Ovarian Cancer Screening (PDQ®): Screening - Health Professional Information [NCI] - Description of the Evidence
A randomized pilot trial in the United Kingdom randomly assigned 10,977 women to a control group and 10,958 women to a screened group in 1989. The primary screen was the CA-125 test, followed by ultrasonography when CA-125 levels were elevated. Women were offered three annual screening rounds, and both groups were followed for 7 years. Compliance was 70.7% for all three screenings and 85.5% for at least one screening. There were 20 ovarian cancers in the control group and 16 in the screened group, only six of which were detected by screening. There was a higher proportion of stage I/II cancers in the screened group than in the control group (31.3% vs. 10.0%). There were 18 ovarian cancer deaths in the control group and nine in the screened group (relative risk [RR], 2.0; 95% CI, 0.78–5.13).
Incorporating data from multiple measures of CA-125 concentrations
Longitudinal measurement of CA-125 concentrations has been proposed as means to increase the performance of single-threshold measurements of CA-125 concentrations. As noted previously, the ROCA method is being evaluated in the UKCTOCS in conjunction with TVS as a two-stage screening process, and results from that trial are pending. Other methods to include multiple longitudinal CA-125 concentrations in order to examine change of CA-125 levels over time have been proposed but none have been independently evaluated for the impact on ovarian cancer mortality. A nested study was conducted within the PLCO trial to determine if the use of ROCA could potentially improve the identification of early-stage (stage I/II) ovarian cancer. The study evaluated the potential impact under two scenarios: best case and stage shift. Best case scenario assumed that all cancers that would have been detected earlier with ROCA compared with single-threshold CA-125 concentrations, would have avoided mortality. The stage shift scenario applied the observed PLCO early-stage survival rates to cases detected at an earlier stage with ROCA. The risk of death from ovarian cancer with ROCA was lower but estimates were not statistically significant (RR of 0.90 for best case scenario [95% CI, 0.69–1.17] and RR of 0.95 for stage shift scenario [95% CI, 0.74–1.23]).
Another retrospective study using annual CA-125 concentrations from the PLCO trials examined the potential impact of parametric empirical Bayes (PEB) longitudinal algorithm for the earlier detection of 44 incident ovarian cancers identified in PLCO. Setting the specificity at 99%, PEB signaled "abnormal" CA-125 concentrations on average 10 months earlier than with the single-threshold cutpoint. Whether or not this translated into a mortality benefit could not be determined.
CA-125 velocity has also been examined using a multiple logistic regression model within the PLCO trial as a predictor for the development of ovarian cancer. Both CA-125 velocity and time intervals between screening tests were associated with the development of ovarian cancer. The risk of ovarian cancer increased as velocity (measured as U/mL per month) increased and the risk of ovarian cancer decreased when the time intervals between screening tests increased.