Prospective Study of Prophylactic Salpingo-Oophorectomy and Longitudinal CA-125 Screening Among Women at Increased Genetic Risk of Ovarian Cancer
Annually, more than 25,500 women develop ovarian cancer (OC) and more than 16,000 die of
this disease in the United States.
Women at high genetic risk of OC have a much higher lifetime risk of developing OC than
women in the general population.
OC is difficult to detect using current screening methods, which include CA-125 monitoring
and transvaginal ultrasound (TVUS); most women are diagnosed when the disease is in advanced
stage, when survival chances are low.
This protocol investigates a novel OC screening strategy [longitudinal CA-125 levels (using
a mathematical algorithm known as ROCA) and TVUS] and surgical methods [risk-reducing
salpingo-oophorectomy (RRSO)] in managing women at high genetic risk of OC.
To pool resources from intramural and extramural OC investigators and obtain the first
prospective data from high-risk women addressing the incidence of critical cancer endpoints
and quality of life, thus determining:
1. . by how much RRSO reduces OC/Breast Cancer (BC) risk,
2. . how RRSO affects quality of life,
3. . which factors influence the decision about which management approach to choose,
4. . how premature menopause affects the risk of developing medical problems,
5. . if there are detectable abnormalities in ovaries which allow for early diagnosis, and
6. . how cellular/molecular malignant processes occur.
Women age 30 or older with no prior history of OC and at least one intact ovary.
Must be at increased genetic risk of OC by meeting one of the following criteria:
1. . Subject or close blood relative has tested positive for a BRCA1/2 mutation, or
2. . Subject has family history of 2 or more close blood relatives with BC and/or OC, or
3. . Subject has family history of 1 or more close blood relatives with BC and/or OC and
Ashkenazi Jewish ancestry, or
4. . Subject has had premenopausal BC and is of Ashkenazi Jewish descent, or
5. . Subject has estimated probability of having a BRCA1/2 mutation using BRCAPRO
If the presence of BC is used for eligibility, at least one BC must be of premenopausal
onset. If menopausal status at the time of BC diagnosis is unknown, age at diagnosis must be
less than 50 years.
International, multi-institution, prospective cohort, collaborative study between NCI's
Clinical Genetics Branch, Gynecologic Oncology Group (GOG), and Cancer Genetics Network.
Two-arm, non-randomized study of women contemplating RRSO to diminish their OC risk.
Women decide whether to undergo RRSO in consultation with their physicians.
1. . Women who choose RRSO have surgery under a standardized procedure. Clinically occult
primary cancers and precursor lesions are sought, and material is banked for molecular
studies. CA-125 levels are measured twice yearly.
2. . Women who decline RRSO choose OC screening with quarterly CA125/ROCA, which provides
estimates of the likelihood that subjects have OC. TVUS and gynecologic oncology
consultation may be arranged. TVUS is done on an annual basis, at minimum.
Subjects from both arms complete demographic, epidemiologic, and psychosocial instruments
and provide blood samples for research-based genetic testing (germline BRCA1/2), CA-125
testing, and serum/plasma/DNA storage.
Primary outcomes are development of OC, fallopian tube cancer, primary peritoneal carcinoma,
Study accrual goals include approximately 800 subjects in the RRSO arm and 2,400 subjects in
the screening arm, each to include at least 400 BRCA1/2 mutation carriers.
Mark H Greene, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|