Abstract

Simple SummaryIn recent years, the adjuvant treatment of endometrial carcinoma has changed due to the integration of the molecular features in the clinical–pathological classification. The new ESGO/ESTRO/ESP guidelines (2021) proposed the evaluation of the adjuvant treatment of endometrial carcinoma using a prognostic-risk group stratification based on pathogenetic, clinical, and molecular features. Moreover, the adjuvant therapy of endometrial carcinoma is currently being re-defined in ongoing studies. This review provides a comprehensive overview of endometrial carcinoma adjuvant therapy, analyzing the “new standards” and “new perspectives”.Endometrial carcinoma is the most frequent cancer of the reproductive female organs. Most endometrial cancers are diagnosed at early stage (75%). Treatment options depend on pathogenetic, histopathologic and clinical characteristic at the diagnosis. To improve patient management in the near future, recent research has focused on new molecular features; evidence has shown that these give a better definition of patient prognosis and can help in tailoring adjuvant treatments by identifying specific subgroups of patients whose tumors may benefit from specific therapeutic approaches. In this review, we will focus on current knowledge of adjuvant treatment of endometrial carcinoma, using a prognostic-risk group stratification based on pathogenetic, clinical and molecular features, and will take a look at the ongoing trials that will further change the therapeutic approach in coming years.

Highlights

  • Endometrial carcinoma (EC) is the fourth most frequently diagnosed cancer in women with 130,051 estimated new cases and 29,963 deaths in Europe in 2020 [1]

  • A recent study suggests that tumors with any of the 11 polymerase epsilon (POLE) exonuclease domain mutation (EDM) identified in the The Cancer Genome Atlas (TCGA) should be classified as POLE-mut EC, independently of MMRd/microsatellite instability (MSI) and p53 status [15]

  • The new European Society of Gynaecological Oncology/European Society for Radiotherapy & Oncology/European Society of Pathology (ESGO/ESTRO/ESP) guidelines for the management of patients with endometrial carcinoma, defined in 2021, give new recommendations for adjuvant treatments which are strongly dependent on the prognostic risk group, defined according to several elements: 1. histopathologic type, according to World Health Organization (WHO) Classification of tumors (5th edition) [6]; 2. grade, using a binary International Federation of Gynecology and Obstetrics (FIGO) grading, which considers grade 1 and grade

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Summary

Introduction

Endometrial carcinoma (EC) is the fourth most frequently diagnosed cancer in women with 130,051 estimated new cases and 29,963 deaths in Europe in 2020 [1]. The Cancer Genome Atlas (TCGA) performed an integrated genomic and proteomic analysis of 373 endometrial cancers that provided insights into disease biology and diagnostic classification with immediate therapeutic application [7] It identified four molecular subgroups: DNA polymerase epsilon (POLE)-mutated (ultra-mutated, (POLEmut)), microsatellite unstable (hypermutated), copy number low, and copy number high. ECs analogous to the somatic copy number alteration (SCNA)-high subclass can be identified by p53 immuno-histochemistry (p53-mutated (p53abn) EC) [14], the microsatellite instability (MSI) subclass by immunohistochemistry for mismatch repair (MMR) proteins (mismatch repair deficient (MMRd) EC), and the POLE subclass by targeted sequencing of the POLE exonuclease domain (POLEmut EC) Tumors lacking these three prior features are classified as p53 wild-type (p53wt EC) [10] or no specific molecular profile subtype (NSMP EC) [11], analogous to the SCNA-low subclass. A recent study suggests that tumors with any of the 11 POLE EDMs identified in the TCGA should be classified as POLE-mut EC, independently of MMRd/MSI and p53 status [15]

Adjuvant Treatment for Endometrial Carcinoma according to the Prognosis
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