lenvatinib is a targeted therapy. As the name suggests, these treatments target specific changes to cancer cells to slow or stop their growth. Lenvatinib targets proteins that help cancer cells form new blood vessels and help tumors grow.

Pembrolizumab is an immunotherapy drug. Immunotherapy uses your own immune system to fight endometrial cancer. In 2022, the FDA approved pembrolizumab for use as a single treatment for particular types of advanced endometrial carcinoma.

In 2023, the FDA approved another immunotherapy drug, dostarlimab (Jemperli), to treat endometrial cancer that has progressed after chemotherapy in people who can’t have curative surgery or radiation. In clinical trials, pembrolizumab and dostarlimab improved survival outcomes.

In addition to new drugs, researchers are also investigating new uses for old drugs, such as metformin (a common diabetes treatment) and different types of hormone therapy.

With so many new treatments already approved and more to come, it can feel overwhelming to figure out which treatment will be best for you. Asking your doctor the following questions will help you learn more about your cancer and the treatment options available so you and your cancer care team can make decisions together about your treatment.

1. Have My Cancer Cells Been Tested for Biomarkers?

Biomarkers are proteins, genes, or molecules that give doctors more information about your cancer. Some new therapies for endometrial cancer are designed to work on cancer cells with specific biomarkers.

Biomarker tests can be done on cancer cells removed during your endometrial biopsy or hysterectomy surgery. Talk to your doctor about the most appropriate tests for your cancer.

Read more about the importance of biomarker testing.

2. What Do My Biomarker Results Say About My Prognosis and Treatment Options?

Along with showing the stage of your cancer, biomarker results can give you more information about your prognosis (outlook) and what treatment options are available.

Biomarkers can tell you and your doctor which genomic subtype of endometrial cancer you have. Following are the four subtypes:

• DNA polymerase epsilon, catalytic subunit (POLE) mutated
• Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR)
• High copy number
• Low copy number

POLE Mutated

Between 5 percent and 10 percent of people with endometrial cancer have mutations (changes) in the POLE gene. They usually have a very good prognosis and rarely experience a recurrence of their cancer.

MSI-H or dMMR Mutations

Around 30 percent of endometrial cancers have MSI-H or dMMR mutations. These mutations make cancer cells susceptible to immunotherapy drugs like pembrolizumab and dostarlimab. Before you take either of these drugs, your doctor must confirm you have this mutation using an FDA-approved test on your cancer cells.

High or Low Copy Number

People with high copy number endometrial cancer usually have a worse prognosis than people with other subtypes. An aggressive type of endometrial cancer called uterine serous carcinoma falls into this category. Cancers classified as low copy number don’t have any of the other biomarkers.

Hormone Receptor Status

Your doctor may also check the hormone receptor status of your cancer cells. They may check for three different hormone receptors — progesterone receptor, estrogen receptor, and human epidermal growth factor-2 (HER2). A meta-analysis (review of past studies) found that higher levels of progesterone and estrogen receptors (hormone receptor-positive) were associated with a better prognosis, while HER2 was associated with a poorer prognosis.

If your endometrial cancer is hormone receptor-positive or HER2-positive, you may have additional treatment options available. Some hormone treatments work best on cancer that’s hormone receptor-positive. Some targeted therapies, such as trastuzumab (Herceptin), specifically target HER2.

3. How Will My Treatment Be Monitored?

Your health care team will use different types of tests to monitor you during and after your treatment. In some cases, this may include a Pap smear, which involves collecting cells from the surface of the cervix and vagina for examination under a microscope. Some medications used to treat endometrial cancer may require special tests. You may need regular blood tests and physical exams.

Imaging Tests

You may need imaging tests to check if your cancer has spread to your lymph nodes or other organs and see if it’s responding to treatment. Examples of imaging tests include:

• X-rays
• CT scan
• MRI scan
• Positron emission tomography (PET) scan

If you or your doctor suspects that cancer has spread to your bladder or rectum, your doctor may use a lighted tube to look inside the organ. This procedure is called a cystoscopy when the tube is used to look into your bladder and a proctoscopy when the tube is used to look into your rectum.

Cancer Antigen 125

Some endometrial cancers release a protein called cancer antigen 125 (CA-125) into the bloodstream. In some people, a high CA-125 level might mean that cancer has spread outside of the uterus. If your CA-125 level is high, your doctor may check it periodically to see if it decreases. Typically, CA-125 levels should drop after surgery when the cancer is removed.

After Treatment

After your treatment is complete, you’ll still have regular follow-up care to check that your cancer hasn’t come back and to check for long-term side effects of your treatment.

4. If My Current Treatment Regimen Isn’t Effective, What Are My Next Options?

As part of your treatment plan, you should find out the next steps if your current treatment isn’t effective. The stage of your cancer is usually the most important factor in choosing the best treatment regimen. If your cancer continues to progress or recurs, your doctor may run many of the same tests you had when you were first diagnosed and restage your cancer. If they haven’t checked already, they may check for biomarkers at this point.

There are many treatment options available for endometrial cancer. It’s a common practice to get a second opinion from a different health care provider about your treatment to confirm the best option.

5. Would You Recommend I Consider Joining a Clinical Trial?

A clinical trial is a research study that tells how well new treatments and medication work to treat a disease. Before the FDA approves an investigative treatment, it's available only through a clinical trial.

Your eligibility to participate in a clinical trial may depend on the stage or type of endometrial cancer you have. Talk to your doctor if you are interested in finding out more about clinical trials.

You can also search for clinical trials on ClinicalTrials.gov, a public government database of clinical trials, or check the National Cancer Institute database of clinical trials.

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 endometrial cancer.

Have you received any of the new treatments for endometrial cancer? Do you have tips for how to talk to your doctor about your treatment options? Share your experience in the comments below, or start a conversation by posting on your Activities page.