OBJECTIVE: To compare the effectiveness of physician assessment with a new multivariate index assay in identifying high-risk ovarian tumors.
METHODS: The multivariate index assay was evaluated in women scheduled for surgery for an ovarian tumor in a prospective, multi-institutional trial involving 27 primary- care and specialty sites throughout the United States. Preoperative serum was collected, and results for the multivariate index assay, physician assessment, and CA 125 were correlated with surgical pathology. Physician assessment was documented by each physician before surgery. CA 125 cutoffs were chosen in accordance with the referral guidelines of the American College of Obstetricians and Gynecologists.
RESULTS: The study enrolled 590 women, with 524 evaluable for the multivariate index assay and CA 125, and 516 for physician assessment. Fifty-three percent were enrolled by nongynecologic oncologists. There were 161 malignancies and 363 benign ovarian tumors. Physician assessment plus the multivariate index assay correctly identified malignancies missed by physician assessment in 70% of nongynecologic oncologists, and 95% of gynecologic oncologists. The multivariate index assay also detected 76% of malignancies missed by CA 125. Physician assessment plus the multivariate index assay identified 86% of malignancies missed by CA 125, including all advanced cancers. The performance of the multivariate index assay was consistent in early- and late-stage cancers.
CONCLUSION: The multivariate index assay demonstrated higher sensitivity and lower specificity compared with physician assessment and CA 125 in detecting ovarian malignancies.
LEVEL OF EVIDENCE: III
The multivariate index assay is a preoperative diagnostic assay with high sensitivity for identifying all stages of ovarian malignancy, facilitating decisions about referral to a gynecologic oncologist.
From the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Kentucky Markey Cancer Center, Lexington, Kentucky; Applied Clinical Intelligence, Bala Cynwyd, Pennsylvania; and the Department of Pathology, Center for Biomarker Discovery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
See related article on page 1298.
For a list of OVA1 trial sites and each primary investigator specialty, see the Appendix online at http://links.lww.com/AOG/A240.
Funded by Vermillion, Inc.
Presented at the 41st Annual Meeting on Women's Cancer, the Society of Gynecologic Oncologists, March 14–17, 2010, San Francisco, California; and at the 42nd Annual Meeting on Women's Cancer, the Society of Gynecologic Oncologists, March 6–9, 2011, Orlando, Florida.
Corresponding author: Frederick R. Ueland, MD, Division of Gynecologic Oncology, University of Kentucky Medical Center, 800 Rose St., Lexington, Kentucky 40536-0298; e-mail: email@example.com.
Financial Disclosure Dr. Frederick Ueland was the principle investigator for the OVA1 trial and has been a member of Vermillion, Inc's speaker's bureau since January, 2011. He has received honoraria from Vermillion. Dr. Alan Smith is an independent statistician hired by Vermillion for data analysis. Dr. Zhen Zhang is an employee for the Johns Hopkins Center for Biomarker Discovery which has a sponsored research grant from Vermillion. He is entitled to royalty payment through a license agreement between Johns Hopkins University and Vermillion. The other authors did not report any potential conflicts of interest.