TUBectomy With Delayed Oophorectomy in High Risk Women to Assess the Safety of Prevention

Study Overview
=================
Brief Summary
-----------------
The aim of the project is to evaluate the risk-reducing salpingectomy with delayed oophorectomy as an alternative for risk-reducing salpingo-oophorectomy in high risk women with respect to ovarian cancer incidence.

Detailed Description
-----------------
In BRCA1/2 gene mutation carriers, a risk-reducing salpingo-oophorectomy (RRSO) is recommended around the age of 40. This recommendation is based on a 10-40% life-time risk of ovarian cancer in this population and disappointing results of ovarian cancer surveillance for early detection. Moreover, the mortality rate of ovarian cancer is high. Effects of RRSO are a decrease in ovarian cancer risk (80-96%) on one hand and immediate onset of menopause and non-cancer related morbidity on the other hand. The fifty percent breast cancer risk reduction after RRSO has become disputable in the last years. Based on multiple studies showing that most high-grade serous ovarian cancers develop at the distal end of the Fallopian tube, an innovative strategy for RRSO has been developed for this study proposal: risk-reducing salpingectomy (RRS) with delayed risk-reducing oophorectomy (RRO). However, the safety of this strategy has not been proven yet. Before implementing this innovative strategy as standard care we need to investigate the long term effects on ovarian cancer incidence.

Official Title
-----------------
TUBectomy With Delayed Oophorectomy as Alternative for Risk-reducing Salpingo-oophorectomy in High Risk Women to Assess the Safety of Prevention: TUBA-WISP II Study.

Conditions
-----------------
BRCA1 Gene Mutation, BRCA2 Gene Mutation, RAD51C Gene Mutation, RAD51D Gene Mutation, BRIP1 Gene Mutation, Ovarian Cancer

Intervention / Treatment
-----------------
* Procedure: Risk-reducing salpingectomy with delayed oophorectomy
* Procedure: Risk-reducing salpingo-oophorectomy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women with a class 5 (definitely pathogenic) BRCA1, BRCA2, RAD51C, RAD51D or BRIP1 germline mutation in one of the participating centers. Age at inclusion; BRCA1: 25-40 years BRCA2: 25-45 years RAD51C, RAD51D, BRIP1: 25-50 years Childbearing completed Presence of at least one fallopian tube Participants may have a personal history of non-ovarian malignancy Informed consent must be obtained and documented according to national and local regulatory requirements and the local rules followed in the institution. Exclusion Criteria: Postmenopausal status (natural menopause or due to treatment) Wish for second stage RRO within two years after RRS Legally incapable Prior bilateral salpingectomy A personal history of ovarian, fallopian tube or peritoneal cancer Current diagnosis or treatment for malignant disease

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Risk-reducing salpingectomy with delayed oophorectomy<br>Risk-reducing salpingectomy after the completion of childbearing with delayed oophorectomy. | Procedure: Risk-reducing salpingectomy with delayed oophorectomy<br>* BRCA1: RRS at age 25-40 and RRO at a maximum age of 45 (advised between 35 and 45). BRCA2: RRS at age 25-45 and RRO at a maximum age of 50 (advised between age 40 and 50). BRIP1, RAD51C, RAD51D: RRS at age 25-50 and RRO at a maximum age of 55 (advised between 45 and 55)<br>|
| Active Comparator: Risk-reducing salpingo-oophorectomy<br>Risk-reducing salpingo-oophorectomy. | Procedure: Risk-reducing salpingo-oophorectomy<br>* BRCA1 at a maximum age of 40 (advised between age 35 and 40) BRCA2 at a maximum age of 45 (advised between age 40 and 45) BRIP1, RAD51C, RAD51D: at a maximum age of 50 (advised between 45 and 50)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High grade serous (ovarian) cancer incidence | High grade serous (ovarian) cancer incidence | Until the age of 45 for BRCA1 and 50 for BRCA2 germline mutation carriers | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of (pre)malignant findings in tubes/ovaries | Incidence of (pre)malignant findings in tubes/ovaries at risk-reducing salpingectomy, oophorectomy and salpingo-oophorectomy. | 6 weeks after each surgery | 
| Peri-operative morbidity and mortality | Peri-operative morbidity and mortality | 6 weeks after each surgery | 
| Incidence of pelvic cancer (other than ovarian cancer) | Incidence of pelvic cancer (other than ovarian cancer) | Up to the age of 70 | 
| Incidence of breast cancer | Incidence of breast cancer | Up to the age of 70 | 
| Uptake of risk reducing oophorectomy | Uptake of risk reducing oophorectomy after risk reducing salpingectomy | Up to the age of 70 |