Quarterly Testing for Biomarker Improves Detection of Early-Stage Ovarian Cancer in High-Risk Women
Biomarker testing can help clinicians diagnose ovarian cancer earlier in some individuals.
Results from 2 ovarian cancer screening trials indicate a personalized approach that uses frequent CA125 testing could detect ovarian cancer at earlier stages in high-risk women.1
CA125 is a protein biomarker. Quarterly measures of CA125 can indicate when levels have risen above individual baseline levels. When increases in CA125 are detected, a subsequent transvaginal ultrasound examination reduced the risk of advanced disease at diagnosis in high-risk women who elected to postpone recommended preventive surgery.
Women at high risk of ovarian cancer are advised to undergo resection of their ovaries and fallopian tubes once their families are complete; however, some women choose to postpone the surgery, explained Steven Skates, PhD, of the Massachusetts General Hospital Cancer Center and the Biostatistics Unit, Boston, Massachusetts. The proportion of tumors detected at early stage in this population is 10%. This rate is increased to 50% with the screening protocol developed by this team.
Both trials used the Risk of Ovarian Cancer Algorithm (ROCA), which follows CA125 levels to identify significant increases from each patient's baseline levels, even when the standard threshold of 35 U/mL is not exceeded.
Researchers ran these trials through the National Cancer Institute's Cancer Genetics Network (CGN) with patients from ovarian Specialized Programs of Research Excellence and Early Detection Research Network sites and through the Gynecologic Oncology Group (GOG).
Both trials enrolled 3692 women at high risk for developing ovarian cancer based on familial history of ovarian and/or breast cancer or of risk-associated mutations in BRCA1/2 in the patients or their families. These women had not undergone risk-reducing surgery.
Patients underwent quarterly CA125 screens using ROCA to identify CA125 values above the patient's personalized baseline.
Women were referred for ultrasonography when ROCA determined they were intermediate risk. Women at a high ROCA risk underwent ultrasound and a clinical evaluation by a gynecologic oncologist or the site's principal investigator. These results guided decisions about salpingo-oophorectomy; however, patients could choose whether to undergo the procedure.
During the trials, clinicians identified 19 malignant tumors, 10 of which were diagnosed during screening. The remaining 9 were identified during preventive surgery.
Of the 10 cases, 4 were likely present at the beginning of the trials, and 6 likely developed during the trials. The results from these 6 cases emphasize the benefits of long-term ROCA screening.
The sensitivity of ROCA was greater than 80%, and 50% of tumors were identified at early stages.
Notably, these results do not determine whether screening reduced deaths due to ovarian cancer. Further research is needed on identifying biomarkers in ovarian cancer and advancing imaging technologies.
1. Skates SJ, Greene MH, Buys SS, et al. Early detection of ovarian cancer using the risk of ovarian cancer algorithm with frequent CA125 testing in women at increased familial risk – combined results from two screening trials. Clin Cancer Res. 2017 Jan 31. doi: 10.1158/1078-0432.CCR-15-2750 [Epub ahead of print]