CA-125 by itself should not be used to decide whether or not to take a patient to surgery. Nevertheless, once the decision to operate has been made, CA-125 can be used in conjunction with HE4 to calculate a Risk of Malignancy Algorithm (ROMA) score. The score is based on menopausal status, and if the calculated risk is elevated, patient referral to a gynecologic oncologist for her surgery should be strongly considered.
Similarly, the OVA1 test is currently approved by the Food and Drug Administration to assess the likelihood of malignancy in patients who are having surgery for an adnexal mass. The test is also based on menopausal status, and if elevated, a referral to a gynecologic oncologist is recommended. In young women with adnexal masses, germ cell tumor markers may be more helpful (lactate dehydrogenase [LDH], human chorionic gonadotropin [hCG], alpha-fetoprotein [AFP]), while in patients with signs or symptoms of estrogen or androgen excess, sex cord-stromal tumor markers (inhibin B, anti-Müllerian hormone [AMH], testosterone, dehydroepiandrosterone [DHEA], estradiol) would be appropriate to obtain. While no tumor marker is "diagnostic," the results may assist in the decision to perform surgery and consider referral to a gynecologic oncologist.
In summary, the workup for an adnexal mass should include a detailed medical and family history, a thorough physical exam, and imaging with pelvic ultrasound. For premenopausal women, there is a higher incidence of adnexal masses, and, in fact, most of them are benign. In these women, one must weigh the risk/benefit of close monitoring with pelvic ultrasound versus surgical intervention. A serum CA-125 can be helpful, but only if it is significantly elevated.
If uncertainty remains after a complete evaluation has been performed, it is appropriate to refer to a gynecologic oncologist. In postmenopausal women, serum biomarkers should be used in conjunction with the history, physical, and ultrasound because of the higher risk of malignancy. In addition, surgical intervention should be offered to these patients regardless of serum marker values in the setting of a complex mass. If there is high suspicion for malignancy by history and imaging or elevated ROMA or OVA1, referral to a gynecologic oncologist is prudent.
Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology, and a professor in the division of gynecologic oncology at the University of North Carolina, Chapel Hill. Dr. Roque is a fellow in the gynecologic oncology program at the University of North Carolina. Neither Dr. Clarke-Pearson nor Dr. Roque has any relevant financial disclosures. E-mail them at obnews@frontlinemedcom.com.