Endometrial Cancer: Surgery, Immunotherapy & Fertility Options

The 2025 ESGO–ESTRO–ESP framework distinguishes low-grade, estrogen-receptor-positive NSMP from high-grade or estrogen-receptor-negative NSMP. Multiple-classifier tumors follow a hierarchy: a qualifying POLE alteration can take priority; MMRd can take priority over an accompanying p53 abnormality. Incomplete testing should not be presented as a complete molecular classification.

Surgery commonly removes the uterus, fallopian tubes and ovaries, with risk-adapted nodal assessment. Sentinel-node mapping can provide staging information while limiting unnecessary node removal in appropriate patients. Surgical fitness and the likelihood of spread shape the plan; selected younger patients require a separate discussion about ovarian preservation.

Some low-risk patients need surveillance only after surgery. Vaginal brachytherapy focuses treatment at the vaginal cuff; external-beam radiotherapy covers a broader area; chemotherapy addresses systemic recurrence risk. Molecular classification, LVSI and stage help choose between these options. A poor-prognosis marker alone does not specify one universal regimen.

Patients who cannot undergo surgery may still have a definitive radiation-based option, including brachytherapy. Assessment should distinguish inability to tolerate surgery from a cancer that cannot be treated with curative intent.

Fertility-sparing treatment is mainly considered for carefully selected grade 1 endometrioid carcinoma confined to the endometrium, without myometrial invasion or other concerning features. Expert pathology review and imaging are essential. Higher-grade, non-endometrioid or hereditary-risk cases cannot simply follow the same pathway.

Treatment may use hysteroscopic resection with oral progestins and/or a levonorgestrel intrauterine device. Repeated endometrial biopsies are needed to confirm response; a normal scan or improvement in bleeding is insufficient. Agree in advance on what happens with no response, progression or recurrence, and discuss definitive surgery after childbearing.

MMR status helps interpret expected benefit and available regimens, but it is not a rule that every pMMR cancer is ineligible for immunotherapy. Current US options for adults with primary advanced or recurrent endometrial cancer include pembrolizumab or dostarlimab with carboplatin/paclitaxel followed by the respective immune drug alone, without a dMMR-only restriction in these combination indications.

The US durvalumab combination with carboplatin/paclitaxel, followed by durvalumab, is restricted to dMMR disease. These drugs are alternatives within their own regimens, not treatments to combine with each other. Evidence, previous treatment, autoimmune disease and transplant history need review.

An isolated vaginal or pelvic recurrence can sometimes be treated with surgery or radiation, depending on previous radiation and the extent of disease. A new biopsy can confirm recurrence and provide material for tests. Widespread recurrence usually requires systemic treatment, with symptom-directed local care when needed.

For adults with advanced MSI-H/dMMR endometrial cancer progressing after prior systemic treatment and not suitable for curative surgery or radiation, the US label includes pembrolizumab alone. Dostarlimab alone has an indication for recurrent/advanced dMMR disease progressing on or after a platinum-containing regimen, also when curative surgery or radiation is unsuitable.

For pMMR/not MSI-H advanced disease progressing after prior systemic therapy and not suitable for curative surgery or radiation, US-approved lenvatinib plus pembrolizumab is an option. Reusing immunotherapy after progression on a prior immune-containing combination needs a specific rationale; older trials do not automatically settle that sequence.

Endocrine therapy can be appropriate for selected hormone-receptor-positive, lower-grade, slower-growing advanced cancers. Receptor status, symptoms and disease pace matter; this approach differs from urgent treatment of rapidly progressive organ-threatening disease.

A randomized phase II study supports adding trastuzumab to carboplatin/paclitaxel in HER2-positive advanced or recurrent uterine serous carcinoma. This is evidence for a defined histological group, not every endometrial cancer. Separately, US accelerated tumor-agnostic approval of trastuzumab deruxtecan covers adults with unresectable/metastatic HER2 IHC 3+ solid tumors after prior systemic therapy with no satisfactory alternative. These are different treatments with different eligibility rules.

Fudan University Shanghai Cancer Center · Shanghai, China

Its gynecologic service brings surgery, radiation and medicines into multidisciplinary care. A review can address postoperative treatment and selected fertility-preserving needs.

MD Anderson Cancer Center · Houston, United States

Offers gynecologic oncology and oncofertility services. The team can review cancer treatment alongside reproductive priorities and clinical research options.

Memorial Sloan Kettering Cancer Center · New York, United States

Reviews pathology and imaging for second opinions and offers risk-adapted surgical care. Useful questions include node assessment, surgical approach and whether further treatment is needed.

Endometrioid carcinoma is the commonest histological type. Serous, clear-cell, undifferentiated/dedifferentiated tumors and carcinosarcoma need distinct pathological interpretation. Uterine carcinosarcoma is managed within high-risk endometrial carcinoma pathways; it should not be confused with a uterine smooth-muscle sarcoma.

Ask which FIGO version appears in your report. FIGO 2023 incorporates tumor biology as well as anatomy. Myometrial invasion, cervical involvement, lymphovascular space invasion (LVSI), nodes, sites of spread and molecular findings may all affect risk assessment. A change in stage label between systems does not necessarily mean the cancer has progressed.

Bleeding after menopause, bleeding between periods or a changed bleeding pattern deserves assessment. These symptoms can have benign causes, but ultrasound alone does not establish the tissue diagnosis. Endometrial sampling, sometimes guided by hysteroscopy, allows a pathologist to look for cancer.

A Pap test examines the cervix and is not a reliable screening test for endometrial cancer. Obesity, prolonged estrogen exposure without adequate progesterone opposition and Lynch syndrome can increase risk. A person does not need these risk factors to develop the disease.

MMRd does not automatically mean Lynch syndrome. The pattern of protein loss, MLH1 methylation where appropriate, personal/family history and germline testing help distinguish acquired changes from inherited risk. A confirmed inherited result may affect colorectal and other cancer surveillance for the patient and relatives.

Follow-up should address new bleeding, pelvic pain, persistent cough or unexplained weight change, as well as menopausal symptoms, sexual health and leg swelling after nodal treatment. Bring the full surgical pathology, molecular reports, radiation plan and drug history to a new consultation. Ask which findings would change treatment now rather than ordering every available test.

Lenvatinib requires monitoring of blood pressure, kidney function and other toxicities. Immune therapy can cause inflammatory problems in multiple organs, and trastuzumab deruxtecan can cause lung inflammation. New breathlessness, severe diarrhea or marked weakness should be reported promptly rather than waiting for the next scheduled scan.