High risk endometrial cancer: Clues towards a revision of the therapeutic paradigm

Introduction: Endometrial cancer (EC) is a major cause of mortality worldwide with nearly 200 000 cases diagnosed annually. The recent ESMO-ESGO-ESTRO guidelines include a new classification defining a heterogeneous high-risk group of recurrence (HR) comprising: (i) endometrioid (type 1) FIGO stage IB grade 3 tumors (type 1/G3ECs), (ii) non-endometrioid tumors (type 2) and (iii) advanced stages whatever the histological type (Colombo et al., 2016). Areas covered: The aim of this review is to summarize current evidence for therapeutic approaches in HR-EC according to the updated ESMO-ESGO-ESTRO classification by discussing the following issues: i) HR-EC heterogeneity, (ii) prognostic factors and current classification, and (iii) optimal staging strategies (site and extent) and the role of adjuvant treatment. Expert commentary: HR-EC treatment is based on surgery, radiation therapy, brachytherapy, and chemotherapy, either alone or sequentially, in combination with other treatments depending on disease stage, histological grade and risk group. Specific trials are needed to establish the role of systematic pelvic and paraaortic lymphadenectomy, adjuvant therapies and targeted drugs. Although molecular characterization has been reported to customize therapeutic strategies and thereby improve therapeutic outcomes in EC, none of the targeted agents investigated (antiangiogenic and mTOR/PI3K pathway inhibitor agents) have resulted in a change in clinical practice in HR-EC.