News Release

Study suggests that annual CA125 screening may reduce ovarian cancer deaths

Initial results from the world's largest screening trial show promise for risk-analysis tool co-developed by MGH investigator

Peer-Reviewed Publication

Massachusetts General Hospital

Initial results from the world’s largest ovarian cancer screening trial suggest that tracking levels of a cancer-associated protein over time may help reduce ovarian cancer deaths by as much as 20 percent. Results of the 14-year study, led by investigators at University College London (UCL), are being published online in The Lancet.

The U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) enrolled more than 200,000 women across the U.K. to investigate whether annual screening with a blood test utilizing the Risk of Ovarian Cancer Algorithm (ROCA), co-developed by Steven Skates, PhD, of the Massachusetts General Hospital (MGH) Biostatistics Unit, can reduce ovarian cancer deaths. ROCA analyzes the results of annual blood tests for CA125, a protein known to be elevated in the blood of women with ovarian cancer.

While monitoring CA125 levels can be useful for predicting a patient’s prognosis and tracking response to treatment, CA125 testing has not been recommended for screening women at average risk of ovarian cancer, since previous studies found the risks of such screening far outweighed potential benefits. Instead of a being one-time blood test, ROCA analyzes a woman’s CA125 pattern over time to identify any significant increase over her baseline levels.

Beginning in 2001 UKCTOCS enrolled more than 202,000 postmenopausal women, ages 50 to 74, without a strong family history of ovarian cancer. Participants were randomly assigned to one of three groups –- annual multimodal screening with ROCA and transvaginal ultrasound as a second-line test, annual ultrasound screening alone, and a control group that received no screening. When ROCA screening identified a significant CA125 increase, the patient’s risk was classified as either elevated, requiring transvaginal ultrasound along with a repeat blood test within the next six weeks, or intermediate, requiring a repeat blood test in three months. Annual screening in the ultrasound-only group resulted in a similar triaging of participants. In both screening groups if abnormal results persisted, participants were referred to a clinician for definitive diagnosis and treatment.

Initial analysis of the study results found that screening was associated with reduced mortality from ovarian cancer -– with a greater reduction in the group receiving multimodal screening –- but the differences were not statistically significant. However, a comparison between the multimodal and control groups that excluded women found to have evidence of ovarian cancer upon entering the study did find that screening was associated with a significant reduction of around 20 percent in the risk of dying from ovarian cancer during the study period. Since the mortality reduction was greatest in the later stages of the trial, the research team believes that the difference will become even larger in subsequent years. They will continue to follow up study participants for an additional three years to confirm the size of the mortality reduction.

Skates developed ROCA in the early 1990s in collaboration with Ian Jacobs, MBBS, FRCOG, who was then at the Royal London Hospital. Now an honorary professor at UCL and vice chancellor at the University of New South Wales in Australia, Jacobs is co-corresponding author of The Lancet paper with Usha Menon, MD, of the UCL Institute for Women’s Health, and Skates is one of several co-investigators.


UKCTOCS was funded by grants from the Medical Research Council, Cancer Research U.K., the U.K. Department of Health and The Eve Appeal. Skates’ initial work in developing ROCA was supported by the National Cancer Institute. Development rights to ROCA have been licensed to Abcodia, Ltd.

Massachusetts General Hospital (, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $760 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine. In July 2015, MGH returned into the number one spot on the 2015-16 U.S. News & World Report list of 'America's Best Hospitals.'

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