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A Biomarker Panel for Risk Stratification of Ovarian Tumors
Figure 1: Survival by Stage at Time of Diagnosis Figure 2: Potential Care Pathway of Managing Ovarian Tumors
Stage I Stage II Stage III Stage IV
Epithelial ovarian cancer is the fourth leading cause of cancer death in women. Since early signs and symptoms are
often unreliable, most ovarian cancers (70%) are discovered in advanced stage (Rosenthal and Jacobs, 1998).
Unfortunately, late-stage ovarian cancer is associated with a poor outcome, with five-year survival rates between 12
and 27%. The survival for early-stage disease is dramatically higher (86% for stage I). The key to improving ovarian
cancer survival is early detection. (Five-year survival by stage of ovarian cancer at diagnosis from Nguyen et al., 1993).
Surgery by Surgery by
general gynecologist gynecological oncologist
A biomarker panel may be a useful addition to a physician’s clinical
Ovarian tumors may be detected on physical examination or because of symptoms. Ovarian tumors are almost
assessment to help determine the risk of malignancy for an ovarian
always assessed by imaging, usually by ultrasound but also by computed tomography and/or magnetic resonance
tumor before surgery. There are dozens of potentially useful biomarkers
imaging. Currently, no biomarkers are cleared by the FDA to evaluate these tumors. Novel biomarker panels may be
useful in helping to assess the risk for malignancy.
in the ovarian cancer literature, yet none has emerged from prospective
clinical trials as being effective in the diagnostic evaluation of an ovarian In the OVA1 prospective study, 21 of 27 pre-menopausal patients with
tumor. The requirements for sensitivity and specificity depend on the goal ovarian cancer had a positive OVA1 biomarker panel but an indeterminate
of the test. A woman with a suspicious ovarian tumor who is a surgical CA125 II score (<200U/ml), including nine of the 12 with stage I or II
candidate should be evaluated by a gynecologic oncologist if there is a disease. In addition, 17 of 23 post-menopausal women had a positive OVA1
high suspicion of malignancy. This scenario requires a test with high biomarker panel and a negative CA125 II (<35U/ml). Overall, 76.0% of
sensitivity and high negative predictive value to limit the number of patients with ovarian cancer had a positive OVA1 biomarker panel despite
ovarian cancer surgeries performed by the non-specialist surgeon. The an indeterminate CA 125 II.
high sensitivity will ensure that a substantial fraction of malignancies will
be detected, and the high negative predictive value will provide the The OVA1 biomarker panel can improve the proportion of cancer patients
generalist with greater confidence in a negative result. in the referral population to a cancer specialist. In the OVA1 study,
physicians utilized their best clinical judgment but still referred the majority
The OVA1 biomarker panel complements the information currently (72%) of benign ovarian tumors for surgery to the gynecologic oncologist.
available to physicians by further identifying patients who could benefit By utilizing the OVA1 result pre-operatively, clinicians would have referred
from referral to a gynecologic oncologist for surgery. The biomarker fewer benign ovarian tumors (57%).
panel was developed through more than eight independent studies in
more than 2,500 women. The panel was validated in a prospective The OVA1 biomarker panel is useful in the pre-operative evaluation of an
clinical trial that was one of the largest ovarian cancer studies ever ovarian tumor for which surgery will be performed, and specifically in
conducted and assessed more than 550 women with a confirmed determining whether a patient would benefit from referral to a
adnexal mass at 27 clinical sites in the US. The OVA1 biomarker panel gynecologic oncologist. This serum biomarker panel offers added benefit
had greater than 90% sensitivity for epithelial ovarian cancer. Moreover, to CA125 II alone, and its high negative predictive value in pre-
the OVA1 biomarker panel has over 90% negative predictive value in menopausal women makes it particularly useful in this patient population.
pre-menopausal women. The modest overall specificity (~43.0%) The biomarker panel may help increase the proportion of cancers in the
means that patients with a benign condition may be referred to a referral population to the gynecologic oncologist by enabling the general
gynecologic oncologist for surgery. However, both the gynecologic physician to better classify benign tumors. When combined with other
oncologist and general surgeon will likely perform the same operation clinical information, the OVA1 triage biomarker panel can help assess the
for a benign ovarian tumor, so there should be no additional surgical risk likelihood of malignancy of an ovarian tumor before surgery and facilitate
to the patient. decisions about referral to a gynecologic oncologist. ■
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