How is Endometrial Cancer Treated?

The treatment for endometrial cancer depends on several factors, including the stage of the cancer, the grade and molecular subtype, your age, your overall health, and whether you wish to preserve fertility. Most women with endometrial cancer are treated primarily with surgery. Additional treatment with radiation therapy, chemotherapy, hormonal therapy, targeted therapy, or immunotherapy may be recommended depending on the cancer's features.

Treatment is best directed by a multidisciplinary team that typically includes a gynecologic oncologist, a radiation oncologist, a medical oncologist, and other specialists. Gynecologic oncologists who are surgeons that specialize in cancers of the female reproductive system typically lead the surgical treatment of endometrial cancer.

Surgery for endometrial cancer

Surgery is the primary treatment for most women with endometrial cancer. The standard surgical procedure is a hysterectomy with bilateral salpingo-oophorectomy which includes the removal of the uterus, cervix, both fallopian tubes, and both ovaries. Surgery also provides important staging information.

Minimally invasive surgery

Most women with endometrial cancer can be treated with minimally invasive surgery, either laparoscopic or robotic-assisted, rather than open abdominal surgery. Minimally invasive approaches have shorter hospital stays, faster recovery, and fewer complications.

Lymph node evaluation

Removing and examining lymph nodes in the pelvis and around the aorta is an important part of surgical staging. For selected patients, sentinel lymph node mapping, a technique that identifies the first lymph nodes likely to receive cancer cells, is increasingly used as an alternative to removing many lymph nodes, with the benefit of lower complication rates.

Fertility-sparing treatment

For young women with early-stage, low-grade endometrial cancer who wish to preserve fertility, fertility-sparing treatment with progestin hormone therapy may be considered in carefully selected cases. This is not standard treatment and requires close follow-up and eventual surgery after childbearing is complete. This option should be discussed in detail with a gynecologic oncologist at a center experienced in this approach.

Radiation therapy for endometrial cancer

Radiation therapy uses high-energy beams to destroy cancer cells. It is used after surgery in some patients to reduce the risk of recurrence, or occasionally as primary treatment for women who cannot undergo surgery:

• Vaginal brachytherapy. A form of internal radiation delivered through a device placed in the vagina. Used to prevent recurrence at the top of the vagina. This is well tolerated and commonly used after surgery in intermediate-risk patients.

• External beam radiation therapy (EBRT). Radiation delivered from outside the body to the pelvis. Used for patients at higher risk of pelvic recurrence.

Chemotherapy for endometrial cancer

Chemotherapy uses drugs to kill cancer cells throughout the body. It is used in combination with radiation therapy or alone for higher-risk, advanced, or recurrent endometrial cancer:

• Carboplatin and paclitaxel. The most commonly used chemotherapy combination for endometrial cancer. It is the standard regimen for advanced or high-grade disease.

• Cisplatin. Sometimes used in combination with radiation therapy for locally advanced disease.

• Other agents. Other chemotherapy drugs may be used in specific settings or clinical trials.

Targeted therapy for endometrial cancer

Targeted therapies are drugs that attack specific proteins or pathways in cancer cells:

• Lenvatinib (Lenvima). A targeted therapy that blocks proteins involved in tumor blood vessel growth. Combined with pembrolizumab, it is approved for advanced endometrial cancer that is not MSI-H/dMMR and has progressed after prior therapy.

• Trastuzumab (Herceptin). An antibody that targets the HER2 protein. Used for HER2-positive serous carcinoma of the uterus in combination with chemotherapy.

• mTOR inhibitors. Drugs such as everolimus and temsirolimus that target the mTOR pathway, which is commonly activated in endometrial cancer.

Immunotherapy for endometrial cancer

Immunotherapy has transformed the treatment of advanced endometrial cancer, particularly for tumors with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H):

• Pembrolizumab (Keytruda). A checkpoint inhibitor that blocks the PD-1 protein, freeing the immune system to attack cancer cells. Pembrolizumab is approved for dMMR/MSI-H endometrial cancer that has progressed after prior chemotherapy. It is also approved in combination with lenvatinib for non-MSI-H advanced endometrial cancer.

• Dostarlimab (Jemperli). Another checkpoint inhibitor approved for dMMR advanced endometrial cancer. It is also being studied in combination with chemotherapy for frontline treatment.

• Combination chemotherapy and immunotherapy. Clinical trials and approvals are expanding the use of immunotherapy into first-line (frontline) treatment of advanced endometrial cancer, particularly for dMMR tumors.

Hormonal therapy for endometrial cancer

Hormonal therapy is used primarily for selected cases of recurrent or metastatic low-grade endometrioid endometrial cancer:

• Progestins (medroxyprogesterone acetate, megestrol acetate). Hormonal agents that oppose estrogen's effect on the endometrium. Used in recurrent low-grade disease, particularly in women who are not candidates for chemotherapy, and in fertility-sparing treatment.

• Aromatase inhibitors. Drugs that reduce estrogen production and may slow the growth of estrogen-sensitive endometrial cancers.

• Tamoxifen. Used in some cases of recurrent endometrial cancer.

Treating recurrent and metastatic endometrial cancer

When endometrial cancer returns, treatment depends on the location and timing of recurrence, prior treatments, molecular features (especially dMMR/MSI-H status), and individual patient factors. Options may include additional surgery, radiation, chemotherapy, targeted therapy, immunotherapy, and clinical trials. Many women with recurrent endometrial cancer can achieve remission or prolonged disease control with treatment.

Supportive and palliative care for endometrial cancer

Treating the symptoms of cancer and the side effects of treatment is called supportive and palliative care. This is an important part of cancer care at every stage. Supportive care can include:

• Pain management

• Management of treatment-related side effects such as fatigue, nausea, neuropathy, and lymphedema

• Nutrition and weight management support

• Mental health support and counseling

• Sexual health support. Surgery and radiation can affect sexual function; a sexual health specialist can help address these concerns.

There is a common misconception that palliative care is only given at the end of life. Palliative and supportive care can be given at any time during cancer treatment.