16Uterine / Endometrial
Snapshot. The commonest gynaecological cancer; mostly endometrioid adenocarcinoma, usually presenting early with postmenopausal bleeding (good prognosis when caught early). Now classified molecularly (TCGA — The Cancer Genome Atlas) into 4 groups that drive BOTH prognosis and adjuvant-treatment intensity: POLE-mutated (a DNA-polymerase gene — excellent prognosis, adjuvant therapy can often be SAFELY OMITTED), MMR-deficient/MSI-high (mismatch-repair-deficient/microsatellite-instability-high — immunotherapy-responsive), p53-abnormal (serous-like, worst prognosis — needs the MOST intensive adjuvant treatment), and NSMP (no specific molecular profile — intermediate risk). Risk = unopposed estrogen (obesity, PCOS [polycystic ovary syndrome], tamoxifen) + Lynch syndrome.
Workup
Endometrial biopsy/hysteroscopy for postmenopausal bleeding · MRI pelvis (myometrial invasion depth) + CT/PET for advanced disease · MMR/MSI (Lynch screen) + molecular classification (POLE, p53) on every case · HER2 on SEROUS histology (opens trastuzumab) — it now drives adjuvant intensity, not just prognosis · surgically staged (FIGO).
Treatment by setting
| Setting | Treatment |
|---|
Early
uterus-confined | Total hysterectomy + bilateral salpingo-oophorectomy ± sentinel / pelvic lymph-node assessment
the mainstay Adjuvant vaginal brachytherapy ± EBRT
external-beam radiotherapy — by risk factors AND molecular class POLE-mutated, stage I–II → consider OMITTING adjuvant therapy entirely (PORTEC-4a)
excellent prognosis (90–100%) regardless Fertility-sparing progestin therapy
only in select early low-grade cases |
High-risk / advanced
serous, high-grade, node-positive | Surgery + adjuvant chemo (carboplatin + paclitaxel) ± radiotherapy p53-abnormal (serous-like) → most intensive combined chemo + RT
this molecular group drives escalation toward maximal adjuvant treatment |
| Advanced / recurrent | 1st line → carboplatin + paclitaxel + immunotherapy → immunotherapy maintenance
dostarlimab (RUBY) or pembrolizumab (NRG-GY018) — both FDA-approved regardless of MMR status · benefit in ALL comers, but LARGEST in dMMR/MSI-high dMMR specifically → durvalumab ± olaparib maintenance is an alternative (DUO-E)
US FDA approval is dMMR-only; the pMMR + olaparib combination has EU but not US approval — confirm locally pMMR/MSS, progressed on prior systemic therapy → lenvatinib + pembrolizumab (KEYNOTE-775)
lenvatinib is a VEGFR (vascular endothelial growth factor receptor) tyrosine kinase inhibitor HER2-positive serous → add trastuzumab Low-grade ER-positive → hormonal (progestin) therapy |
Watch
Carboplatin/paclitaxel (myelosuppression, neuropathy); pelvic radiotherapy → bowel/bladder/vaginal toxicity; lenvatinib → hypertension, proteinuria, fatigue; immunotherapy (dostarlimab/pembrolizumab/durvalumab) → irAEs (immune-related adverse events); olaparib → cytopenias.