To evaluate RRS with delayed RRO as an alternative for RRSO in BRCA1/2 gene germline mutation carriers. We hypothesize that RRS with delayed RRO leads to an equal ovarian cancer incidence when compared to RRSO.
ID
Source
Brief title
Condition
- Reproductive tract and breast disorders congenital
- Ovarian and fallopian tube disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary study outcome is high grade serous (ovarian) cancer incidence at the
age of 45 for BRCA1 and 50 for BRCA2 germline mutation carriers
Secondary outcome
Secondary endpoints are:
• High grade serous (ovarian) cancer incidence at the age of 70
• Incidence of (pre)malignant findings in tubes/ovaries
• Peri-operative morbidity and mortality
• Incidence of pelvic cancer (other than ovarian cancer)
• Breast cancer
• Uptake of risk reducing oophorectomy
Background summary
In BRCA 1/2 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.
Study objective
To evaluate RRS with delayed RRO as an alternative for RRSO in BRCA1/2 gene
germline mutation carriers. We hypothesize that RRS with delayed RRO leads to
an equal ovarian cancer incidence when compared to RRSO.
Study design
A prospective preference study.
Intervention
Standard treatment: RRSO
o BRCA1 at a maximum age of 40 (advised between age 35 and 40)
o BRCA2 at a maximum age of 45 (advised between age 40 and 45)
Innovative treatment: RRS when childbearing is completed with delayed RRO
o BRCA1: RRS at age 25-40 and RRO at a maximum age of 45 (advised between 35
and 45).
o BRCA2: RRS at age 25-45 and RRO at a maximum age of 50 (advised between age
40 and 50).
Study burden and risks
Participants are followed via their treating physician. At the moment of
inclusion, baseline characteristics will be reported to the study group. Within
three months after surgery, pathological and surgical outcomes will be
reported. During long-term follow up a biennial update will report on baseline
demographics, ovarian cancer incidence, prophylactic breast surgery, incidence
of non-ovarian pelvic cancer, breast cancer and surgery related morbidity.
Biennial screening is not obligatory, the biennial update may be based upon a
national pathology database. If women exceed the recommended age limit for
oophorectomy, we recommend a yearly contact to monitor these women and
reconsider the second surgery.
The most important risk for participants is the risk of developing ovarian
cancer within the interval between RRS and RRO. We estimate that risk to be
about 1-2% when RRO is postponed for five years in the scenario that the
earlier salpingectomy does not reduce ovarian cancer risk at all. Furthermore,
in the innovative treatment, the participant will undergo laparoscopy twice.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
• Women with a class 5 (definitely pathogenic) BRCA1 or BRCA2 germline mutation
in one of the participating centers.
• Age at inclusion;
o BRCA1: 25-40 years
o BRCA2: 25-45 years
• Childbearing completed
• Presence of at least one fallopian tube
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
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL70691.091.19 |