What is the approach to a patient with endometrial cancer (EC)?

Approach to Endometrial Cancer

The management of endometrial cancer begins with comprehensive surgical staging via total hysterectomy with bilateral salpingo-oophorectomy, preceded by thorough preoperative evaluation including endometrial biopsy, transvaginal ultrasound, pelvic MRI, and molecular classification of the tumor. 1

Initial Diagnostic Workup

Mandatory Preoperative Evaluation

• Obtain tissue diagnosis through endometrial biopsy (Pipelle) or dilation and curettage (D&C) before any surgical intervention 1
• Perform transvaginal ultrasound to assess endometrial thickness, myometrial invasion, and rule out ovarian involvement 1
• Order pelvic MRI with dynamic contrast enhancement - this is the most accurate imaging modality for assessing myometrial invasion (98% accuracy) and cervical stromal invasion (90% accuracy) 1
• Complete laboratory workup: full blood count, liver function tests, renal function profiles 1
• Conduct clinical and gynecological examination to assess disease extent 1

Critical Pathology Requirements

All endometrial cancer specimens must undergo molecular classification through immunohistochemistry for p53 and MMR proteins (MLH1, PMS2, MSH2, MSH6) combined with POLE hotspot sequencing, regardless of histological type 1. This molecular profiling has stronger prognostic impact than traditional histopathological characteristics and guides adjuvant therapy decisions 2.

Additional Imaging for High-Risk Disease

• Consider FDG-PET-CT for patients with suspected extrauterine disease - it demonstrates high specificity for detecting distant metastases and lymph node involvement 1
• Order chest and abdominal CT scan when clinical features suggest advanced disease (high-grade histology, deep myometrial invasion, non-endometrioid histology) 1

Surgical Management

Standard Surgical Approach

Perform total hysterectomy with bilateral salpingo-oophorectomy as the cornerstone of treatment 1. The surgical approach should be:

• Minimally invasive surgery (laparoscopic or robotic) is preferred over laparotomy, providing equivalent oncologic outcomes with superior perioperative benefits: shorter hospital stay, less pain, lower complication rates, and improved quality of life 1
• Robotic approach offers particular benefit in obese patients, with significantly lower major complication rates (6.4% vs 20%) compared to laparotomy 1

Lymphadenectomy Considerations

The role of systematic lymphadenectomy remains nuanced:

• Routine systematic pelvic lymphadenectomy does NOT improve overall survival or disease-free survival in stage I endometrial cancer based on large randomized trials (ASTEC, Italian study) 1
• However, lymphadenectomy provides critical prognostic information and guides adjuvant therapy decisions 1
• Recommend complete surgical staging (pelvic ± para-aortic lymphadenectomy) for intermediate-to-high-risk disease: stage IA grade 3, stage IB, non-endometrioid histology, deep myometrial invasion, or lymphovascular space invasion 1
• Use preoperative risk stratification (via expert ultrasound, MRI, or intraoperative frozen section) to determine which patients require lymphadenectomy 1

Special Surgical Situations

• Ovarian preservation may be considered in premenopausal patients with FIGO stage IA grade 1 endometrioid cancer, but is contraindicated in Lynch syndrome or BRCA mutation carriers 1
• Staging omentectomy should be performed for serous carcinoma and carcinosarcoma 1
• Modified radical hysterectomy is indicated for stage II disease with macroscopic cervical involvement 3

Risk Stratification

After surgical staging, stratify patients based on:

• FIGO stage (surgical staging system) 1
• Histological type and grade 1
• Depth of myometrial invasion (≥50% vs <50%) 1
• Lymphovascular space invasion 1
• Lymph node status 1
• Molecular classification (POLE ultra-mutated, microsatellite instable, copy-number-low, copy-number-high) 1, 2

Adjuvant Therapy Framework

Low-Risk Disease (Stage IA Grade 1-2)

• Surgery alone is adequate - no adjuvant therapy required 1, 2

Intermediate-Risk Disease

• Vaginal brachytherapy is recommended to maximize local control with minimal side effects and no impact on quality of life 1, 2
• External beam radiation reduces locoregional recurrence but does NOT improve overall survival 1, 2

High-Risk Disease (Stage I-II with risk factors)

• Pelvic radiotherapy is supported by recent randomized trials for stage I-II disease with adverse features 2

Advanced Disease (Stage III, Serous Histology)

• Combined chemotherapy and radiotherapy increases both recurrence-free and overall survival compared to either modality alone 2
• Provides superior pelvic and para-aortic nodal control 2

Medically Inoperable Patients

For patients with significant comorbidities (obesity, cardiac disease, diabetes) precluding surgery:

• External beam radiotherapy and/or brachytherapy are acceptable alternatives 1
• Consider medroxyprogesterone acetate for palliative treatment of inoperable or metastatic disease 4

Critical Pitfalls to Avoid

• Never perform uterine morcellation without ruling out malignancy - this risks spreading cancerous tissue and compromises pathological assessment 1
• Do not rely on clinical staging alone - it underestimates disease extent in 13-22% of cases 3
• Avoid incomplete surgery (subtotal hysterectomy or ovarian preservation in postmenopausal women) when cancer is suspected 1
• Recognize discrepancies between preoperative and final pathology occur frequently - be prepared to adjust treatment plans 1