Adult granulosa cell tumors (GCT): 56 years of clinicopathologic outcomes including FOXL2 mutational status.

Abstract

5536 Background: GCT account for 2-3% of ovarian cancers with a tendency for late relapse. Treatment is primarily surgical. The role of chemotherapy and hormonal therapy is more controversial. The FOXL2 mutation (402C→G) has been identified as a potential driver mutation and may be useful in diagnosis and treatment. Methods: We performed a retrospective review of GCT patients (pts) referred to the Auckland Gynae-Oncology Multidisciplinary Team from 1955 to 2011. Baseline characteristics, clinical course, histopathology and survival data was recorded. FOXL2 mutation status was determined by DNA sequencing, and correlated with clinical data. Results: 56 GCT pts were identified. Median (med) age 48.6 years (y) (22-86). Stage I were 82.1%. 48% of tumours were ≥10cm. Med follow up was 10.0y (0.2-40.4). 25 pts progressed, med time to progression (TTP) was 4.5y (0.1-17.7). Med progression free survival was 14.5y. Med overall survival (OS) was 21.8y but med disease specific survival was not reached. 9/18 pts died of disease. Stage III GCT and size ≥10cm had a higher risk of relapse (RR 3.1 and 2.9) and death (RR 8.2 and 8.6) respectively. 17/46 (37%) Stage I pts progressed. Med TTP was 8.3y (1.3 to 17.7), med OS was 29.0y. Stage I relapse rate was higher in tumours ≥10cm (RR 3.9 p<0.01). 12/17 1st relapses were treated with surgery. 10/17 pts received ≥1 line of chemotherapy and 7 ≥1 hormonal therapy. Clinical benefit rates (CR, PR and SD>6m) for first-line chemotherapy was 25% and 71% for hormones. All 7 Stage III pts progressed with med OS of 6.3yr (0.2-12.3y). Currently the FOXL2 mutation statuses are known for 18 patients. 89% carried the mutation. Homozygous, heterozygous and wild-type mutations had no difference in risk of relapse or death. Further FOXL2 mutation analysis is ongoing. Conclusions: This long term series confirms the protracted natural history of this disease. Early stage GCT, despite progression has a good prognosis with med OS >25y. Stage and tumour size remain the most consistent prognostic factors. Whilst surgery remains the mainstay of therapy, the high response rate to hormonal therapy deserves investigation. Currently the FOXL2 mutation status does not appear prognostic but this needs further research.