Ueland.qxp 12/1/09 11:27 Page 63
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
100
86%
Physical exam
80
60
51%
40
27%
Imaging
20
12%
0
Stage I Stage II Stage III Stage IV
Biomarker evaluation
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. ■
1. Morgan RJ Jr, et al., Oncology (Williston Park), 1996;10:293–310. 12. NIH consensus conference, Ovarian cancer, JAMA, 20. Im SS, et al., Obstet Gynecol, 2005;105:35–41.
2. Hoskins W, et al., Oncology (Williston Park), 1997;11:896–900, 1995;273:491–7. 21. Dearking AC, et al., Obstet Gynecol, 2007;110:841–8.
903–4. 13. ACOG Committee Opinion: number 280, December 2002, Obstet 22. Gostout BS, Brewer MA, Clinical Obstet Gynecol,
3. Birkmeyer JD, J Clin Oncol, 2004;22:2765–6. Gynecol, 2002;100:1413–16. 2006;49(3):448–58.
4. Gillis CR, Hole DJ, BMJ, 1996;312:145–8. 14. Allen DG, et al, Ann Oncol, 1993;4(Suppl. 4):83–8. 23. Tingulstad S, et al., Obstet Gynecol, 1999;93:448–52.
5. Herr HW, et al., J Clin Oncol, 2004;22:2781–9. 15. Myers E, Bastian L, Havrilesky L, Kulasingam S, et al., Management 24. Maggina T, et al., Gynecol Oncol, 1994;54(2):117–23.
6. Engelen MJ, et al., Cancer, 2006;106:589–98. of Adnexal Mass, Rockville, MD: US Department of Health and 25. Schutter E, et al., Cancer, 1994;74(4):1398–406.
7. Hillner BE, et al., J Clin Oncol, 200;18:2327–40. Human Services, 2006. 26. Jacobs I, et al., Br J Obstet Gynecol, 1990;97(10):922–9.
8. Trimbos JB, Bolis G, Obstet Gynecol Surv, 1994;49: 814–16. 16. Earle CC, et al., J Natl Cancer Inst, 2006;98:172–80. 27. Ueland F, et al., Gynecol Oncol, 2003;91:46–50.
9. Giede KC, et al., Gynecol Oncol, 2005;99:447–61. 17. Ueland FR, et al., Gynecol Oncol, 2005;99:400–403. 28. Timmerman D, et al., J Clin Oncol, 2007;25:4194–4200.
10. Ozols RF, Oncology (Williston Park), 1997;11:95–105. 18. DePriest PD, et al., Gynecol Oncol, 1993;51:7–11.
11. Elit L, et al., SOGC Clinical Practice Guidelines, 2000;97:1–5. 19. Modesitt SC, et al., Obstet Gynecol, 2003;102:594–9.
US OBSTETRICS & GYNECOLOGY 63
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84