Endometrial Uterine Cancer

The most common and important early symptom is postmenopausal vaginal bleeding — any vaginal bleeding occurring more than 12 months after the last menstrual period. This symptom accounts for why the majority of endometrial cancers are diagnosed at an early, highly treatable stage. In premenopausal women, abnormal uterine bleeding (irregular, heavy, or prolonged periods) can also indicate endometrial pathology and should be investigated, particularly over age 40.

The term 'endometrial cancer' refers specifically to cancers arising from the endometrium (inner lining of the uterus), which account for the vast majority (~95%) of uterine cancers. 'Uterine cancer' is a broader term that also includes uterine sarcomas arising from the muscle wall (myometrium) or connective tissue of the uterus. When most clinicians and information sources use 'uterine cancer,' they are generally referring to endometrial cancer.

The four TCGA/ProMisE molecular subtypes are: (1) POLE-ultramutated — caused by mutations in the POLE proofreading gene; excellent prognosis regardless of grade; (2) MMR-deficient/MSI-High — caused by mismatch repair protein loss; highly responsive to pembrolizumab immunotherapy; (3) TP53-mutant/Serous-like — copy number-high tumours with worst prognosis; includes most serous and clear cell carcinomas; and (4) NSMP (No Specific Molecular Profile) — the remaining group, mostly low-grade endometrioid tumours, intermediate prognosis.

Pembrolizumab (Keytruda) is an anti-PD-1 checkpoint inhibitor that has been approved in combination with carboplatin-paclitaxel chemotherapy for advanced or recurrent endometrial cancer that is MMR-deficient (lacking mismatch repair proteins) or MSI-High (microsatellite instability-high). These molecular features make the tumour highly immunogenic and sensitive to checkpoint blockade. Pembrolizumab has shown dramatic improvements in progression-free and overall survival in this subset. A tumour MMR/MSI test is required to determine eligibility.

Surgery (total hysterectomy with bilateral salpingo-oophorectomy) is the standard curative treatment for most endometrial cancer patients. However, in carefully selected younger women with Grade 1 Stage IA disease who desire fertility preservation, conservative management with high-dose progestins and regular hysteroscopic surveillance is an option. This approach requires specialist gynaecologic oncology guidance, strict monitoring, and a commitment to surgery once childbearing is complete or if the cancer does not respond to hormonal therapy.

Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) is an inherited condition caused by germline mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS2). It carries a lifetime risk of endometrial cancer of 40–60%, making it the most common cancer manifestation for many Lynch syndrome carriers. All endometrial cancer patients should be tested for MMR protein expression, and those with MMR-deficient tumours require germline testing to identify or exclude Lynch syndrome — which has major implications for other cancer surveillance in the patient and their relatives.

Recurrent endometrial cancer treatment depends on the site of recurrence, prior treatments, and molecular subtype. Isolated vaginal vault recurrence may be treated with salvage radiotherapy or surgery in previously unirradiated patients. Systemic recurrence options include carboplatin-paclitaxel chemotherapy, lenvatinib + pembrolizumab (approved regardless of MMR status), pembrolizumab-based combinations (in MMR-deficient disease), hormonal therapy in low-grade ER-positive tumours, and clinical trial participation. Molecular profiling of the recurrent tumour guides therapy selection.

Yes. CancerFax assists endometrial cancer patients with molecular profiling and pathology report review, coordination of second opinions with specialist gynaecologic oncologists, and access to pembrolizumab, lenvatinib, HER2-directed therapies, and emerging clinical trials — including programmes at advanced centres in India, China, and internationally. Whether you are newly diagnosed, navigating adjuvant therapy decisions, or seeking options for recurrent or advanced disease, our team can help identify the right pathway for your specific molecular subtype and stage.