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Advanced or recurrent endometrial cancer has spread beyond the uterus or come back after treatment. Chemotherapy plus an immune checkpoint antibody is now the first treatment for everyone, with the biggest gains in mismatch-repair-deficient tumours, and lenvatinib with pembrolizumab is the standard when platinum chemotherapy stops working.
Advanced disease means stage III with nodal or adnexal spread or stage IV with bladder, bowel or distant metastasis, and recurrence after primary treatment behaves in the same way. Treatment begins with surgery where debulking is feasible, then systemic therapy chosen by mismatch-repair status and, increasingly, HER2 and hormone receptor status. Carboplatin-paclitaxel had been the first-line standard since GOG-0209 showed it as effective as and less toxic than the older three-drug regimen, and for pelvic-confined recurrence radiotherapy or exenteration can still be curative.
Three phase 3 trials reported in 2023 changed first-line care. RUBY added dostarlimab to carboplatin-paclitaxel and extended median overall survival in the whole population from 28.2 to 44.6 months, with a hazard ratio of 0.69 and a progression-free survival hazard ratio of 0.28 in mismatch-repair-deficient tumours. NRG-GY018 added pembrolizumab and cut the hazard of progression to 0.30 in deficient and 0.54 in proficient tumours. DUO-E added durvalumab, with a hazard ratio of 0.42 in deficient tumours, and durvalumab plus olaparib maintenance gave 0.57 in proficient tumours. Regulators approved pembrolizumab and dostarlimab with chemotherapy for all comers in 2024, and the gain in proficient disease, though real, is smaller and the subject of debate about cost and toxicity.
After platinum, KEYNOTE-775 established lenvatinib with pembrolizumab, which extended median survival from 11.4 to 18.3 months against doxorubicin or weekly paclitaxel in mismatch-repair-proficient disease, at the price of hypertension, fatigue and diarrhoea that force dose reductions in most patients. Trastuzumab deruxtecan gives responses in HER2-expressing tumours after DESTINY-PanTumor02, endocrine therapy suits low-grade receptor-positive disease, and antibody-drug conjugates against TROP2 and folate receptor alpha (sacituzumab tirumotecan, rinatabart sesutecan) are in phase 3. Maintenance selinexor in TP53-wild-type disease failed in XPORT-EC-042 in 2026, and the sequencing of these agents after first-line immunotherapy is the open clinical question.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
Most high-grade ovarian cancers begin at the tip of the fallopian tube; endometrial cancer lines the uterus, cervical cancer starts at the transformation zone; each drains to a different node group.
Same organ: Adenosquamous carcinoma of the cervix, Small cell neuroendocrine carcinoma of the cervix, Bartholin gland carcinoma, Vulvar melanoma, Vaginal melanoma, High-grade serous ovarian cancer, Low-grade serous ovarian cancer, Clear cell ovarian cancer, Mucinous ovarian cancer, Adult granulosa cell tumour of the ovary, Ovarian cancer, Endometrial cancer, Cervical cancer, Vulvar cancer, Gestational trophoblastic neoplasia, Uterine sarcoma, Vaginal cancer, POLE-ultramutated endometrial cancer, Mismatch-repair-deficient endometrial cancer, p53-abnormal endometrial cancer, including uterine serous carcinoma, Endometrial cancer with no specific molecular profile, Uterine carcinosarcoma, Early cervical cancer and fertility-sparing surgery, Locally advanced cervical cancer, Recurrent or metastatic cervical cancer, Platinum-sensitive ovarian cancer, Platinum-resistant ovarian cancer, HPV-associated vulvar squamous cell carcinoma, HPV-independent vulvar squamous cell carcinoma (p53-mutant), Vaginal squamous cell carcinoma (HPV-associated), Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma), Low-risk gestational trophoblastic neoplasia (FIGO score 0 to 6), High-risk gestational trophoblastic neoplasia (FIGO score 7 or more, including ultra-high-risk), Placental-site trophoblastic tumour and epithelioid trophoblastic tumour
Carboplatin-paclitaxel with dostarlimab (RUBY) or pembrolizumab (NRG-GY018), then maintenance immunotherapy for up to three years or two years respectively.
Carboplatin-paclitaxel with pembrolizumab or dostarlimab, or durvalumab followed by durvalumab-olaparib maintenance (DUO-E); trastuzumab added for HER2-positive serous carcinoma.
Lenvatinib with pembrolizumab (KEYNOTE-775); trastuzumab deruxtecan for HER2-expressing tumours; aromatase inhibitors or progestins for low-grade receptor-positive disease.
Single-agent dostarlimab or pembrolizumab.
Radiotherapy with brachytherapy for vaginal recurrence after surgery alone; exenteration in selected central recurrences after radiotherapy.
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Durvalumab-based chemo-immunotherapy is a third first-line option with RUBY and NRG-GY018, and durvalumab plus olaparib maintenance is approved for mismatch repair-proficient disease in some regions.
Together with RUBY, this trial made chemo-immunotherapy the first-line standard for advanced endometrial cancer in both molecular groups, with the largest effect in mismatch repair-deficient tumours.
Women with newly diagnosed advanced or recurrent endometrial cancer should receive a PD-1 antibody (dostarlimab or pembrolizumab) with their chemotherapy, and mismatch repair testing is now essential because women with dMMR tumours gain a very large and durable benefit. The gain in mismatch-repair-proficient tumours is real but smaller, and molecular classification (POLE, p53, MMR) is increasingly used to decide who benefits most.
Lenvatinib-pembrolizumab is the standard second-line treatment for mismatch repair-proficient endometrial cancer after platinum, though its toxicity is considerable and its place after first-line immunotherapy is unclear.
Query for this cancer: (TITLE:"Advanced or recurrent endometrial cancer" OR ABSTRACT:"Advanced or recurrent endometrial cancer" OR TITLE:"Stage III to IV endometrial cancer" OR ABSTRACT:"Stage III to IV endometrial cancer" OR TITLE:"Metastatic endometrial cancer" OR ABSTRACT:"Metastatic endometrial cancer" OR TITLE:"Relapsed endometrial cancer" OR ABSTRACT:"Relapsed endometrial cancer" OR TITLE:"Primary advanced endometrial cancer" OR ABSTRACT:"Primary advanced endometrial cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Advanced or recurrent endometrial cancer, not a curated reading list.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
A swollen painful calf, or sudden breathlessness with chest pain; the tamoxifen boxed warning covers pulmonary embolism and stroke.
A swollen painful calf, or sudden breathlessness with chest pain; venous thromboembolism including pulmonary embolism is a labelled warning.
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
See all on the product pages:CarboplatinDostarlimabDurvalumabLenvatinibLetrozole (and other aromatase inhibitors)OlaparibPaclitaxel / nab-paclitaxelPembrolizumabProgestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD)·Printable cards in the navigator
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Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
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