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 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.

Figure 1. The Analytic Framework of the U.S. Preventive Services Task Force

Generic analytic framework for evaluating a screening test, adapted from the U.S. Preventive Services Task Force. From Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, et al. 2001. Current methods of the U.S. Preventive Services Task Force: A review of the process. Am. J. Prev. Med. 20(3S): 21–35.

Figure 2. Lead-time Bias

Figure 3. Survival versus Mortality: The Mayo Lung Project

Figure 3 demonstrates that although 5-year survival is improved in the screening arm compared with the control arm, deaths due to lung cancer were actually greater in the screening arm. This illustrates the problem with using survival rather than mortality calculations when attempting to evaluate the worth of a screening modality—lead-time bias gives a misleading appearance of benefit in survival rates even when there is increased disease-specific mortality in the screened population. From reference .

Figure 4. U.S. Trends in Localized versus Distant Cancer Incidence for Breast Cancer, Prostate Cancer, and Melanoma

Figure 4 depicts total, localized, and distant cancer incidence rates for breast, prostate, and skin cancer (melanoma) per 100,000 persons ages 40 and older in the U.S. “Localized” and “distant” are defined as by SEER historic stage A: “Localized” is an invasive cancer confined to the organ of origin; “distant” is an extension of metastasis to organs not adjacent to that of origin or to distal lymph nodes. From: Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 9 Regs Limited-Use, Nov 2008 Sub (1973–2006) <Katrina/Rita Population Adjustment> - Linked To County Attributes - Total U.S., 1969–2006 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2009, based on the November 2008 submission.

Figure 4. U.S. Trends in Localized versus Distant Cancer Incidence for Breast Cancer, Prostate Cancer, and Melanoma

Figure 4 depicts total, localized, and distant cancer incidence rates for breast, prostate, and skin cancer (melanoma) per 100,000 persons ages 40 and older in the U.S. “Localized” and “distant” are defined as by SEER historic stage A: “Localized” is an invasive cancer confined to the organ of origin; “distant” is an extension of metastasis to organs not adjacent to that of origin or to distal lymph nodes. From: Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 9 Regs Limited-Use, Nov 2008 Sub (1973–2006) <Katrina/Rita Population Adjustment> - Linked To County Attributes - Total U.S., 1969–2006 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2009, based on the November 2008 submission.