Global Variations in Concurrent Hysterectomy During Risk-Reducing Surgery for BRCA1/2 Carriers: An Integrated Quantitative and Qualitative Analysis

Highlight

– Rates of concurrent hysterectomy during risk-reducing salpingo-oophorectomy (RRSO) vary widely internationally, with highest rates in the Americas and lowest in Europe.
– BRCA1 pathogenic variant carriers in the Americas are more likely to undergo hysterectomy than BRCA2 carriers.
– Diverse clinical indications and considerable regional, cultural, and institutional variability exist regarding the decision to perform hysterectomy.
– Lack of consensus guidelines and limited conclusive evidence contribute to heterogeneity in practice.

Study Background

Women carrying pathogenic variants (PVs) in BRCA1 or BRCA2 genes are at substantially increased risk for tubo-ovarian cancer, necessitating preventive strategies. Risk-reducing salpingo-oophorectomy (RRSO) between ages 35 and 45 years is recommended to mitigate this elevated risk. However, the role of concurrent hysterectomy during RRSO remains controversial. Although hysterectomy may further reduce endometrial cancer risk, its necessity and indications are debated given potential added surgical risks and absence of strong supporting evidence. Current international practices and factors influencing the decision to perform hysterectomy concurrently with RRSO have not been comprehensively characterized.

Study Design

This mixed-methods investigation combined quantitative and qualitative components to evaluate international trends and determinants related to concurrent hysterectomy during RRSO among BRCA1/2 PV carriers. The quantitative analysis incorporated prospectively collected data from the WISP and TUBA-WISP II prospective preferential trials, which assess preventive surgical strategies for tubo-ovarian cancer. The sample included 2181 women who underwent RRSO, categorized by continent: Europe (75.5%), North and South America (22.8%), and Australia (1.7%). Data on concurrent hysterectomy rates and associated factors were extracted from electronic case report forms. Statistical comparisons were made using Kruskal-Wallis tests and univariable logistic regression.

The qualitative arm involved focus group interviews with 23 gynecologic care providers from 12 countries who manage patients at increased genitourinary cancer risk. These interviews aimed to elucidate clinical indications, barriers, and facilitators affecting decisions about hysterectomy during RRSO, exploring medical, cultural, and systemic influences on practice variability.

Key Findings

The quantitative results revealed marked geographical disparities in the execution of concurrent hysterectomy during RRSO:

• North and South America showed the highest rates at 48.8%.
• Australia had intermediate rates at 14.2%.
• Europe exhibited the lowest rate at 2.8%.

The differences were statistically highly significant (p<0.001). Regression analysis demonstrated that among women in the Americas, those harboring a BRCA1 PV were significantly more likely to undergo hysterectomy concurrently than BRCA2 PV carriers (adjusted odds ratio 0.4, 95% CI 0.2–0.7), suggesting genotype-specific risk influence on surgical decisions.

The qualitative analysis identified 31 barriers and 32 facilitators influencing hysterectomy decisions concurrent with RRSO. Providers cited eight distinct clinical indications for hysterectomy; however, consensus was lacking on their validity and weighting. Key determinants included:

• Lack of definitive, evidence-based clinical guidelines addressing hysterectomy at RRSO.
• Cultural differences and prevailing medical practices across countries affecting surgical choices.
• Variability in departmental consensus and institutional policies.
• Divergent interpretations of endometrial cancer risk in BRCA1/2 PV carriers.

These multifactorial influences contribute substantially to global heterogeneity in surgical management approaches.

Expert Commentary

This study robustly elucidates the international divergence in surgical preventive care for BRCA mutation carriers, highlighting a critical gap in uniform clinical guidance. The notably low hysterectomy rates in Europe likely reflect prevailing interpretations that endometrial cancer risk may not justify additional surgical morbidity absent concrete evidence. In contrast, higher rates in the Americas may stem from more aggressive risk-reduction philosophies or differing perceptions of uterine cancer risk linked to BRCA1 mutations. However, the absence of randomized controlled data or large cohort studies directly comparing outcomes with and without hysterectomy limits the ability to establish firm recommendations. Further research, including prospective studies assessing endometrial cancer incidence, surgical morbidity, and quality of life outcomes, is essential to guide optimal practice.

Additionally, the qualitative insights underscore the importance of incorporating sociocultural and institutional contexts in guideline development and implementation. Multidisciplinary consensus panels should address current uncertainties, balancing cancer risk reduction against surgical risks and patient preferences.

Conclusion

This mixed-methods international study reveals substantial variation in the use of concurrent hysterectomy during risk-reducing surgery among BRCA1/2 pathogenic variant carriers. The high utilization in the Americas contrasts sharply with minimal use in Europe, reflecting divergent interpretations of cancer risk, cultural factors, and lack of robust clinical guidelines. The findings emphasize an urgent need for improved evidence-based clinical protocols and consensus recommendations that consider genotype-specific risks and patient-centered decision-making. Such endeavors will help harmonize practices worldwide, ensure appropriate risk mitigation, and avoid unnecessary surgical morbidity.

Funding and ClinicalTrials.gov

This study was supported by [funding sources as per original study, if available]. The WISP and TUBA-WISP II studies are registered clinical trials designed to evaluate preventive surgical strategies in BRCA1/2 pathogenic variant carriers.

References

• Gootzen TA, et al. International Trends in Concurrent Hysterectomy at Risk-Reducing Surgery in BRCA1/2 pathogenic variant carriers: A mixed-methods study. Am J Obstet Gynecol. 2026 Jun 20.
• Domchek SM, et al. Risk-Reducing Salpingo-Oophorectomy in BRCA1/2 Mutation Carriers: Use and Outcomes. J Clin Oncol. 2010.
• Rebbeck TR, et al. Efficacy of Risk-Reducing Salpingo-Oophorectomy in BRCA1/2 Mutation Carriers: A Meta-Analysis. J Natl Cancer Inst. 2009.
• American Society of Clinical Oncology. Clinical Practice Guideline Update: Genetic Testing and Management of BRCA Mutations. J Clin Oncol. 2015.