What is the recommended adjuvant treatment for a 65-year-old woman with intermediate to high-risk endometrial (uterine lining) carcinoma?

Adjuvant Treatment for Intermediate-High Risk Endometrial Carcinoma

For a 65-year-old woman with intermediate-high risk endometrial carcinoma, the recommended adjuvant treatment is vaginal brachytherapy for intermediate-risk disease, or combined chemotherapy (carboplatin/paclitaxel) plus radiotherapy for high-risk disease, based on specific pathologic features including grade, depth of myometrial invasion, and lymphovascular space invasion status. 1

Risk Stratification Framework

The treatment decision hinges on precise risk categorization after complete surgical staging:

Intermediate-Risk Disease

Vaginal brachytherapy alone is the standard adjuvant treatment for patients with Stage I endometrioid carcinoma, Grade 1-2, with ≥50% myometrial invasion and negative lymphovascular space invasion (LVSI). 1

• The PORTEC-2 trial demonstrated that vaginal brachytherapy provides equivalent overall survival and progression-free survival compared to external beam radiation, but with superior quality of life. 2
• This approach reduces locoregional recurrence without the toxicity burden of pelvic radiation. 2
• Recurrence risk for Stage IB disease is approximately 22.4%. 1

High-Intermediate Risk Disease

Limited field external beam radiotherapy (EBRT) is recommended for patients with Grade 3 tumors or unequivocally positive LVSI, even with surgical nodal staging showing negative nodes. 1

• Patients with two of three major risk factors (age ≥60 years, deeply invasive tumors, or Grade 3) have locoregional relapse rates >15% and benefit from adjuvant pelvic radiotherapy. 2
• At age 65, this patient meets one age-related risk criterion, making additional pathologic features critical for decision-making. 2

High-Risk Disease

Combined chemotherapy and radiotherapy is the evidence-based standard for Stage I Grade 3 with ≥50% myometrial invasion, or any non-endometrioid histology (serous, clear cell, undifferentiated, carcinosarcoma). 1, 3

• Two randomized trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) demonstrated that sequential chemotherapy plus radiotherapy reduced the risk of relapse or death by 36% (HR 0.64,95% CI 0.41-0.99; P=0.04) compared to radiotherapy alone. 2
• Cancer-specific survival significantly favored combined modality treatment (HR 0.55,95% CI 0.35-0.88; P=0.01). 2
• The standard chemotherapy regimen is carboplatin/paclitaxel for 3-6 cycles. 1, 4

Specific Treatment Algorithms

For Endometrioid Histology:

• Grade 1-2, <50% invasion, LVSI negative: Observation only 1
• Grade 1-2, ≥50% invasion, LVSI negative: Vaginal brachytherapy 1
• Grade 1-2, ≥50% invasion, LVSI positive: Limited field EBRT 1
• Grade 3, ≥50% invasion: EBRT with limited fields, consider adding chemotherapy 1
• Grade 3 with additional adverse features (age, LVSI, high tumor volume): Combined chemotherapy and radiotherapy 2

For Non-Endometrioid Histology:

All serous, clear cell, undifferentiated carcinomas, and carcinosarcomas require aggressive adjuvant therapy with combined chemotherapy and radiotherapy, regardless of stage, due to significantly higher recurrence rates. 1, 3

Chemotherapy Considerations

Platinum-based chemotherapy should be strongly considered in Stage I Grade 3 with adverse risk factors including patient age (this 65-year-old qualifies), lymphovascular space invasion, and high tumor volume. 2

• A Japanese multicenter trial showed chemotherapy appeared superior to pelvic radiotherapy in patients aged >70 years with outer half myometrial invasion and Grade 3 disease, suggesting age-related benefit. 2
• The standard regimen is carboplatin (AUC 6) plus paclitaxel (175 mg/m²) every 21 days for 3-6 cycles. 1, 4

Critical Pitfalls to Avoid

Overtreatment with external beam radiotherapy when vaginal brachytherapy would suffice is a common error in intermediate-risk disease, leading to unnecessary toxicity without survival benefit. 1

Underestimating the importance of surgical staging for guiding adjuvant therapy decisions can result in inappropriate treatment selection. 1

Failing to recognize that Grade 3 histology or positive LVSI elevates risk and may warrant more aggressive adjuvant treatment approaches beyond simple observation or brachytherapy alone. 1

Not considering combined modality therapy for high-risk features represents undertreatment, as radiotherapy alone has shown inferior outcomes compared to chemoradiation in high-risk populations. 2

Evidence Strength Considerations

The recommendation against progestins in adjuvant treatment is Level I evidence and should not be used. 2

While the GOG-249 trial (2019) showed no superiority of vaginal brachytherapy plus chemotherapy over pelvic radiotherapy alone in high-intermediate and high-risk early-stage disease, pelvic nodal recurrences were more common with the chemotherapy approach (9% vs 4%), supporting continued use of pelvic radiotherapy in appropriate cases. 5