The TCGA Molecular Classification of Endometrial Cancer and Its Possible Impact on Adjuvant Treatment Decisions

SIMPLE SUMMARY: The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) is a recently developed tool to identify four distinct molecular subgroups of endometrial cancer. Patients identified as Polymerase Epsilon exonuclease domain mutated (POLE EDM) or p53-mutated have significantly altered prognosis compared to patients allocated to the mismatch repair deficient (MMRd) or p53 wt groups. The aim of this review is to give a broad overview over the initial development and refinement of the classifier as well as possible effects on the recommended adjuvant treatment. We have summarized the clinical data of 8 studies including 3650 endometrial cancer patients and analyzed the distribution of tumor stage and adjuvant treatment received in respect to the molecular subgroups. Based on the findings of the summarized studies treatment de-escalation might be feasible for POLE EDM patients while p53 abn patients should receive adjuvant (chemo-)radiotherapy. ABSTRACT: Adjuvant treatment decisions for endometrial cancer (EC) are based on stage, the histological grade of differentiation, histological subtype, and few histopathological markers. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identified four risk groups of EC patients using a combination of immunohistochemistry and mutation analysis: Polymerase Epsilon exonuclease domain mutated (POLE EDM), mismatch repair deficient (MMRd), p53 wild-type/copy-number-low (p53 wt), and p53-mutated/copy-number-high (p53 abn). Patients allocated to the POLE or abnormal p53 expression subtype are faced with a significantly altered outcome possibly requiring a modified adjuvant treatment decision. Within this review, we summarize the development of ProMisE, characterize the four molecular subtypes, and finally discuss its value in terms of a patient-tailored therapy in order to prevent significant under or overtreatment.