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CA-125 Testing, CT Scans Still Used for Ovarian Cancer Surveillance Despite Lack of Proven Benefit

August 16, 2016, by NCI Staff

Blood samples in test tubes
Credit: National Cancer Institute

Despite evidence of no benefit from a 2009 randomized clinical trial, a new study shows that doctors appear to still routinely use the CA-125 blood test to monitor women for recurrent ovarian cancer. The findings, published July 21 in JAMA Oncology, also suggest that computed tomography (CT) scans continue to be routinely used to check for recurrences even though clinical practice guidelines discourage this practice. 

Many women who are in remission after treatment for ovarian cancer will eventually have a recurrence of the disease. One approach doctors have used to monitor patients for a recurrence and make decisions about care is regular blood testing to look for a rise in levels of CA-125, a protein that may be found in high amounts in women with ovarian cancer. However, results of a randomized, phase III clinical trial reported at a national conference in 2009 and published in 2010 showed that CA-125 testing for early detection of recurrent disease increased the use of chemotherapy and decreased patients’ quality of life without improving overall survival.

The new findings, from an analysis of data from six U.S. cancer centers, suggest that physicians at these centers “either did not find the [2009-2010] reports of the clinical trial on CA-125 testing compelling enough to change their practice patterns, or chose not to change their patterns,” said Elise Kohn, M.D., of NCI’s Division of Cancer Treatment and Diagnosis.

Theory Versus Practice

“The reason to monitor for recurrent disease is that, in theory, if you catch it early there may be options to treat it differently or better,” said Katharine Esselen, M.D., M.B.A., of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, who led the analysis. “But there is no consensus on how to follow ovarian cancer patients for detection of recurrent disease when they are in remission.”

Clinical signs of recurrence tend to appear a few months after CA-125 levels start to rise, Dr. Esselen continued. These clinical signs can include abdominal pain, bloating, or discomfort, and symptoms such as vaginal bleeding or nausea and vomiting.

“But just because we catch [a recurrence] earlier doesn’t mean we have the tools to treat it better at that stage,” she said.

To investigate the use of CA-125 testing and CT scans in clinical practice, Dr. Esselen and her colleagues used data from the National Comprehensive Cancer Network Ovarian Cancer Outcomes Database. This database contains information on all patients with ovarian, fallopian tube, or primary peritoneal cancers who were diagnosed and treated at six NCI-Designated Cancer Centers in the United States between January 1, 2004, and December 31, 2011.

In particular, the researchers examined the use of CA-125 testing and CT scans to monitor patients in remission and make decisions about treatment with additional chemotherapy in 1,241 women with ovarian cancer who were followed through December 31, 2012. They compared the use of the two tests before and after results of the phase III clinical trial were presented at the 2009 annual meeting of the American Society of Clinical Oncology.

Dr. Esselen’s team found that the use of routine CA-125 testing and CT scans, and the time to retreatment, did not differ significantly either before and after the clinical trial data were first presented, in 2009, or before and after their publication in The Lancet, in October 2010.

Using 2015 Medicare reimbursement rates and the mean numbers of CA-125 tests and CT scans performed per patient in their study, Dr. Esselen's team also estimated the costs of using the two tests for routine population surveillance of U.S. women with ovarian cancer in remission. The mean cost of such testing is about $16.2 million per year, they calculated, with most of the cost (about $14.2 million per year) being spent on CT scans.  

Why Routine CA-125 Testing May Persist

Dr. Esselen cited two main reasons why doctors may be continuing to use CA-125 testing for routine monitoring of women with ovarian cancer in remission. “One is that it is much easier to adopt a new technology or new practice than to stop one that is already in place,” she said. The other is that the CA-125 test “may provide benefits to both the patient and provider that are not easily studied or measured.”

For women with ovarian cancer, Dr. Esselen continued, knowing the results of this test may provide peace of mind or help them prepare for next steps, even if additional treatment isn’t started immediately. And some doctors may feel that knowing sooner about a recurrence might better enable them to help some patients find a clinical trial or have a second surgery that could treat the recurrent disease.

In an accompanying editorial, James Goodwin, M.D., of the University of Texas Medical Branch, Galveston, wrote that “Shared decision making does not require that physicians present the patient with harmful options”—in this case, CA-125 testing for patients in remission after treatment for ovarian cancer.

But Dr. Esselen and Dr. Kohn both noted that patients often ask about CA-125 testing after hearing about it from other women with ovarian cancer or reading about it online. In her own practice, Dr. Esselen reviews the role of this test and other ways of monitoring the disease with individual patients.

“We should be educating our patients about the true meaning of CA-125 test results,” agreed Dr. Kohn. “The decision about testing should be more of a team decision, where the patient is part of the team. In our research clinic at NCI, I tell patients straight off that ‘I do not treat numbers, I treat patients.’”

Dr. Kohn also explains to patients that CA-125 levels vary between and within individuals, and that she may use results of the test to help inform decisions on when to start or stop certain treatments. She also tells patients the clinical and radiologic factors that she uses to guide those decisions.

“It’s very easy to talk about CA-125 testing on a grand scale and its lack of impact on overall survival,” added Dr. Esselen. “But when there’s an individual who has a history of ovarian cancer sitting in front of you, it’s a completely different story.”

And as researchers learn more about ovarian cancer and the options for treatment of recurrent disease expand, she said, they may find that there are subsets of patients in remission for whom it is appropriate to use CA-125 testing to guide decisions about care.

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