Metastatic Endometrial Cancer: What to Ask

This page is for people with advanced or metastatic endometrial cancer and their families. It explains the tumor tests and main trials behind treatment, and suggests questions for your care team.

Endometrial cancer is no longer sorted only by how it looks under a microscope. Molecular classification, a lab test of the tumor's genes and proteins, splits it into four groups. The group shapes your risk level and decisions about drug treatment.

NCI states that this testing is encouraged in all patients with endometrial cancer where it is available and feasible. Whether you get the full set of tests can depend on the lab and on whether enough tissue was taken. Ask what was actually run on your sample.

The four groups and what they signal:

• POLEmut, a pathogenic POLE mutation. Good prognosis. NCI notes that adjuvant therapies (extra treatment after surgery) are avoided in this subtype.
• MMRd, mismatch repair deficient (also written dMMR), sometimes reported as MSI-high. Intermediate prognosis, and it predicts immunotherapy response.
• NSMP, no specific molecular profile. Intermediate prognosis.
• p53abn, abnormal TP53. Poor prognosis.

Two practical points follow:

• The test can be done on a biopsy. If it is, it does not need to be repeated on the uterus removed at surgery (hysterectomy).
• In FIGO staging, the standard staging system, a known molecular group is written with an "m" and a subscript. An example is Stage IIm p53abn. NCI notes that this applies to early stages only. Stage III and stage IV are not changed by molecular group, though the group is still recorded.

Ask which of the four your tumor is. If it has not been tested, ask whether it can be, using tissue already in the laboratory.

Grade describes how abnormal the cancer cells look. Some cell types are high grade by definition, however they look under the microscope. NCI lists these: serous adenocarcinoma, clear cell adenocarcinoma, mesonephric-like carcinoma, gastrointestinal-type mucinous endometrial carcinoma, undifferentiated carcinoma, and carcinosarcoma.

For endometrioid carcinomas (the most common type), grade depends on how much of the tumor grows in solid sheets rather than in glands. Grade 1 is 5% or less. Grade 2 is 6% to 50%. Grade 3 is more than 50%.

Grade 3 endometrioid carcinoma is the group NCI singles out. NCI says this type varies in prognosis (likely outcome), in behavior, and in molecular makeup. It also calls it the type that gains most from molecular classification. Without that testing, NCI says, these cancers cannot be properly assigned to a risk group.

Two large trials set the first treatment when the cancer is stage III, stage IV, or recurrent (has come back). Both added an immunotherapy drug to the chemotherapy drugs carboplatin and paclitaxel. Both reported results separately by mismatch repair status.

KEYNOTE-868 enrolled 810 people. All received six cycles of paclitaxel and carboplatin, with pembrolizumab or placebo, then up to 14 cycles of maintenance.

• In the 222 people with dMMR tumors, 1-year progression-free survival (being alive without the cancer growing) was 74% with pembrolizumab and 38% with placebo.
• In the 588 with mismatch repair proficient tumors, median progression-free survival was 13.1 months versus 8.7 months.

These figures come from the National Cancer Institute’s “Endometrial Cancer Treatment.”

RUBY used dostarlimab instead. It was given by vein every 3 weeks for six cycles with chemotherapy. It then continued as maintenance at a larger amount every 6 weeks for up to 3 years. Unlike the pembrolizumab trial, some people without measurable disease could enroll.

• Across the whole group, the risk of progression or death fell by 36%.
• In the dMMR group, it fell by 72%.
• Overall survival improved in both. The hazard ratio (a measure of risk compared with placebo; lower is better) was 0.64 overall and 0.30 in the dMMR group.

The pattern is consistent. Both drugs help everyone somewhat and help dMMR tumors dramatically. That is why the mismatch repair result is the single most important number to ask for.

Study 309, also called KEYNOTE-775, tested a two-drug pair:

• Pembrolizumab by vein every 3 weeks for up to 35 cycles
• Lenvatinib capsules by mouth daily, at the trial's full 20 mg starting strength

The comparison was chemotherapy chosen by the doctor. Everyone enrolled had progressed after a platinum-based regimen. All cell types were allowed except carcinosarcoma and sarcoma.

Median progression-free survival was 7.3 months with pembrolizumab and lenvatinib, against 3.8 months with chemotherapy. Median overall survival was 18.7 months versus 11.9 months. NCI notes the benefit held regardless of mismatch repair status.

Lenvatinib is a daily pill with real side effects, and doses are often lowered. Ask what dose you would start at, and what the plan is if your blood pressure rises. Your dose is whatever your oncologist prescribes, not the trial figure.

Endometrial cancer that has spread is not one situation either. The word covers disease in pelvic and abdominal lymph nodes, deposits on the lining of the abdomen, and spread to the lungs, liver, or bone.

Those patterns are treated differently. Cancer in lymph nodes may still be treated with radiation to a set area. Widespread disease is managed with drugs. A single new spot may be treated on its own.

Ask which pattern your scans show. Ask whether radiation to a specific site is part of the plan, or whether the whole approach is systemic (drugs that travel through the body).

About testing:

• Which of the four molecular groups is my tumor, and what does that change?
• Was the classification done on my biopsy or on the surgical specimen?
• If I am dMMR, does that raise a question about Lynch syndrome for my family?

About treatment:

• Which trial does my recommended regimen come from, and did that trial include people like me?
• Is my cell type one of the ones excluded from a given trial?
• What is the maintenance phase, and how long does it run?

About the sequence:

• If this stops working, what comes next?
• Does starting this now affect eligibility for a trial later?

Advanced endometrial cancer brings symptoms that need attention on their own timeline. Bleeding, pelvic pain, leg swelling, and fatigue are the common ones. Palliative care manages those alongside cancer treatment. It can start at the first visit.

Ask who coordinates your care. Several clinicians are usually involved: a gynecologic oncologist, a medical oncologist, and your primary clinician. Knowing who is in charge can help avoid delays.

For how stage is assigned and what tumor testing adds, see cancer staging and biomarker testing. For the disease overview, see endometrial cancer.

• Call 911 or go to an emergency department if vaginal bleeding is heavy and will not slow, and you feel dizzy or faint or your heart is racing. Those can be signs of shock. Go too for sudden breathlessness or chest pain, which can mean a blood clot has reached the lungs. Also go for black, tarry stools or vomiting blood (MedlinePlus). On lenvatinib, MedlinePlus lists a sudden, severe headache, confusion, trouble speaking, weakness on one side and sudden vision changes as reasons to get emergency treatment, so call 911 for any of these. We add a severe headache with home blood pressure readings much higher than your normal, to be safe. Do not drive yourself.
• Call your care team right away, day or night, if your temperature is 100.4°F (38°C) or higher, or shaking chills come on, while you are having chemotherapy. For CDC, a fever during chemotherapy counts as a medical emergency. If you cannot reach the team, go to an emergency department and say you are on chemotherapy. Call right away too for severe cramping belly pain with vomiting and no gas or stool passing, which can mean the bowel is blocked. Call right away too for a new mouth sore, sore throat, or burning or pain when you urinate during chemotherapy (CDC). On dostarlimab, pembrolizumab or lenvatinib, call right away for diarrhea several times more often than usual, blood or mucus in your stool, or a new cough or breathlessness (MedlinePlus). On dostarlimab or pembrolizumab, a fever can also come from the drug inflaming an organ, so it still needs a call.
• Call your care team right away if one leg is newly swollen, warm and painful, which can be a blood clot (CDC).
• Call your care team the same day if you are passing much less urine than usual, or have new pain in your side or back, which can mean a ureter is blocked.
• Call your care team within a day or two if a leg or the lower belly is slowly swelling, if pelvic pain is building, or if you feel unusually tired, cold or heavy in a way that is new. Immunotherapy can affect the thyroid and other hormone glands, and that is treatable. Do the same for numbness or tingling in your hands or feet on paclitaxel.

• National Cancer Institute, Endometrial Cancer Treatment PDQ, health professional version, updated May 14, 2025; accessed August 6, 2026
• National Cancer Institute, Immune Checkpoint Inhibitors; accessed August 11, 2026
• National Cancer Institute, Infection and Neutropenia During Cancer Treatment; accessed August 11, 2026
• National Cancer Institute, Gastrointestinal Complications PDQ, health professional version; accessed August 11, 2026
• CDC, Watch Out for Fever (Preventing Infections in Cancer Patients); accessed September 27, 2026
• CDC, About Venous Thromboembolism (Blood Clots); accessed September 27, 2026
• MedlinePlus, Lenvatinib; accessed September 29, 2026
• MedlinePlus, Shock; accessed September 27, 2026
• MedlinePlus, Intestinal obstruction; accessed September 27, 2026