What is the staging and treatment approach for endometrial cancer?

Endometrial Cancer Staging and Treatment

Endometrial cancer is surgically staged using the FIGO 2009 system, which classifies disease based on myometrial invasion depth, cervical stromal involvement, and lymph node metastases, with treatment centered on total hysterectomy and bilateral salpingo-oophorectomy, followed by risk-stratified adjuvant therapy. 1, 2

FIGO 2009 Staging System

The current standard staging system divides endometrial cancer into four main stages 1, 3:

Stage I: Tumor Confined to Uterine Corpus

• Stage IA: No myometrial invasion or invasion to less than half of the myometrium 1, 3
• Stage IB: Invasion equal to or more than half of the myometrium 1, 3

Stage II: Cervical Involvement

• Tumor invades cervical stroma but does not extend beyond the uterus 1, 3

Stage III: Local/Regional Spread

• Stage IIIA: Tumor invades serosa of corpus uteri and/or adnexae 1, 3
• Stage IIIB: Vaginal and/or parametrial involvement 1, 3
• Stage IIIC: Metastasis to pelvic and/or para-aortic lymph nodes 1, 3

Stage IV: Advanced Disease

• Stage IVA: Tumor invasion of bladder and/or bowel mucosa 1, 3
• Stage IVB: Distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes 1, 3

Preoperative Evaluation

Before surgical intervention, obtain the following workup 2, 3:

• Endometrial biopsy for histopathological confirmation 1, 2
• Transvaginal ultrasound to assess endometrial thickness and myometrial invasion 1, 2
• Contrast-enhanced dynamic MRI - this is the most accurate imaging modality for assessing myometrial invasion and cervical stromal invasion 1, 2, 3
• Laboratory tests: complete blood count, liver function tests, renal function profiles 1, 2
• Chest X-ray to evaluate for distant metastases 1, 3
• Clinical and gynecological examination 1, 2

Surgical Treatment Approach

Primary Surgical Management

The cornerstone of treatment is total hysterectomy with bilateral salpingo-oophorectomy, including peritoneal washings and thorough abdominal exploration 1, 2:

• Minimally invasive surgery is preferred over laparotomy, providing equivalent oncologic outcomes with superior perioperative benefits 2
• Robotic approach offers particular benefit in obese patients, with significantly lower major complication rates compared to laparotomy 2

The Lymphadenectomy Controversy

Routine systematic pelvic lymphadenectomy does NOT improve overall survival or disease-free survival in stage I endometrial cancer 1, 2:

• Large randomized trials (Italian study with 514 patients and ASTEC trial) demonstrated no survival benefit from routine lymphadenectomy in stage I disease 1
• However, lymphadenectomy provides critical prognostic information and guides adjuvant therapy decisions 1, 2
• Complete surgical staging with lymphadenectomy is recommended for intermediate-to-high-risk endometrioid cancer (stage IA G3 and IB) 1

Stage-Specific Surgical Approaches

For Stage II disease, the traditional surgical approach consists of radical hysterectomy with bilateral salpingo-oophorectomy and systematic pelvic lymphadenectomy with or without para-aortic lymphadenectomy 1:

• In stage II, lymphadenectomy is essential to guide surgical staging and adjuvant therapy 1

For high-risk cases (serous carcinomas), omentectomy and retroperitoneal lymph node dissection are often recommended, although their effect on survival is unclear 1

Risk Stratification

Approximately 75% of patients present with Stage I disease, which can be subdivided into three risk categories 1, 3:

Low-Risk Disease

• Stage IA, grade 1-2, endometrioid histology 1, 3
• Surgery alone is adequate; no adjuvant therapy required 2, 4

Intermediate-Risk Disease

• Stage IB, grade 1-2, endometrioid histology 3
• Vaginal brachytherapy is recommended to maximize local control with minimal side effects and no impact on quality of life 2, 4

High-Risk Disease

• Stage IB grade 3, deep myometrial invasion with lymphovascular space invasion (LVSI), or non-endometrioid histology 3
• Platinum-based chemotherapy can be considered in stage I G3 with adverse risk factors (patient age, LVSI, high tumor volume) 1

Adjuvant Treatment Framework

Radiotherapy

External beam radiation reduces locoregional recurrence in intermediate-risk disease but does NOT improve overall or disease-specific survival 1:

• Three large randomized studies (PORTEC-1, GOG 99, and ASTEC MRC-NCIC CTG EN.5) failed to demonstrate survival benefit from radiation 1
• PORTEC-2 trial showed vaginal brachytherapy and external beam radiation had equivalent survival outcomes, but quality of life was better with vaginal brachytherapy 1

Chemotherapy

Platinum-based chemotherapy should be considered for stage II-III disease 1:

• Randomized trials comparing chemotherapy with external pelvic radiation in high-risk patients showed no difference in progression-free survival or overall survival 1

Medically Inoperable Patients

When surgery is not feasible due to medical contraindications (5-10% of patients), external radiation therapy with or without intracavitary brachytherapy to the uterus and vagina is suitable 1, 2

Critical Pitfalls to Avoid

• Never perform uterine morcellation without ruling out malignancy - this risks spreading cancerous tissue and compromises pathological assessment 2
• Do not rely on clinical staging alone - it underestimates disease extent in some cases 2
• Avoid incomplete surgery when cancer is suspected 2
• Recognize that discrepancies between preoperative and final pathology occur frequently - be prepared to adjust treatment plans 2
• Do not upstage tumors based on LVSI alone without tissue involvement - for example, LVSI in the outer half of myometrium with invasion confined to inner half remains stage IA 5

Emerging Molecular Classification

Molecular classification (POLE-mutated, microsatellite instability, copy-number-low, copy-number-high) has stronger prognostic impact than histopathological characteristics 4, 6:

• The 2023 FIGO staging update incorporates molecular classification to better reflect tumor biology 6, 7
• When molecular subtype is known, this is recorded in the FIGO stage with "m" for molecular classification and a subscript indicating the specific subtype 6