Article Text
Abstract
Introduction/Background Risk-reducing surgery, medical prevention, and breast cancer (BC) surveillance offer the opportunity to manage BC and ovarian cancer (OC) risk in BRCA1/BRCA2/PALB2/RAD51C/RAD51D/BRIP1 cancer-susceptibility-gene (CSG) carriers, but their cost-effectiveness remains poorly addressed. We aimed to estimate the cancers and deaths prevented and cost-effectiveness of eligible prevention and surveillance strategies in BRCA1/BRCA2/PALB2/RAD51C/RAD51D/BRIP1 CSG-carriers. This analysis was used to inform the NICE guideline on women at high-risk of OC.
Methodology A decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and where relevant risk-reducing mastectomy (RRM) compared with non-surgical interventions (BC-surveillance and medical prevention for increased BC-risk) in BRCA1/BRCA2/PALB2/RAD51C/RAD51D/BRIP1 PV-carriers. The analysis was conducted from UK health-system payer-perspective, with incremental cost-effectiveness ratio (ICER) calculated as incremental cost per quality-adjusted life-year (QALY) gained. Sensitivity and scenario analyses were performed. OC/BC cases and deaths prevented were estimated.
Results Undergoing both RRSO and RRM was most cost-effective for BRCA1 (RRM: 30-years; RRSO: 35-years), BRCA2 (RRM: 35-years; RRSO: 40-years), PALB2 (RRM: 40-years; RRSO: 45-years) PV-carriers. The corresponding ICERs were £-1,942/QALY, £-89/QALY, £2,381/QALY respectively. RRSO at age 45-years was cost-effective for RAD51C/RAD51D/BRIP1 PV-carriers compared with non-surgical strategies. The corresponding ICERs were £962/QALY, £771/QALY, £2,355/QALY respectively. The most cost-effective preventive strategy per 1000 PV-carriers could prevent 923 OC/BC cases/302 deaths in BRCA1; 686 OC/BC cases/170 deaths in BRCA2; 464 OC/BC cases/130 deaths in PALB2; 102 OC cases/64 deaths in RAD51C; 118 OC cases/76 deaths in RAD51D; and 55 OC cases/37 deaths in BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM was most cost-effective in 96.5%, 89.2%, 84.8% simulations for BRCA1/BRCA2/PALB2, while RRSO was cost-effective in 100% simulations for RAD51C/RAD51D/BRIP1.
Conclusion RRSO with/without RRM at varying respective optimal ages was cost-effective compared with non-surgical strategies for individual BRCA1/BRCA2/PALB2/RAD51C/RAD51D/BRIP1 PV-carriers. These findings support and enable personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC-risk management.
Disclosures RM reports receiving grants from GSK, NHS Innovation Accelerator (NIA), and Yorkshire Cancer Research outside the submitted work, and honoraria for advisory board membership from Astrazeneca/MSD/GSK/EGL. No other disclosures were reported.