A COMBINATION OF SERUM MARKERS FOR DISCRIMINATION OF MALIGNANT OVARIAN MASS

SAN FRANCISCO -- A presurgical assay predicted ovarian cancer and metastases with greater than 90% sensitivity and cancer stage with almost 100% sensitivity, according to a study reported here.

The test, which incorporates five assays, had a specificity of 78% for masses that were not epithelial ovarian cancer and 75% for masses of low malignant potential.

"The OVA1 test successfully classifies patients into high or low probability of malignancy," Frederick Ueland, MD, of the University of Kentucky in Lexington, said at the Society of Gynecologic Oncologists meeting.

"The OVA1 has high sensitivity in pre- and postmenopausal women, all stages of ovarian malignancies, and its performance is independent of physician specialty."

However, the test's low specificity raised some concern, as verbalized by an invited discussant of the study.

Recently approved by the FDA, the OVA1 incorporates five assays that have been found useful for evaluating ovarian cancer: CA125, transthyretin, apolipoprotein A1, beta 2 microglobulin, and transferrin.

On the basis of assay results, a proprietary computer software algorithm creates risk index with a range of 0 to 10. For premenopausal women, a score of <5.0>

"The OVA1 is intended to complement, not replace, the standard preoperative evaluation," said Ueland. "When combined with other clinical information, the OVA1 test can determine the risk of malignancy before surgery and facilitate decisions about referral to a gynecologic oncologist."

Ueland reported findings from a multicenter evaluation of the test in women scheduled for surgery for an ovarian mass. All patients had an ovarian tumor documented by imaging and planned surgical intervention within three months of the imaging results.

Physicians at 27 primary care and specialty sites enrolled patients in the study. Preoperative evaluation consisted of imaging to confirm tumor presence, serum collection, and a clinical assessment that led a physician to judge a tumor as malignant or nonmalignant.

The study involved 516 patients, 235 of whom were premenopausal. The patients' median age was 52 (48 among premenopausal women and 54 among postmenopausal women).

Pathology showed the following:

• 355 (69%) of the tumors were benign
• 96 (19%) were epithelial ovarian cancer
• 28 (5%) were tumors with low malignant potential
• 18 (4%) were nonprimary ovarian malignancy with involvement of the ovaries
• 9 (2%) were other primary ovarian malignancies
• 10 (2%) were pelvic malignancies without involvement of the ovaries

The OVA1 test alone achieved an overall sensitivity of 92%, specificity of 43%, positive predictive value of 42%, and negative predictive value of 93%.

When added to physician assessment, the test increased sensitivity from 60% to 89% in premenopausal women and from 81% to 98% in postmenopausal women.

Negative predictive value increased from 90% to 94% and from 85% to 96% in pre- and postmenopausal women, respectively.

Combining the OVA1 with physician preoperative assessment led to a decline in specificity from 83% to 40% in premenopausal women and from 74% to 28% in postmenopausal women.

Positive predictive decreased from 46% to 26% and from 69% to 49% in the pre- and postmenopausal groups.

The OVA1 had a sensitivity of 99% for epithelial ovarian cancer, 94% for metastases, 78% for nonepithelial ovarian cancer, and 75% for tumors with low malignant potential. The test predicted stage I disease with 90% sensitivity and stages II-IV with 100% sensitivity.

During the discussion, Robin Farias-Eisner, MD, PhD, of the University of California Los Angeles, asked Ueland whether the data provided any explanations for the 43% overall specificity of the test.

Noting that physician assessment alone resulted in relatively high specificity and positive predictive value, Ueland said low specificity resulting from the addition of the OVA1 "made no sense to me."

"We went back to the data and, to my surprise, we found that when the physicians' preoperative assessment was negative, 46% of the time the patient was still referred to a gynecologic oncologist," Ueland explained. "That told us that general gynecologists don't have confidence in their own negative assessments."