Clinical performance of a multivariate index assay for detecting early-stage ovarian cancer.
OBJECTIVE
We sought to analyze the effectiveness of a multivariate index assay (MIA) in identifying early-stage ovarian malignancy compared to clinical assessment, CA 125-II, and modified American Congress of Obstetricians and Gynecologists (ACOG) guidelines among women undergoing surgery for an adnexal mass.


METHODS
Patients were recruited in 2 related prospective, multi-institutional trials involving 44 sites. All women had preoperative imaging and biomarker analysis. Preoperative biomarker values, physician assessment of ovarian cancer risk, and modified ACOG guideline risk stratification were correlated with surgical pathology.


RESULTS
A total of 1016 patients were evaluable for MIA, CA 125-II, and clinical assessment. Overall, 86 patients (8.5%) had primary-stage I/II primary ovarian malignancy, with 70.9% having stage I disease and 29.1% having stage II disease. For all early-stage ovarian malignancies, MIA combined with clinical assessment had significantly higher sensitivity (95.3%; 95% confidence interval [CI], 88.6-98.2) compared to clinical assessment alone (68.6%; 95% CI, 58.2-77.4), CA 125-II (62.8%; 95% CI, 52.2-72.3), and modified ACOG guidelines (76.7%; 95% CI, 66.8-84.4) (P < .0001). Among the 515 premenopausal patients, the sensitivity for early-stage ovarian cancer was 89.3% (95% CI, 72.8-96.3) for MIA combined with clinical assessment, 60.7% (95% CI, 42.4-76.4) for clinical assessment alone, 35.7% (95% CI, 20.7-54.2) for CA 125-II, and 78.6% (95% CI, 60.5-89.8) for modified ACOG guidelines. Early-stage ovarian cancer in postmenopausal patients was correctly detected in 98.3% (95% CI, 90.9-99.7) of cases by MIA combined with clinical assessment, compared to 72.4% (95% CI, 59.8-82.2) for clinical assessment alone, 75.9% (95% CI, 63.5-85.0) for CA 125-II, and 75.9% (95% CI, 63.5-85.0) for modified ACOG guidelines.


CONCLUSIONS
MIA combined with clinical assessment demonstrated higher sensitivity for early-stage ovarian malignancy compared to clinical assessment alone, CA 125-II, and modified ACOG guidelines with consistent performance across menopausal status.
Department of Obstetrics and Gynecology, Irvine-Medical Center, University of California, Orange, CA.
Teresa C
TC
Longoria
Department of Obstetrics and Gynecology, University of Kentucky Medical Center, Lexington, KY.
Frederick R
FR
Ueland
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD.
Zhen
Z
Zhang
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD.
Daniel W
DW
Chan
Applied Clinical Intelligence, Bala Cynwyd, PA.
Alan
A
Smith
Vermillion Inc, Mountain View, CA.
Eric T
ET
Fung
Vermillion Inc, Austin, TX.
Donald G
DG
Munroe
Department of Obstetrics and Gynecology, Irvine-Medical Center, University of California, Orange, CA. Electronic address: rbristow@uci.edu.
Robert E
RE
Bristow
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis*; D011446:Prospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D055815:Young Adult
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen
detection; early stage; ovarian cancer