What is the step-by-step treatment approach for endometrial cancer based on the stage, according to the latest National Comprehensive Cancer Network (NCCN) guidelines?

Treatment of Endometrial Cancer Based on Stage According to Latest NCCN Guidelines

The treatment of endometrial cancer should follow a stage-based approach with total hysterectomy and bilateral salpingo-oophorectomy (TH/BSO) with surgical staging as the cornerstone of management for most patients, followed by tailored adjuvant therapy based on risk factors including stage, histologic grade, myometrial invasion, and lymphovascular space invasion. 1

Initial Evaluation and Staging

• Preoperative evaluation should include clinical and gynecological examination, transvaginal ultrasound, blood counts, liver and renal function profiles 1
• Chest X-ray is recommended for all patients 1
• CT scan is indicated for investigating extrapelvic disease 1
• Dynamic contrast-enhanced MRI is the best tool to assess cervical involvement 1
• FDG-PET/CT may be useful for detecting distant metastases 1
• Endometrial biopsy is essential for histologic diagnosis 1

Stage-Based Treatment Approach

Stage I Disease (Confined to Uterus)

Stage IA (No or <50% Myometrial Invasion)

• Primary Treatment: Total hysterectomy and bilateral salpingo-oophorectomy (TH/BSO) with surgical staging 1
• Adjuvant Treatment:
  • Grade 1-2: Observation is preferred for most patients; vaginal brachytherapy for patients ≥60 years and/or with LVSI 1
  • Grade 3: Vaginal brachytherapy preferred; observation if no myometrial invasion; consider EBRT (category 2B) if age ≥70 years or LVSI present 1

Stage IB (≥50% Myometrial Invasion)

• Primary Treatment: TH/BSO with surgical staging 1
• Adjuvant Treatment:
  • Grade 1-2: Vaginal brachytherapy preferred; observation if no adverse risk factors; consider EBRT if age ≥60 years and/or LVSI present 1
  • Grade 3: EBRT and/or vaginal brachytherapy; consider adding systemic therapy (category 2B) if adverse risk factors present 1

Stage II Disease (Cervical Stromal Invasion)

• Primary Treatment: TH/BSO with surgical staging; radical or modified radical hysterectomy may improve local control 1
• Adjuvant Treatment:
  • After extrafascial hysterectomy: EBRT with (or without) vaginal brachytherapy 1
  • After radical hysterectomy with negative margins: EBRT (preferred) and/or vaginal brachytherapy with (or without) systemic therapy (category 2B) 1

Stage III Disease (Local/Regional Spread)

• Primary Treatment: TH/BSO with surgical staging and debulking to no gross residual disease 1
• Adjuvant Treatment: Combined modality treatment with chemotherapy and radiation therapy is recommended 1, 2
  • The PORTEC-3 trial showed improved 5-year overall survival with chemoradiotherapy versus radiotherapy alone (81.4% vs 76.1%) 1
  • Patients with serous cancers and stage III disease benefit most from combined therapy 1

Stage IV Disease (Distant Metastasis)

• Primary Treatment:
  • For resectable disease: Consider surgical cytoreduction 1
  • For unresectable disease: Systemic therapy with or without EBRT 1
• Adjuvant Treatment: Systemic therapy is the mainstay; consider SBRT for limited metastatic disease (1-5 lesions) 1

Special Considerations

Fertility-Sparing Treatment

• For young women with grade 1 endometrioid adenocarcinoma with no myometrial invasion who desire fertility preservation 1:
  • Continuous progestin-based therapy (megestrol acetate, medroxyprogesterone, or levonorgestrel IUD) 1
  • Close monitoring with endometrial sampling every 3-6 months 1
  • TH/BSO with staging recommended after childbearing is complete, if progression occurs, or if cancer persists after 6-12 months of therapy 1

Non-Endometrioid Histologies (Serous, Clear Cell, Carcinosarcoma)

• More aggressive surgical staging similar to ovarian cancer 1
• Even for stage IA with no myometrial invasion, consider chemotherapy ± vaginal brachytherapy 1
• For stage IA with myometrial invasion and higher stages: Chemotherapy ± tumor-directed RT 1
• For HER2-positive uterine serous carcinoma: Consider carboplatin/paclitaxel/trastuzumab regimen 1

Patients Not Suitable for Surgery

• EBRT and/or brachytherapy is the preferred approach 1
• Alternatively, consider progestational agents 1
• For suspected cervical involvement: EBRT and brachytherapy with or without platinum-based chemosensitization 1
• Re-evaluate for surgical resection based on treatment response 1

Common Pitfalls to Avoid

• Overtreatment of low-risk patients with unnecessary radiation therapy 2
• Undertreatment of high-risk patients with vaginal brachytherapy alone when EBRT is indicated 2
• Delaying adjuvant radiation therapy beyond 12 weeks after surgery 1
• Failing to consider molecular classification in treatment planning, as recent evidence shows molecular subtypes have stronger prognostic impact than traditional histopathological characteristics 3