Endometrial Cancer Treatment: Surgery, Radiation, Systemic Therapy by Stage

Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Treatment is stage- and histology-driven, guided by NCCN/ESGO/FIGO.

Staging (FIGO 2009, updated 2023 molecular integration)

• Stage I: Confined to uterus (IA <50% myometrial invasion, IB ≥50%).
• Stage II: Cervical stromal invasion.
• Stage III: Local/regional spread (IIIA serosa/adnexa, IIIB vagina/parametria, IIIC pelvic/para-aortic nodes).
• Stage IV: Bladder/bowel mucosa (IVA), distant mets (IVB).

Molecular Classification (TCGA / ProMisE) — Guides Adjuvant Therapy

• POLE-ultramutated: Excellent prognosis; no adjuvant needed.
• MMR-deficient (MSI-H): Lynch syndrome screen; immunotherapy-responsive.
• p53-abnormal (p53abn): Worst prognosis; aggressive chemo-radiation.
• No specific molecular profile (NSMP): Intermediate; risk-stratified by clinicopathologic factors.

Treatment by Modality

Surgery (Cornerstone for Stages I–III)

• Total hysterectomy + bilateral salpingo-oophorectomy (BSO) — laparoscopic/robotic preferred.
• Sentinel lymph node mapping (SLN) (ICG/technetium) ± pelvic/para-aortic lymphadenectomy (per risk).
• Omentectomy for serous/clear cell, high-grade, or intraop suspicion.
• Fertility-sparing (progestin IUD ± oral) for select Stage IA, grade 1, no LVSI, desire fertility.

Radiation Therapy

• Vaginal brachytherapy (VBT): Standard for Stage I–II intermediate risk; fewer GI toxicities than EBRT.
• External beam (EBRT): Pelvic ± para-aortic for Stage IIIC, high-risk I/II, positive margins.
• IMRT/VMAT: Spares bowel, bladder, bone marrow.

Systemic Therapy

• Chemotherapy: Carboplatin/paclitaxel (q3wk × 6) for Stage III–IV, high-risk I/II, serous/clear cell.
• Immunotherapy: Pembrolizumab + chemo for dMMR/MSI-H advanced/recurrent; dostarlimab (anti-PD-1) approved.
• Targeted: Lenvatinib + pembrolizumab for pMMR advanced (KEYNOTE-775).
• Hormonal: Progestins (MA, MPA), aromatase inhibitors, tamoxifen — low-grade, ER/PR+, recurrent/metastatic, non-surgical candidates.

Follow-Up

• q3–6mo × 2y, q6–12mo × 3y, then annually: History, exam, CA-125 (if elevated), imaging per risk.
• Vaginal cuff surveillance (recurrence risk).

Multidisciplinary tumor board (gyn-onc, rad-onc, path, genetics) optimizes personalized therapy.