September is Ovarian Cancer Awareness Month, and recent news confirms the challenges presented by this uncommon but usually fatal disease. Last week, The U.S. Preventive Services Task Force (USPSTF) reiterated a recommendation it first made in 2004: screening healthy women without a family history of ovarian cancer probably does more harm than good.
The USPSTF announcement follows its recent reports questioning the value of biennial mammograms for women between the ages of 40 and 49 years and recommending against prostate-specific antigen (PSA) testing for healthy men.
The 2004 USPSTF report on ovarian cancer stated that screening asymptomatic, average-risk women with transvaginal ultrasound or serum CA-125 measurement followed by ultrasound for a positive result can detect ovarian cancer at an earlier stage than it would be detected in an unscreened population. However, the low incidence of ovarian cancer makes the positive predictive value of either test low—according to one estimate, only 3% of women with a positive ultrasound and 15% with a positive CA-125 test who undergo surgery actually have cancer. In 2004, no mortality data on screened vs. unscreened populations were available.
Since the 2004 report was released, results of the PLCO (Prostate, Lung, Colorectal, Ovarian) Cancer Screening Trial became available. This study randomized >78,000 women aged 55 to 74 years to annual screening (CA-125 testing and transvaginal ultrasound for 4 years, then CA-125 testing for an additional 2 years) or usual care (offered no interventions and only received their usual medical care) and followed them for up to 13 years. The rate of ovarian cancer diagnosis and the rate of ovarian cancer mortality were both nonsignificantly higher in the group that was offered annual screening. False-positive results in the screened group led to 1,080 unnecessary surgeries, in which there was a 15% rate of serious complications.
Based in part on the PLCO trial, the USPSTF again recommended against routine ovarian cancer screening for asymptomatic women at low risk, stating that “there is at least moderate certainty that the harms of screening for ovarian cancer outweigh the benefits.” The authors emphasized that this recommendation does not apply to women at high risk, including those with BRCA1 or BRCA2 mutations, Lynch syndrome, or a family history of ovarian cancer.
Considering mortality data when recommending for or against cancer screening makes good sense, but as Pamela Hartzband and Jerome Groopman argue in a recent editorial in the New England Journal of Medicine, “there’s more to life than death.” Patients, the authors point out, have a more nuanced view of risk than the simple chance of dying. Among the benefits of cancer screening is the sense of reassurance that comes with a negative result, and to obtain that benefit patients may be willing to risk the consequences of a false positive test.
Research on the diagnosis of ovarian cancer continues. Progress has been made in identifying biomarkers that may prove helpful in differentiating primary ovarian tumors from metastatic tumors and estimating prognosis. MicroRNAs, gene-regulatory RNA molecules that negatively regulate messenger RNA translation, may eventually be found to play important roles in both diagnosis and treatment of ovarian cancer. For now, however, the holy grail of a simple blood test that would detect ovarian cancer at an early stage remains elusive.
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