title: Optimal treatment of early-stage ovarian cancer.
abstract: BACKGROUND
  There is no clear consensus regarding systemic treatment of early-stage ovarian cancer (OC). Clinical trials are challenging because of the relatively low incidence and good prognosis. Initial results of the International Collaborative Ovarian Neoplasm (ICON)1 trial demonstrated benefit in both overall survival (OS) and recurrence-free survival (RFS) with adjuvant chemotherapy. We report results of 10-year follow-up to establish whether benefits are maintained longer term and discuss how this and other available evidence from randomised trials can be used to guide treatment options regarding the need for, and choice of, adjuvant chemotherapy regimen.
  
  
  METHODS
  ICON1 recruited women with OC following primary surgery in whom there was uncertainty as to whether adjuvant chemotherapy was indicated. Patients were randomly assigned to adjuvant or no adjuvant chemotherapy. Platinum-based chemotherapy was recommended and 87% received single-agent carboplatin. Analyses of long-term treatment benefits and interaction with risk groups were carried out. A high-risk group of women was defined with stage 1B/1C grade 2/3, any stage 1 grade 3 or clear-cell histology.
  
  
  RESULTS
  With a median follow-up of 10 years, the estimated hazard ratio (HR) for RFS was 0.69 [95% confidence interval (CI) 0.51-0.94, P = 0.02] and OS 0.71 (95% CI 0.52-0.98, P = 0.04) in favour of chemotherapy. In absolute terms, there was a 10% (60%-70%) improvement in RFS and a 9% (64%-73%) improvement in OS; the benefit of chemotherapy might be greater in high-risk disease (18% improvement in OS). Uncertainty remains about the optimal chemotherapy regimen. The only randomised trial data available are from a subset of 120 stage 1 patients in ICON3 where the treatment difference, comparing carboplatin with carboplatin/paclitaxel was estimated with relatively wide CIs [progression-free survival HR = 0.71 (95% CI 0.39-1.32) and OS HR = 0.98 (95% CI 0.49-1.93)].
  
  
  CONCLUSIONS
  Extended follow-up from ICON1 confirms that adjuvant chemotherapy should be offered to women with early-stage OC, particularly those with high-risk disease.
  
  
  BACKGROUND
  ISRCTN11916376 for ICON1 and ISRCTN57157825 for ICON3.
authors.affiliation: Clinical Trials Research Unit, Institute of Clinical Trials Research, University of Leeds, Leeds.
authors.forename: F
authors.initials: F
authors.lastname: Collinson
authors.affiliation: Cambridge Cancer Trials Centre/Cambridge Clinical Trials Unit, Cancer Theme, Cambridge University Hospitals NHS Foundation Trust, Medical Research Council Biostatistics Unit Hub for Trials Methodology, Cambridge, UK.
authors.forename: W
authors.initials: W
authors.lastname: Qian
authors.affiliation: Department of Oncology, Mario Negri Institute, Milan.
authors.forename: R
authors.initials: R
authors.lastname: Fossati
authors.affiliation: Department of Gynecology and Obstetrics, S. Gerardo Hospital, Monza, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lissoni
authors.affiliation: Department of Medical Oncology, University Hospital Bristol, Bristol, Avon.
authors.forename: C
authors.initials: C
authors.lastname: Williams
authors.affiliation: Medical Research Unit Clinical Trials Unit at University College London, London m.parmar@ucl.ac.uk.
authors.forename: M
authors.initials: M
authors.lastname: Parmar
authors.affiliation: UCL Cancer Institute, University College London, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Ledermann
authors.affiliation: Division of Gynecologic Oncology, European Institute of Oncology, University of Milan Bicocca, Milan, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Colombo
authors.affiliation: Norwich Clinical Trials Unit, Norwich Medical School, University of East Anglia, Norwich Research Park, UK.
authors.forename: A
authors.initials: A
authors.lastname: Swart
mesh_terms: D000328:Adult; D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D017671:Platinum Compounds / Q000627:therapeutic use*
chemical_list: D017671:Platinum Compounds
keywords: ICON1; ICON3; adjuvant chemotherapy; early-stage ovarian cancer