Prolonged Disease-Free Survival in a Relapsed Adult Granulosa Cell Tumor of the Ovary Treated by Combined Leuprolide and Letrozole: Case Report

Abstract

Relapsing ovarian granulosa-cell tumor (GCT) is a challenge for physicians due to the lack of effective therapy. Current strategies did not improve the 80% death rate of recurrent disease. GCTs synthesize estrogens and express follicle-stimulating hormone, gonadotropin-releasing hormone, and estrogen and progesterone receptors. The FOXL2-C134W mutation is shared in all GCTs, and its downregulation of hormone-related apoptosis appears causal in induction of tumor phenotype. On these assumptions, hormone anti-estrogenic therapies have been proposed for recurrent GCTs. A 32-year-old woman suffering from GCT was first treated by surgery in 2004 and staged as IA disease. Two subsequent pelvic relapses were diagnosed in 2006 and 2007, and the patient underwent surgery and chemotherapy to treat both recurrences. Overall, she underwent five subsequent surgical interventions and two chemotherapy instances. A third single pelvic relapse above the vaginal cuff was diagnosed in 2013. Based on the patient’s refusal to undergo further surgery we proposed an anti-estrogen therapy consisting of combined GnRH analogue leuprolide and the aromatase inhibitor letrozole. Complete remission was obtained after 3 months from the start of therapy. Subsequently, we found that disease-free survival was maintained over 9 years of treatment. Although recent reports indicate poor effectiveness of hormone therapy to treat recurrent GCTs, the success of this case indicates that a subset of patients with recurrent GCT maintain a tumor phenotype highly responsive to anti-estrogen drugs.