One study does not a recommendation make, and results of a larger clinical trial are pending, but a new 2 stage approach to ovarian cancer screening is starting to look like something reasonable for ovarian cancer screening.
In a multi-center study led by researchers at MD Anderson Cancer Center, over 4,000 women were followed with annual Ca125 levels for 11 years, using an established algorithm (ROCA or Risk for Ovarian Cancer) that stratifies women into low, intermediate or high risk for ovarian cancer based on changes in ca125 levels over time, even when Ca125 levels are in the normal range. Based on the ROCA, which was re-calculated after each periodic screening, low risk women continued with annual Ca125 levels, intermediate risk women had repeat Ca125 levels done in 3 months, and high risk women went to immediate sonogram.
By confining sonogram use to only those women with concerning increases in Ca125 (0.9% annual rate of sonogram referral), the researchers were able to avoid the high rates of unnecessary surgery for false positives that has kept sonogram from being an effective screening tool for ovarian cancer. Their results are impressive for the small number of surgeries done – only 10 over 11 years – and the relatively high rate of pathology found at those surgeries –
The average annual rate of referral to a CA125 test in 3 months was 5.8%, and the average annual referral rate to TVS and review by a gynecologic oncologist was 0.9%. Ten women underwent surgery on the basis of TVS, with 4 invasive ovarian cancers (1 with stage IA disease, 2 with stage IC disease, and 1 with stage IIB disease), 2 ovarian tumors of low malignant potential (both stage IA), 1 endometrial cancer (stage I), and 3 benign ovarian tumors, providing a positive predictive value of 40% (95% confidence interval = 12.2%, 73.8%) for detecting invasive ovarian cancer. The specificity was 99.9% (95% confidence interval = 99.7%, 100%). All 4 women with invasive ovarian cancer were enrolled in the study for at least 3 years with low-risk annual CA125 test values prior to rising CA125 levels.
If the cost of Ca125 screens is low, this strategy could begin to make sense as a screening strategy for ovarian cancer. This all depends of course, on whether it actually reduces mortality. The answer to that question will await the results of the much larger UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), which will randomize over 200,000 women to either Ca125-ROCA (as in the Texas study), annual sono or routine care. Enrollment in that study has closed, and initial results are expected in 2015. It’s also important to note that other ovarian cancer markers are currently under investigation, both alone and in combination with one another and Ca125, and may prove superior to Ca125 alone.
Bottom line
Interesting, but not yet practice changing. Stay tuned.
