Many Gene-Based Ovarian Ca Tests Don’t Lower Mortality

November 1, 2006

Clinical studies do not validate the power of manygenomic tests developed to diagnose andguide the treatment of ovarian cancer todecrease the disease’s mortality or improvethe quality of life of patients, accordingto a report released by the Agencyfor Healthcare Research and Quality(AHRQ).

ROCKVILLE, Maryland--Clinicalstudies do not validate the power of manygenomic tests developed to diagnose andguide the treatment of ovarian cancer todecrease the disease's mortality or improvethe quality of life of patients, accordingto a report released by the Agencyfor Healthcare Research and Quality(AHRQ). The medical-literature reviewevaluated tests for single-gene products,genetic variations affecting the riskof ovarian cancer, gene expression, andproteomics.

Laboratory Data
"There are reasonable data on the clinicallaboratory performance of most radioimmunoassays,but the majority of thedata on other genomic tests comes fromresearch laboratories," the report said."Although research remains promising,adaptation of genomic tests into clinicalMany Gene-Based Ovarian Ca Tests Don't Lower Mortalitypractice must await appropriately designedand powered studies in relevantclinical settings."

Current strategies have failed to provideeffective ways to prevent and screenfor ovarian cancer. As a result, investigatorshave explored genomics and proteomicsto identify potential biomarkersthat could help reduce the morbidity andmortality of the often-fatal disease, whichstrikes more than 20,000 Americanwomen annually. Key findings from thereport include:

  • Published data on clinical laboratoryperformance suggest that currentlyavailable radioimmunoassays for singlegeneproducts have acceptable reproducibilityand reliability, but the level of variabilitymay have some impact on theclinical interpretation of results.
  • Insufficient evidence exists to estimatehow newer technologies, such asmicroarrays or protein profiles, wouldperform in a typical clinical laboratory.
  • Other than CA-125, single-geneproducts have yet to show an ability todiagnose ovarian cancer in symptomaticor asymptomatic women. "Small samplesizes, lack of detail on the prediagnosishistory of patients, and an unrealisticallyhigh prevalence of ovarian cancer in themajority of studies make it difficult toassess how any of these tests would performin clinical practice," the report said.The report noted that estimating the clinicalvalue of more complex tests, usingmultiple genes and/or protein markers,is even more difficult.
  • The review failed to identify any evidencethat tests other than CA-125 candetect ovarian cancer in asymptomaticwomen.
  • Although evidence suggests that genomictests, particularly CA-125, can indicatedifferential outcomes, the reviewfound no studies showing that changesin case management based on the resultsof the tests lead to improved outcomes.A previous evidence report found thatCA-125 can help distinguish between malignantand benign tumors in postmenopausalwomen.
  • Few data exist on the harm of genebasedtesting for ovarian cancer, includingthe psychological effects of receivinga false-positive finding or having treatmentdelayed because of a false-negativereport.

Based on a computer simulationmodel developed by the team, the researchersconcluded that even highly accuratescreening tests will not result in alarge drop in the ovarian cancer mortalityrate unless testing is done at intervalsof less than 1 year. Such frequent testing,however, would also yield a large numberof false-positives results.

The study, "Genomic Tests for OvarianCancer Detection and Management,"was conducted by Evan R. Myers,MD, and his colleagues at the Duke UniversityEvidence-based Practice Center,which is funded by AHRQ. It is the firstof five evidence reports to be issued aspart of a collaboration between AHRQand the Centers for Disease Control andPrevention.