Advanced Granulosa Cell Tumors of the Ovary: A Review with a Focus on Current and Novel Therapeutic Approaches

Granulosa cell tumor (GCT) is the most common nonepithelial ovarian malignancy. Still, it is considered rare, with a paucity of high-level evidence guiding management, particularly in the metastatic setting. Advancements in molecular pathology allowed the identification of several targetable mutations that play an important role in GCT pathogenesis. Although current management approaches rely on guidelines extrapolated from the more common epithelial subtype, the unique histopathologic and molecular characteristics of GCTs entail a more focused approach. Systemic therapy remains the cornerstone treatment for advanced disease, and although chemotherapy has been the standard for decades, targeted treatments have gained considerable attention lately. Due to the rarity of this disease, validation of new therapies in large trials is the rate-limiting step for developing evidence-based recommendations. This review sheds light on pathogenesis, clinical and molecular characteristics, and prognostic factors, and discusses current treatment options including the role of novel therapies and immune checkpoint inhibitors in advanced GCT.