Staging and Management of Endometrial Cancer

Introduction to Staging

• The International Federation of Gynecology and Obstetrics (FIGO) recommends surgical staging of endometrial cancer using the FIGO 2009 system, which includes total hysterectomy with bilateral salpingo-oophorectomy, assessment of myometrial invasion depth, and systematic pelvic and para-aortic lymphadenectomy in most patients 1, 2
• The FIGO 2009 system is the current standard for staging endometrial cancer, despite a 2023 update being introduced 1, 2

Staging Definitions

• Stage IA is defined as no myometrial invasion or invasion to less than half of the myometrium 1, 2
• Stage IB is defined as invasion equal to or more than half of the myometrium 1, 2
• Stage II is defined as tumor invasion of cervical stroma but does not extend beyond the uterus 1, 2
• Stage IIIA is defined as tumor invades serosa of the corpus uteri and/or adnexae (ovaries/fallopian tubes) 1, 3
• Stage IIIB is defined as vaginal and/or parametrial involvement 1, 3
• Stage IIIC1 is defined as positive pelvic lymph nodes 1, 3
• Stage IIIC2 is defined as positive para-aortic lymph nodes with or without pelvic nodes 1, 3
• Stage IVA is defined as tumor invasion of bladder and/or bowel mucosa 4, 5
• Stage IVB is defined as distant metastases including intra-abdominal or inguinal lymph nodes 4, 5

Preoperative Diagnostic Workup

• Office endometrial biopsy is the initial diagnostic step, with a diagnostic accuracy of 90% but a 10% false-negative rate 2
• Complete blood count, liver and renal function tests, and chest X-ray are essential components of the preoperative workup 4, 2
• Clinical and gynecological examination with transvaginal ultrasound is recommended 5, 6
• Contrast-enhanced dynamic MRI is the best tool to assess cervical involvement when suspected 4, 6, 2
• Abdominal CT scan is recommended for investigating extrapelvic disease 5, 6
• FDG-PET/CT may be useful to detect distant metastases accurately 5, 6

Surgical Staging Requirements

• The minimal surgical staging procedure includes total hysterectomy with bilateral salpingo-oophorectomy, acquisition of peritoneal fluid or washings, thorough exploration of the abdominal cavity, assessment of depth of myometrial invasion, and evaluation of cervical stromal or glandular involvement 4, 2
• 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 7, 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

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, 7
• 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, 7

Pathologic Assessment Requirements

• The pathology report must document the ratio of depth of myometrial/stromal invasion to myometrial thickness, cervical stromal or glandular involvement, tumor size and location, histologic subtype with grade, lymphovascular space invasion (LVSI), and level of nodal involvement 2, 4

Risk Stratification Based on Stage

• Approximately 75% of patients present with Stage I disease, which can be subdivided into three risk categories: low-risk, intermediate-risk, and high-risk 8, 1, 2
• Low-risk patients have Stage IA, grade 1-2, endometrioid histology, and no LVSI, and do not require adjuvant therapy 8, 1
• Intermediate-risk patients have Stage IB, grade 1-2, endometrioid histology, and may benefit from adjuvant pelvic radiotherapy 1, 8
• High-risk patients have Stage IB grade 3, deep myometrial invasion with LVSI, or non-endometrioid histology, and may benefit from adjuvant chemotherapy and pelvic radiotherapy 1, 8

Advanced Stage Management

• 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 8
• Carboplatin and paclitaxel is an alternative option due to toxicity considerations 8, 3

FIGO Grading and Staging in Endometrial Cancer – Evidence‑Based Guidelines

FIGO Grading System

• Definition – FIGO grade evaluates tumor differentiation by architectural pattern and nuclear atypia on histologic specimens. 9
• Grade 1 – Well‑differentiated tumor with ≤ 5 % solid (non‑squamous, non‑morula) growth. 9
• Grade 2 – Moderately differentiated tumor with 5–50 % solid growth. 9
• Grade 3 – Poorly differentiated tumor with > 50 % solid growth. 9
• Nuclear‑atypia upgrade rule – When marked nuclear atypia is present that is discordant with the architectural grade, the tumor is upgraded by one grade level (e.g., G1→G2, G2→G3). 9
• Specimen source – Grade is assigned from either pre‑operative endometrial biopsy or the final surgical pathology specimen. [9][10]
• Prognostic relevance – Grade is an independent predictor of outcome and, together with stage, drives risk stratification. 9
• Biopsy‑to‑final‑pathology discordance – Pre‑operative biopsy grade may differ from the final surgical grade in up to ~25 % of cases. 9

FIGO Staging System (2009)

• Purpose – Surgical‑pathologic FIGO stage describes the anatomic extent of disease based on operative and pathological findings. 10
• Historical improvement – The 2009 FIGO system replaced the 1970 clinical staging, which mis‑staged 15–20 % of patients. 10
• Stage I (uterine‑confined)
  
  • IA – Myometrial invasion < 50 %. 10
  • IB – Myometrial invasion ≥ 50 %. 10
• Stage II – Tumor invades cervical stromal tissue but does not extend beyond the uterus; isolated endocervical glandular involvement without stromal invasion remains Stage I. 10
• Stage III (local/regional spread)
  
  • IIIC1 – Positive pelvic lymph nodes only. 10
  • IIIC2 – Positive para‑aortic lymph nodes, with or without pelvic node involvement. 10
• Stage IV (distant spread) – Not detailed here because citations focus on earlier stages.
• Peritoneal cytology – Positive peritoneal washings no longer upstage disease in the 2009 FIGO system, although they remain an independent adverse risk factor. 10
• Mandatory surgical staging – Requires total hysterectomy with bilateral salpingo‑oophorectomy, peritoneal washings, thorough abdominal exploration, and assessment of myometrial invasion depth. [9][10]

Risk Stratification Combining Grade and Stage

• Population distribution – Approximately 75 % of patients present with Stage I disease. 9
• Low‑risk group – Stage IA, Grade 1–2, endometrioid histology. 9
• Intermediate‑risk group – Stage IB, Grade 1–2 or Stage IA, Grade 3, endometrioid histology. 9
• High‑risk group – Stage IB, Grade 3 or any stage with serous, clear‑cell, or undifferentiated histology. 9

Common Pitfalls (Guideline Recommendations)

• Do not equate pre‑operative biopsy grade with final pathology grade – discordance occurs in up to ~25 % of cases. 9
• Do not upstage disease based solely on positive peritoneal cytology – cytology does not alter FIGO stage in the 2009 system. 10
• Do not classify endocervical glandular involvement without stromal invasion as Stage II – such cases remain Stage I. 10