Cancer overdiagnosis: a challenge in the era of screening

Abstract

"Screening" is a search for preclinical, asymptomatic disease, including cancer. Widespread cancer screening has led to large increases in early-stage cancers and pre-cancers. Ubiquitous public messages emphasize the potential benefits to screening for these lesions based on the underlying assumption that treating cancer at early stages before spread to other organs should make it easier to treat and cure, using more tolerable interventions. The intuition is so strong that public campaigns are sometimes launched without conducting definitive trials directly comparing screening to usual care. An effective cancer screening test should not only increase the incidence of early-stage preclinical disease but should also decrease the incidence of advanced and metastatic cancer, as well as a subsequent decrease in cancer-related mortality. Otherwise, screening efforts may be uncovering a reservoir of non-progressive and very slowly progressive lesions that were not destined to cause symptoms or suffering during the person's remaining natural lifespan: a phenomenon known as "overdiagnosis." We provide here a qualitative review of cancer overdiagnosis and discuss specific examples due to extensive population-based screening, including neuroblastoma, prostate cancer, thyroid cancer, lung cancer, melanoma, and breast cancer. The harms of unnecessary diagnosis and cancer therapy call for a balanced presentation to people considering undergoing screening, even with a test of accepted benefit, with a goal of informed decision-making. We also discuss proposed strategies to mitigate the adverse sequelae of overdiagnosis.

Keywords: Cancer overdiagnosis; Screening.

Fig. 1

(A) Length-time bias/length-biased sampling. Green lines, cancers picked up by screening; Red lines, cancers missed by screening; Dx, time when disease is clinically obvious without testing. (B) Overdiagnosis. *, lifespan unchanged. (C) Cancer overdiagnosis due to tumor heterogeneity. (Courtesy of H. Gilbert Welch, Brigham and Women's Center for Surgery and Public Health).

Fig. 2

Overdiagnosis with stable true cancer incidence. (Adapted from H.G. Welch et al., N Engl J Med 381(14):1378–1386, 2019).

Fig. 3

(A) Age-standardized incidence and mortality rate of neuroblastoma in Osaka. (Adapted from W. Ajiki et al., Cancer Causes Control 9(6):631–636, 1998) (B) Incidence and mortality rates of neuroblastoma cases before and after cessation of the mass screening program in Japan (Adapted from T. Shinagawa et al., Int J Cancer 140:618–625, 2017).

Fig. 4

Breast cancer long-term trends in SEER Incidence (1975–2018) and US mortality (1975–2019). The delay-adjusted incidence curve includes correction of incidence for the most recent historical trends in delayed reporting from SEER sites.