CA125 May Be Useful Ovarian Cancer Screening
A screening strategy that evaluates change of carbohydrate antigen 125 (CA125) levels over time may be able to identify early-stage ovarian cancer, according to a study published online Aug. 26 in Cancer. To date, no strategy has proven effective for the early detection for ovarian cancer. CA125 marker, which has been used to predict ovarian […]
A screening strategy that evaluates change of carbohydrate antigen 125 (CA125) levels over time may be able to identify early-stage ovarian cancer, according to a study published online Aug. 26 in Cancer. To date, no strategy has proven effective for the early detection for ovarian cancer. CA125 marker, which has been used to predict ovarian cancer recurrence, is imperfect as it can be elevated for other reasons potentially leading to false positives as a screening tool. “Ovarian cancer screening requires invasive surgery and removal of the ovaries in order to make a definitive diagnosis. Therefore, any screening strategy for ovarian cancer must minimize false positives in order to decrease the number of unnecessary operations,” write the authors, led by Karen Lu, M.D., from M. D. Anderson Cancer Center in Houston. Complicating screening efforts is the low prevalence of the disease in the general population. To achieve a positive predictive value (PPV) of 10 percent, a generally accepted limit for balancing risk with benefit, the authors say the screening strategy must exhibit a sensitivity greater than 75 percent for asymptomatic disease and a specificity of more than 99.6 percent. In the current study, postmenopausal women (aged 50 to 74 years) had annual CA125 blood tests. The Risk of Ovarian Cancer Algorithm (ROCA), based on the patient’s age and CA125 score, stratified women into one of three risks groups, which dictated their follow-up protocol: annual CA125 test (low risk), repeat CA125 test in three months (intermediate risk), or transvaginal ultrasound (TVS) and referral to a gynecologic oncologist (high risk). The researchers found that based on 4,051 women participating over 11 years at seven sites (4.2 average screen years per woman), the average annual rate for triage to the normal-risk group was 93.3 percent, whereas the rate of three-month follow-up was 5.8 percent and the average annual referral rate to TVS 0.9 percent. Of the 117 women classified as high-risk, 82 women had a normal TVS and 11 had benign ovarian findings. Of the 10 women with suspicious TVS findings, all underwent surgery, with four invasive ovarian cancers (all stage I and II), two ovarian tumors of low malignant potential (both stage I), one endometrial cancer (stage I), and three benign ovarian tumors. All four women with invasive ovarian cancer were enrolled in the study for at least three years with low-risk classification prior to rising CA125 levels. The specificity for the two-stage screening strategy was 99.9 percent with a PPV for identifying invasive ovarian cancer of 40 percent. This U.S. trial had similar findings to the United Kingdom Collaborative Trial of Ovarian Cancer Screening, both of which “greatly exceed” the minimum clinical benchmark of 10 percent PPV. “Data from our study suggests that incident cases detected through ROCA are likely to be early-stage cancers. This contrasts with the current presentation of ovarian cancer in which more than 75 percent of women are diagnosed with stage III or IV disease,” write the authors. Lu added in a statement, “I’ve become an admitted skeptic of ovarian cancer screening. Now . . . I’m cautiously optimistic that in the not too distant future, we may be able to offer a screening method that can detect the disease in its earliest, curable stage.” Lu says the next steps in the project include assessing the strategy’s effect on decreasing ovarian cancer mortality. Additionally, her group will assess if combining other biomarkers (such as HE4, CA72.4, and MMP7) with CA125 improve sensitivity without decreasing specificity. Several study authors report financial ties to the diagnostics industry, including Robert Bast, M.D., who discovered CA-125 and receives royalties. Takeaway: Risk stratifying women based on assessments of changes in CA125 markers over time may constitute an effective strategy to begin population-based screenings for ovarian cancer, which while not perfectly sensitive, will aid in identifying more earlier-stage cancers than are presently detected.