Screening for lung cancer with low-dose computed tomography: systematic reviews on effectiveness and patient preferences

Abstract

Abstract

We synthesized evidence for three questions on screening for lung cancer with computed tomography (CT): benefits (from randomized trials) and harms of screening versus no screening/minimal intervention or alternative screening approaches (e.g., selection criteria, screening intervals); relative importance that informed patients place on the potential benefits and harms of screening (patient preferences); and comparative effects from observational studies of different CT screening selection criteria (using risk prediction models) or nodule classification systems compared with those used in the screening trials. An expert working group provided input on eligibility criteria and potential effect moderators, rated outcomes, and developed decision thresholds for assessing certainty of the evidence and making conclusions. Critical outcomes of screening effects included all-cause mortality, lung-cancer mortality, and overdiagnosis; important outcomes included false positives (FPs), incidental findings, major complications, and psychosocial harms. For patient preferences, we sought data on (i) disutilities of relevant health states, (ii) direct preference-based data, such as outcome trade-offs, and (iii) relative importance of benefits versus harms inferred from attitudes, intentions, and behaviors towards screening among informed patients. For screening benefits and harms and for patient preferences, we searched three databases (MEDLINE, Embase, and Central and MEDLINE, Scopus, and EconLit, respectively) to July 2025. For screening studies published prior to 2015, we relied on other reviews, and for patient preferences our search was limited to 2012 onwards. For comparative effects, we searched MEDLINE and Embase from 2019 to September 2025, relying on other reviews for studies published 2012–2018. Reference lists were scanned and trial registries searched. Two independent reviewers screened titles and abstracts then full texts. Data extraction and analysis were undertaken by single reviewers, with verification; risk of bias and GRADE certainty assessments were undertaken independently by at least two reviewers. Data were pooled where suitable using random-effects methods appropriate to the outcome metric and prevalence. Subgroup analyses explored heterogeneity. When not pooled, data were analyzed by grouping studies based on PICO factors, with consideration of study size and risk of bias. Conclusions and certainty assessments for screening effects were based on estimates of absolute effects. We included 85 studies ( N = 640,537; 13 trials) on screening benefits and harms, 59 on patient preferences (33 [ N = 42,219] on disutilities; 26 [ N = 10,829] other studies), and 16 for comparing trial (National Lung Screening Trial [NLST]) and LungRADs nodule management, either directly (2 studies, N = 26,978) or indirectly (14 studies, N = 1,102,285). Screening benefits and harms: Nine trials ( N = 94,530) examining low-dose CT (LDCT) screening on all-cause (RR 0.97, 95% CI 0.93 to 1.01; 3.7 fewer [8.5 fewer to 1.2 more] per 1000) and lung-cancer mortality (RR 0.87, 95% CI 0.79 to 0.96; 4.0 fewer [1.2 to 6.4 fewer] per 1000) offered low and moderate certainty, respectively, that screening previous/current 20–30 pack-year smokers 50–74 years old 3–4 times will probably result in at least 1 (all-cause) and 2 (cause-specific) fewer deaths per 1000 screened after 10–12 years. The absolute effects may not apply to participants at the lowest baseline risk for lung-cancer incidence (e.g., < 1.5% over 6 years) or death. Certainty for overdiagnosis (7 trials, N = 35,161; RR 1.19, 95% CI 1.03 to 1.37; 8.4 [1.3 to 16.3] per 1000) was moderate that LDCT screening 3–4 times will probably result in at least 2.5 cases of overdiagnosis per 1000 screened over 10 years. High-certainty evidence was found for results for FPs and incidental findings (any and clinically significant) surpassing their decision thresholds, whereas little-to-no harm was found for major complications from invasive procedures among those having a FP. Requiring diagnostic follow-up after a positive scan probably causes at least some psychosocial harm. Patient preferences: Most results had low-certainty evidence, with the exception of moderate certainty for little-to-no (< 0.04 [range 0–1.0]) disutility from a positive screening test; a small, but important disutility (0.04–0.08) for stage IIIB–IV lung cancer during first-line treatment; and a small majority (51–75%) of people eligible for screening probably weighing the benefits as more important than the harms from screening in a relatively moderate net-benefit scenario. Comparative effects: Using LungRADs instead of NLST nodule management (among NLST-eligible people) probably reduces the FP rate substantially (about half), though the number of FPs still exceeded the decision threshold of 75 per 1000 and the effects for benefits or other harm outcomes are not known. This review provides contemporary data on the benefits and harms of LDCT screening after at least a decade of follow-up. Findings indicate that screening previous/current 20–30 pack-year smokers aged 50–74 years with 3–4 rounds of LDCT will lead to benefits and harms for which a majority probably find acceptable and worthwhile. While current nodule management using LungRADs likely reduces FPs, whether it impacts the benefits of screening is less certain and worth further research. Further, comparative prospective studies are lacking to determine the effects from screening for those not meeting the minimum age (50 years) and smoking history criteria in the trials, despite having an equivalent risk for lung cancer.