What are the indications for using Vaginal Brachytherapy (VBT) alone as adjuvant treatment in patients with endometrial cancer?

Indications for Vaginal Brachytherapy (VBT) Alone in Endometrial Cancer

Vaginal brachytherapy alone is indicated for intermediate-risk and select high-intermediate-risk endometrial cancer patients after surgical staging, specifically targeting vaginal recurrence prevention while avoiding the toxicity of external beam radiation therapy.

Stage IA Disease

Grade 1-2 Tumors

• VBT is strongly recommended for patients ≥60 years of age and/or those with lymphovascular space invasion (LVSI), even with minimal myometrial invasion 1
• Observation remains acceptable for younger patients (<60 years) without LVSI 1

Grade 3 Tumors

• VBT is the preferred option for stage IA grade 3 disease, particularly after surgical staging 1
• Observation can be considered only if absolutely no myometrial invasion is present 1
• If additional risk factors exist (age ≥70 years or LVSI), external beam radiation therapy (EBRT) should be considered instead 1

Stage IB Disease (≥50% Myometrial Invasion)

Grade 1-2 Tumors (Intermediate-Risk)

• VBT is the preferred adjuvant treatment for stage IB grade 1-2 disease without LVSI, providing excellent vaginal control with minimal toxicity 1
• The PORTEC-2 trial demonstrated that VBT alone achieved approximately 2% vaginal recurrence rates at 5 years, equivalent to EBRT but with superior quality of life 1, 2
• Observation is acceptable only if no adverse risk factors are present (younger age, no LVSI) 1
• EBRT should be considered for grade 2 tumors if additional risk factors exist, such as age ≥60 years and/or LVSI 1

Grade 3 Tumors

• VBT alone is generally insufficient for stage IB grade 3 disease 1
• These patients typically require EBRT and/or systemic therapy in addition to or instead of VBT 1

High-Intermediate-Risk Disease (After Surgical Nodal Staging)

VBT alone is recommended for high-intermediate-risk patients only when comprehensive surgical nodal staging has been performed and nodes are negative 1:

With Negative Lymph Nodes

• Stage I grade 3 with <50% myometrial invasion, regardless of LVSI status: VBT alone is recommended 1
• Stage I grade 1-2 with unequivocally positive (substantial, not focal) LVSI, regardless of depth of invasion: VBT alone is recommended 1
• These recommendations carry Level III evidence with Strength B 1

Without Surgical Nodal Staging

• EBRT is recommended for LVSI unequivocally positive disease to address pelvic nodal recurrence risk 1
• VBT alone is recommended only for grade 3 disease that is LVSI negative 1

Stage II Disease (After Radical Hysterectomy)

• VBT alone (with or without systemic therapy) is an option only for patients who underwent radical hysterectomy with negative surgical margins and no evidence of extrauterine disease 1
• EBRT is generally preferred for stage II disease 1
• Standard extrafascial hysterectomy for stage II disease typically requires EBRT and/or VBT 1

Critical Exclusion Criteria for VBT Alone

VBT alone should NOT be used in the following scenarios:

• Unequivocally positive LVSI without surgical nodal staging (requires EBRT) 1
• Stage IB grade 3 with adverse risk factors (requires EBRT and/or chemotherapy) 1
• Any stage with positive lymph nodes (requires systemic therapy ± EBRT) 1
• Non-endometrioid histologies (serous, clear cell) generally require more aggressive treatment 1
• Lower uterine segment involvement in high-risk settings may warrant EBRT consideration 3

Important Clinical Considerations

Timing

• VBT should be initiated as soon as the vaginal cuff has healed, but no later than 12 weeks after surgery 1

Toxicity Profile

• VBT alone demonstrates significantly lower toxicity compared to EBRT, with minimal impact on quality of life 1, 4
• No Grade 3 or higher acute or late radiation toxicity was noted in patients receiving VBT alone 5

Salvage Potential

• Combined EBRT and brachytherapy for vaginal recurrence after initial observation achieves 89% complete remission rates, though with higher toxicity than primary adjuvant VBT 1, 2
• This salvage option does not justify withholding VBT in appropriate candidates, as treatment-related toxicity is significantly higher with salvage therapy 1

Common Pitfall

The most critical error is using VBT alone in patients with substantial LVSI who have not undergone surgical nodal staging, as these patients have significantly elevated pelvic nodal recurrence risk that VBT cannot address 1, 6. A pooled analysis from PORTEC-1 and -2 demonstrated that LVSI and grade 3 are independent risk factors for regional nodal recurrence, which VBT alone does not prevent 1.