Ovarian Cancer Screening (PDQ®): Screening - Health Professional Information [NCI] - Description of the Evidence
Other Potential Markers
Research continues to find other biomarkers that either alone or in combination with CA-125 concentrations may lead to the early detection of ovarian cancer. A panel of biomarkers that included CA-125, HE4, transthyretin, CA15.3, and CA72.4 was evaluated using specimens assembled from multiple cohort and randomized trials, including the PLCO trial. The phase II and III biomarker studies concluded that CA-125 remained the "single-best biomarker" for ovarian cancer. Another retrospective study, nested within the PLCO trial and included 118 ovarian cancer cases and 8 controls per case, evaluated 7 proteomic biomarkers (apolipoprotein A1, truncated transthyretin, transferrin, hepcidin, beta-2 microglobulin, connective tissue activating protein III, and inter-alpha-trypsin inhibitor heavy-chain) in addition to CA-125. The addition of the seven protein biomarkers to CA-125 did not improve the sensitivity beyond the use of CA-125 levels alone. This contrasted with this same group's preliminary evaluation of these markers using postdiagnostic rather than prediagnostic blood samples.
Harms From Screening
The PLCO trial provides the most reliable data to date on screening-related harms. The rate of minor complications associated with CA-125 and TVU such as bruising or fainting occurred at a rate of 58.3 cases per 10,000 women screened with CA-125 and 3.3 cases per 10,000 women screened with TVU. Major complications associated with the diagnostic procedures among women diagnosed with ovarian cancer included infections, blood loss, bowel injury, and cardiovascular events. At least one major complication was reported among 52% of women diagnosed in the usual care group and 45% among women diagnosed with ovarian cancer in the screened group.
False-positive tests occurred among 3,285 women, translating to a rate of about 5% at each screening round. The majority of false-positive tests (60%) result from TVU. Of the 3,285 women with false-positive results, 33% underwent surgery. Of the 1,080 women who underwent surgery, 15% had 222 major complications, for a rate of 20.6 complications per 100 surgical procedures.
Women in the intervention group were more likely to have had an oophorectomy than those in the control group. Rates of oophorectomy were 85.7 per 10,000 person-years in the screened group compared with 64.2 per 10,000 person-years in the usual care group (rate ratio, 1.33; 95% CI, 1.24–1.43).
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