What are the treatment options for endometrial cancer?

Treatment Options for Endometrial Cancer

The primary treatment for endometrial cancer is surgery consisting of total hysterectomy with bilateral salpingo-oophorectomy, with additional treatments determined by disease stage and risk factors. 1

Surgical Management

• Total hysterectomy with bilateral salpingo-oophorectomy (TH/BSO) is the cornerstone of treatment for apparent uterine-confined endometrial cancer 1
• Surgery should include systematic exploration, inspection, and palpation of the entire abdomen 1
• Surgical approaches include:
  • Laparotomy (traditional open surgery)
  • Minimally invasive techniques (laparoscopy or robotic surgery) which provide equivalent oncologic outcomes with shorter hospital stays, less pain, and fewer complications 2
• Lymph node assessment is crucial for staging and treatment planning:
  • Pelvic lymphadenectomy provides important prognostic information 1
  • Para-aortic nodal evaluation may be utilized for high-risk tumors (deeply invasive lesions, high-grade histology) 1
  • Sentinel lymph node mapping is an emerging option for selected patients 1

Stage-Based Treatment Approach

Stage I Disease

• For grade 1 and 2 stage IA tumors:
  • Follow-up alone is standard after surgery 2, 1
  • Vaginal brachytherapy may be considered for grade 3 stage IA disease 2
• For grade 1 and 2 stage IB tumors:
  • Options include vaginal brachytherapy or follow-up alone 2, 1
• For grade 3 stage IB tumors and stage IC disease:
  • External pelvic radiotherapy with or without vaginal brachytherapy boost (level of evidence B) 2
  • Vaginal brachytherapy alone (level of evidence C) 2, 1

Stage II Disease

• When cervical involvement is confirmed:
  • Modified radical hysterectomy (Piver type II) is recommended for macroscopic cervical lesions 1
  • Treatment options include:
    • External radiotherapy with brachytherapy 2
    • Brachytherapy followed by surgery 2
    • Surgery followed by adjuvant radiotherapy based on prognostic factors 2
• For stage IIA tumors with myometrial penetration <50% or grade 1-2:
  • Postoperative vaginal brachytherapy is standard 2
• For stage IIA with myometrial penetration >50% or grade 3:
  • External radiotherapy with brachytherapy boost is recommended 2
• For stage IIB disease:
  • Postoperative external pelvic radiotherapy with brachytherapy boost is standard 2

Stage III Disease

• Debulking surgery is the standard approach:
  • Total hysterectomy with salpingo-oophorectomy
  • Bowel resection if possible
  • Partial or total bladder resection if possible 2
• Additional treatment options include:
  • For stage IIIA (ovarian involvement or positive peritoneal cytology):
    • Postoperative pelvic radiotherapy or abdomino-pelvic radiotherapy 2
  • For stage IIIB:
    • Pelvic external beam irradiation with brachytherapy 2
  • For stage IIIC with pelvic nodes involved:
    • Post-operative pelvic radiotherapy with or without brachytherapy boost 2
  • For stage IIIC with para-aortic nodes involved:
    • Extended postoperative radiotherapy (pelvic and para-aortic) with or without brachytherapy 2
• Combined chemoradiation has shown improved recurrence-free and overall survival in high-risk cases 1, 3

Stage IV Disease

• Cytoreductive surgery is undertaken with:
  • Total hysterectomy plus BSO
  • Gut resection (if complete resection is possible or to avoid obstruction)
  • Partial or total bladder resection with urinary diversion 2
• For stage IVB:
  • Anterior or posterior pelvectomy depending on location with pelvic clearance 2
  • Post-operative pelvic radiotherapy with or without brachytherapy 2
  • Consideration of hormone therapy or chemotherapy 2

Special Considerations

• Omentectomy should be performed for serous adenocarcinoma, clear cell adenocarcinoma, or carcinosarcoma histology 1
• Fertility-sparing options may be considered in well-differentiated (grade 1) endometrioid adenocarcinoma limited to the endometrium in young patients 1
• Ovarian preservation may be considered in young women (<50 years) with low-grade, early-stage endometrioid endometrial cancer 1
• Systemic therapy options include:
  • Chemotherapy for advanced or recurrent disease 3
  • Hormonal therapy for selected patients 4
  • Targeted therapies based on molecular classification are emerging 3

Clinical Pitfalls and Caveats

• Preoperative imaging is important for evaluating operability but no examination is sufficiently sensitive to distinguish between stage I and II disease 1
• CA125 is not diagnostic for endometrial cancer but may predict extra-uterine extension at levels >35 U/ml 1
• Performance status should be considered when planning treatment; for poor performance status patients with stage III disease, total hysterectomy plus BSO by abdominal approach may be preferable to radiotherapy alone 2
• Recent molecular classification of endometrial cancer (POLE ultra-mutated, microsatellite instable hypermutated, copy-number-low, and copy-number-high) has stronger prognostic impact than traditional histopathological characteristics and may guide future treatment decisions 3