Estimation of Overdiagnosis of Lung Cancer in Low-Dose Computed Tomography Screening

Heleno, Bruno; Siersma, Volkert; Brodersen, John

doi:10.1001/jamainternmed.2018.3056

Cited by 71 publications

(64 citation statements)

References 6 publications

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“…20 Screening for specific cancer types, like prostate (PSA testing), 41,42 lung (low-dose computed tomography), 43,44 and breast (mammography) 45,46 have available evidence and potential risks associated with overdiagnosis; however, the magnitude of risk associated with overdiagnosis remains highly variable. [41][42][43][44][45][46] This magnitude of risk may be of particular concern for cancer types with conflicting recommendations and guidelines regarding initiation and frequency of screening. 18 Communicating overdiagnosis in PDAs may not be as high of a concern among other cancer types that have lower magnitude of risk for overdiagnosis, such as with colorectal cancer screening based on US recommendations and guidelines.…”

Section: Discussionmentioning

confidence: 99%

A Review of the Presentation of Overdiagnosis in Cancer Screening Patient Decision Aids

Housten

Lowenstein

Hoffman

et al. 2019

MDM Policy & Practice

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Introduction. Patient decision aid (PDA) certification standards recommend including the positive and negative features of each option of the decision. This review describes the inclusion of concepts related to overdiagnosis and overtreatment, negative features often ambiguously defined, in cancer screening PDAs. Methods. Our process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We reviewed 1) current systematic reviews of decision aids, 2) the Ottawa Hospital Research Institute Decision Aid Library Inventory, and 3) a web-based, gray literature search. Two independent reviewers identified and evaluated PDAs using content analysis. Reviewers coded whether overdiagnosis/overtreatment was described as 1) detecting cancer that would not lead to death, 2) detecting cancer that would not cause symptoms, and/or 3) a potential harm or consequence of screening. Coding discrepancies were resolved through consensus. Results. A total of 904 records (e.g., articles, PDAs) were reviewed and 85 PDAs were identified: prostate ( n = 36), breast ( n = 26), lung ( n = 10), colorectal ( n = 10), and other ( n = 3). Sixty-seven PDAs included concepts related to overdiagnosis/overtreatment; 57 (67.1%) used a term other than overdiagnosis/overtreatment, 23 (27.1%) used the specific term “overdiagnosis,” and 13 (15.3%) used “overtreatment.” PDAs described overdiagnosis/overtreatment as a potential harm or consequence of screening ( n = 62) and/or a detection of a cancer that would not cause symptoms (n = 49). Thirty-six described overdiagnosis as the detection of a cancer that would not result in death. Twenty PDAs described the probabilities associated with overdiagnosis/overtreatment. Conclusions. Over three quarters of cancer screening PDAs addressed concepts related to overdiagnosis/overtreatment, yet terminology was inconsistent and few included probability estimates. Consistent terminology and minimum standards to describe overdiagnosis/overtreatment would help guide the design and certification of cancer screening PDAs.

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Section: Discussionmentioning

confidence: 99%

A Review of the Presentation of Overdiagnosis in Cancer Screening Patient Decision Aids

Housten

Lowenstein

Hoffman

et al. 2019

MDM Policy & Practice

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“…In our literature search, we identified the nine trials investigating LDCT screening, of which we already knew (table S1) [17,[23][24][25][26][29][30][31][32]. This paper was first submitted to the journal Breathe on 20 January 2020.…”

Section: Resultsmentioning

confidence: 99%

Overdiagnosis of lung cancer with low-dose computed tomography screening: meta-analysis of the randomised clinical trials

Brodersen

Voss

Martiny

et al. 2020

Breathe

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In low-dose computed tomography (LDCT) screening for lung cancer, all three main conditions for overdiagnosis in cancer screening are present: 1) a reservoir of slowly or nongrowing lung cancer exists; 2) LDCT is a high-resolution imaging technology with the potential to identify this reservoir; and 3) eligible screening participants have a high risk of dying from causes other than lung cancer. The degree of overdiagnosis in cancer screening is most validly estimated in high-quality randomised controlled trials (RCTs), with enough follow-up time after the end of screening to avoid lead-time bias and without contamination of the control group.Nine RCTs investigating LDCT screening were identified. Two RCTs were excluded because lung cancer incidence after the end of screening was not published. Two other RCTs using active comparators were also excluded. Therefore, five RCTs were included: two trials were at low risk of bias, two of some concern and one at high risk of bias. In a meta-analysis of the two low risk of bias RCTs including 8156 healthy current or former smokers, 49% of the screen-detected cancers were overdiagnosed. There is uncertainty about this substantial degree of overdiagnosis due to unexplained heterogeneity and low precision of the summed estimate across the two trials.Key pointsNine randomised controlled trials (RCTs) on low-dose computed tomography screening were identified; five were included for meta-analysis but only two of those were at low risk of bias.In a meta-analysis of recent low risk of bias RCTs including 8156 healthy current or former smokers from developed countries, we found that 49% of the screen-detected cancers may be overdiagnosed.There is uncertainty about the degree of overdiagnosis in lung cancer screening due to unexplained heterogeneity and low precision of the point estimate.If only high-quality RCTs are included in the meta-analysis, the degree of overdiagnosis is substantial.Educational aimsTo appreciate that low-dose computed tomography screening for lung cancer meets all three main conditions for overdiagnosis in cancer screening: a reservoir of indolent cancers exists in the population; the screening test is able to “tap” this reservoir by detecting biologically indolent cancers as well as biologically important cancers; and the population being screened is characterised by a relatively high competing risk of death from other causesTo learn about biases that might affect the estimates of overdiagnosis in randomised controlled trials in cancer screening

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“…The Italian Lung Cancer Screening trial (ITALUNG) revealed no overdiagnosis, which indicates that this trial was either biased and/or that CT screening was limited in its ability to detect the earliest-stage lung cancers [97]. The Danish Lung Cancer Screening Trial (DLCST) concluded that 67.2% of screening-detected cancers were overdiagnosed, with little degree of contamination bias but a potential minor uneven distribution at randomisation: more heavy smokers and participants with COPD in the intervention group [98]. The most recent NELSON results did not disclose the estimate of overdiagnosis; however, the cumulative incidences of lung cancer in the intervention and control arms indicated some degree of overdiagnosis [15].…”

Section: Overdiagnosis and Harmsmentioning

confidence: 97%

“…The estimate of overdiagnosis is prone to bias [93] because it is linked to a pathological reference standard [94]. Thereby, several metrics become altered, including diagnostic test accuracy, incidence and prevalence, stage shift and survival rates [95]. The degree of overdiagnosis should be accounted for when using risk models and estimating outcomes.…”

Section: Overdiagnosis and Harmsmentioning

confidence: 99%

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ESR/ERS statement paper on lung cancer screening

et al. 2020

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In Europe, lung cancer ranks third among the most common cancers, remaining the biggest killer. Since the publication of the first European Society of Radiology and European Respiratory Society joint white paper on lung cancer screening (LCS) in 2015, many new findings have been published and discussions have increased considerably. Thus, this updated expert opinion represents a narrative, non-systematic review of the evidence from LCS trials and description of the current practice of LCS as well as aspects that have not received adequate attention until now. Reaching out to the potential participants (persons at high risk), optimal communication and shared decision-making will be key starting points. Furthermore, standards for infrastructure, pathways and quality assurance are pivotal, including promoting tobacco cessation, benefits and harms, overdiagnosis, quality, minimum radiation exposure, definition of management of positive screen results and incidental findings linked to respective actions as well as cost-effectiveness. This requires a multidisciplinary team with experts from pulmonology and radiology as well as thoracic oncologists, thoracic surgeons, pathologists, family doctors, patient representatives and others. The ESR and ERS agree that Europe's health systems need to adapt to allow citizens to benefit from organised pathways, rather than unsupervised initiatives, to allow early diagnosis of lung cancer and reduce the mortality rate. Now is the time to set up and conduct demonstration programmes focusing, among other points, on methodology, standardisation, tobacco cessation, education on healthy lifestyle, cost-effectiveness and a central registry.

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Estimation of Overdiagnosis of Lung Cancer in Low-Dose Computed Tomography Screening

Abstract: Denmark, contributed with data acquisition and received financial compensation for her work. 1. Pedersen JH, Ashraf H, Dirksen A, et al. The Danish randomized lung cancer CT screening trial: overall design and results of the prevalence round.

Cited by 71 publications

References 6 publications

A Review of the Presentation of Overdiagnosis in Cancer Screening Patient Decision Aids

A Review of the Presentation of Overdiagnosis in Cancer Screening Patient Decision Aids

Overdiagnosis of lung cancer with low-dose computed tomography screening: meta-analysis of the randomised clinical trials

ESR/ERS statement paper on lung cancer screening

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