A PROMISING APPROACH FOR OVARIAN CANCER SCREENING

May 21, 2010 — A new approach to ovarian cancer screening appears feasible and effective for women at average risk of developing the disease. The Risk of Ovarian Cancer Algorithm (ROCA), which is based on patient age and trends in CA-125 blood testing, demonstrated very few false positives and had a specificity of 99.9%.

Although 2 borderline cases were not detected by the ROCA, no cases of invasive ovarian cancer were missed, explained lead author Karen Lu, MD, professor of gynecologic oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Lu reported her findings during a presscast that previewed several presentations from the forthcoming American Society of Clinical Oncology (ASCO) 46th Annual Meeting. These data will be presented on June 6.

"The beauty of the algorithm is that each individual woman ultimately established her own baseline, based on her prior CA-125 values," she said.

The incidence of ovarian cancer in postmenopausal women is 1 in 2500; it is the most lethal gynecologic cancer. Unfortunately, more than 75% of cases present with advanced-stage disease, when cure rates are less than 30%, explained Dr. Lu.

If a diagnosis is made at an early stage, then outcomes are generally much better, with reported cure rates of 60% to 90%. "But currently, there are no effective screening methods," Dr. Lu pointed out during her talk.

The purpose of the study was to assess the specificity and positive predictive value of a 2-step screening strategy for healthy postmenopausal women, which incorporated changes in CA-125 over time and age of the participant, to more accurately estimate risk for ovarian cancer. Part of the strategy included referral of woman with high ROCA scores to transvaginal sonography (TVS) and to a clinical evaluation with a gynecologic oncologist.

In this prospective single-group study, 3238 postmenopausal women from 50 to 74 years of age were enrolled over the course of 9 years. None of the participants had any significant family history of breast or ovarian cancer.

The ROCA offers 3 possible pathways, Dr. Lu explained. Women at low risk will return for an annual CA-125 blood screening, women at intermediate risk will have their CA-125 test repeated in 3 months, and women at high risk will be referred for TVS and clinical evaluation.

The majority of women (n = 2666; 86%) continued with annual CA-125 screening. "Over the 9-year period, only 2.6% of women were ever triaged to a transvaginal ultrasound," Dr. Lu said, "and 8 women underwent surgery."

The average annual rate of referral to 3 month CA-125 screenings was 6.8%; cumulatively, it was 15.4% (n = 501). The average annual rate of TVS and gynecologic oncologist referral was only 0.9%.

Of the 8 women who underwent study-directed surgery, 5 ovarian cancers were detected.

All 5 were diagnosed at an early stage, Dr. Lu noted. Of the 5 cancers, 3 were invasive disease and 2 were borderline ovarian tumors. The remaining 3 women who underwent surgery had benign lesions, although 1 was later diagnosed with endometrial cancer.

The 3 invasive ovarian cancers that were detected were all high-grade epithelial tumors, but at an early stage; 2 were stage 1C and 1 was stage IIB. The 3 women diagnosed with invasive disease all had low-risk annual CA-125 scores before their values rose.

In 2 of the cases of ovarian cancer, the CA-125 levels were normal and then rose abruptly after several years of screening, Dr. Lu explained. "In the third case, levels were low (in the 10 to 12 range), but in the fourth year of screening, they doubled to 22," she said. "The ROCA picked up that her baseline had doubled and that triggered her ultrasound and subsequent surgery."

Overall, the ROCA provided a positive predictive value of 37.5% (95% confidence interval [CI]. 8.5% - 75.5%). The combined specificity of ROCA followed by TVS for referral to surgery was 99.7% (95% CI, 99.5% - 99.9%).

Dr. Lu emphasized that "it is important to stress the clinical ramifications of the study; it is not practice changing at this time."

"We await the results of the definitive trial that examines mortality as an end point, which is currently ongoing in the United Kingdom," she added.

The large-scale study of the ROCA that is currently underway involves more than 200,000 women, and results are expected in 2015.

"The ROCA represents yet another example of personalized medicine," said Douglas W. Blayney, MD, president of ASCO. "Here we have it personalized toward a screening strategy. It also represents a more refined application of known technologies that are widely available."

Dr. Blayney reiterated that caution is needed before embracing this approach to screening. The relative rarity of this cancer was seen in this study, so it is very important that this strategy "not be adopted widely until a confirmatory study is done," he said.

Coauthor Herbert Fritsche reports receiving research funding from Roche Diagnostics. Coauthor Robert Bast reports serving in a consulted/advisory role for Fujiresio Diagnostics Inc.

American Society of Clinical Oncology (ASCO) 46th Annual Meeting: Abstract 5003. To be presented June 6, 2010.