Efficacy of lung cancer screening appears to increase with prolonged intervention: results from the MILD trial and a meta-analysis
2019; Elsevier BV; Volume: 30; Issue: 7 Linguagem: Inglês
10.1093/annonc/mdz145
ISSN1569-8041
AutoresMatteo Rota, Margherita Pizzato, Carlo La Vecchia, Paolo Boffetta,
Tópico(s)Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
ResumoThe long-term results of the Multicentric Italian Lung Detection (MILD) study [1.Pastorino U. Silva M. Sestini S. et al.Prolonged lung cancer screening reduced 10-year mortality in the MILD Trial.Ann Oncol. 2019; 30: 1162-1169Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar] show a reduced lung cancer (LC) mortality at 10 years in the screened compared with the control arm [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.39–0.95); the HR for all-cause mortality was 0.80 (95% CI 0.62–1.03). Screening benefits were more evident beyond the fifth year of screening, with HRs of 0.42 (95% CI 0.22-0.79) for LC mortality and 0.68 (95% CI 0.49–0.94) for all-cause mortality. These important findings add to our knowledge of low-dose CT scan (LDCT) screening efficacy. The National Lung Screening Trial (NLST) showed that screening with LDCT reduces LC mortality by 20% as compared with chest X-ray after a median follow-up of 6.5 years [2.Aberle D.R. Adams A.M. Berg C.D. et al.Reduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med. 2011; 365: 395-409Crossref PubMed Scopus (6877) Google Scholar]. The results of the NLST were initially not replicated by smaller European trials [3.Infante M. Cavuto S. Lutman F.R. et al.Long-term follow-up results of the DANTE trial, a randomized study of lung cancer screening with spiral computed tomography.Am J Respir Crit Care Med. 2015; 191: 1166-1175Crossref PubMed Scopus (258) Google Scholar, 4.Paci E. Puliti D. Lopes Pegna A. et al.Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial.Thorax. 2017; 72: 825-831Crossref PubMed Scopus (165) Google Scholar, 5.Wille M.M. Dirksen A. Ashraf H. et al.Results of the randomized Danish Lung Cancer Screening Trial with focus on high-risk profiling.Am J Respir Crit Care Med. 2016; 193: 542-551Crossref PubMed Scopus (234) Google Scholar], although preliminary results of the NEderlands Leuvens Longkanker Screenings ONderzoek (NELSON) trial—the only European trial with adequate power—showed a reduction in LC mortality at 10 years [6.De Koning H. Van Der Aalst C. Ten Haaf K. Oudkerk M. Effects of volume CT lung cancer screening: mortality results of the NELSON randomised-controlled population based trial.J Thorac Oncol. 2018; 13: S185Abstract Full Text Full Text PDF Google Scholar]. While waiting for full publication of the NELSON trial, we carried out a systematic review and meta-analysis of the currently available evidence on LDCT screening for LC, including new results of the MILD [1.Pastorino U. Silva M. Sestini S. et al.Prolonged lung cancer screening reduced 10-year mortality in the MILD Trial.Ann Oncol. 2019; 30: 1162-1169Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar] and preliminary results of the NELSON [6.De Koning H. Van Der Aalst C. Ten Haaf K. Oudkerk M. Effects of volume CT lung cancer screening: mortality results of the NELSON randomised-controlled population based trial.J Thorac Oncol. 2018; 13: S185Abstract Full Text Full Text PDF Google Scholar]. We carried out a literature search in MEDLINE through PubMed and EMBASE from their inception date to 31 March 2019. Randomized controlled trials (RCTs) of lung cancer screening with LDCT as compared with other screening techniques were included. Both pilot and full RCTs were considered, without restrictions on publication type. Primary outcomes were LC mortality and all-cause mortality at the longest follow-up available, at 5 years of follow-up, and beyond the fifth year of follow-up for studies reporting long-term results. Secondary outcomes were LC incidence, detection of LC at early stages (IA and IB) and detection of lung adenocarcinoma with LDCT. A random-effects meta-analytic model [7.DerSimonian R. Laird N. Meta-analysis in clinical trials.Control Clin Trials. 1986; 7: 177-188Abstract Full Text PDF PubMed Scopus (29058) Google Scholar] of between-study variance was used to pool the estimates across studies. For LC mortality, all-cause mortality and LC incidence, we pooled together both HRs and relative risks (RRs) derived from the studies eligible for the meta-analysis. The estimates at 5 years of follow-up and those beyond the fifth year were extracted from the Kaplan–Meier curves using the methods described by Tierney et al. [8.Tierney J.F. Stewart L.A. Ghersi D. et al.Practical methods for incorporating summary time-to-event data into meta-analysis.Trials. 2007; 8PubMed Google Scholar], or derived from the cumulative number of events and number of person-years at 5 years of follow-up or beyond. For detection of LC at early stages and detection of lung adenocarcinoma, the study-specific RRs were computed using as a denominator the total number of LCs detected within each study arms. A total of 460 records were retrieved from the literature search, of which 49 were assessed for eligibility by full-text reading. Three pilot RCTs [9.Gohagan J.K. Marcus P.M. Fagerstrom R.M. et al.Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer.Lung Cancer. 2005; 47: 9-15Abstract Full Text Full Text PDF PubMed Scopus (265) Google Scholar, 10.Blanchon T. Bréchot J.M. Grenier P.A. et al.Baseline results of the DEPISCAN study: a French randomized pilot trial of lung cancer screening comparing low dose CT scan (LDCT) and chest X-ray (CXR).Lung Cancer. 2007; 58: 50-58Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar, 11.Field J.K. Duffy S.W. Baldwin D.R. et al.The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer.Health Technol Assess. 2016; 20: 1-146Crossref PubMed Scopus (163) Google Scholar] and eight RCTs [1.Pastorino U. Silva M. Sestini S. et al.Prolonged lung cancer screening reduced 10-year mortality in the MILD Trial.Ann Oncol. 2019; 30: 1162-1169Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar, 2.Aberle D.R. Adams A.M. Berg C.D. et al.Reduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med. 2011; 365: 395-409Crossref PubMed Scopus (6877) Google Scholar, 3.Infante M. Cavuto S. Lutman F.R. et al.Long-term follow-up results of the DANTE trial, a randomized study of lung cancer screening with spiral computed tomography.Am J Respir Crit Care Med. 2015; 191: 1166-1175Crossref PubMed Scopus (258) Google Scholar, 4.Paci E. Puliti D. Lopes Pegna A. et al.Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial.Thorax. 2017; 72: 825-831Crossref PubMed Scopus (165) Google Scholar, 5.Wille M.M. Dirksen A. Ashraf H. et al.Results of the randomized Danish Lung Cancer Screening Trial with focus on high-risk profiling.Am J Respir Crit Care Med. 2016; 193: 542-551Crossref PubMed Scopus (234) Google Scholar, 6.De Koning H. Van Der Aalst C. Ten Haaf K. Oudkerk M. Effects of volume CT lung cancer screening: mortality results of the NELSON randomised-controlled population based trial.J Thorac Oncol. 2018; 13: S185Abstract Full Text Full Text PDF Google Scholar, 12.Becker N. Motsch E. Gross M.L. et al.Randomized study on early detection of lung cancer with MSCT in Germany: results of the First 3 years of follow-up after randomization.J Thorac Oncol. 2015; 10: 890-896Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 13.Yang W. Qian F. Teng J. et al.Community-based lung cancer screening with low-dose CT in China: results of the baseline screening.Lung Cancer. 2018; 117: 20-26Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar] were considered eligible, including a total of 51 426 subjects at high risk of LC randomized to LDCT and 50 322 to the control arm (Table 1). For the NLST trial [2.Aberle D.R. Adams A.M. Berg C.D. et al.Reduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med. 2011; 365: 395-409Crossref PubMed Scopus (6877) Google Scholar] and its pilot study—the Lung Screening Study (LSS) [9.Gohagan J.K. Marcus P.M. Fagerstrom R.M. et al.Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer.Lung Cancer. 2005; 47: 9-15Abstract Full Text Full Text PDF PubMed Scopus (265) Google Scholar]—subjects randomized to the control group underwent chest X-ray examination, while in the remaining studies [1.Pastorino U. Silva M. Sestini S. et al.Prolonged lung cancer screening reduced 10-year mortality in the MILD Trial.Ann Oncol. 2019; 30: 1162-1169Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar, 3.Infante M. Cavuto S. Lutman F.R. et al.Long-term follow-up results of the DANTE trial, a randomized study of lung cancer screening with spiral computed tomography.Am J Respir Crit Care Med. 2015; 191: 1166-1175Crossref PubMed Scopus (258) Google Scholar, 4.Paci E. Puliti D. Lopes Pegna A. et al.Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial.Thorax. 2017; 72: 825-831Crossref PubMed Scopus (165) Google Scholar, 5.Wille M.M. Dirksen A. Ashraf H. et al.Results of the randomized Danish Lung Cancer Screening Trial with focus on high-risk profiling.Am J Respir Crit Care Med. 2016; 193: 542-551Crossref PubMed Scopus (234) Google Scholar, 6.De Koning H. Van Der Aalst C. Ten Haaf K. Oudkerk M. Effects of volume CT lung cancer screening: mortality results of the NELSON randomised-controlled population based trial.J Thorac Oncol. 2018; 13: S185Abstract Full Text Full Text PDF Google Scholar, 10.Blanchon T. Bréchot J.M. Grenier P.A. et al.Baseline results of the DEPISCAN study: a French randomized pilot trial of lung cancer screening comparing low dose CT scan (LDCT) and chest X-ray (CXR).Lung Cancer. 2007; 58: 50-58Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar, 11.Field J.K. Duffy S.W. Baldwin D.R. et al.The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer.Health Technol Assess. 2016; 20: 1-146Crossref PubMed Scopus (163) Google Scholar, 12.Becker N. Motsch E. Gross M.L. et al.Randomized study on early detection of lung cancer with MSCT in Germany: results of the First 3 years of follow-up after randomization.J Thorac Oncol. 2015; 10: 890-896Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 13.Yang W. Qian F. Teng J. et al.Community-based lung cancer screening with low-dose CT in China: results of the baseline screening.Lung Cancer. 2018; 117: 20-26Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar] no screening was offered to subjects randomized to the control arm. The frequency (annual and/or biennial) and the number of LDCT examinations varied between studies, from three annual LDCT in NLST [2.Aberle D.R. Adams A.M. Berg C.D. et al.Reduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med. 2011; 365: 395-409Crossref PubMed Scopus (6877) Google Scholar] to four annual in NELSON [6.De Koning H. Van Der Aalst C. Ten Haaf K. Oudkerk M. Effects of volume CT lung cancer screening: mortality results of the NELSON randomised-controlled population based trial.J Thorac Oncol. 2018; 13: S185Abstract Full Text Full Text PDF Google Scholar] and seven annual LDCT in MILD [1.Pastorino U. Silva M. Sestini S. et al.Prolonged lung cancer screening reduced 10-year mortality in the MILD Trial.Ann Oncol. 2019; 30: 1162-1169Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar]. The DANTE (Detection and Screening of Early Lung Cancer by Novel Imaging Technology and Molecular Essays) study [3.Infante M. Cavuto S. Lutman F.R. et al.Long-term follow-up results of the DANTE trial, a randomized study of lung cancer screening with spiral computed tomography.Am J Respir Crit Care Med. 2015; 191: 1166-1175Crossref PubMed Scopus (258) Google Scholar] included only men. The age of participants ranged between 45 and 75 years. Median follow-up duration was 5.2 years in the LSS pilot study [9.Gohagan J.K. Marcus P.M. Fagerstrom R.M. et al.Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer.Lung Cancer. 2005; 47: 9-15Abstract Full Text Full Text PDF PubMed Scopus (265) Google Scholar], 6.5 years in the NLST trial [2.Aberle D.R. Adams A.M. Berg C.D. et al.Reduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med. 2011; 365: 395-409Crossref PubMed Scopus (6877) Google Scholar], 8.3 years in DANTE [3.Infante M. Cavuto S. Lutman F.R. et al.Long-term follow-up results of the DANTE trial, a randomized study of lung cancer screening with spiral computed tomography.Am J Respir Crit Care Med. 2015; 191: 1166-1175Crossref PubMed Scopus (258) Google Scholar], nearly 10 years in ITALUNG (Italian Lung Cancer Screening Trial) [4.Paci E. Puliti D. Lopes Pegna A. et al.Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial.Thorax. 2017; 72: 825-831Crossref PubMed Scopus (165) Google Scholar] and DLCST (Danish Lung Cancer Screening Trial) [5.Wille M.M. Dirksen A. Ashraf H. et al.Results of the randomized Danish Lung Cancer Screening Trial with focus on high-risk profiling.Am J Respir Crit Care Med. 2016; 193: 542-551Crossref PubMed Scopus (234) Google Scholar] and above 10 years in MILD [1.Pastorino U. Silva M. Sestini S. et al.Prolonged lung cancer screening reduced 10-year mortality in the MILD Trial.Ann Oncol. 2019; 30: 1162-1169Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar] and NELSON [6.De Koning H. Van Der Aalst C. Ten Haaf K. Oudkerk M. Effects of volume CT lung cancer screening: mortality results of the NELSON randomised-controlled population based trial.J Thorac Oncol. 2018; 13: S185Abstract Full Text Full Text PDF Google Scholar] studies. The German Lung Cancer Screening Intervention (LUSI) trial reported the results of the first 3 years of follow-up after randomization [12.Becker N. Motsch E. Gross M.L. et al.Randomized study on early detection of lung cancer with MSCT in Germany: results of the First 3 years of follow-up after randomization.J Thorac Oncol. 2015; 10: 890-896Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar] and a Chinese community-based LC screening study only reported results of the baseline screening [13.Yang W. Qian F. Teng J. et al.Community-based lung cancer screening with low-dose CT in China: results of the baseline screening.Lung Cancer. 2018; 117: 20-26Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar]. These studies were therefore not included in the meta-analysis.Table 1Randomized trials of LDCT and lung cancerStudyCountryScreening test and descriptionAge and sex of participantsSmoking statusParticipantsMedian length of follow-upLDCTControlLDCTControlPilot trials LSS: Gohagan et al. [9.Gohagan J.K. Marcus P.M. Fagerstrom R.M. et al.Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer.Lung Cancer. 2005; 47: 9-15Abstract Full Text Full Text PDF PubMed Scopus (265) Google Scholar] and Doroudi et al. [14.Doroudi M. Pinsky P.F. Marcus P.M. Lung cancer mortality in the Lung Screening Study Feasibility Trial.JNCI Cancer Spectrum. 2018; 2: pky042Crossref PubMed Scopus (21) Google Scholar]US2 annual LDCT2 annual CXRM and F 55–74Current ≥30 pack-years, former quit <10 years160016585.2 years DEPISCAN: Blanchon et al. [10.Blanchon T. Bréchot J.M. Grenier P.A. et al.Baseline results of the DEPISCAN study: a French randomized pilot trial of lung cancer screening comparing low dose CT scan (LDCT) and chest X-ray (CXR).Lung Cancer. 2007; 58: 50-58Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar]FranceBaseline LDCTUsual careM and F 50–75Current ≥15 cigarettes/day, former quit <15 years330291Only baseline findings UKLS: Field et al. [11.Field J.K. Duffy S.W. Baldwin D.R. et al.The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer.Health Technol Assess. 2016; 20: 1-146Crossref PubMed Scopus (163) Google Scholar]UKBaseline LDCTUsual careM and F 50–755 years lung cancer risk ≥5% according to Liverpool Lung Project risk prediction model20282027Only baseline findingsTrials NLST: Aberle et al. [2.Aberle D.R. Adams A.M. Berg C.D. et al.Reduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med. 2011; 365: 395-409Crossref PubMed Scopus (6877) Google Scholar]US3 annual LDCT3 annual CXRM and F 55–74Current ≥30 pack-years, former quit <15 years26722267326.5 years DANTE: Infante et al. [3.Infante M. Cavuto S. Lutman F.R. et al.Long-term follow-up results of the DANTE trial, a randomized study of lung cancer screening with spiral computed tomography.Am J Respir Crit Care Med. 2015; 191: 1166-1175Crossref PubMed Scopus (258) Google Scholar]Italy4 annual LDCT4 annual medical visitsM 60–74Current ≥20 pack-years, former quit 25 years or ≥10 cigarettes/day for >30 years, former quit <10 years20292023≈5 years DLCST: Wille et al. [5.Wille M.M. Dirksen A. Ashraf H. et al.Results of the randomized Danish Lung Cancer Screening Trial with focus on high-risk profiling.Am J Respir Crit Care Med. 2016; 193: 542-551Crossref PubMed Scopus (234) Google Scholar]Denmark5 annual LDCT5 annual medical visitsM and F 50–70Current ≥20 pack-years, former quit <10 years205220529.8 years ITALUNG: Paci et al. [4.Paci E. Puliti D. Lopes Pegna A. et al.Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial.Thorax. 2017; 72: 825-831Crossref PubMed Scopus (165) Google Scholar]Italy4 annual LDCTUsual careM and F 55–69Current ≥20 pack-years, former quit <10 years161315939.3 years AME: Yang et al. [13.Yang W. Qian F. Teng J. et al.Community-based lung cancer screening with low-dose CT in China: results of the baseline screening.Lung Cancer. 2018; 117: 20-26Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar]ChinaBaseline LDCTUsual careM and F 45–70Current ≥20 pack-years, former quit 30 years or ≥15 cigarettes/day for >25 years, former quit 10 years MILD: Pastorino et al. [1.Pastorino U. Silva M. Sestini S. et al.Prolonged lung cancer screening reduced 10-year mortality in the MILD Trial.Ann Oncol. 2019; 30: 1162-1169Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar]Italy7 annual LDCT/4 biennial LDCTUsual careM and F 49–75Current ≥20 pack-years, former quit 10 yearsLDCT, low-dose CT scan; CXR, chest X-Ray; LSS, Lung Screening Study; UKLS, UK Lung Cancer Screening; NLST, National Lung Screening Trial; DANTE, Detection and Screening of Early Lung Cancer by Novel Imaging Technology and Molecular Essays; LUSI, Lung Cancer Screening Intervention; DLCST, Danish Lung Cancer Screening Trial; ITALUNG, Italian Lung Cancer Screening Trial; AME, written on behalf of the AME Publishing Company Thoracic Surgery Collaborative Group; NELSON, NEderlands Leuvens Longkanker Screenings ONderzoek; MILD, Multicentric Italian Lung Detection. Open table in a new tab LDCT, low-dose CT scan; CXR, chest X-Ray; LSS, Lung Screening Study; UKLS, UK Lung Cancer Screening; NLST, National Lung Screening Trial; DANTE, Detection and Screening of Early Lung Cancer by Novel Imaging Technology and Molecular Essays; LUSI, Lung Cancer Screening Intervention; DLCST, Danish Lung Cancer Screening Trial; ITALUNG, Italian Lung Cancer Screening Trial; AME, written on behalf of the AME Publishing Company Thoracic Surgery Collaborative Group; NELSON, NEderlands Leuvens Longkanker Screenings ONderzoek; MILD, Multicentric Italian Lung Detection. Mortality results were reported from eight studies [1.Pastorino U. Silva M. Sestini S. et al.Prolonged lung cancer screening reduced 10-year mortality in the MILD Trial.Ann Oncol. 2019; 30: 1162-1169Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar, 2.Aberle D.R. Adams A.M. Berg C.D. et al.Reduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med. 2011; 365: 395-409Crossref PubMed Scopus (6877) Google Scholar, 3.Infante M. Cavuto S. Lutman F.R. et al.Long-term follow-up results of the DANTE trial, a randomized study of lung cancer screening with spiral computed tomography.Am J Respir Crit Care Med. 2015; 191: 1166-1175Crossref PubMed Scopus (258) Google Scholar, 4.Paci E. Puliti D. Lopes Pegna A. et al.Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial.Thorax. 2017; 72: 825-831Crossref PubMed Scopus (165) Google Scholar, 5.Wille M.M. Dirksen A. Ashraf H. et al.Results of the randomized Danish Lung Cancer Screening Trial with focus on high-risk profiling.Am J Respir Crit Care Med. 2016; 193: 542-551Crossref PubMed Scopus (234) Google Scholar, 6.De Koning H. Van Der Aalst C. Ten Haaf K. Oudkerk M. Effects of volume CT lung cancer screening: mortality results of the NELSON randomised-controlled population based trial.J Thorac Oncol. 2018; 13: S185Abstract Full Text Full Text PDF Google Scholar, 12.Becker N. Motsch E. Gross M.L. et al.Randomized study on early detection of lung cancer with MSCT in Germany: results of the First 3 years of follow-up after randomization.J Thorac Oncol. 2015; 10: 890-896Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 14.Doroudi M. Pinsky P.F. Marcus P.M. Lung cancer mortality in the Lung Screening Study Feasibility Trial.JNCI Cancer Spectrum. 2018; 2: pky042Crossref PubMed Scopus (21) Google Scholar]. The pooled estimate for LC mortality was 0.80 (95% CI 0.71–0.90) (Figure 1). As also shown in MILD [1.Pastorino U. Silva M. Sestini S. et al.Prolonged lung cancer screening reduced 10-year mortality in the MILD Trial.Ann Oncol. 2019; 30: 1162-1169Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar], reduction of LC mortality in the model estimate was greater beyond the fifth year of screening (RR 0.69, 95% CI 0.56–0.86). All-cause mortality was also reduced (RR 0.94, 95% CI 0.89–1.00), with a greater effect beyond the fifth year of screening (RR 0.82, 95% CI 0.71–0.95). Results for secondary outcomes showed that incidence of LC was higher in the LDCT arm (RR 1.69, 95% CI 1.30–2.19), and that LDCT screening allowed for the more frequent detection of LC cases at early stages IA and IB (RR 2.07, 95% CI 1.50–2.85), as well as lung adenocarcinomas (RR 1.20, 95% CI 1.03–1.38). Thus, the evidence on the efficacy of LDCT as screening for lung cancer in high-risk individuals that accumulated after the publication of the NLST in 2011 [2.Aberle D.R. Adams A.M. Berg C.D. et al.Reduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med. 2011; 365: 395-409Crossref PubMed Scopus (6877) Google Scholar] largely confirms the results of that landmark trial. The prolonged follow-up of the MILD, including its landmark analysis showing an HR of 0.42 beyond the fifth year of screening, provides the most convincing evidence to date of the long-term benefit of LDCT compared with a shorter duration [15.Pastorino U. Rossi M. Rosato V. et al.Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial.Eur J Cancer Prev. 2012; 21: 308-315Crossref PubMed Scopus (350) Google Scholar]. The likely explanation is that screening with LDCT works by identifying nodules that would have been diagnosed as LC several years later: the effect of screening therefore increases with repeated tests over a prolonged period. Replication of MILD results beyond 5 years of intervention and follow-up, either from NELSON [6.De Koning H. Van Der Aalst C. Ten Haaf K. Oudkerk M. Effects of volume CT lung cancer screening: mortality results of the NELSON randomised-controlled population based trial.J Thorac Oncol. 2018; 13: S185Abstract Full Text Full Text PDF Google Scholar] or from other studies, is essential to quantify the full effect of sustained LDCT screening on LC mortality and develop recommendations for long-term screening of high-risk individuals. MP is covered by a PhD Scholarship (no grant numbers apply).
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