4.6 Article

Clear cell carcinoma of the endometrium

Journal

GYNECOLOGIC ONCOLOGY
Volume 164, Issue 3, Pages 658-666

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2022.01.012

Keywords

Clear cell endometrial cancer; Immunotherapy; Target therapy; Uterine cancer

Funding

  1. NIH/NCI Cancer Center Support Grant [P30 CA008748]

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Clear cell endometrial carcinoma is a rare and poorly understood cancer type. Genetic profiling can assess prognosis, with most patients characterized by p53 abnormality or NSMP type. Patients with POLE mutation have a good prognosis, while chemotherapy is effective for NSMP and p53 abnormal patients. MMRd patients may not benefit from chemotherapy, and immune checkpoint inhibitors may be more suitable for them. Further clinical trials are needed to clarify the treatment strategies for clear cell endometrial carcinoma.
Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma. (C) 2022 Elsevier Inc. All rights reserved.

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