Treatment of High-Risk Endometrial Carcinoma: Stages IA2m through IVAm
High-risk endometrial carcinoma spans a range of stages and molecular profiles. This protocol addresses the specific subpopulations — defined by staging and molecular classification — for which a combined modality treatment strategy is indicated.
Clinical Scenario
This protocol applies to endometrial carcinoma meeting high-risk criteria across four defined categories:
- Stages IA2m, IA3m, or IBm — NSMP high-grade or oestrogen receptor-negative (or both), or p53abn
- Stages IIm (IIA, IIB, or IIC) — NSMP high-grade or oestrogen receptor-negative (or both), or p53abn
- Stages IIIm (IIIA, IIIB, or IIIC) — NSMP low-grade and oestrogen receptor-positive, NSMP high-grade or oestrogen receptor-negative (or both), or p53abn
- Stages IVAm — NSMP low-grade and oestrogen receptor-positive, NSMP high-grade or oestrogen receptor-negative (or both), or p53abn
Treatment Approach (Overview)
Management involves a combination of radiotherapy and chemotherapy — with different scheduling options available. The complete sequencing, selection criteria, and all alternatives 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.
- For patients with high-risk endometrial carcinoma, external beam radiotherapy with concurrent and adjuvant chemotherapy (I, A) or, alternatively, sequential chemotherapy and radiotherapy, are recommended (I, B).
- Chemotherapy with or without brachytherapy is an alternative option (I, B).
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