What is the recommended treatment for intermediate risk endometrial cancer?

Treatment for Intermediate Risk Endometrial Cancer

For intermediate risk endometrial cancer, the recommended treatment includes total hysterectomy with bilateral salpingo-oophorectomy followed by adjuvant vaginal brachytherapy, with lymphadenectomy considered for staging purposes. 1

Surgical Management

The surgical approach for intermediate risk endometrial cancer consists of:

• Total hysterectomy and bilateral salpingo-oophorectomy as the standard surgical approach 1
• Lymphadenectomy can be considered for staging purposes, with sentinel lymph node dissection (SLND) being an option 1
• Minimally invasive surgery (laparoscopic or robotic) is recommended for intermediate-risk endometrial cancer 1

Lymphadenectomy Considerations

While lymphadenectomy is important for determining prognosis and tailoring adjuvant therapies, its therapeutic value remains debated:

• Randomized trials have failed to show survival benefit for systematic pelvic lymphadenectomy in stage I endometrial cancer 1
• For intermediate risk cases, lymphadenectomy can be considered primarily for staging purposes 1
• The SEPAL study suggested potential benefit from more aggressive surgical staging in high-risk patients 1

Adjuvant Treatment

After surgery, adjuvant treatment for intermediate risk endometrial cancer (defined as Stage I endometrioid, G1-2, ≥50% myometrial invasion, LVSI negative) includes:

• Adjuvant vaginal brachytherapy as the recommended treatment 1
• No adjuvant treatment is an option, especially for patients <60 years old 1
• For cases with G3 histology or unequivocally positive LVSI, adjuvant chemotherapy (combined and/or sequential) should be considered 1

Evidence for Adjuvant Radiotherapy

• The PORTEC-2 trial demonstrated that vaginal brachytherapy is as effective as external beam radiation for intermediate risk patients, but with better quality of life 1
• External beam radiation has been shown to reduce locoregional recurrence but does not improve overall or disease-specific survival 1
• Three large randomized studies (PORTEC-1, GOG 99, and ASTEC MRC-NCIC CTG EN.5) failed to demonstrate survival improvement with external beam radiation 1

Special Considerations

For patients with specific risk factors:

• If surgical nodal staging was performed and nodes are negative:

  • For G1-2 tumors with negative LVSI: vaginal brachytherapy 1
  • For G3 tumors or positive LVSI: limited field external beam radiotherapy (EBRT) 1

• If G3 or LVSI unequivocally positive:

  • Consider adjuvant chemotherapy (combined and/or sequential) 1

Molecular Classification

Recent advances in molecular classification are changing the landscape of endometrial cancer treatment:

• Four molecular classes have been identified: POLE ultra-mutated, microsatellite instable hypermutated, copy-number-low, and copy-number-high 2
• These molecular subgroups have stronger prognostic impact than traditional histopathological characteristics 2
• Future treatment approaches may incorporate molecular classification to guide adjuvant therapy decisions 2

Common Pitfalls and Caveats

• Overtreatment with external beam radiation when vaginal brachytherapy would suffice for intermediate risk disease 1
• Underestimating the importance of surgical staging for guiding adjuvant therapy decisions 1
• Failing to consider age and comorbidities when deciding on adjuvant therapy options 1
• Not recognizing that patients with G3 histology or positive LVSI may benefit from more aggressive adjuvant treatment approaches 1