TUBectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy in high-risk women to assess the safety of prevention: the TUBA-WISP II study protocol

Abstract

BackgroundRisk-reducing salpingectomy with delayed oophorectomy has gained interest for individuals at high risk for tubo-ovarian cancer as there is compelling evidence that especially high-grade serous carcinoma originates in the fallopian tubes. Two studies have demonstrated a positive effect of salpingectomy on menopause-related quality of life and sexual health compared with standard risk-reducing salpingo-oophorectomy.Primary ObjectiveTo investigate whether salpingectomy with delayed oophorectomy is non-inferior to the current standard salpingo-oophorectomy for the prevention of tubo-ovarian cancer among individuals at high inherited risk.Study HypothesisWe hypothesize that postponement of oophorectomy after salpingectomy, to the age of 40–45 (BRCA1) or 45–50 (BRCA2) years, compared with the current standard salpingo-oophorectomy at age 35–40 (BRCA1) or 40–45 (BRCA2) years, is non-inferior in regard to tubo-ovarian cancer risk.Trial DesignIn this international prospective preference trial, participants will choose between the novel salpingectomy with delayed oophorectomy and the current standard salpingo-oophorectomy. Salpingectomy can be performed after the completion of childbearing and between the age of 25 and 40 (BRCA1), 25 and 45 (BRCA2), or 25 and 50 (BRIP1, RAD51C,andRAD51Dpathogenic variant carriers) years. Subsequent oophorectomy is recommended at a maximum delay of 5 years beyond the upper limit of the current guideline age for salpingo-oophorectomy. The current National Comprehensive Cancer Network (NCCN) guideline age, which is also the recommended age for salpingo-oophorectomy within the study, is 35–40 years forBRCA1, 40–45 years forBRCA2,and 45–50 years forBRIP1,RAD51C, andRAD51Dpathogenic variant carriers.Major Inclusion/Exclusion CriteriaPremenopausal individuals with a documented class IV or V germline pathogenic variant in theBRCA1, BRCA2, BRIP1, RAD51C,orRAD51Dgene who have completed childbearing are eligible for participation. Participants may have a personal history of a non-ovarian malignancy.Primary EndpointThe primary outcome is the cumulative tubo-ovarian cancer incidence at the target age: 46 years forBRCA1and 51 years forBRCA2pathogenic variant carriers.Sample sizeThe sample size to ensure sufficient power to test non-inferiority of salpingectomy with delayed oophorectomy compared with salpingo-oophorectomy requires 1500BRCA1and 1500BRCA2pathogenic variant carriers.Estimated Dates for Completing Accrual and Presenting ResultsParticipant recruitment is expected to be completed at the end of 2026 (total recruitment period of 5 years). The primary outcome is expected to be available in 2036 (minimal follow-up period of 10 years).Trial Registration NumberNCT04294927.