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    Another disappointment for ovarian cancer screening

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    Of all cancers in women, perhaps none produces more fear among patients and providers than ovarian cancer. Although breast, lung, and colorectal cases will account for more than 50% of new cancer diagnoses in 2011, ovarian cancer will account for only 3% of new cancers, albeit 5% of cancer deaths in women.1


    Charles J. Lockwood, MD, MHCM
    The lifetime risk of ovarian cancer is only about 2% and its annual incidence is around 22,000 cases, accounting for 13,850 deaths each year.1 Thus, it is not its frequency that strikes terror, but rather a combination of the cancer's lack of symptoms and the ovaries' lack of ready accessibility. It is these characteristics that promote the late stage at diagnosis and associated poor prognosis of the disease.

    Those who had hoped that the combination of routine screening with cancer antigen 125 (CA-125) and pelvic ultrasound would promote an earlier diagnosis and improved survival recently were dealt a harsh blow.

    The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial group randomized a large cohort of asymptomatic women between the ages of 55 and 74 years to either annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years (n=34,253) or routine care (n=34,304).2 Ovaries were classified as abnormal if they had an overall volume or cyst volume greater than 10 cm3 or any solid component or papillary projection in the cyst cavity. Screening was conducted between 1993 and 2001, and participants then were followed up to 13 years (median, 12.4 years; range, 10.9-13.0 years) to determine whether they died from and/or developed cancer.

    Cause of death was based on careful review of death certificates and medical records. The primary endpoint was mortality from ovarian, primary peritoneal, and fallopian tube cancers. Secondary endpoints included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures. There was minimal contamination by CA-125 testing (2.3% to 3.2% per year) and vaginal ultrasound (2.7% to 4.6% per year) in the routine care group. Conversely, compliance with screening was higher in the intervention group (around 80%).

    The PLCO investigators detected ovarian cancer slightly more often in the screened group compared with routine-care group (212 women [5.7 per 10,000 person-years] vs 176 [4.7 per 10,000 person-years]; rate ratio [RR], 1.21; 95% confidence interval [CI], 0.99-1.48). Interestingly, fallopian tube and primary peritoneal cancers accounted for 20% and 14% of "ovarian" cancers in the screen versus routine-care groups, respectively.

    The key finding in the study was that there were no differences in ovarian cancer mortality among screened versus unscreened women (118 deaths [3.1 per 10,000 person-years] vs 100 deaths [2.6 per 10,000 person-years]; mortality RR, 1.18; 95% CI, 0.82-1.71). An indication of the futility of screening was the observation that there were no differences in the stage of cancer at detection in the screening versus routine care groups, with 77% and 78% identified at stages III and IV, respectively. There also were no differences in all-cause mortality between the groups.

    Perhaps the most distressing aspect of this study was the finding that of the 3,285 women with false-positive results, 1,080 had undergone surgery and 15% had experienced at least 1 serious complication, including infection, surgical damage, and cardiovascular and pulmonary complications. The investigators concluded wisely that screening was not effective in reducing ovarian cancer mortality.

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    Charles J. Lockwood, MD, MHCM
    Dr. Lockwood, Editor-in-Chief, is Dean of the Morsani College of Medicine and Senior Vice President of USF Health, University of South ...

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