Low-grade serous carcinoma: molecular features and contemporary treatment strategies

Abstract

Epithelial ovarian carcinoma consists of several subtypes, including high-grade and low-grade serous carcinoma. In the recent past, women with all subtypes of epithelial ovarian carcinoma have been treated similarly and are included in the same clinical trials. However, a distinction has emerged between the type I, low-grade tumors and the type 2, higher-grade epithelial malignancies. Low-grade serous carcinoma exhibits different molecular and clinical features from the other epithelial subtypes, as well as some degree of chemotherapy resistance. This review summarizes the genetic, molecular and clinical characteristics of low-grade serous disease and provides an appraisal of the management strategies

Keywords:

• chemoresistance
• chemotherapy
• epithelial ovarian cancer
• hormonal therapies
• low-grade serous cancer
• surgical cytoreduction
• targeted agents
• two-tier grading system

Financial and competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• The most common epithelial ovarian carcinoma subtype is serous carcinoma (70%), of which 10% of the tumors are low-grade serous carcinoma (LGSC).

• A two-tier grading system has proven to be reproducible and clinically meaningful for the categorization of serous carcinomas. It is based primarily on the assessment of nuclear atypia and mitotic rate.

• LGSC has different molecular, genetic, histologic and pathogenic features compared to its high-grade counterpart.

• LGSC is diagnosed at a younger age and is associated with a longer overall survival compared to high-grade carcinoma.

• Surgery is the cornerstone of treatment.

• Although progression-free and overall survival are overall better in LGSC compared with high-grade serous carcinoma, surgical cytoreduction to microscopic residual is critical to achieving this improved survival outcome.

• Retrospective studies that included women receiving conventional chemotherapy in the frontline, neoadjuvant and recurrent settings for the treatment of LGSC have demonstrated relative chemoresistance.

• Targeted therapies, including the MEK, AKT and VEGF inhibitors, together with select hormonal therapies are promising treatment options being studied in women with LGSC.

Notes