A prospective multi-center ovarian cancer screening study in women at increased risk

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5510 Background: No proven ovarian cancer (OC) screening strategy exists for women who are at increased risk for the disease. A risk of ovarian cancer algorithm (ROCA) using serial CA125 values has previously shown greater positive predictive value (PPV) and sensitivity than a single CA125 in screening women at general population risk. We hypothesized that using ROCA would yield a reasonable PPV for ovarian cancer screening in a cohort at increased risk. Methods: Between 7/2001 and 9/2006, 25 sites (14 Cancer Genetics Network, 3 ovarian SPOREs, 1 EDRN, 7 others) prospectively enrolled patients. Inclusion criteria included: among self, 1° or 2° relatives in same lineage either (i) BRCA1/2 mutation, or (ii) two of OC or early onset (age = 50) breast cancer (BC), or (iii) Ashkenazi ethnicity and 1 of OC or BC. A previous diagnosis of OC excluded subjects. Subjects underwent CA125 every 3 months and the risk of having ovarian cancer based on the CA125 profile was recalculated after each test. ROCA referred subjects with risk > 1% to ultrasound (US), and risk > 10% additionally to a gynecologic oncologist. Objectives included PPV for study indicated surgery, sensitivity, and compliance. Sample size was chosen to observe 8 OC endpoints with a power of 80% to rule out PPV = 10% if the true PPV = 20%. Results: 2,343 high risk women enrolled, with 6,284 women years of screening and 19,549 CA125s obtained. There were 628 (10%/yr) referrals to US with 414 US performed. 38 women underwent study indicated surgeries. 9 OCs were identified during screening, 3 were prevalent (1 early, 2 late stage), and 6 were incident (5/6 = 83% early, 1 late). 3 of the 6 incident cases were found on prophylatic oophorectomy in early stage. ROCA detected 2 in early stage of remaining 3 incident cases, and 3 of 3 prevalent cases. The PPV was 5/38 = 13% (95% CI 4.4%, 28%) and sensitivity was 5/6 = 83%, CI (36%, 99%). There was high compliance with CA125 testing throughout study, with 84%, 85%, 85%, 82% subjects returning within 1 month of schedule for first 4 tests. Conclusions: Frequent CA125 testing using ROCA results in an acceptable PPV and high compliance in a cohort of women at increased risk for OC. A definitive screening study (= 30 incident cases) using ROCA with serial CA125 and possibly additional markers is required to define sensitivity for early stage OC. [Table: see text]