Principles of Cancer Screening: Lessons From History and Study Design Issues

Early detection of cancer has held great promise and intuitive appeal in the medical community for well over a century. Its history developed in tandem with that of the periodic health examination, in which any deviations-subtle or glaring-from a clearly demarcated normal were to be rooted out, given the underlying hypothesis that diseases develop along progressive linear paths of increasing abnormalities. This model of disease development drove the logical deduction that early detection, by breaking the chain of cancer development, must be of benefit to affected individuals. In the latter half of the 20th century, researchers and guidelines organizations began to explicitly challenge the core assumptions underpinning many clinical practices. A move away from intuitive thinking began with the development of evidence-based medicine. One key method developed to explicitly quantify the overall risk-benefit profile of a given procedure was the analytic framework. The shift away from pure deductive reasoning and reliance on personal observation was driven, in part, by a rising awareness of critical biases in cancer screening that can mislead clinicians, including healthy volunteer bias, length-biased sampling, lead-time bias, and overdiagnosis. A new focus on the net balance of both benefits and harms when determining the overall worth of an intervention also arose: it was recognized that the potential downsides of early detection were frequently overlooked or discounted because screening is performed on basically healthy persons and initially involves relatively noninvasive methods. Although still inconsistently applied to early detection programs, policies, and belief systems in the United States, an evidence-based approach is essential to counteract the misleading-even potentially harmful-allure of intuition and individual observation. Semin Oncol 37:202-215. Published by Elsevier Inc.