Cancer of the endometrium: 2023 FIGO staging^*¶

FIGO: International Federation of Gynecology and Obstetrics; ITCs: isolated tumor cells; EEC: endometrioid carcinoma; LVSI: lymphovascular space involvement; SLN: sentinel lymph node; ESGO: European Society of Gynaecological Oncology; ESTRO: European SocieTy for Radiotherapy and Oncology; ESP: European Society of Pathology.

* Endometrial cancer is surgically staged and pathologically examined. In all stages, the grade of the lesion, the histological type and LVSI must be recorded. If available and feasible, molecular classification testing (POLEmut, MMRd, NSMP, p53abn) is encouraged in all patients with endometrial cancer for prognostic risk-group stratification and as factors that might influence adjuvant and systemic treatment decisions.

¶ In early endometrial cancer, the standard surgery is a total hysterectomy with bilateral salpingo-oophorectomy via a minimally invasive laparoscopic approach. Staging procedures include infracolic omentectomy in specific histological subtypes, such as serous and undifferentiated endometrial carcinoma, as well as carcinosarcoma, due to the high risk of microscopic omental metastases. Lymph node staging should be performed in patients with intermediate-high/high-risk patients. SLN biopsy is an adequate alternative to systematic lymphadenectomy for staging proposes. SLN biopsy can also be considered in low-/low-intermediate-risk patients to rule out occult lymph node metastases and to identify disease truly confined to the uterus. Thus, the ESGO-ESTRO-ESP guidelines allow an approach of SLN in all patients with endometrial carcinoma, which is endorsed by FIGO. In assumed early endometrial cancer, an SLN biopsy is an adequate alternative to systematic lymphadenectomy in high-intermediate and high-risk cases for the purpose of lymph node staging and can also be considered in low-/intermediate-risk disease to rule out occult lymph node metastases. An SLN biopsy should be done in association with thorough (ultrastaging) staging as it will increase the detection of low-volume disease in lymph nodes.

Δ Low-grade EECs involving both the endometrium and the ovary are considered to have a good prognosis, and no adjuvant treatment is recommended if all the below criteria are met. Disease limited to low-grade endometrioid carcinomas involving the endometrium and ovaries (Stage IA3) must be distinguished from extensive spread of the endometrial carcinoma to the ovary (Stage IIIA1), by the following criteria: (1) no more than superficial myometrial invasion is present (<50%); (2) absence of extensive/substantial LVSI; (3) absence of additional metastases; and (4) the ovarian tumor is unilateral, limited to the ovary, without capsule invasion/rupture (equivalent to pT1a).

◊ LVSI as defined in WHO 2021: extensive/substantial, ≥5 vessels involved.

• Serous adenocarcinomas, clear cell adenocarcinomas, mesonephric-like carcinomas, gastrointestinal-type mucinous endometrial carcinoma, undifferentiated carcinomas, and carcinosarcomas are considered high-grade by definition. For EECs, grade is based on the proportion of solid areas: low grade = grade 1 (≤5%) and grade 2 (6 to 50%), and high grade = grade 3 (>50%). Nuclear atypia excessive for the grade raises the grade of a grade 1 or 2 tumor by one. The presence of unusual nuclear atypia in an architecturally low-grade tumor should prompt the evaluation of p53 and consideration of serous carcinoma. Adenocarcinomas with squamous differentiation are graded according to the microscopic features of the glandular component.
• Non-aggressive histological types are composed of low-grade (grade 1 and 2) EECs. Aggressive histological types are composed of high-grade EECs (grade 3), serous, clear cell, undifferentiated, mixed, mesonephric-like, gastrointestinal mucinous type carcinomas, and carcinosarcomas.
• It should be noted that high-grade EECs (grade 3) are a prognostically, clinically, and molecularly heterogenous disease, and the tumor type that benefits most from applying molecular classification for improved prognostication and for treatment decision-making. Without molecular classification, high-grade EECs cannot appropriately be allocated to a risk group and thus molecular profiling is particularly recommended in these patients. For practical purposes and to avoid undertreatment of patients, if the molecular classification is unknown, high-grade EECs were grouped together with the aggressive histological types in the actual FIGO classification.

¥ Micrometastases are considered to be metastatic involvement (pN1 [mi]). The prognostic significance of ITCs is unclear. The presence of ITCs should be documented and is regarded as pN0(i+). According to TNM8, macrometastases are >2 mm in size, micrometastases are >0.2 to 2 mm and/or >200 cells, and isolated tumor cells are ≤0.2 mm and ≤200 cells. Based on staging established by FIGO and the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th ed (Springer 2017).