What is the recommended adjuvant treatment for a patient with uterine endometrioid adenocarcinoma with deep (>2/3) myometrial invasion and no surgical nodal assessment?

Management of Endometrioid Adenocarcinoma with Deep Myometrial Invasion and No Nodal Staging

For endometrioid adenocarcinoma with >2/3 myometrial invasion and no surgical nodal assessment, adjuvant external beam radiotherapy (EBRT) is recommended, with combined chemotherapy plus EBRT offering greater evidence of benefit than either modality alone. 1

Risk Classification

Your patient falls into the high-risk category based on deep myometrial invasion (>2/3 = >50%), regardless of tumor grade or LVSI status. 1 The absence of nodal staging is critical here—it means occult nodal disease cannot be ruled out, which directly influences treatment intensity. 1

Treatment Algorithm Based on Tumor Grade

If Grade 1-2 (Lower High-Risk)

• Adjuvant EBRT is the baseline recommendation for pelvic control when nodes were not assessed. 1
• Combined chemotherapy plus EBRT can be considered, though the evidence is stronger for Grade 3 disease. 1
• If nodes had been assessed and were negative, vaginal brachytherapy alone would have been an option for G1-2 without LVSI. 1

If Grade 3 (Higher High-Risk)

• Combined chemotherapy plus EBRT is strongly recommended over either modality alone, as this combination addresses both locoregional and distant recurrence risk. 1, 2
• The standard regimen consists of EBRT 48.6 Gy with concurrent cisplatin 50 mg/m² for two cycles, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m². 2
• Grade 3 with deep invasion carries a 48% 5-year distant metastasis-free survival when both risk factors are present, compared to 89% with only one factor. 3
• Approximately 80% of recurrences in stage IB/IC Grade 3 disease are extra-pelvic, occurring at a median of 22.5 months, with 75% mortality among those who recur. 4

Critical Importance of LVSI Status

You must determine LVSI status from the final pathology report. 1, 5

• LVSI-negative: Maintains high-risk classification; proceed with EBRT ± chemotherapy based on grade as above. 1
• LVSI-positive: Substantially increases distant recurrence risk and strengthens the indication for combined chemoradiotherapy, particularly for Grade 3 disease. 5, 3
• LVSI presence independently predicts systemic failure and is a pivotal factor in treatment escalation decisions. 3, 4

Why Nodal Staging Matters

The absence of surgical nodal assessment creates uncertainty about true stage (could be occult stage IIIC). 1 Had comprehensive pelvic and para-aortic lymphadenectomy been performed and nodes were negative:

• Grade 1-2 without LVSI: Vaginal brachytherapy alone would suffice. 1
• Grade 3 or LVSI-positive: Limited-field EBRT would be recommended. 1
• The detection rate for nodal metastases in deep myometrial invasion ranges from 2.6-5.1% depending on assessment method. 6

Molecular Classification Considerations

If molecular profiling is available, refine your treatment decision: 2, 5

• p53-abnormal tumors: Strong indication for chemotherapy (23% absolute recurrence-free survival improvement). 2, 5
• POLE-ultramutated tumors: Excellent prognosis without chemotherapy; may not require intensive treatment even with deep invasion. 2, 5
• MMR-deficient/NSMP tumors: Follow standard risk-based algorithms as outlined above. 2

Common Pitfalls to Avoid

• Do not use observation alone when nodes are unstaged and myometrial invasion is deep—this is inadequate for high-risk disease. 1
• Do not use vaginal brachytherapy alone without nodal assessment in deep invasion cases; this is only appropriate for intermediate-risk disease or node-negative high-risk disease. 1, 7
• Do not rely on pre-operative biopsy grade—base all decisions on final surgical pathology, as grade can be upgraded in 20-30% of cases. 7
• Do not delay treatment beyond 12 weeks post-surgery if radiation is planned. 7

Toxicity Considerations

Combined chemoradiotherapy carries significant toxicity: 2

• Grade 3+ adverse events occur in 60% of patients (versus 12% with radiation alone). 2
• Most grade 3 events are hematologic (45%). 2
• Persistent sensory neuropathy occurs in 6% at 5 years. 2
• However, the 5-year overall survival benefit is 81.4% versus 76.1% with radiation alone (HR 0.70, p=0.034). 2

Summary Treatment Pathway

1. Confirm final pathology: Grade, depth of invasion (>2/3), LVSI status. 1, 5
2. Obtain molecular profiling if available (p53, POLE, MMR status). 2, 5
3. Grade 1-2, LVSI-negative: Adjuvant EBRT; consider adding chemotherapy. 1
4. Grade 3 OR LVSI-positive: Combined chemotherapy plus EBRT (standard regimen: EBRT 48.6 Gy + concurrent cisplatin → carboplatin/paclitaxel × 4 cycles). 1, 2
5. Initiate treatment within 12 weeks of surgery. 7