FIGO Grading of Endometrial Cancer
Endometrial cancer is graded using a three-tiered histological system based on the percentage of solid growth pattern, where Grade 1 (G1) has ≤5% solid growth, Grade 2 (G2) has 5-50% solid growth, and Grade 3 (G3) has >50% solid growth, with notable nuclear atypia upgrading G1 or G2 tumors by one grade. 1
FIGO Histological Grading System
The grading applies specifically to endometrioid carcinomas and is defined as follows:
- Grade 1 (G1): Non-squamous, non-morular solid growth pattern comprises ≤5% of the tumor 1
- Grade 2 (G2): Non-squamous, non-morular solid growth pattern comprises 5-50% of the tumor 1
- Grade 3 (G3): Non-squamous, non-morular solid growth pattern comprises >50% of the tumor 1
Critical caveat: If notable nuclear atypia is present that is inappropriate for the architectural grade, the tumor grade must be raised by one level (e.g., G1 becomes G2, G2 becomes G3) 1. This nuclear grading override is frequently missed and can significantly alter treatment decisions.
FIGO Staging System (2009)
The FIGO 2009 staging system remains the most widely used surgical staging classification 1, 2:
Stage I: Confined to the uterus
- Stage Ia: Tumor limited to the endometrium 1
- Stage Ib: Invasion to less than half of the myometrium 1
- Stage Ic: Invasion to more than half of the myometrium 1
Stage II: Extension to the uterine cervix
Stage III: Extension beyond the uterus
- Stage IIIa: Tumor invades serosa and/or adnexa, and/or positive peritoneal cytology 1
- Stage IIIb: Vaginal involvement 1
- Stage IIIc: Metastasis to pelvic or para-aortic lymph nodes 1
Stage IV: Invasion in neighboring organs or distant metastases
- Stage IVa: Tumor invasion of the bladder and/or bowel mucosa 1
- Stage IVb: Distant metastases including intra-abdominal or inguinal lymph nodes 1
Risk Stratification Based on Stage and Grade
Approximately 75% of patients present with Stage I disease, which is subdivided into three prognostic risk categories that directly determine adjuvant therapy 1, 2:
Low-Risk Disease
- Stage Ia/Ib, Grade 1 or 2, endometrioid histology 1
- Management: No adjuvant therapy required after surgery 1, 3
Intermediate-Risk Disease
- Stage Ic, Grade 1 or 2, endometrioid histology 1
- Stage Ia/Ib, Grade 3, endometrioid histology 1
- Management: Adjuvant pelvic radiotherapy significantly reduces pelvic/vaginal relapses but does not improve overall survival 1. For patients ≥60 years with deeply invasive G1-G2 or superficially invasive G3 tumors where locoregional relapse risk exceeds 15%, adjuvant radiotherapy is recommended 1
High-Risk Disease
- Stage Ic, Grade 3, endometrioid histology 1
- Any stage (Ia, Ib, or Ic) with serous, clear cell, small cell, or undifferentiated histology 1
- Management: Pelvic radiotherapy for locoregional control plus platinum-based chemotherapy, which significantly improves overall survival and progression-free survival compared to radiotherapy alone 1, 2
Impact on Surgical Management
The grade and stage directly determine the extent of surgical staging 1, 2:
- All patients: Total hysterectomy with bilateral salpingo-oophorectomy, peritoneal washings, thorough abdominal exploration 1, 2
- High-risk cases (Grade 3, non-endometrioid histology): Retroperitoneal lymph node dissection and omentectomy (specifically for serous carcinomas) are recommended, though survival benefit remains debated 1
Important Prognostic Factors Beyond Grade
Established independent prognostic factors that work in conjunction with FIGO stage and histological grade include 1:
- Depth of myometrial invasion 1
- Histological type 1, 4
- Tumor diameter 1
- Lymphovascular space involvement 1
- Endocervical stromal invasion 1
- Patient age 1
Critical Pitfalls in Grading
Preoperative grading is unreliable: The preoperative histological diagnosis (type and grade) based on endometrial sampling changes at final histological evaluation in up to 25% of cases 1. This means treatment planning must remain flexible until final pathology is available.
Frozen section limitations: There is no fully reliable method to assess an individual patient's risk category intraoperatively using frozen section 1. Definitive surgical decisions requiring lymphadenectomy should be based on preoperative risk assessment rather than intraoperative frozen section alone.
Special Histological Considerations
Serous and clear cell carcinomas are automatically classified as high-risk regardless of stage or grade, requiring aggressive treatment with chemotherapy and consideration of pelvic radiotherapy 1, 4. These histologies exhibit different biological behavior with 70% having extrauterine spread at presentation 4.
Carcinosarcomas are now considered a special, poor-prognosis subtype of endometrial carcinoma rather than a separate entity 1.
Emerging Molecular Classification
While the traditional FIGO grading system remains standard, molecular classification is increasingly recognized as prognostically significant 2, 4, 5. The four genomic subtypes (POLE-mutated, mismatch repair deficient, copy number-low/p53 wild-type, copy number-high/p53 abnormal) provide independent prognostic information beyond conventional grading 4, 5. However, routine molecular classification is not yet required for standard clinical practice 5.