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      Low-dose computed tomography (LDCT) versus other cancer screenings in early diagnosis of lung cancer : A meta-analysis

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          Abstract

          Background:

          Lung cancer is the leading cause of cancer mortality worldwide. It is often diagnosed at an advanced stage when treatment is no longer possible. Early population-based screening may provide an opportunity for early diagnosis and reduce mortality rates.

          Methods:

          Study characteristics were collected and outcome data (lung cancer diagnosis and mortality) were extracted and used for meta-analysis. Statistical analyses were performed using OpenMetaAnalyst-0.1503 software. The odds ratio (OR) and 95% confidence interval (CI) were used to assess LDCT compared to other screening methods under the random-effects model. The I2 statistic was used to assess heterogeneity.

          Results:

          Pooling data from 4 studies (64,129 patients) showed a higher incidence of diagnosed lung cancer with LDCT screening (OR = 1.86, 95% CI: 1.02–3.37), compared to other screening tools. However, no significant difference (OR = 1.13, 95% CI: 0.78–1.64) was found in lung cancer mortality between both groups.

          Conclusions:

          Although no significant difference was found between LDCT and other control groups in terms of lung cancer mortality, this meta-analysis suggests an increased diagnosis of lung cancer with LDCT as compared with other screening modalities. This meta-analysis displays the potential but also the limitations of LDCT for early lung cancer detection.

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          Most cited references27

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          Results of the two incidence screenings in the National Lung Screening Trial.

          Denise R Aberle, Sarah DeMello, Christine D Berg … (2013)
          The National Lung Screening Trial was conducted to determine whether three annual screenings (rounds T0, T1, and T2) with low-dose helical computed tomography (CT), as compared with chest radiography, could reduce mortality from lung cancer. We present detailed findings from the first two incidence screenings (rounds T1 and T2). We evaluated the rate of adherence of the participants to the screening protocol, the results of screening and downstream diagnostic tests, features of the lung-cancer cases, and first-line treatments, and we estimated the performance characteristics of both screening methods. At the T1 and T2 rounds, positive screening results were observed in 27.9% and 16.8% of participants in the low-dose CT group and in 6.2% and 5.0% of participants in the radiography group, respectively. In the low-dose CT group, the sensitivity was 94.4%, the specificity was 72.6%, the positive predictive value was 2.4%, and the negative predictive value was 99.9% at T1; at T2, the positive predictive value increased to 5.2%. In the radiography group, the sensitivity was 59.6%, the specificity was 94.1%, the positive predictive value was 4.4%, and the negative predictive value was 99.8% at T1; both the sensitivity and the positive predictive value increased at T2. Among lung cancers of known stage, 87 (47.5%) were stage IA and 57 (31.1%) were stage III or IV in the low-dose CT group at T1; in the radiography group, 31 (23.5%) were stage IA and 78 (59.1%) were stage III or IV at T1. These differences in stage distribution between groups persisted at T2. Low-dose CT was more sensitive in detecting early-stage lung cancers, but its measured positive predictive value was lower than that of radiography. As compared with radiography, the two annual incidence screenings with low-dose CT resulted in a decrease in the number of advanced-stage cancers diagnosed and an increase in the number of early-stage lung cancers diagnosed. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).
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            Screening for lung cancer with low-dose computed tomography: a systematic review to update the US Preventive services task force recommendation.

            Linda Humphrey, Mark E Deffebach, Miranda Pappas … (2013)
            Lung cancer is the leading cause of cancer-related death in the United States. Because early-stage lung cancer is associated with lower mortality than late-stage disease, early detection and treatment may be beneficial. To update the 2004 review of screening for lung cancer for the U.S. Preventive Services Task Force, focusing on screening with low-dose computed tomography (LDCT). MEDLINE (2000 to 31 May 2013), the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth quarter of 2012), Scopus, and reference lists. English-language randomized, controlled trials or cohort studies that evaluated LDCT screening for lung cancer. One reviewer extracted study data about participants, design, analysis, follow-up, and results, and a second reviewer checked extractions. Two reviewers rated study quality using established criteria. Four trials reported results of LDCT screening among patients with smoking exposure. One large good-quality trial reported that screening was associated with significant reductions in lung cancer (20%) and all-cause (6.7%) mortality. Three small European trials showed no benefit of screening. Harms included radiation exposure, overdiagnosis, and a high rate of false-positive findings that typically were resolved with further imaging. Smoking cessation was not affected. Incidental findings were common. Three trials were underpowered and of insufficient duration to evaluate screening effectiveness. Overdiagnosis, an important harm of screening, is of uncertain magnitude. No studies reported results in women or minority populations. Strong evidence shows that LDCT screening can reduce lung cancer and all-cause mortality. The harms associated with screening must be balanced with the benefits. Agency for Healthcare Research and Quality.
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              Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial.

              Ugo Pastorino, Carlo La Vecchia, Giuseppe Pelosi … (2012)
              The efficacy and cost-effectiveness of low-dose spiral computed tomography (LDCT) screening in heavy smokers is currently under evaluation worldwide. Our screening program started with a pilot study on 1035 volunteers in Milan in 2000 and was followed up in 2005 by a randomized trial comparing annual or biennial LDCT with observation, named Multicentric Italian Lung Detection. This included 4099 participants, 1723 randomized to the control group, 1186 to biennial LDCT screening, and 1190 to annual LDCT screening. Follow-up was stopped in November 2011, with 9901 person-years for the pilot study and 17 621 person-years for Multicentric Italian Lung Detection. Forty-nine lung cancers were detected by LDCT (20 in biennial and 29 in the annual arm), of which 17 were identified at baseline examination; 63% were of stage I and 84% were surgically resectable. Stage distribution and resection rates were similar in the two LDCT arms. The cumulative 5-year lung cancer incidence rate was 311/100 000 in the control group, 457 in the biennial, and 620 in the annual LDCT group (P=0.036); lung cancer mortality rates were 109, 109, and 216/100 000 (P=0.21), and total mortality rates were 310, 363, and 558/100 000, respectively (P=0.13). Total mortality in the pilot study was similar to that observed in the annual LDCT arm at 5 years. There was no evidence of a protective effect of annual or biennial LDCT screening. Furthermore, a meta-analysis of the four published randomized trials showed similar overall mortality in the LDCT arms compared with the control arm.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Medicine (Baltimore)
                Journal ID (iso-abbrev): Medicine (Baltimore)
                Journal ID (publisher-id): MEDI
                Title: Medicine
                Publisher: Wolters Kluwer Health
                ISSN (Print): 0025-7974
                ISSN (Electronic): 1536-5964
                Publication date Collection: July 2018
                Publication date (Electronic): 06 July 2018
                Volume: 97
                Issue: 27
                Electronic Location Identifier: e11233
                Affiliations
                [a ]Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, Department of Respiration
                [b ]Department of Gynecological Oncology, First Affiliated Hospital, Bengbu Medical College, Bengbu
                [c ]Department of Immunology, Research Center of Immunology, Bengbu Medical College, Anhui, P.R. China.
                Author notes
                [∗ ]Correspondence: Hongtao Wang, and Yuqing Chen, Department of Immunology, Research Center of Immunology, Bengbu Medical College, 2600 Dong Hai Avenue, Longzihu District (University City), Bengbu, Anhui 233030, P.R. China (e-mails: bb_wanghongtao@ 123456126.com , bbmccyq@ 123456126.com ).
                Article
                Publisher ID: MD-D-17-07347 Accession ID: 11233
                DOI: 10.1097/MD.0000000000011233
                PMC ID: 6076107
                PubMed ID: 29979385
                SO-VID: 6dd9df22-3bb1-4a32-9986-de8b84c07467
                Copyright © Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                Date received : 24 November 2017
                Date accepted : 1 June 2018
                Categories
                Subject: 6800
                Subject: Research Article
                Subject: Systematic Review and Meta-Analysis
                Custom metadata
                OPEN-ACCESS TRUE

                Keywords: low-dose computed tomography,lung cancer,meta-analysis,screening
                Data availability:
                Keywords: low-dose computed tomography, lung cancer, meta-analysis, screening

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