Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer

Author:

Wei Xia12,Sun Li12,Slade Eric3,Fierheller Caitlin T.2,Oxley Samuel24,Kalra Ashwin24,Sia Jacqueline24,Sideris Michail24,McCluggage W. Glenn5,Bromham Nathan3,Dworzynski Katharina3,Rosenthal Adam N.67,Brentnall Adam2,Duffy Stephen2,Evans D. Gareth8,Yang Li9,Legood Rosa12,Manchanda Ranjit12410

Affiliation:

1. Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London, United Kingdom

2. Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom

3. National Institute for Health and Care Excellence, London, United Kingdom

4. Department of Gynaecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, United Kingdom

5. Department of Pathology, Belfast Health & Social Care Trust, Royal Victoria Hospital, Belfast, United Kingdom

6. Department of Gynaecology, University College London Hospitals NHS Foundation trust, London, United Kingdom

7. Department of Women’s Cancer, UCL EGA Institute for Women’s Health, University College London, London, United Kingdom

8. Manchester Centre for Genomic Medicine, Division of Evolution, Infection and Genomic Sciences, University of Manchester, MAHSC, Manchester, United Kingdom

9. School of Public Health, Peking University, Beijing, China

10. MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, Faculty of Population Health Sciences, University College London, London, United Kingdom

Abstract

ImportancePathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1, BRCA2, PALB2, RAD51C, and RAD51D PVs also conferring an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance offer the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs remains poorly addressed.ObjectiveTo estimate the cost-effectiveness of prevention strategies for OC and BC among individuals carrying PVs in the previously listed CSGs.Design, Setting, and ParticipantsIn this economic evaluation, a decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and, where relevant, risk-reducing mastectomy (RRM) compared with nonsurgical interventions (including BC surveillance and medical prevention for increased BC risk) from December 1, 2022, to August 31, 2023. The analysis took a UK payer perspective with a lifetime horizon. The simulated cohort consisted of women aged 30 years who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. Appropriate sensitivity and scenario analyses were performed.ExposuresCSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention.Main Outcomes and MeasuresThe incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. OC and BC cases and deaths were estimated.ResultsIn the simulated cohort of women aged 30 years with no cancer, undergoing both RRSO and RRM was most cost-effective for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) PVs. The corresponding ICERs were −£1942/QALY (−$2680/QALY), −£89/QALY (−$123/QALY), and £2381/QALY ($3286/QALY), respectively. RRSO at age 45 years was cost-effective for RAD51C, RAD51D, and BRIP1 PV carriers compared with nonsurgical strategies. The corresponding ICERs were £962/QALY ($1328/QALY), £771/QALY ($1064/QALY), and £2355/QALY ($3250/QALY), respectively. The most cost-effective preventive strategy per 1000 PV carriers could prevent 923 OC and BC cases and 302 deaths among those carrying BRCA1; 686 OC and BC cases and 170 deaths for BRCA2; 464 OC and BC cases and 130 deaths for PALB2; 102 OC cases and 64 deaths for RAD51C; 118 OC cases and 76 deaths for RAD51D; and 55 OC cases and 37 deaths for BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM were most cost-effective in 96.5%, 89.2%, and 84.8% of simulations for BRCA1, BRCA2, and PALB2 PVs, respectively, while RRSO was cost-effective in approximately 100% of simulations for RAD51C, RAD51D, and BRIP1 PVs.Conclusions and RelevanceIn this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management.

Publisher

American Medical Association (AMA)

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