Normal Risk Ovarian Screening Study: 21-Year Update.

PURPOSE: The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in postmenopausal women at conventional hereditary risk where significantly rising cancer antigen (CA)-125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer. METHODS: A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 woman-years in a single-arm study (ClinicalTrials.gov identifier: NCT00539162). Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was unchanged and <1:2,000, women returned in a year. If risk increased above 1:500, TVS was undertaken immediately, and if risk was intermediate, CA125 was repeated in 3 months with a further increase in risk above 1:500 prompting referral for TVS. An average of 2% of participants were referred to TVS annually. RESULTS: Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors with 12 in early stage (I-II). In addition, seven endometrial cancers were detected with six in stage I. As four ovarian cancers and two borderline tumors were diagnosed with a normal ROCA, the sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23), and 70% of ROCA-detected cases (12 of 17) were in stage I-II. NROSS screening reduced late-stage (III-IV) disease by 34% compared with UKCTOCS controls and by 30% compared with US SEER values. The positive predictive value (PPV) was 50% (17 of 34) for detecting ovarian cancer and 74% (25 of 34) for any cancer, far exceeding the minimum acceptable study end point of 10% PPV. CONCLUSION: While the NROSS trial was not powered to detect reduced mortality, the high specificity, PPV, and marked stage shift support further development of this strategy.

A 2-stage ovarian cancer screening strategy using the Risk of Ovarian Cancer Algorithm (ROCA) identifies early-stage incident cancers and demonstrates high positive predictive value.

BACKGROUND: A 2-stage ovarian cancer screening strategy was evaluated that incorporates change of carbohydrate antigen 125 (CA125) levels over time and age to estimate risk of ovarian cancer. Women with high-risk scores were referred for transvaginal ultrasound (TVS). METHODS: A single-arm, prospective study of postmenopausal women was conducted. Participants underwent an annual CA125 blood test. Based on the Risk of Ovarian Cancer Algorithm (ROCA) result, women were triaged to next annual CA125 test (low risk), repeat CA125 test in 3 months (intermediate risk), or TVS and referral to a gynecologic oncologist (high risk). RESULTS: A total of 4051 women participated over 11 years. The average annual rate of referral to a CA125 test in 3 months was 5.8%, and the average annual referral rate to TVS and review by a gynecologic oncologist was 0.9%. Ten women underwent surgery on the basis of TVS, with 4 invasive ovarian cancers (1 with stage IA disease, 2 with stage IC disease, and 1 with stage IIB disease), 2 ovarian tumors of low malignant potential (both stage IA), 1 endometrial cancer (stage I), and 3 benign ovarian tumors, providing a positive predictive value of 40% (95% confidence interval = 12.2%, 73.8%) for detecting invasive ovarian cancer. The specificity was 99.9% (95% confidence interval = 99.7%, 100%). All 4 women with invasive ovarian cancer were enrolled in the study for at least 3 years with low-risk annual CA125 test values prior to rising CA125 levels. CONCLUSIONS: ROCA followed by TVS demonstrated excellent specificity and positive predictive value in a population of US women at average risk for ovarian cancer.

Rapid group B streptococci screening using a real-time polymerase chain reaction assay.

OBJECTIVE: To estimate the clinical performance characteristics of a real-time polymerase chain reaction (PCR) assay using vaginal/rectal swabs from antepartum (35-37 weeks of gestation) and intrapartum women. METHODS: The assay evaluated is a qualitative, automated, real-time PCR test for the detection of group B streptococci, with results available in approximately 75 minutes. Enrollment in this multicenter clinical study occurred between October 2005 and January 2006. Vaginal/rectal swabs were analyzed by nursing personnel (intrapartum tests) or by laboratory technologists (all others). Polymerase chain reaction assay results were compared with culture using standard methods, including selective broth medium, and to a predicate nucleic acid amplification test. RESULTS: Of 1,028 enrolled women, 234 were deemed ineligible, and 10 had unresolved test results. Of the 784 remaining women, valid PCR assay results were obtained on the first test attempt for 93.0%. Performance characteristics relative to culture were sensitivity 91.1%, specificity 96.0%, positive predictive value 87.8%, negative predictive value 97.1%, and accuracy 94.8%. These results exceeded those obtained using the predicate nucleic acid amplification test. CONCLUSION: Performance characteristics of the PCR assay exceed the threshold recommended by the Centers for Disease Control and Prevention when compared with culture. The test is sufficiently robust to be performed for intrapartum patients in a point-of-care setting by medical professionals. LEVEL OF EVIDENCE: II.