ESMO E-Learning: Molecular Testing in Endometrial Cancer

In this E-Learning module, the author emphasizes that until recently, treatment options for patients with endometrial cancer has been limited and illustrates how it has rapidly evolved with molecular analysis based approaches. The main goal of this module is to describe the current state of molecular testing in patients with endometrial cancer, the impact of molecular subtypes on treatment decisions and to elucidate future developments in this field.

Endometrial cancer remains the only gynaecologic malignancy with a rising incidence and mortality. Newer risk stratification models aimed at improving treatment algorithms for patients with endometrial cancer are centred around molecular classification. The author explains that The Cancer Genome Atlas identified four subgroups of endometrial cancer with distinct genetic profiles and how clinical outcomes are closely tied to these molecular subgroups.

The author explores the knowledge gained from molecular classification of endometrial cancer by putting into perspective the findings from different clinical trials, not only in the overall study population, but also highlighting the clinical benefits in relevant molecular subgroups and by illustrating the results from the exploratory biomarker analyses.

The practice usefulness of this module is enhanced by a very clear division of predictive biomarkers in endometrial cancer into those linked to established, exploratory, and investigational actionable targets.

The module concludes that endometrial cancer comprises different tumour subtypes with different prognosis and molecular profiling requiring different treatments. Immune checkpoint inhibitors are currently approved in the first-, second-line and beyond settings, alone or in combination with platinum-based chemotherapy or tyrosine kinase inhibitor, and potentially moving upfront. PARP inhibitors are entering the treatment landscape for selected patients with MMR-proficient endometrial cancer.

Moving forward, the MMR-deficient/MSI and MMR-proficient/MSS dichotomic classification is required to select the best candidates for the most appropriate therapy. Biomarkers driven trials are the future in the treatment of patients with endometrial cancer.