Can CT Screening Give Rise to a Beneficial Stage Shift in Lung Cancer Patients? Systematic Review and Meta-Analysis

<div><p>Objectives</p><p>To portray the stage characteristics of lung cancers detected in CT screenings, and explore whether there’s universal stage superiority over other methods for various pathological types using available data worldwide in a meta-analysis approach.</p><p>Materials and Methods</p><p>EMBASE and MEDLINE were searched for studies on lung cancer CT screening in natural populations through July 2015 without language or other filters. Twenty-four studies (8 trials and 16 cohorts) involving 1875 CT-detected lung cancer patients were enrolled and assessed by QUADAS-2. Pathology-confirmed stage information was carefully extracted by two reviewers. Stage I or limited stage proportions were pooled by random effect model with Freeman-Tukey double arcsine transformation.</p><p>Results</p><p>Pooled stage I cancer proportion in CT screenings was 73.2% (95% confidence interval: 68.6%, 77.5%), with a significant rising trend (<i>P</i>_trend<0.05) from baseline (64.7%) to ≥5 repeat rounds (87.1%). Relative to chest radiograph and usual care, the increased stage I proportions in CT were 12.2% (<i>P</i>>0.05), and 46.5% (<i>P</i><0.05), respectively. Pathology-specifically, adenocarcinomas (66%) and squamous cell lung cancers (17%) composed the majority of CT-detected lung cancers, and had significantly higher stage I proportions relative to chest radiograph (bronchioloalveolar adenocarcinomas, 80.9% vs 51.4%; other adenocarcinomas, 58.8% vs 38.3%; squamous cell lung cancers, 52.3% vs 38.3%; all <i>P</i><0.05). However, the percentage of small cell lung cancer was lower using CT than other detection routes, and no significant difference in limited stage proportion was observed (6.8% vs 10.8%, <i>P</i>>0.05).</p><p>Conclusion</p><p>CT screening can detect more early stage non-small cell lung cancers, but not all of them could be beneficial as there are a considerable number of indolent ones such as bronchioloalveolar adenocarcinomas. Still, current evidence is lacking regarding small cell lung cancers.</p></div

Study selection flow chart.

<p>A list of the full-text excluded articles are available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0164416#pone.0164416.s006" target="_blank">S2 Text</a>. ^a We excluded the two summary reports from the International Early Lung Cancer Action Program and another two reports of its individual sites because only clinical stage information could be obtained, which is heterogeneous to the pathological staging method and could overestimate the estimates in this study.</p

Individual patient data subgroup analysis of sources of heterogeneity regarding the proportion of stage I cancers in CT lung cancer screening studies.

<p>Individual patient data subgroup analysis of sources of heterogeneity regarding the proportion of stage I cancers in CT lung cancer screening studies.</p

Basic characteristics of the included CT lung cancer screening studies.

<p>Basic characteristics of the included CT lung cancer screening studies.</p

Pathologically specific stage distributions of lung cancers detected using CT in six studies.

<p>Data pooled from the Münster[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0164416#pone.0164416.ref004" target="_blank">4</a>], Israel[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0164416#pone.0164416.ref006" target="_blank">6</a>], Mayo[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0164416#pone.0164416.ref008" target="_blank">8</a>], Toronto[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0164416#pone.0164416.ref016" target="_blank">16</a>],NELSON[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0164416#pone.0164416.ref018" target="_blank">18</a>],and ITALUNG[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0164416#pone.0164416.ref019" target="_blank">19</a>]studies.</p

Differences between the proportion of stage I cancers detected using CT and other routes (data shown as CT minus other routes).

<p>Differences between the proportion of stage I cancers detected using CT and other routes (data shown as CT minus other routes).</p

Study level subgroup analysis of sources of heterogeneity regarding the proportion of stage I cancers in CT lung cancer screening studies.

<p>Study level subgroup analysis of sources of heterogeneity regarding the proportion of stage I cancers in CT lung cancer screening studies.</p

Proportion of round specific stage I cancer in six studies and summary estimates with 95% confident interval lines.

<p>Data are shown as stage I cancers/total cancers. Cancer stages and the detected rounds were determined by the time they were diagnosed. ^a and ^b: separately summarized and smoothed in the figure lines because of the small total number of cancers (<9).</p

Lung cancer distributions according to the reported histological types.

<p>(A.1) Cancers detected in the CT arm of the National Lung Study Trial. (A.2) Cancers detected in the chest radiograph arm of the National Lung Study Trial. (B.1) Summary results for CT detected cancers from randomized control trials (RCTs) other than the National Lung Study Trial. (B.2) Summary results for cancers detected in the control arms (chest radiograph or usual care) from RCTs other than the National Lung Study Trial. (C) Summary results for CT detected cancers from all available reports (including cohorts and RCTs). Only studies reporting the full spectrum of histological compositions were used.</p

Patient characteristics.

<p>Patient characteristics.</p