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Updated on May 30, 2025
Endometrial cancer is cancer that begins in the endometrium, the inner lining of the uterus (womb). It is the most common type of cancer that affects the female reproductive organs in the United States
Treatment for endometrial cancer often includes surgery to remove the cancer and reproductive organs. Surgery is often used in combination with other cancer treatments, such as chemotherapy and radiation therapy. Immunotherapy, targeted therapy, and hormone therapy can also be used in treatment, especially when cancers are advanced and/or when the cancer has not responded to initial treatment.
If you or a loved one has been diagnosed with endometrial cancer that has not responded to initial treatment, here are some things to consider when deciding on the next steps in treatment.
Understand second-line treatments
First-line therapy refers to the first treatment given for cancer. A first-line therapy can include multiple steps, such as surgery followed by chemotherapy. Second-line therapy refers to a therapy that is used when a first-line therapy hasn’t worked or has stopped working. It’s helpful to be familiar with second-line therapies when talking to your healthcare team.
Common second-line therapies in the treatment of endometrial cancer:
- Chemotherapy. If the cancer did not respond to chemotherapy, a healthcare team may recommend a different regimen of chemotherapy drugs. Different chemotherapy drugs work in different ways. Sometimes, if a cancer does not respond to one type of chemotherapy, it may respond to another.
- Immunotherapy. Immunotherapies are cancer medications that help the body’s immune system identify and/or destroy cancer cells. Immune checkpoint inhibitors are a type of immunotherapy used to treat endometrial cancer. These drugs work by disabling checkpoint proteins that prevent the immune system from attacking cancerous cells.
- Targeted therapies. Different targeted therapies work in different ways, but in general, all act on specific biomarkers found on or in cancer cells. Some targeted therapies block proteins or hormones that cancer cells need to grow. Others block tumors from forming blood vessels. Others attach to cancer cells to deliver chemotherapy agents with greater precision than standard chemotherapy.
- Hormone therapy. For hormone receptor-positive endometrial cancers, various hormone therapies might be considered, particularly if not tried previously.
These treatment options are also used to treat endometrial cancer that has recurred, or come back after treatment. Surgery and radiation therapy may also be used to treat cancer recurrence.
Talk to your healthcare team about your next treatment options, including potential benefits, potential side effects, treatment goals, how these treatment options work, and how they are different from previous treatment options.
Revisit biomarker testing
A biomarker is a biological feature of a cell, such as a protein or hormone found on or in a cancer cell. Biomarker testing refers to tests that identify specific biomarkers found in cancer cells.
Biomarker testing includes genomic testing, which examines the DNA found inside cancer cells, to look for genes or genetic changes (mutations). This can provide important information about how the cancer is behaving and can help predict what treatments a cancer is more likely to respond to.
Biomarker testing can help guide the choice of specific therapies, including immunotherapy and targeted therapy drugs. This has become an important aspect of guiding treatment decisions for endometrial cancer (and other types of cancer as well).
You may have had biomarker testing as part of a diagnosis of endometrial cancer. If the cancer has not responded to initial therapy, it may be helpful to revisit the results of those tests—or order additional tests—when choosing a second-line therapy.
Think about what you need right now
Knowing that cancer may not respond to treatment is one thing, living with cancer that hasn’t responded to treatment is another. It can be frustrating. It can add to the significant feelings of uncertainty and unfairness that often accompany a diagnosis of endometrial cancer. In other words, it’s not easy. And like many aspects of cancer, it’s different for everyone.
Think about what you need, who you can talk to, and what type of support would be helpful at this point in treatment:
- Talk to your healthcare team about how you are feeling, especially if you are feeling overwhelmed, hopeless, or depressed, or experiencing other types of low moods.
- Find someone who you can talk to about what you are experiencing, such as a counselor, mental health professional, or spiritual advisor. Writing down how you are feeling can also help.
- Consider participating in a support group for people affected by endometrial cancer or other types of gynecologic cancers.
- Make time for yourself and the things you enjoy, whether it’s time with friends and loved ones, hobbies, or just time to relax.
Remember, your best source of information will be a healthcare team. Cancers can respond differently to different treatments, and treatment for endometrial cancer is different for everyone.
