How do you distinguish a malignant pelvic mass from a benign pelvic mass? Imaging, biomarkers, or none of the above.

The 125th attempt to develop a monoclonal antibody against ovarian cancer in a laboratory at the Dana-Farber Cancer Institute (Boston, MA) led to the discovery of one of the most widely used tumor markers, CA-125. Over the past two decades, the value of CA-125 has been tested in monitoring response to treatment, detecting recurrent disease, and screening for early-stage ovarian cancer. CA-125 has proven useful in determining prognosis and response to treatment for women undergoing chemotherapy. Persistent elevation of CA-125 has detected residual disease after primary treatment with high specificity. A rise in serum CA-125 levels often precedes clinical symptoms or imaging detection of recurrent disease by 3 to 6 months. While the use of a “good marker” to track a “bad disease” in these settings has been questioned, information provided by CA-125 provides additional time for patients to receive and to benefit from the many currently active drugs. As treatment of persistent and recurrent disease becomes more effective in the era of targeted therapy, CA-125 and other biomarkers should become of even greater value in patient management. While a single value of CA-125 lacks the specificity and sensitivity required for early detection, greater specificity has been attained by measuring CA-125 over time and by combining CA125 with ultrasonography. Statistical analysis, such as the Risk of Ovarian Cancer Algorithm (ROCA model) developed by Skates et al, can examine changes in CA-125 levels over time. The United Kingdom Collaborative Trial on Ovarian Cancer Screening has completed accrual of 200,000 women, testing the value of a rising CA-125 to trigger transvaginal sonography in postmenopausal women at average risk for ovarian cancer. If this trial succeeds, there is clearly room for improvement, as 20% of ovarian cancers fail to express significant amounts of CA-125. A greater fraction of patients with early-stage disease might be detected with a panel of biomarkers that complement or replace CA-125. CA-125 has also been tested for the ability to distinguish malignant from benign pelvic masses. The ability to predict whether a tumor is malignant or benign before surgery is important. Approximately 20% of women will develop an ovarian cyst or pelvic mass in their lifetime and many of these women will undergo unnecessary surgery. Conversely, if surgery is indicated, the location in which the surgery is performed is critical. Despite modest gains in the fraction of women cured, optimal management of malignant ovarian cancers has significantly improved survival over the past 30 years. With the development and application of cytoreductive surgery, primary platinum-taxane chemotherapy and active second-line agents, the 5-year survival rate for ovarian cancer patients has improved from 20% to 50%. Several different reports have shown that patients treated by gynecologic oncologists will more often undergo full surgical staging or an optimal cytoreductive operation. More recently, multiple studies have shown ovarian cancer patients treated in tertiary care centers with multidisciplinary teams specializing in the management of ovarian cancer have fewer complications and longer survival rates. The triage of women to centers of excellence in the management of ovarian malignancy is critical for optimal treatment. Tests that permit the identification of women at high risk for the presence of a malignancy will be instrumental for the triage of patients to appropriate centers. Despite a number of trials examining CA-125, with or without the use of sonography, in women with a pelvic mass, it has become increasingly clear that no one modality will be sufficient to predict accurately the presence of an ovarian malignancy. Many different tumor markers have been analyzed, but none has achieved the sensitivity or specificity to be clinically useful as an individual test. Recently, the addition of HE-4 to CA-125, without the use of ultrasound, has increased the sensitivity of CA-125 by 22% at a specificity of 90%. Jacobs et al have used the combination of ultrasound, CA-125, and menopausal status to create a risk of malignancy index (RMI), achieving a sensitivity of 85% with a specificity of 97% for predicting the presence of ovarian cancers in women with pelvic masses. The contribution of CA-125 to the RMI was critical for assigning masses to the malignant category, whereas sonography was particularly important in identifying benign disease. One of the advantages of the RMI is its simplicity, making it appropriate for everyday clinical use. DePriest et al developed a morphology index utilizing the architectural features of ovarian neoplasms on pelvic ultrasound to predict a probability of malignancy without the use of CA-125. The morphology index achieved a positive predictive value of up to 0.45. Although JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 25 NUMBER 27 SEPTEMBER 2