What is the role of radiation therapy in the treatment of a postmenopausal woman with endometrial carcinoma?

Radiation Therapy in Endometrial Carcinoma: A Risk-Stratified Approach

Radiation therapy in endometrial carcinoma is not routinely indicated for all patients; its use depends entirely on surgical stage and risk stratification, with low-risk disease requiring no adjuvant therapy, intermediate-risk disease benefiting from vaginal brachytherapy alone, and high-risk or advanced disease requiring pelvic external beam radiotherapy, often combined with chemotherapy. 1

Primary Treatment Context

Surgery remains the cornerstone of treatment, with total hysterectomy and bilateral salpingo-oophorectomy as the standard approach for most patients. 2 However, for medically inoperable patients with stage I/II disease who cannot undergo surgery due to obesity, cardiac morbidity, or diabetes, external beam radiotherapy and/or brachytherapy serves as definitive primary treatment. 2

Risk-Stratified Adjuvant Radiotherapy Recommendations

Low-Risk Disease (Stage IA, Grade 1-2, <50% myometrial invasion, LVSI negative)

• No adjuvant therapy is recommended. 1
• Recurrence risk is approximately 10.4%, which does not justify the toxicity of radiation. 1
• Observation alone is the standard of care. 2

Intermediate-Risk Disease (Stage I, Grade 1-2, ≥50% myometrial invasion, LVSI negative)

• Vaginal brachytherapy is the preferred adjuvant treatment. 1
• This approach significantly reduces vaginal/pelvic relapses without impacting overall survival. 2
• Vaginal brachytherapy provides equivalent survival to external beam radiation but with superior quality of life and reduced toxicity. 1
• Recurrence risk is approximately 22.4% for Stage IB disease. 1

High-Intermediate Risk Disease (Age ≥60 years with deeply invasive tumors OR Grade 3)

• Patients with two of three major risk factors (age ≥60 years, deep myometrial invasion, Grade 3) have locoregional relapse rates >15% and benefit from adjuvant pelvic radiotherapy. 2, 1
• For Grade 1-2 with negative LVSI: vaginal brachytherapy is recommended. 1
• For Grade 3 or unequivocally positive LVSI: limited field external beam radiotherapy is recommended. 1

High-Risk Disease (Stage I, Grade 3, ≥50% myometrial invasion)

• Adjuvant external beam radiotherapy with limited fields is recommended to increase locoregional control. 2, 1
• However, pelvic radiotherapy alone does not improve overall survival due to high rates of distant metastases. 2
• Combined chemotherapy and radiotherapy is superior to radiotherapy alone, reducing the risk of relapse or death by 36% (HR 0.64, P=0.04) and improving cancer-specific survival (HR 0.55, P=0.01). 2, 1

Stage II Disease (Cervical involvement)

• Stage IIA (endocervical glandular involvement only): treated as Stage I based on other risk factors. 2
• Stage IIB (cervical stromal invasion): adjuvant pelvic radiotherapy with or without vaginal brachytherapy is recommended after radical hysterectomy. 2

Advanced Disease (Stage III-IV)

• For optimally debulked Stage III-IV disease, combined chemotherapy and radiotherapy is the standard approach. 2, 1
• Chemotherapy alone (doxorubicin-cisplatin) significantly improves both progression-free survival (50% vs 38%, P=0.07) and overall survival (55% vs 42%, P=0.004) compared to whole abdominal radiation. 2
• Pelvic radiotherapy increases pelvic control but does not address systemic disease. 2

Critical Evidence Regarding Survival Impact

A crucial caveat: randomized trials including PORTEC-1, GOG-99, and ASTEC/EN.5 consistently demonstrate that adjuvant radiotherapy reduces locoregional recurrence but does NOT improve overall survival in early-stage disease. 2 This finding underscores why risk stratification is essential—radiotherapy should only be used when the locoregional recurrence risk justifies the treatment toxicity.

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

High-risk non-endometrioid cancers require more aggressive adjuvant therapy with combined chemotherapy and radiotherapy, as recurrence rates are significantly higher than endometrioid types. 1 These histologies behave more aggressively regardless of stage and warrant intensified treatment approaches.

Common Pitfalls to Avoid

• Overtreatment with external beam radiotherapy when vaginal brachytherapy would suffice for intermediate-risk disease. 1 This exposes patients to unnecessary gastrointestinal toxicity without survival benefit.
• Using radiotherapy alone for high-risk Stage I or Stage III disease when combined chemoradiation is indicated. 2, 1 This represents undertreatment with inferior outcomes.
• Failing to recognize that positive LVSI or Grade 3 histology elevates patients to higher risk categories requiring more aggressive treatment. 1
• Administering progestational agents as adjuvant therapy—this does NOT increase survival and is not recommended (Level I evidence). 2, 1

Toxicity Considerations

Late complications of external beam radiotherapy are predominantly gastrointestinal (diarrhea, proctitis, bowel obstruction), while brachytherapy complications include rectal injury and vaginal stenosis. 1 This toxicity profile explains why vaginal brachytherapy is preferred over external beam radiation when oncologically appropriate—it provides equivalent local control with significantly better quality of life. 1