title: Stage I granulosa cell tumours: A management conundrum? Results of long-term follow up.
abstract: Optimal management of women with early stage granulosa cell tumours (GCT) presents a management conundrum - they have excellent prognosis but a third will relapse. Advances uncovering the molecular characteristics of GCT have not been matched by improvements in our understanding and treatment.
  
  
  METHODS
  Stage I GCT patients referred to Auckland City Hospital (1955-2012) and Princess Margaret Cancer Centre (1992-2012) were identified. Baseline characteristics, histopathology and outcomes were recorded retrospectively.
  
  
  RESULTS
  One hundred and sixty stage I GCT patients were identified with a median age of 49 years. Median follow-up was 7.0 years (range 0.1-44.2 years). Fifty-one patients (32%) relapsed with a median time to relapse (TTR) of 12.0 years (1.3-17.7 years) - 20 initial relapses occurred 10 years post-diagnosis. Higher relapse rates (43% vs. 24% p=0.02) and shorter TTR (10.2 vs. 16.2 years p=0.007) were seen with stage Ic versus stage Ia disease. Cyst rupture was associated with increased relapse (p=0.03). Surgery was the main therapeutic modality at relapse. Eighty six percent of patients received non-surgical management at least once post-relapse. Clinical benefit rate was 43% with chemotherapy, 61% with hormonal therapy and 86% with radiation. Five- and 10-year overall survival (OS) were 98.5 and 91.6%, respectively. Median OS was similar in patients with (24.3 years) and without relapse (22.3 years).
  
  
  CONCLUSIONS
  Surgery remains fundamental at diagnosis and relapse. Caution should be exercised in recommending adjuvant chemotherapy at initial diagnosis given median OS was greater than 20 years even with relapse. Hormonal therapy at relapse appears encouraging but needs further assessment. Novel treatment strategies need exploration with international collaboration essential for this.
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Canada; Department of Medical Oncology, Auckland City Hospital, New Zealand.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Wilson
authors.affiliation: Department of Medical Oncology, Auckland City Hospital, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Fong
authors.affiliation: Department of Medical Oncology, Auckland City Hospital, New Zealand.
authors.forename: Soizick
authors.initials: S
authors.lastname: Mesnage
authors.affiliation: Department of Medical Oncology, Auckland City Hospital, New Zealand.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Chrystal
authors.affiliation: Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
authors.forename: Andrew
authors.initials: A
authors.lastname: Shelling
authors.affiliation: Department of Pathology, Auckland City Hospital, New Zealand.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Payne
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Mackay
authors.affiliation: Department of Statistics, Princess Margaret Cancer Centre, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Surgical Oncology, Princess Margaret Cancer Centre, Canada.
authors.forename: Stephane
authors.initials: S
authors.lastname: Laframboise
authors.affiliation: Department of Pathology, Princess Margaret Cancer Centre, Canada.
authors.forename: Marjan
authors.initials: M
authors.lastname: Rouzbahman
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, Canada.
authors.forename: Wilfred
authors.initials: W
authors.lastname: Levin
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Canada. Electronic address: amit.oza@uhn.ca.
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006106:Granulosa Cell Tumor / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
keywords: FOXL2; Granulosa cell tumours; Multi-centre review; Ovary; Stromal cell ovarian cancer