What is the staging process for endometrial cancer, including diagnosis, treatment, and management options?

Staging of Endometrial Cancer

Endometrial cancer is staged surgically using the FIGO 2009 system, which requires total hysterectomy with bilateral salpingo-oophorectomy, assessment of myometrial invasion depth, and systematic pelvic and para-aortic lymphadenectomy in most patients, though sentinel lymph node mapping is an acceptable alternative. 1, 2

FIGO 2009 Staging System (Current Standard)

The International Federation of Gynecology and Obstetrics (FIGO) transitioned to surgical staging in 1988 and revised it in 2009, which remains the current standard despite a 2023 update being introduced 1, 3:

Stage Definitions

• Stage IA: No myometrial invasion or invasion to less than half of the myometrium 1, 2
• Stage IB: Invasion equal to or more than half of the myometrium 1, 2
• Stage II: Tumor invasion of cervical stroma but does not extend beyond the uterus 1, 2
• Stage IIIA: Tumor invades serosa of the corpus uteri and/or adnexae (ovaries/fallopian tubes) 1, 4
• Stage IIIB: Vaginal and/or parametrial involvement 1, 4
• Stage IIIC1: Positive pelvic lymph nodes 1, 4
• Stage IIIC2: Positive para-aortic lymph nodes with or without pelvic nodes 1, 4
• Stage IVA: Tumor invasion of bladder and/or bowel mucosa 5
• Stage IVB: Distant metastases including intra-abdominal or inguinal lymph nodes 5

Preoperative Diagnostic Workup

Essential Components

• Office endometrial biopsy as the initial diagnostic step (diagnostic in 90% of cases, but has 10% false-negative rate) 2
• Complete blood count, liver and renal function tests 5, 2
• Chest X-ray 5, 2
• Clinical and gynecological examination with transvaginal ultrasound 5

Advanced Imaging When Indicated

• Contrast-enhanced dynamic MRI is the best tool to assess cervical involvement when suspected 5, 2
• Abdominal CT scan for investigating extrapelvic disease 5
• FDG-PET/CT may be useful to detect distant metastases accurately 5
• MRI accuracy for myometrial invasion is comparable to ultrasound, though ultrasound is operator-dependent with accuracies varying between 77% and 91% 5

Surgical Staging Requirements

Standard Surgical Procedure

The minimal surgical staging procedure includes: 5, 2

• Total hysterectomy with bilateral salpingo-oophorectomy 5
• Acquisition of peritoneal fluid or washings 5, 4
• Thorough exploration of the abdominal cavity 5, 4
• Assessment of depth of myometrial invasion (ratio of invasion to total myometrial thickness) 5, 2
• Evaluation of cervical stromal or glandular involvement 2

Lymph Node Assessment

The lymphadenectomy controversy is critical to understand: Systematic pelvic and para-aortic lymphadenectomy provides prognostic information and helps tailor adjuvant therapy, but randomized trials failed to show survival or relapse-free survival benefit in stage I endometrial cancer 5, 1.

Sentinel lymph node mapping is an acceptable alternative to complete lymphadenectomy, with a sensitivity of 97.2% and negative predictive value of 99.6% when using indocyanine green and following NCCN surgical algorithm 1, 2. This approach reduces surgical morbidity while maintaining diagnostic accuracy.

Complete lymphadenectomy should be performed in intermediate-high-risk endometrioid cancer (stage IA G3 and IB) 5. Lymphadenectomy can be omitted in patients assessed intraoperatively to be at low risk for lymph node metastasis (<2 cm grade 1 tumors with superficial myometrial invasion) 6.

Surgical Approach Options

Minimally invasive surgery (laparoscopy or robotic-assisted) provides equivalent disease-free survival and overall survival compared to laparotomy, with additional benefits including shorter hospital stay, less pain medication use, lower complication rates, and improved quality of life 5. The GOG LAP2 study demonstrated similar operative outcomes between minimally invasive surgery and laparotomy 5.

Robotic surgery shows particular benefit in obese women, with significantly lower major complication rates (6.4% versus 20%) compared to laparotomy, particularly related to wound complications and infections 5.

Pathologic Assessment Requirements

The pathology report must document 2:

• Ratio of depth of myometrial/stromal invasion to myometrial thickness 2
• Cervical stromal or glandular involvement 2
• Tumor size and location 2
• Histologic subtype with grade 2
• Lymphovascular space invasion (LVSI) 2
• Level of nodal involvement 2

Risk Stratification Based on Stage

Approximately 75% of patients present with Stage I disease, which can be subdivided into three risk categories 5, 1, 2:

Low-Risk

• Stage IA, grade 1-2, endometrioid histology, no LVSI 5, 1
• No adjuvant therapy recommended 5

Intermediate-Risk

• Stage IB, grade 1-2, endometrioid histology 1
• Adjuvant pelvic radiotherapy significantly reduces pelvic/vaginal relapses but has no impact on overall survival 5
• In patients with two of three major risk factors (age ≥60 years, deeply invasive or G3 tumors), loco-regional relapse rate is >15%, and adjuvant pelvic and/or intravaginal radiotherapy may be recommended 5

High-Risk

• Stage IB grade 3, deep myometrial invasion with LVSI, or non-endometrioid histology 1
• Pelvic radiotherapy is recommended to increase loco-regional control 5
• Recent studies have shown survival benefit of adjuvant chemotherapy 5

Critical Pitfalls to Avoid

• Never rely on a negative office endometrial biopsy in a symptomatic patient due to the 10% false-negative rate; fractional dilation and curettage is required if symptoms persist 2
• Clinical staging alone is inadequate, as it understages disease in 15-20% of patients 2
• Do not upstage tumors based on LVSI alone without tissue involvement; for example, LVSI in the outer half of myometrium in a carcinoma with myoinvasion confined to the inner half remains FIGO stage IA 7
• Avoid routine systematic lymphadenectomy in all Stage I patients, as randomized trials showed no improvement in disease-free or overall survival 2

Advanced Stage Management

Stage II

• Stage IIA (endocervical glandular involvement only): treated as stage I 5
• Stage IIB (cervical stromal invasion): extended radical hysterectomy, bilateral salpingo-oophorectomy and lymph node dissection 5

Stage III-IV

For optimally debulked stage III and IV disease, cisplatin and doxorubicin combination chemotherapy significantly improves progression-free survival and overall survival compared to whole abdominal radiation therapy with pelvic boost 5. Carboplatin and paclitaxel is an alternative option due to toxicity considerations 5, 4.