• Daniel E Jonas, Daniel S Reuland, Shivani M Reddy, Max Nagle, Stephen D Clark, Rachel Palmieri Weber, Chineme Enyioha, Teri L Malo, Alison T Brenner, Charli Armstrong, Manny Coker-Schwimmer, Jennifer Cook Middleton, Christiane Voisin, and Russell P Harris.
• RTI International, University of North Carolina at Chapel Hill Evidence-based Practice Center.
• JAMA. 2021 Mar 9; 325 (10): 971-987.

ImportanceLung cancer is the leading cause of cancer-related death in the US.ObjectiveTo review the evidence on screening for lung cancer with low-dose computed tomography (LDCT) to inform the US Preventive Services Task Force (USPSTF).Data SourcesMEDLINE, Cochrane Library, and trial registries through May 2019; references; experts; and literature surveillance through November 20, 2020.Study SelectionEnglish-language studies of screening with LDCT, accuracy of LDCT, risk prediction models, or treatment for early-stage lung cancer.Data Extraction And SynthesisDual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings. Data were not pooled because of heterogeneity of populations and screening protocols.Main Outcomes And MeasuresLung cancer incidence, lung cancer mortality, all-cause mortality, test accuracy, and harms.ResultsThis review included 223 publications. Seven randomized clinical trials (RCTs) (N = 86 486) evaluated lung cancer screening with LDCT; the National Lung Screening Trial (NLST, N = 53 454) and Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON, N = 15 792) were the largest RCTs. Participants were more likely to benefit than the US screening-eligible population (eg, based on life expectancy). The NLST found a reduction in lung cancer mortality (incidence rate ratio [IRR], 0.85 [95% CI, 0.75-0.96]; number needed to screen [NNS] to prevent 1 lung cancer death, 323 over 6.5 years of follow-up) with 3 rounds of annual LDCT screening compared with chest radiograph for high-risk current and former smokers aged 55 to 74 years. NELSON found a reduction in lung cancer mortality (IRR, 0.75 [95% CI, 0.61-0.90]; NNS to prevent 1 lung cancer death of 130 over 10 years of follow-up) with 4 rounds of LDCT screening with increasing intervals compared with no screening for high-risk current and former smokers aged 50 to 74 years. Harms of screening included radiation-induced cancer, false-positive results leading to unnecessary tests and invasive procedures, overdiagnosis, incidental findings, and increases in distress. For every 1000 persons screened in the NLST, false-positive results led to 17 invasive procedures (number needed to harm, 59) and fewer than 1 person having a major complication. Overdiagnosis estimates varied greatly (0%-67% chance that a lung cancer was overdiagnosed). Incidental findings were common, and estimates varied widely (4.4%-40.7% of persons screened).Conclusions And RelevanceScreening high-risk persons with LDCT can reduce lung cancer mortality but also causes false-positive results leading to unnecessary tests and invasive procedures, overdiagnosis, incidental findings, increases in distress, and, rarely, radiation-induced cancers. Most studies reviewed did not use current nodule evaluation protocols, which might reduce false-positive results and invasive procedures for false-positive results.

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