title: Specifying the ovarian cancer risk threshold of 'premenopausal risk-reducing salpingo-oophorectomy' for ovarian cancer prevention: a cost-effectiveness analysis.
abstract: Risk-reducing salpingo-oophorectomy (RRSO) is the most effective intervention to prevent ovarian cancer (OC). It is only available to high-risk women with >10% lifetime OC risk. This threshold has not been formally tested for cost-effectiveness.
  
  
  
  To specify the OC risk thresholds for RRSO being cost-effective for preventing OC in premenopausal women.
  
  
  
  The costs as well as effects of surgical prevention ('RRSO') were compared over a lifetime with 'no RRSO' using a decision analysis model. RRSO was undertaken in premenopausal women >40 years. The model was evaluated at lifetime OC risk levels: 2%, 4%, 5%, 6%, 8% and 10%. Costs and outcomes are discounted at 3.5%. Uncertainty in the model was assessed using both deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Outcomes included in the analyses were OC, breast cancer (BC) and additional deaths from coronary heart disease. Total costs and effects were estimated in terms of quality-adjusted life-years (QALYs); incidence of OC and BC; as well as incremental cost-effectiveness ratio (ICER).
  
  
  
  Published literature, Nurses Health Study, British National Formulary, Cancer Research UK, National Institute for Health and Care Excellence guidelines and National Health Service reference costs. The time horizon is lifetime and perspective: payer.
  
  
  
  Premenopausal RRSO is cost-effective at 4% OC risk (life expectancy gained=42.7 days, ICER=£19 536/QALY) with benefits largely driven by reduction in BC risk. RRSO remains cost-effective at >8.2% OC risk without hormone replacement therapy (ICER=£29 071/QALY, life expectancy gained=21.8 days) or 6%if BC risk reduction=0 (ICER=£27 212/QALY, life expectancy gained=35.3 days). Sensitivity analysis indicated results are not impacted much by costs of surgical prevention or treatment of OC/ BC or cardiovascular disease. However, results were sensitive to RRSO utility scores. Additionally, 37%, 61%, 74%, 84%, 96% and 99.5% simulations on PSA are cost-effective for RRSO at the 2%, 4%, 5%, 6%, 8% and 10% levels of OC risk, respectively.
  
  
  
  Premenopausal RRSO appears to be extremely cost-effective at ≥4% lifetime OC risk, with ≥42.7 days gain in life expectancy if compliance with hormone replacement therapy is high. Current guidelines should be re-evaluated to reduce the RRSO OC risk threshold to benefit a number of at-risk women who presently cannot access risk-reducing surgery.
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK Department of Women's Cancer, Gynaecological Cancer Research Centre, Institute for Women's Health, University College London, London, UK Department of Gynaecological Oncology, St Bartholomew's Hospital, London, UK.
authors.forename: Ranjit
authors.identifier: 0000-0003-3381-5057
authors.initials: R
authors.lastname: Manchanda
authors.affiliation: Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Rosa
authors.initials: R
authors.lastname: Legood
authors.affiliation: Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.affiliation: Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Gordeev
authors.affiliation: Department of Women's Cancer, Gynaecological Cancer Research Centre, Institute for Women's Health, University College London, London, UK.
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
mesh_terms: D000328:Adult; D003362:Cost-Benefit Analysis; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000517:prevention & control* / Q000601:surgery*; D010052:Ovariectomy / Q000191:economics / Q000379:methods; D017697:Premenopause / Q000502:physiology*; D019057:Quality-Adjusted Life Years; D012306:Risk
keywords: Ovarian cancer; cost-effectiveness; risk reducing salpingo-oophorectomy; risk threshold; surgical prevention