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

Abstract

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 20 th 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 evidencebased approach is essential to counteract the misleading-even potentially harmful--allure of intuition and individual observation.

Assessment of lead-time bias in estimates of relative survival for breast cancer

“…Over-diagnosis is often defined as the detection of tumours that, if left untreated, would not lead to symptoms or harm to the individual within the individual's lifetime [13,14]. Over-diagnosis can occur if there are tumours that lack true malignant potential or if they are so slow-growing that the individual would die due to other causes before her life is threatened by the cancer.…”

“…Lead-time is survival time that is added to a patient's survival time because of an earlier diagnosis irrespective of a possibly postponed time of death [13,14]. In the presence of lead-time, the survival times of the patients are prolonged by an early diagnosis, and the survival proportion at any given time point is therefore increased even if no real improvement in survival is experienced.…”

Az alacsony dózisú CT-vel végzett tüdőrákszűrés magyarországi egészség-gazdaságtani elemzésének koncepcionális terve

“…Egyrészt pszichológiailag kedvezőtlen hatással van a betegre, szorongást és depressziót válthat ki, másrészt a pozitív eredmény után a beteg további kivizsgáláson, beavatkozásokon eshet át, amelyek mellékhatásokat okozhatnak, valamint jelentős anyagi terhet jelenthetnek a betegnek és az egészségügyi rendszernek egyaránt [41]. A modellépítés során a szűréshez kapcsolódó negatív hatásokat, a költségekhez hasonlóan, figyelembe kell venni.…”

“…A tapasztalatok azt mutatják, hogy azok, akik a részvétel mellett döntenek, magasabb iskolai végzettsé-gűek, jobb anyagi helyzetűek és fogékonyabbak az egészséget érintő témákra, így több testmozgást végez-nek, kevesebbet dohányoznak és kevesebb alkoholt fogyasztanak [41]. Ezáltal a szűrésen részt vevőknek általá-nosságban jobb az egészségi állapotuk és jobbak az életkilátásaik, mint a szűrést elutasítóknak, amely az ön-kéntes részvételből származó torzításhoz vezet.…”

Advances in the prevention and treatment of lung cancer

“…44 Finally, although some screening studies have suggested improvements in lung cancer mortality in the screened population, other investigators have suggested that this may simply be due to detection of cancer earlier within its natural history or so-called 'lead-time' bias. 45 …”