Endometrial carcinosarcoma

Endometrial carcinosarcoma (ECS) is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with that of the more common endometrioid counterpart, although ECS is more frequently diagnosed at an advanced stage. ECS is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of ECSs are characterized by p53 abnormalities. The proportion of POLE and MSI-H is directly related by the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components. The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of recurrent endometrial cancer patients, patients with ECS were excluded from the most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after the progression on chemotherapy and single agent immunotherapy in MSI-H cancers. In the era of precision medicine, the emerging knowledge on the molecular ECS landscape is opening new promising therapeutic options for more personalized treatment. The present review outlines the state-of-the-art knowledge and the future directions on the horizon for patients with ECS.