Treatment of High-Risk Endometrial Carcinoma: Stages IA2m–IVAm with NSMP High-Grade, p53abn, or ER-Negative Classification
This protocol addresses endometrial carcinoma that meets high-risk criteria based on molecular classification and surgical staging — encompassing early through advanced-stage disease with specific molecular profiles.
Clinical Scenario
High-risk endometrial carcinoma spans four distinct subgroups. Early-stage tumours at stages IA2m, IA3m, or IBm qualify when classified as NSMP high-grade, oestrogen receptor-negative, or p53abn. Stage IIm disease (IIA, IIB, or IIC) meets this threshold under the same molecular criteria. Stage IIIm (IIIA, IIIB, or IIIC) includes NSMP low-grade and ER-positive, as well as NSMP high-grade, ER-negative, or p53abn tumours. Stage IVAm similarly encompasses NSMP low-grade ER-positive alongside NSMP high-grade, ER-negative, and p53abn subtypes.
Surgical Approach (Partial Overview)
For early-stage disease, the standard surgical procedure involves complete uterine removal with bilateral adnexal excision and lymph node evaluation. In patients presenting with clinically evident advanced-stage disease, a more extensive surgical approach targeting maximal tumour removal may be considered when certain feasibility and safety conditions are met.
Complete staging criteria, extent of lymph node evaluation, and post-surgical management are detailed in the full protocol.
References
DOI: 10.1016/S1470-2045(25)00167-6
- High-risk includes four categories (figures 3, 4; red cells).
- First, stages IA2m, IA3m, or IBm NSMP high-grade or oestrogen receptor-negative (or both), or stages IA2m, IA3m, or IBm p53abn endometrial carcinomas.
- Second, stages IIm (IIA, IIB, or IIC) NSMP high-grade or oestrogen receptor-negative (or both), or p53abn endometrial carcinoma.
- Third, stages IIIm (IIIA, IIIB, or IIIC) MMRd, NSMP low-grade and oestrogen receptor-positive, NSMP high-grade or oestrogen receptor-negative (or both), or p53abn endometrial carcinomas.
- Fourth, stages IVAm MMRd, NSMP low-grade and oestrogen receptor-positive, NSMP high-grade or oestrogen receptor-negative (or both), or p53abn endometrial carcinomas.
- Standard surgery for stage I and II endometrial carcinoma is total hysterectomy with bilateral salpingo-oophorectomy and lymph node staging (II, A for stage I and IV, B for stage II).
- In patients with stage III and IV endometrial carcinoma (including carcinosarcoma), surgical cytoreduction—including resection of suspicious lymph nodes—should be considered when complete macroscopic resection is feasible with an acceptable morbidity and quality of life, following full pre-operative staging and discussion by a multidisciplinary team (IV, B).
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