Cumulative Incidence of False-Positive Results in Repeated, Multimodal Cancer Screening

Abstract

PURPOSE Multiple cancer screening tests have been advocated for the general population; however, clinicians and patients are not always well-informed of screening burdens. We sought to determine the cumulative risk of a false-positive screening result and the resulting risk of a diagnostic procedure for an individual participating in a multimodal cancer screening program.METHODS Data were analyzed from the intervention arm of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial to determine the effects of prostate, lung, colorectal, and ovarian cancer screening on disease-specifi c mortality. The 68,436 participants, aged 55 to 74 years, were randomized to screening or usual care. Women received serial serum tests to detect cancer antigen 125 (CA-125), transvaginal sonograms, posteroanterior-view chest radiographs, and fl exible sigmoidoscopies. Men received serial chest radiographs, fl exible sigmoidoscopies, digital rectal examinations, and serum prostate-specifi c antigen tests. Fourteen screening examinations for each sex were possible during the 3-year screening period.RESULTS After 14 tests, the cumulative risk of having at least 1 false-positive screening test is 60.4% (95% CI, 59.8%-61.0%) for men, and 48.8% (95% CI, 48.1%-49.4%) for women. The cumulative risk after 14 tests of undergoing an invasive diagnostic procedure prompted by a false-positive test is 28.5% (CI, 27.8%-29.3%) for men and 22.1% (95% CI, 21.4%-22.7%) for women. CONCLUSIONSFor an individual in a multimodal cancer screening trial, the risk of a false-positive fi nding is about 50% or greater by the 14th test. Physicians should educate patients about the likelihood of false positives and resulting diagnostic interventions when counseling about cancer scree ning. Ann Fam Med 2009;7:212-222. DOI: 10.1370/afm.942. INTRODUCTIONN umerous cancer screening tests are promoted to the healthy public. [1][2][3][4][5][6][7][8] The motivating factor behind regular cancer screening is the theory that the earlier one detects a malignancy or premalignancy, the more likely treatment is to be effective in increasing lifespan while minimizing harms caused by the therapy. 9 Although this model has intuitive appeal, it is often used without actual proof in hand and without full consideration of potential adverse consequences. The most common potential adverse consequence is a false-positive result, which often brings with it physical, psychological, and economic burdens of further diagnostic testing. [10][11][12][13] The false-positive rate of a single screening test has been studied, but the cumulative false-positive rate of repeating the test at regular intervals is infrequently reported, [14][15][16][17] and the cumulative false-positive rate of multiple tests has not, to our knowledge, been reported at all. The ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is designed to assess the benefi ts and harms of screening for 4 major causes of cancer mortality. As...

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“…9 A large number of such procedures will lead to a small number of serious adverse consequences, such as serious infection, induced cardiovascular event, or even anaphylaxis or death. Considering the imprecise estimates of both benefits and harms, and factoring patient values, it seems reasonable that some well-informed health-conscious rational adults might choose to not screen.…”