Adjuvant Treatment Recommendations in Early-Stage Endometrial Cancer: What Changes With the Introduction of The Integrated Molecular-Based Risk Assessment

Camilla Nero, Francesca Ciccarone, Antonella Pietragalla, Simona Duranti, Gennaro Daniele, Giovanni Scambia, Domenica Lorusso, Camilla Nero, Francesca Ciccarone, Antonella Pietragalla, Simona Duranti, Gennaro Daniele, Giovanni Scambia, Domenica Lorusso

Abstract

Adjuvant therapy recommendations for endometrial cancer were historically based on the individual patient's risk of disease recurrence using clinicopathologic factors such as age, stage, histologic subtype, tumor grade, and lymphovascular space invasion. Despite the excellent prognosis for early stages, considerable under- and overtreatment remains. Integrated genomic characterization by the Cancer Genome Atlas (TCGA) in 2013 defined four distinct endometrial cancer subgroups (POLE mutated, microsatellite instability, low copy number, and high copy number) with possible prognostic value. The validation of surrogate markers (p53, Mismatch repair deficiency, and POLE) to determine these subgroups and the addition of other molecular prognosticators (CTNNB1, L1CAM) resulted in a practical and clinically useful molecular classification tool. The incorporation of such molecular alterations into established clinicopathologic risk factors resulted in a refined, improved risk assessment. Thus, the ESGO/ESTRO/ESP consensus in 2020 defined for the first time different prognostic risk groups integrating molecular markers. Finally, the feasibility and clinical utility of molecular profiling for tailoring adjuvant therapy in the high-intermediate-risk group is currently under investigation (NCT03469674).

Keywords: adjuvant treatment; endometrial cancer; molecular classification; recommendations; risk factors.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Nero, Ciccarone, Pietragalla, Duranti, Daniele, Scambia and Lorusso.

Figures

Figure 1
Figure 1
Distribution of molecular features across different EC histotypes.

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