Ovarian cancer screening strategy seems promising but is years away

While very preliminary findings from the largest randomized ovarian cancer screening study — and the first to directly compare ultrasound alone and ultrasound plus CA-125 — show some promise, any answer on whether the screening strategy saves lives is several years away, researchers note in a study published in the April issue of The Lancet Oncology.

Developing a test that identifies ovarian cancer early is important because symptoms are often non-existent, vague, or mimic those of other, less serious maladies. Although women whose cancers are caught in the early stages have a 90% chance of survival, the majority of ovarian cancers are not diagnosed until after they have spread, when women have, at best, a 30% chance of survival.

Currently there is no screening test for ovarian cancer. Levels of CA-125 are monitored to track progression of ovarian cancer in a woman who has already been diagnosed, but the CA-125 test has not been used to screen for the disease because so many other conditions such as pregnancy, normal menstruation, and endometriosis can cause elevated levels of the protein.

The ongoing study includes more than 202,000 postmenopausal women between the ages 50 and 74 at the time they entered into the study. The researchers randomly assigned them to undergo no screening (usual care), annual screening with ultrasound alone, or annual screening with ultrasound and the CA-125 blood test for 10 years.

An analysis of early results from the study showed that, for all primary ovarian and tubal cancers, CA-125 plus ultrasound could detect disease 89.4% of the time (termed “sensitivity” of the screening test) and could rule out disease 99.8% of the time (specificity). Results also showed the chance that a woman with positive test results really did have ovarian cancer was 43.3% (positive predictive value of the test).

The total number of cancers detected in the two screening groups was similar. However, the group screened with ultrasound alone resulted in more false positive results, which led to more unnecessary follow-up surgeries. In the ultrasound only group, 845 women underwent surgery and only 45 actually had cancer. In the group prescreened with a test for CA-125 only, 97 women underwent surgery to identify 42 with cancer. Use of ultrasound alone resulted in 8 cancers that were missed while the multi-screen approach missed 4 cancers. In addition, both methods of screening detected more early-stage cancers than in the group that did not undergo any screening tests. Almost half of the cancers detected in both screening groups were early-stage, the timeframe in which cancer is more treatable.

The preliminary results are encouraging, said researcher Usha Menon of University College London, because they suggest that both ultrasound and CA-125 can be used on a large scale to identify ovarian cancers. "However, we must wait until 2015 before we can conclude whether or not a wider screening program could produce a fall in deaths due to ovarian cancer," she added.

Lead investigator Ian Jacobs, director of the University College London Institute for Women's Health, cautioned that screening can cause more harm than good. He pointed out that screening often causes anxiety and leads some people to undergo unnecessary operations. “So experts must therefore balance any benefits offered by screening with these downsides.”

Long experience with using PSA to screen for prostate cancer has shown that it is not clear that it is as valuable as once thought. For more on this, see the news article Prostate Cancer Screening Studies Don’t Settle Question of Clinical Utility.

Sources

Menon, U. et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). The Lancet Oncology 2009; 10: 327 – 340. Available online at http://www.thelancet.com/journals/lanonc/issue/vol10no4/PIIS1470-2045(09)X7098-1 through http://www.thelancet.com. Accessed March 31.

Press release. Screening may provide early ovarian cancer warning. Cancer Research UK. Available online at http://info.cancerresearchuk.org/news/archive/newsarchive/2009/march/19070441 through http://info.cancerresearchuk.org. Issued March 12, 2009. Accessed March 31, 2009.

Salynn Boyles. New Test for Early-Stage Ovarian Cancer: Study Shows That New Way of Evaluating a Protein Blood Test Could Detect Ovarian Cancer. Available online at http://www.webmd.com/ovarian-cancer/news/20090310/new-test-for-early-stage-ovarian-cancer through http://www.webmd.com. Issued March 10, 2009. Accessed March 31, 2009.