Abstract
Endometrial carcinoma (EC) is traditionally treated with surgery and adjuvant treatment depending on clinicopathological risk factors. The genomic analysis of EC in 2013 and subsequent studies using immunohistochemistry have led to the current EC molecular classification into: polymerase epsilon mutated (POLEmut), p53 abnormal (p53abn), mismatch repair deficient (MMRd), and no specific molecular profile (NSMP). The four groups have prognostic value and represent a promising tool for clinical decision-making regarding adjuvant treatment. Molecular classification was integrated into the recent European Society of Gynecologic Oncology (ESGO) management guidelines. POLEmut EC has favorable outcomes and retrospective studies found that omitting adjuvant treatment is safe in this group; two prospective clinical trials, PORTEC-4 and TAPER, are ongoing to assess this. p53 abn is associated with increased recurrence, decreased survival, and benefitted from chemotherapy in the PORTEC-3 subgroup molecular analysis. The clinical trials PORTEC-4a and CANSTAMP will prospectively assess this. MMRd and NSMP groups have intermediate prognosis and will likely continue to rely closely on clinicopathological features for adjuvant treatment decisions. In addition, the molecular classification has led to exploring novel treatments such as checkpoint inhibitors. Overall, the molecular perspective on EC and associated clinical trials will likely refine EC risk stratification to optimize care and avoid overtreatment.
Highlights
Endometrial cancer (EC) is the most common gynecological cancer, and the fourth most common malignancy in women in developed countries [1]
The current review provides a summary of landmark trials defining traditional management in endometrial cancer, discusses the introduction of molecular classification, interprets trials in the context of the new molecular classification, and discusses current or proposed trials to define optimal treatment based on molecular classification
IHC and sequencing has brought along a new promising avenue by classifying EC into four molecular subgroups: POLE mutated, p53 abnormal, mismatch repair deficient (MMRd), and no specific molecular profile (NSMP)
Summary
Endometrial cancer (EC) is the most common gynecological cancer, and the fourth most common malignancy in women in developed countries [1]. The standard treatment for endometrial cancer is surgery involving total hysterectomy with bilateral salpingoophorectomy and lymph node assessment. The clinical and surgical histopathological features assist in classifying patients into risk categories to decide on need and type of adjuvant treatment. Oncologists strive to achieve an optimal patient selection and provide an adequate balance between decreasing the risk of recurrence, optimizing survival, and avoiding side-effects associated with unnecessary overtreatment. A recent important addition for achieving optimal patient selection for adjuvant treatment in the management of EC is the comprehensive genomic analysis by The Cancer. The current review provides a summary of landmark trials defining traditional management in endometrial cancer, discusses the introduction of molecular classification, interprets trials in the context of the new molecular classification, and discusses current or proposed trials to define optimal treatment based on molecular classification
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