Study design

Aim

The primary objective is to prove that RRS with DO is non-inferior to the current standard RRSO regarding ovarian cancer risk.

Primary outcome measure: cumulative ovarian cancer incidence at target age: 46 for BRCA1 and 51 for BRCA2-PV carriers
Secondary outcome measures: incidence of (pre)malignancies in fallopian tubes and/or ovaries, incidence of non-ovarian pelvic cancer and breast cancer, peri-operative morbidity and mortality, uptake of prophylactic breast surgery and uptake of risk-reducing oophorectomy.

Study population

Inclusion criteria

• Premenopausal women with a documented class IV or V pathogenic variant in the BRCA1, BRCA2, BRIP1, RAD51C, RAD51D or PALB2 gene
• Age 25-40 years for BRCA1, 25-45 years for BRCA2 and 25-50 years for BRIP1, RAD51C, RAD51D and PALB2 carriers
• Childbearing completed
• Presence of at least one fallopian tube
• Participants may have a personal history of a non-ovarian malignancy
• Informed consent must be obtained and documented according to national and local regulatory requirement

Exclusion criteria

• Postmenopausal status (natural menopause or due to (cancer) treatment)
• Wish for second stage oophorectomy within two years after RRS (if clear at enrollment)
• Legally incapable
• Prior bilateral salpingectomy
• A personal history of ovarian, fallopian tube or peritoneal cancer
• Current clinical signs, diagnosis or treatment for malignant disease

The aimed sample size is 3000 women: 1500 BRCA1 and 1500 BRCA2 pathogenic variant carriers.
Women with a BRIP1, RAD51C, or RAD51D pathogenic variant can participate in the study, but will not contribute to the sample size or the primary outcome.

Study flowchart

Data collection

All data will be collected in a web-based electronic database including Case Report Forms (CRFs) and questionnaires.

At inclusion (prior to surgery)

• Baseline characteristics
• In- and exclusion criteria
• Questionnaire to be completed by patient

After surgery (within three months)

• Surgical outcomes
• Histopathological outcomes

Follow-up (annually)

• (non-) ovarian pelvic cancer
• breast cancer
• uptake of preventive breast surgery
• uptake of risk-reducing oophorectomy (in the arm choosing salpingectomy with delayed oophorectomy)

Three methods of annual follow-up are allowed: 1) annual out-patient visit and physician completes CRF, 2) patients completes a yearly questionnaire, 3) yearly assessment of a nationwide pathology database

Visualization of data collection.