Stephanie Portes-Antoine, Brandel France de Bravo, MPH, and Laura Gottschalk, PhD, Cancer Prevention and Treatment Fund
Ovarian cancer is a deadly disease because it is rarely diagnosed early. There is not yet an effective, life-saving screening tool for the early diagnosis of ovarian cancer.
When ovarian cancer is diagnosed in the early stage—before the cancer has spread beyond the ovaries—chances of a woman’s survival are very good, with about 93% of women surviving at least 5 years. Unfortunately, only 15% of cases are caught this early, because the symptoms of ovarian cancer are not obvious. For women diagnosed with advanced ovarian cancer, the chances of 5-year survival drop to less than 30%. Given the dramatic differences in survival outcomes between advanced and early onset diagnosis, it is vitally important to detect ovarian cancer early.
Most women whose ovarian cancer is detected in the late stages will have a relapse (usually many times) following their initial treatment, requiring additional treatment. The most widely used test to screen for the recurrence of ovarian cancer is the CA-125. This blood test measures a protein that tends to be higher in women with ovarian cancer. The test was approved for use on women who have already been diagnosed with ovarian cancer once. In 2008, Dr. Vladimir Nosov from UCLA Medical Center and his co-authors reported that elevated levels of the CA-125 biomarker are found in approximately 83% of women with advanced stage ovarian cancer and 50% of patients with stage I disease.
Is testing for this “biomarker” an effective way to tell early on if a woman’s ovarian cancer has returned? And what about women who have never been diagnosed with ovarian cancer? Why can’t the CA-125 test be used to screen them?
Women with No Symptoms or Who Have Never Been Diagnosed with Ovarian Cancer
Other studies have confirmed that CA-125 by itself is not sensitive enough to diagnose ovarian cancer in the very early stage of the disease, before there are symptoms. Dr. Saundra S. Buys is co-director of the Family Cancer Assessment Clinic at the Huntsman Cancer Institute in Salt Lake City, Utah. According to Dr. Buys, CA125 testing “may be appropriate to screen for ovarian cancer in women who have abdominal symptoms, but for women who have no medical symptoms, doing screening for ovarian cancer results in a lot of false-positives.” False positives are test results that inaccurately show the person might have cancer. Dr. Buys based her conclusions on data for women ages 55 to 75 who were participating in a large study called the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial.
In 2011, Dr. Buys and her colleagues published more results from that trial which involved more than 78,000 women. They concluded that using the CA-125 blood test to screen for ovarian cancer doesn’t prevent women from dying from the disease, it actually is harmful. False positives resulted in many women having unnecessary surgery: 3,285 women received false positives and 1080 of these women underwent biopsy surgery. In 15% of cases, the unnecessary surgery caused serious complications. At the same time, there was no benefit in terms of survival for the women who took the test as compared with those who did not.
Women Who Have Previously Had Ovarian Cancer
CA-125 by itself is clearly not reliable at detecting early ovarian cancer in women of low or average risk—women who have never before been diagnosed with ovarian cancer, and women who have no symptoms. Is it at least effective at detecting a recurrence of ovarian cancer? In 2010, Dr. Gordon Rustin of the Mount Vernon Cancer Centre in England published the results of a study done with women who had already been diagnosed with and treated for ovarian cancer. He found that women who started chemotherapy early, based on a CA125 test result indicating relapse of ovarian cancer, did not live any longer than women who did not begin treatment until symptoms of relapse appeared.
The Future of Ovarian Cancer Screening
Research is underway to evaluate whether the CA-125 test can be used more reliably, either by administering it only to women with other biomarkers that indicate increased risk (such as elevated levels of the protein HE4) or combined with other screening tests such as vaginal ultrasound.
Dr. Karen Lu from the MD Anderson Center at the University of Texas has had success correctly identifying postmenopausal women at high risk for ovarian cancer by measuring CA-125 at regular intervals and relying on a mathematical model. Only women whose CA-125 levels went up over time were given a vaginal ultrasound, and only those with suspicious findings on the ultrasound had surgery. This two-staged approach seemed potentially effective . However, when this approach was studied on more than 200,00 women, it did not significantly prevent death from ovarian cancer.
The Bottom Line:
The CA-125 test by itself is not a good screening tool for ovarian cancer. When used alone on women with no symptoms or previous history of ovarian cancer, it leads to many false positives. Among women who have already been treated for ovarian cancer once, it doesn’t seem to matter whether they get treatment for their ovarian cancer recurrence based on CA-125 results or based on their symptoms. Either way, women who relapsed and got treatment lived about the same amount of time.
- The National Cancer Institute. Surveillance Epidemiology and End Results. SEER Stat Fact Sheets. Cancer: Ovary. http://seer.cancer.gov/statfacts/html/ovary.html
- NCI Cancer Bulletin. Early Chemo to Prevent Ovarian Cancer Recurrence Fails to Increase Survival. June 2, 2009. Volume 6/Number 11. http://www.cancer.gov/ncicancerbulletin/060209/page2
- Nosov V., et al. The early detection of ovarian cancer: from traditional methods to proteomics. Can we really do better than serum CA-125? American Journal of Obstetrics and Gynecology. September 2008: 199(3): 215-223.
- Reinberg, S. Ovarian screening Methods Inaccurate. National Women’s Health Resource Center. November 7, 2005. http://www.healthywomen.org/resources/womenshealthinthenews/dbhealthnews/ovariancancerscreeningmethodsinaccurate
- Buys S.S., et al. Ovarian cancer screening in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial: Findings from the initial screening of a randomized trial. American Journal of Obstetrics and Gynecology. November 2005: 193(5): 1630-1639.
- Buys S.S., et al. Effects of Screening on Ovarian Cancer Mortality: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. The Journal of the American Medical Association. July 2011; 2011 (616):1.
- Rustin, G.J. and van der Burg. Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomized trial. Lancet. October 2010
- Lu, Karen 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. Cancer. September 2013; 2013 (119):17.
- Jacobs IJ, Menon U, Ryan A, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial . Lancet. doi:10.1016/S0140-6736(15)01224-6.