Screening for lung cancer with low-dose computed tomography

Abstract

Importance Lung cancer is the leading cause of cancer-related death in the US. Objective To review the evidence on screening for lung cancer with low-dose computed tomography (LDCT) to inform the US Preventive Services Task Force (USPSTF). Data Sources MEDLINE, Cochrane Library, and trial registries through May 2019; references; experts; and literature surveillance through November 20, 2020. Study Selection English-language studies of screening with LDCT, accuracy of LDCT, risk prediction models, or treatment for early-stage lung cancer. Data Extraction and Synthesis Dual 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 Measures Lung cancer incidence, lung cancer mortality, all-cause mortality, test accuracy, and harms. Results This 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 Relevance Screening 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.This systematic review to support the 2021 US Preventive Services Task Force Recommendation Statement on screening for lung cancer summarizes published evidence about the relative benefits and harms of low-dose computed tomography to identify lung cancer in persons at high risk.