Clinically undetectable ovarian and tubal tumors may be present in high-risk patients

1. A non-randomized control trial of 996 women at high risk for developing ovarian and tubal cancer found that 2.6% of cases had undetectable neoplasms on pathology after risk-reducing salpingo-oophorectomy.

2. Positive BRCA 1/2 mutation status, older age, postmenopausal status, and abnormal CA-125 levels were associated with clinically undetectable malignancies.

Evidence Rating Level: 3 (Average)

Study Rundown: Carriers of mutations in the BRCA1/2 gene are at higher risk for developing breast and ovarian cancer. In patients with high risk of ovarian cancer, risk-reducing salpingo-oophorectomy (RRSO) have been previously demonstrated to reduce mortality. However, it is not known whether this protection is superior to the traditional CA-125 or transvaginal ultrasound (TVU) screening. In this study, 966 women at high risk of ovarian cancer who elected to have RRSO rather than screening were included. This cohort of patients demonstrated no clinical signs of malignancy and also had CA-125 as well as TVU data available at the time of surgery. Pathology of the surgical specimens demonstrated that 25 patients (2.6%) had clinically undetected ovarian/tubal malignancies. In women who were BRCA1 carriers, BRCA2 carriers, or non-carriers, the rate of occult malignancy was 4.6%, 2.5%, and 0.5%, respectively. The authors also found that elevated CA-125 or abnormal TVU, postmenopausal status, and age were also independently associated with occult neoplasms. Interestingly, 4 of the 25 patients with occult disease had normal screening results, suggesting that there may be a small advantage to RRSO over screening. However, this study was limited in that patients could not be randomized to RRSO, making it very likely that some patients with vague clinical features were preferentially directed to surgery.

Click to read the study in the Journal of Clinical Oncology

Relevant reading: Risk-Reducing Salpingo-oophorectomy in Women with a BRCA1 or BRCA2 Mutation

In-Depth [cross-sectional study]: In this study, standardized pathology results from 966 women from the National Ovarian Cancer Prevention and Early Detection Study (GOG0199) who elected to have RRSO rather than screening were included. 25 patients were found to have occult invasive carcinoma (21) or serous tubal intraepithelial carcinoma (4). Risk of occult malignancy was highest in BRCA1 mutation carriers (4.6%, 95% CI: 2.3-6.9%), followed by BRCA2 mutation carriers (3.5%, 95% CI: 1.1%-5.8%). Only 2 of 403 (0.5%, 95% CI: -0.2-1.2%) non-carriers demonstrated occult malignancy on pathological analysis. Women who were older had higher rates of detected cancers (52.7 years vs 47.1 years, P<0.001). Disease was detected more in postmenopausal women (4.5% vs 1.2%, P = 0.003). Elevated CA-125 and/or abnormal TVU was also associated with higher occult malignancy rates (10.6% vs 1.6%, P<0.001). In multivariate analysis, positive BRCA mutation status (OR: 8.3; 95% CI: 1.9-37.0), postmenopausal status (OR: 4.8, 95% CI: 1.8-13.2), and abnormal CA-125/TVU (OR: 13.8, 95% CI: 5.2-36.3) were independently associated with occult neoplasms at RRSO.

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