Monitoring CA-125 Shows Promise as a Screening Tool for Ovarian Cancer

Karen H. Lu, MD, professor and chair of the Department of Gynecologic Oncology at the University of Texas MD Anderson Cancer Center in Houston

Karen H. Lu, MD

Measuring carbohydrate antigen 125 (CA-125), the protein that predicts ovarian cancer recurrence, has shown promise as a screening tool for the disease, according to update results of an 11-year study aimed at providing a strategy for early detection.

The findings, reported in the journalCancer, support the use of blood tests to measure CA-125, coupled with follow-up ultrasounds and, if appropriate, further treatment.

“Finding a screening mechanism would be the Holy Grail in the fight against ovarian cancer, because when caught early it is not just treatable, but curable,” said Karen H. Lu, MD, professor and chair of the Department of Gynecologic Oncology at the University of Texas MD Anderson Cancer Center in Houston and the study’s lead author, in a statement.

At the present time, there are no proven strategies for early detection of ovarian cancer. Lu et al noted that approximately 70% of women who present with the disease are diagnosed at a late stage, when long-term cure rates are less than 30%. However, when the disease is caught at an early stage, survival rates can reach 75% to 90%.

Past studies have shown that neither a fixed cutpoint value of CA-125 nor an abnormal transvaginal ultrasound (TVS) as a first-line test have the necessary specificity to achieve a positive predictive value (PPV) of at least 10%, or 10 operations for each case of ovarian cancer detected, which is a generally accepted risk-benefit limit. Specificity and sensitivity could be improved when a rising CA-125 value, which is associated with progressive growth of ovarian cancer, is able to prompt the use of TVS.

The study, conducted from 2001 through 2011, enrolled 4051 postmenopausal women between the ages of 50 and 74 years old with at least one ovary and no strong family history of breast or ovarian cancer. They were stratified into different risk groups based on results from the Risk of Ovarian Cancer Algorithm (ROCA).

Patients who were classified as “normal risk” were asked to return in one year for a follow-up test. Participants in the “intermediate risk” category were asked to return in 3 months, and patients who tested “high risk” were referred for a TVS and a visit with a gynecologic oncologist. Specificity was the study’s primary endpoint, with PPV serving as an additional endpoint.

Preliminary results were reported at the American Society of Clinical Oncology Annual Meeting in 2010. In the updated results released Monday, the study found that the annual rates of referral to the three risk categories were 93.3% to the normal-risk group, 5.8% to the intermediate-risk group, and 0.9% to the high-risk group.

During the course of the study, 117 women (2.9%) were determined to be high risk, and all but 14 of these patients underwent TVS, investigators reported. Of these patients, TVS results indicated suspicion of ovarian cancer for 10 patients, who subsequently underwent surgery. Among this group, four patients had high-grade ovarian cancer, one had endometrioid adenocarcinoma, two had tumors of low malignant potential, and three had benign cystadenoma.

These findings translated into a PPV of 40% (95% CI, 12.2%—73.8%). The researchers found that the specificity was 99.9% (95% CI, 99.7%–100%). The screening failed to detect two cases of borderline ovarian cancers.

The researchers noted that the four women who had high-grade epithelial tumors had been enrolled in the study for at least 3 years with low-risk annual CA-125 levels before their values began to rise. These patients were identified when they still had early-stage disease (stage IC or IIB).

The encouraging results came with numerous caveats, as researchers called for prospective randomized trials in order to appropriately assess the effectiveness of the approach described in this particular study.

A second trial that will evaluate four blood tests, including CA-125, to detect tumors that might otherwise be missed with CA-125 alone is being planned. A large, randomized prospective screening trial is also currently being conducted in the United Kingdom, and results from the screening of more than 200,000 women should become available by 2015. Additionally, this particular study is continuing, with researchers planning to look at combining CA-125 with other markers to determine the impact over time.

“As a clinician treating women with this disease for more than 10 years, I’ve become an admitted skeptic of ovarian cancer screening,” Lu said. “Now, with these findings, 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 stages and make a difference in the lives of women with this now-devastating disease.”

Lu KH, Skates S, Hernandez MA, et al. A 2-stage ovarian cancer screening strategy using the risk of ovarian cancer algorithm (ROCA) identifies early-stage incident cancers and demonstrates high positive predictive value [published online ahead of print August 26, 2013].Cancer. doi:10.1002/cncr.28183.