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.

BACKGROUND: Risk-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 OBJECTIVE: To 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 HYPOTHESIS: We 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 DESIGN: In 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, and RAD51D pathogenic 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 for BRCA1, 40-45 years for BRCA2, and 45-50 years for BRIP1, RAD51C, and RAD51D pathogenic variant carriers. MAJOR INCLUSION/EXCLUSION CRITERIA: Premenopausal individuals with a documented class IV or V germline pathogenic variant in the BRCA1, BRCA2, BRIP1, RAD51C, or RAD51D gene who have completed childbearing are eligible for participation. Participants may have a personal history of a non-ovarian malignancy. PRIMARY ENDPOINT: The primary outcome is the cumulative tubo-ovarian cancer incidence at the target age: 46 years for BRCA1 and 51 years for BRCA2 pathogenic variant carriers. SAMPLE SIZE: The sample size to ensure sufficient power to test non-inferiority of salpingectomy with delayed oophorectomy compared with salpingo-oophorectomy requires 1500 BRCA1 and 1500 BRCA2 pathogenic variant carriers. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Participant 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 NUMBER: NCT04294927.

Successful centralisation of patients with vulvar carcinoma: a population-based study in The Netherlands.

INTRODUCTION: In general, centralisation of care for patients with rare malignancies is advised in order to improve outcome with respect to prognosis and treatment related morbidity. Therefore, centralisation of women with vulvar squamous cell carcinoma (SCC), which is an extremely rare tumour, has been advocated by the national guidelines of the Dutch Society of Obstetrics and Gynaecology in 2000. The objective of this study was to determine whether this advice has been adapted and has led to improved survival. METHODS: All patients diagnosed with vulvar malignancies between 1989 and 2008 in the Eastern part of the Netherlands were retrieved from the population-based cancer registry held by the Comprehensive Cancer Centre, The Netherlands. Patient- and tumour characteristics and vital status until January 2011 were retrieved. Data of patients diagnosed in two periods (before and after release of the guideline; 1989-1999 and 2000-2008) were compared. Relative survival rates were calculated as a good approximation of cause-specific survival. RESULTS: A total number of 382 patients with vulvar SCC with invasion > 1mm, who had an indication for groin surgery, were included in the analysis. In the first decade 62% (123 of 198 patients) were treated in a specialised oncology centre, which increased to 93% (172 of 184 patients) in the more recent period. Overall, the 5 year relative survival improved slightly from 69% (95% confidence interval (CI) 60-77%) to 75% (95% CI 65-83%). After adjustment for age and stage, being treated in a specialised oncology centre was an independent prognostic factor for survival. CONCLUSION: Centralisation of care for vulvar SCC patients has been well adopted in the Eastern part of the Netherlands. Being treated in a specialised oncology centre was associated with a better survival after adjustment for age and stage.