What are the indications for radiotherapy in post-operative cases of endometrial (ca endometrium) cancer?

Indications for Radiotherapy in Post-Operative Endometrial Cancer

Adjuvant radiotherapy recommendations are risk-stratified: low-risk disease requires no adjuvant therapy, intermediate-risk disease benefits from vaginal brachytherapy for local control, high-intermediate and high-risk disease requires pelvic external beam radiotherapy (EBRT) with or without brachytherapy, and advanced stage disease (III-IV) requires combined chemoradiation for optimal survival outcomes. 1, 2

Risk Stratification Framework

The decision for adjuvant radiotherapy depends on surgical stage, tumor grade, depth of myometrial invasion, lymphovascular space invasion (LVSI), histologic type, and patient age 1, 2:

Low-Risk Disease (No Radiotherapy Indicated)

• Stage IA, Grade 1-2, endometrioid histology with <50% myometrial invasion and negative LVSI: Observation alone is standard 1, 2
• Recurrence risk approximately 10.4% with surgery alone 2

Intermediate-Risk Disease (Vaginal Brachytherapy)

• Stage IB (≥50% myometrial invasion), Grade 1-2, endometrioid histology, LVSI negative: Vaginal brachytherapy is recommended 1, 2
• Brachytherapy significantly reduces vaginal/pelvic relapses but has no impact on overall survival 1
• Typical dosing: 21 Gy in 3 fractions prescribed to 0.5 cm depth 3
• Recurrence risk approximately 22.4% for Stage IB disease 2

High-Intermediate Risk Disease (Selective Radiotherapy)

• Patients ≥60 years with two of three risk factors (age ≥60, deep myometrial invasion, Grade 3): Locoregional relapse rate >15%, adjuvant pelvic radiotherapy recommended 1, 2
• Stage I with surgical nodal staging, node negative: Vaginal brachytherapy for Grade 1-2 with negative LVSI; limited field EBRT for Grade 3 or LVSI unequivocally positive 2

High-Risk Disease (Pelvic EBRT ± Brachytherapy)

• Stage IC, Grade 3 with ≥50% myometrial invasion: Pelvic EBRT with or without vaginal brachytherapy boost recommended 1, 2
• Non-endometrioid histology (serous, clear cell, undifferentiated, carcinosarcoma): More aggressive adjuvant therapy with combined chemotherapy and radiotherapy 2
• Stage IIB (cervical stromal invasion): Postoperative external pelvic radiotherapy with brachytherapy boost is standard 1, 4
• Typical EBRT dosing: 45 Gy in 25 fractions 3

Advanced Stage Disease (Combined Chemoradiation)

Stage III Disease:

• Stage IIIA (serosa/adnexal involvement or positive cytology): External pelvic radiotherapy or abdomino-pelvic radiotherapy 1
• Stage IIIB (vaginal involvement): Postoperative external radiotherapy with brachytherapy 1
• Stage IIIC (pelvic lymph node involvement): External pelvic radiotherapy followed by brachytherapy boost is standard 1
• Stage IIIC with para-aortic nodes: Extended field radiotherapy including pelvic and para-aortic nodes with or without brachytherapy 1

Stage IV Disease:

• Postoperative external radiotherapy with or without brachytherapy after maximal cytoreduction 4
• Combined chemoradiation increases both recurrence-free and overall survival compared to radiotherapy alone 2, 5

Chemotherapy Integration

For high-risk Stage I and all Stage III-IV disease, combined chemotherapy and radiotherapy is superior to radiotherapy alone:

• Sequential chemotherapy plus radiotherapy reduced risk of relapse or death by 36% (HR 0.64, P=0.04) compared to radiotherapy alone 2
• Cancer-specific survival significantly favored combined modality treatment (HR 0.55, P=0.01) 2
• Standard chemotherapy regimen: Carboplatin/paclitaxel for 3-6 cycles 2, 4
• Platinum-based chemotherapy strongly considered in Stage I Grade 3 with adverse risk factors (age, LVSI, high tumor volume) 2

Critical Caveats and Pitfalls

Common errors to avoid:

• Overtreatment: Using pelvic EBRT when vaginal brachytherapy alone suffices for intermediate-risk disease increases toxicity without survival benefit 2, 6
• Undertreatment: Radiotherapy alone for high-risk features shows inferior outcomes compared to chemoradiation 2
• Inadequate surgical staging: Failing to perform lymphadenectomy prevents accurate risk stratification and may lead to inappropriate treatment decisions 6, 7
• Ignoring LVSI status: Positive LVSI in Stage I disease warrants escalation from brachytherapy alone to pelvic EBRT 2

Important considerations:

• Progestational agents in adjuvant treatment do not increase survival and are not recommended (Level I evidence) 1, 2
• Most recurrences occur within first 3 years, justifying intensive surveillance during this period 1
• Late complications of EBRT are predominantly gastrointestinal; brachytherapy complications include rectal injury and vaginal stenosis 1