Cost-Effectiveness of Risk-Reducing Surgery for Breast and Ovarian Cancer Prevention: A Systematic Review

SIMPLE SUMMARY: Synthesised cost-effectiveness evidence is necessary for resource allocation for risk-reducing surgery in breast cancer (BC)/ovarian cancer (OC)/endometrial cancer (EC) prevention strategies. We aimed to review evidence on the cost-effectiveness of surgical prevention for BC/OC/EC in high/intermediate/low-risk populations. From 22 included studies, risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO) were cost-effective for BRCA1/2, and RRSO was also cost-effective at a lower lifetime OC risk-threshold of 4–5%. Risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) was cost-effective compared to RRSO in one-study. Hysterectomy with bilateral salpingo-oophorectomy (BSO) was cost-effective in Lynch syndrome women. Opportunistic bilateral salpingectomy (OBS) was cost-effective when conducted with hysterectomy for benign gynaecology surgery or in lieu of tubal sterilisation. This systematic review found that surgical prevention is cost-effective for women who are at high risk of BC, intermediate/high risk of OC and high risk of EC. The results are sensitive to age, disutility and uptake rates regarding RRS along with the effect sizes in terms of OC-risk reduction from salpingectomy. These areas require further research. Key points: Question: What is the evidence on the cost-effectiveness of risk-reducing surgery for breast, ovarian and endometrial cancer prevention? Findings: This systematic review found that surgical prevention is cost-effective for women in high-income countries who are at a high risk of breast cancer, intermediate/high risk of ovarian cancer and high risk of endometrial cancer. The results, while robust for most strategies, are sensitive to certain parameters, especially the disutility from surgery and the effect sizes of ovarian cancer risk reduction from salpingectomy. Implications: Risk-reducing surgery is cost-effective for breast/ovarian/endometrial cancer prevention across most settings, but more research is needed on the disutility from all preventive surgery and the precision in terms of the cancer risk reduction from salpingectomy. ABSTRACT: Policymakers require robust cost-effectiveness evidence of risk-reducing-surgery (RRS) for decision making on resource allocation for breast cancer (BC)/ovarian cancer (OC)/endometrial cancer (EC) prevention. We aimed to summarise published data on the cost-effectiveness of risk-reducing mastectomy (RRM)/risk-reducing salpingo-oophorectomy (RRSO)/risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) for BC/OC prevention in intermediate/high-risk populations; hysterectomy and bilateral salpingo-oophorectomy (BSO) in Lynch syndrome women; and opportunistic bilateral salpingectomy (OBS) for OC prevention in baseline-risk populations. Major databases were searched until December 2021 following a prospective protocol (PROSPERO-CRD42022338008). Data were qualitatively synthesised following a PICO framework. Twenty two studies were included, with a reporting quality varying from 53.6% to 82.1% of the items scored in the CHEERS checklist. The incremental cost-effectiveness ratio/incremental cost-utility ratio and cost thresholds were inflated and converted to US$2020, using the original currency consumer price index (CPI) and purchasing power parities (PPP), for comparison. Eight studies concluded that RRM and/or RRSO were cost-effective compared to surveillance/no surgery for BRCA1/2, while RRESDO was cost-effective compared to RRSO in one study. Three studies found that hysterectomy with BSO was cost-effective compared to surveillance in Lynch syndrome women. Two studies showed that RRSO was also cost-effective at ≥4%/≥5% lifetime OC risk for pre-/post-menopausal women, respectively. Seven studies demonstrated the cost-effectiveness of OBS at hysterectomy (n = 4), laparoscopic sterilisation (n = 4) or caesarean section (n = 2). This systematic review confirms that RRS is cost-effective, while the results are context-specific, given the diversity in the target populations, health systems and model assumptions, and sensitive to the disutility, age and uptake rates associated with RRS. Additionally, RRESDO/OBS were sensitive to the uncertainty concerning the effect sizes in terms of the OC-risk reduction and long-term health impact. Our findings are relevant for policymakers/service providers and the design of future research studies.