Many genomic tests that are currently used to diagnose and guide treatment of ovarian cancer are not shown to decrease the number of women who die from the disease or improve their quality of life, according to a new report supported by a partnership between the Agency for Healthcare Research and Quality (Washington) the Centers for Disease Control and Prevention's (Atlanta) Division of Cancer Prevention and Control, and CDC's National Office of Public Health Genomics.

The researchers performed a review of the literature and found few studies that evaluated genetic tests other than CA-125 or BRCA1 and BRCA2 to diagnose ovarian cancer or identify women at risk. Among the tests evaluated in the report, the researchers found no studies showing that changing treatment based on test results reduced deaths or improved quality of life in women who were diagnosed with ovarian cancer.

They also said that there is little data on the harm of gene-based tests for ovarian cancer, including the psychological impact of false-positive tests or delays in treatment that can result from a false-negative test.

Gurnaveet Randhawa, MD, Evidence-Based Program Task Officer for AHRQ, told Diagnostics & Imaging Week that while there may be no "unique" harms accompanying genetic testing for ovarian cancer than other types of genetic tests, such as confidentiality and potential employer discrimination issues that must be resolved, but the question still remains, "How many harms occur, and how frequently they occur?"

Because there is no data on the harms or benefits, it would be "premature" to make any recommendations, he said.

"We need more information before guideline developers can start making clinical guidelines to recommend either for or against testing," Randhawa said.

According to the report, researchers sought evidence on: "The analytic performance of tests in clinical laboratories"; "the sensitivity and specificity of tests in different patient populations"; "the clinical impact of testing in asymptomatic women, women with suspected ovarian cancer, and women with diagnosed ovarian cancer"; "the harms of genomic testing"; and "the impact of direct-to-consumer and direct-to-physician advertising on appropriate use of tests."

Ovarian cancer causes more deaths than any other cancer of the female reproductive system. More than 20,000 women are diagnosed with the disease annually, and about 15,000 die from it. The risk for ovarian cancer increases with age and most often is diagnosed in white women over the age of 50.

If diagnosed during stage I, ovarian cancer has a survival rate of more than 90%. However, most cases are diagnosed in advanced stages, when the cancer has spread to other organs.

Physical exams, ultrasounds and other routine screening efforts for reducing the number of women affected by the disease, and in turn the number who die from it, have been unsuccessful compared with similar efforts aimed at other causes of cancer deaths in women, according to the research report.

Because current strategies have not proven to be effective, there is broad interest in identifying the disease in its earliest stages by looking at genes, gene expression levels, proteins, and tumor markers.

These tests focus on (1) detecting a gene-based tumor marker, such as CA-125, or (2) identifying genetic mutations such as BRCA1 and BRCA2 that indicate increased risk for developing cancer, or (3) identifying genetic changes that predict response to therapy in women with ovarian cancer.

A computer simulation model developed by the research team suggests that screening, even with the highly accurate tests, will not result in large reductions in deaths from ovarian cancer unless testing is very frequent (less than one year between tests). However, such frequent screening would also yield a large number of false-positive test results. The team stated that research aimed at improving treatment options and the discovery of treatment, lifestyle, or dietary choices that could prevent ovarian cancer would likely offer greater promise for major reductions in deaths from the disease.

"Ovarian cancer and its effects can be devastating for women diagnosed with the disease. The findings from this report will help to guide further research aimed at better treatment that may lead to fewer deaths from ovarian cancer," said Jean Slutsky, director of AHRQ's Center for Outcomes and Evidence.

The results determined that "no evidence that genomic tests for ovarian cancer have unique harms beyond those common to other tests for genetic susceptibility or other tests used in screening, diagnosis and management of ovarian cancer."

The researchers also determined that studies of a direct-to-consumer campaign for BRCA testing "suggest increased utilization, but the effect on ‘appropriateness' was unclear."

According to the study, the researchers concluded that "although research remains promising, adaptation of genomic tests into clinical practice must await appropriately designed and powered studies in relevant clinical settings."

This report is the first of a series of five evidence reports that are part of an inter-agency collaboration between AHRQ and CDC. As part of the CDC-supported Evaluation of Genomic Applications in Practice and Prevention (EGAPP) project, the EGAPP working group will evaluate the evidence presented in the report and make recommendations in the near future about the use of these tests for screening, diagnosis, and treatment of ovarian cancer.

Other evidence reports requested by EGAPP will evaluate the use of genetic tests for specific diseases or conditions, such as determining an individual patient's response to drugs used in the treatment of depression.

"This first-ever collaboration of the CDC's cancer and genomics programs with AHRQ provides important evidence-based guidance to inform both public health and medical practitioners about the appropriate use of genetic testing in cancer prevention and control," said Janet Collins, PhD, director of CDC's National Center for Chronic Disease Prevention and Health Promotion.

The report was prepared by a team of researchers led by Evan Myers, MD, of AHRQ's Duke University Evidence-based Practice Center (Durham, North Carolina).

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