Performance of the American College of Obstetricians and Gynecologists’ Ovarian Tumor Referral Guidelines With a Multivariate Index Assay Rachel Ware Miller, MD, Alan Smith, MS, Christopher P. DeSimone, MD, Leigh Seamon, DO, MPH, Scott Goodrich, MD, Iwona Podzielinski, MD, Lori Sokoll, PhD, John R. van Nagell Jr, MD, Zhen Zhang, PhD, and Frederick R. Ueland, MD OBJECTIVE: The American College of Obstetricians and Gynecologists (the College) published referral guidelines for women with a pelvic mass that incorporate CA 125. A new multivariate index assay assesses the malignant risk of ovarian tumors before surgery. Our objective was to estimate the performance of the College guidelines with this new multivariate index assay. METHODS: This prospective, multi-institutional trial in- cluded 27 primary care and specialty sites throughout the United States. The College guidelines were evaluated in women scheduled for surgery for an ovarian mass. Clin- ical criteria and blood for biomarkers were collected before surgery. A standard CA 125-II assay was used and the value applied to the multivariate index assay algo- rithm and the CA 125 analysis. Study results were corre- lated with surgical pathology. RESULTS: Of the 590 women enrolled with ovarian mass on pelvic imaging, 516 were evaluable. There were 161 malignancies (45 premenopausal and 116 postmeno- pausal). The College referral criteria had a modest sensi- tivity in detecting malignancy. Replacing CA 125 with the multivariate index assay increased the sensitivity (77– 94%) and negative predictive value (87–93%) while de- creasing specificity (68 –35%) and positive predictive value (52– 40%). Similar trends were noted for premeno- pausal women and early-stage disease. CONCLUSION: Replacing CA 125 with the multivariate index assay improves the sensitivity and negative predic- tive value of the College referral guidelines while de- creasing specificity and positive predictive value. The high sensitivity is maintained in premenopausal women and early-stage disease. (Obstet Gynecol 2011;117:000–000) DOI: 10.1097/AOG.0b013e31821b1d80 LEVEL OF EVIDENCE: III T he National Institutes of Health released a consen- sus statement in 1994 declaring “women with ovarian masses who have been identified preopera- tively as having a significant risk of ovarian cancer should be given the option of having their surgery performed by a gynecologic oncologist.” 1 There have been numerous publications and guidelines recom- mending that women with ovarian cancer be under the care of a gynecologic oncologist. 2–8 Reports indi- cate that only one third of women with malignant For a list of OVA1 trial sites and each primary investigator specialty, see the Appendix online at http://links.lww.com/AOG/A243. 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 Institu- tions, Baltimore, Maryland. Funded by Vermillion Inc., Austin, Texas. Data from this article were 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: Rachel Ware Miller, MD, Assistant Professor of Gyne- cologic Oncology, University of Kentucky Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0298; e-mail: raware00@uky.edu. Financial Disclosure Dr. Frederick Ueland was the principle investigator for the OVA1 trial and became a member of Vermillion’s speaker’s bureau in January 2011. He also has received honoraria as a speaker for Vermillion. Dr. Alan Smith is an independent statistician hired by Vermillion for data analysis. Dr. Zhen Zhang is an employee of 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. © 2011 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/11 VOL. 117, NO. 6, JUNE 2011 OBSTETRICS & GYNECOLOGY 1