Evaluation of Early Lung Cancer Detection in a Population at High Risk due to Occupation.

When Will Enough Ever Be Enough?

Expansion of Guideline-Recommended Lung Cancer Screening Eligibility: Implications for Health Equity of Joint Screening and Cessation Interventions

In lung cancer, 81% of patients detected are late-stage, since early-stage patients are generally asymptomatic. Winnebago County has a 14% higher mortality rate for lung cancer when compared to the national rate; hence, to improve early detection of lung cancer in the Winnebago County, we implemented low-dose computed tomography (LDCT) screening. Currently, LDCT is used to detect lung cancer at early-stages, and the CDC has proposed new guidelines for early screening of lung cancer in individuals between 55-77 years of age with a 30 pack/year smoking history. Using circulating DNA from lung cancer patients and examining changes in methylation patterns in genes that are expressed in lung cancer patients can be used for early detection. Epidermal growth factor receptor (EGFR) is shown to be expressed in lung cancer patients’ serum in all stages; hence, it can be used as a potential biomarker for early detection. To improve early detection of lung cancer in the Winnebago County, we educated physicians/smokers about LDCT screenings to promote early detection of lung cancer. We evaluated the number of LDCTs performed and recorded the number of lung cancer cases detected in the Winnebago County between June 2015 to October 2017. To explore EGFR as a promising biomarker, plasma was separated from whole blood and collected. Circulating DNA was extracted with the MagMax cell-free circulating kit and bisulfite converted. Identification of percent methylation patterns in the EGFR promoter region in CpG islands was obtained after next generation sequencing (NGS) followed by bioinformatics analysis. In our study, 1,116 LDCT screenings occurred in the Winnebago County. Lung cancer was diagnosed in 19 patients, out of which 11 patients (57.8%) were early-stage patients. We detected 45.4% of patients screened that were present with nodules compared to 24.2% of patients in the National Lung Cancer Screening Trial. We observed that 1.70% of patients referred for LDCT screening were diagnosed with lung cancer, compared to 0.87% of patients in the National Lung Cancer Screening Trial. This may be due to the higher incidence of smoking in Winnebago County (18%) compared to the nation (15.5%). Our screening study had 96.3% false positives, which is comparable (96.4%) to the results obtained in the National Lung Cancer Screening Trial. Using NGS, methylation in the promoter region of EGFR was studied using degenerate EGFR primers. In the promoter region of EGFR, our analysis showed that there are regions of hypermethylation (68-86%) in three CpG islands in sequences at the beginning of the promoter (8-241 bases). However, there was hypomethylation (6-21%) at four CpG island further downstream (375-689 bases from the beginning of the promoter). Currently we are studying the methylation patterns in normal subjects to determine whether these regions which could be used as predictive biomarkers for early detection. Citation Format: Adijan Kuckovic, Joseph Berei, Shylendra Sreenivasappa, Joseph Ross, Sandra Martell, Connie Vitali, William Schulz, Neelu Puri. Lung cancer screening initiative and identification of novel blood biomarkers for early detection of lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3329.

Computed tomography (CT) screening of the chest has shown promise for early detection of lung cancer, but evidence for a reduction in lung cancer mortality by CT screening is not available. We reviewed 208 articles to synthesize available evidence for efficacy of CT screening in detecting potentially curative stages of lung cancer and for evidence in reducing lung cancer mortality. Other outcomes of interest included detection rate of cancer and of suspicious lesions, histology and stage of cancer at detection, screening-related morbidity, and the identification of populations uniquely suited for CT screening. We identified eight papers that reported the outcomes for CT of the chest in lung cancer screening. Since none of the studies utilized a control group, quantitative pooling was not done. In two studies, both CT and chest radiography (CXR) were used as screening tools in the same cohorts. A total of 19,107 subjects were screened using CT. The detected prevalence rate for lung cancer ranged from 0.40% to 13.6% and was a function of the subjects' age and smoking history. CT screening resulted in a 3-fold higher detection rate and a 5-fold increase in the rate of resectable cancers compared to CXR. Data on lung cancer and overall mortality and screening-related morbidity and mortality were incomplete. CT screening resulted in selective detection of adenocarcinomas with an approximately 2- to 3-fold oversampling of this histologic subtype. The positive predictive value of CT screening was highest for subjects in the 8th decade of life, and it was virtually nil for those in their 5th decade. Evidence regarding lung cancer screening by CT shows that this technology detects earlier-stage and smaller lung cancers with greater frequency than other screening methods. To date, no trials have demonstrated that CT screening leads to a reduction in lung cancer mortality. Until mortality trials are completed, low-dose CT screening should be considered an investigative tool rather than the standard of care.

Lung Cancer Early Detection: The Role of Circulating MicroRNAs

Lung cancer kills more people than any other cancer in the UK (5-year survival < 13%). Early diagnosis can save lives. The USA-based National Lung Cancer Screening Trial reported a 20% relative reduction in lung cancer mortality and 6.7% all-cause mortality in low-dose computed tomography (LDCT)-screened subjects. To (1) analyse LDCT lung cancer screening in a high-risk UK population, determine optimum recruitment, screening, reading and care pathway strategies; and (2) assess the psychological consequences and the health-economic implications of screening. A pilot randomised controlled trial comparing intervention with usual care. A population-based risk questionnaire identified individuals who were at high risk of developing lung cancer (≥ 5% over 5 years). Thoracic centres with expertise in lung cancer imaging, respiratory medicine, pathology and surgery: Liverpool Heart & Chest Hospital, Merseyside, and Papworth Hospital, Cambridgeshire. Individuals aged 50-75 years, at high risk of lung cancer, in the primary care trusts adjacent to the centres. A thoracic LDCT scan. Follow-up computed tomography (CT) scans as per protocol. Referral to multidisciplinary team clinics was determined by nodule size criteria. Population-based recruitment based on risk stratification; management of the trial through web-based database; optimal characteristics of CT scan readers (radiologists vs. radiographers); characterisation of CT-detected nodules utilising volumetric analysis; prevalence of lung cancer at baseline; sociodemographic factors affecting participation; psychosocial measures (cancer distress, anxiety, depression, decision satisfaction); and cost-effectiveness modelling. A total of 247,354 individuals were approached to take part in the trial; 30.7% responded positively to the screening invitation. Recruitment of participants resulted in 2028 in the CT arm and 2027 in the control arm. A total of 1994 participants underwent CT scanning: 42 participants (2.1%) were diagnosed with lung cancer; 36 out of 42 (85.7%) of the screen-detected cancers were identified as stage 1 or 2, and 35 (83.3%) underwent surgical resection as their primary treatment. Lung cancer was more common in the lowest socioeconomic group. Short-term adverse psychosocial consequences were observed in participants who were randomised to the intervention arm and in those who had a major lung abnormality detected, but these differences were modest and temporary. Rollout of screening as a service or design of a full trial would need to address issues of outreach. The health-economic analysis suggests that the intervention could be cost-effective but this needs to be confirmed using data on actual lung cancer mortality. The UK Lung Cancer Screening (UKLS) pilot was successfully undertaken with 4055 randomised individuals. The data from the UKLS provide evidence that adds to existing data to suggest that lung cancer screening in the UK could potentially be implemented in the 60-75 years age group, selected via the Liverpool Lung Project risk model version 2 and using CT volumetry-based management protocols. The UKLS data will be pooled with the NELSON (Nederlands Leuvens Longkanker Screenings Onderzoek: Dutch-Belgian Randomised Lung Cancer Screening Trial) and other European Union trials in 2017 which will provide European mortality and cost-effectiveness data. For now, there is a clear need for mortality results from other trials and further research to identify optimal methods of implementation and delivery. Strategies for increasing uptake and providing support for underserved groups will be key to implementation. Current Controlled Trials ISRCTN78513845. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 40. See the NIHR Journals Library website for further project information.

Chest low dose computed tomography (LDCT) is reported to be a sensitive tool for the detection of lung cancer at asymptomatic stage, thus reducing mortality. The review assesses the effect of LDCT screening on all-cause mortality, lung cancer mortality and incidence rates. We conducted literature searches of PubMed, SCOPUS, and the Cochrane Library from inception through January 2020 to identify relevant studies assessing the diagnostic accuracy of LDCT for lung cancer. We used Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for reporting this meta-analysis and review. The inclusion criteria were a) Randomized control trials, b) Comparing LDCT to any other form of screening or standard of care, and (c) Primary outcome studied: all-cause mortality, lung cancer-specific mortality, rate of early detection of lung cancer. A total of 11 studies encompassing 97,248 patients were included. When compared with controls (no screening or CXR), LDCT screening was associated with statistically significant reduction in lung cancer mortality (pooled RR 0.86; 95% CI 0.75-0.98); low heterogeneity was observed (I2= 27.86). However, LDCT screening was not associated with statistically significant reduction in all-cause mortality (RR =0.96; 95% CI: 0.92 -1.01). Notably, the LDCT screening was associated with statistically significant increase in lung cancer detection (RR =1.76; 95% CI: 1.14-2.72). LDCT screening has the potential to reduce mortality due to lung cancer among high-risk individuals. LDCT could be considered as a screening modality after careful assessment of other factors like prevalence of TB, proportion of high-risk population, cost, access and availability of LDCT.

One-off low-dose CT for lung cancer screening in China: a multicentre, population-based, prospective cohort study

Background Lung cancer is the number one cause of cancer death worldwide.(1) It is the fifth most commonly diagnosed cancer in Australia (12,741 cases diagnosed in 2018) and the leading cause of cancer death.(2) The number of years of potential life lost to lung cancer in Australia is estimated to be 58,450, similar to that of colorectal and breast cancer combined.(3) While tobacco control strategies are most effective for disease prevention in the general population, early detection via low dose computed tomography (LDCT) screening in high-risk populations is a viable option for detecting asymptomatic disease in current (13%) and former (24%) Australian smokers.(4) The purpose of this Evidence Check review is to identify and analyse existing and emerging evidence for LDCT lung cancer screening in high-risk individuals to guide future program and policy planning. Evidence Check questions This review aimed to address the following questions: 1. What is the evidence for the effectiveness of lung cancer screening for higher-risk individuals? 2. What is the evidence of potential harms from lung cancer screening for higher-risk individuals? 3. What are the main components of recent major lung cancer screening programs or trials? 4. What is the cost-effectiveness of lung cancer screening programs (include studies of cost–utility)? Summary of methods The authors searched the peer-reviewed literature across three databases (MEDLINE, PsycINFO and Embase) for existing systematic reviews and original studies published between 1 January 2009 and 8 August 2019. Fifteen systematic reviews (of which 8 were contemporary) and 64 original publications met the inclusion criteria set across the four questions. Key findings Question 1: What is the evidence for the effectiveness of lung cancer screening for higher-risk individuals? There is sufficient evidence from systematic reviews and meta-analyses of combined (pooled) data from screening trials (of high-risk individuals) to indicate that LDCT examination is clinically effective in reducing lung cancer mortality. In 2011, the landmark National Lung Cancer Screening Trial (NLST, a large-scale randomised controlled trial [RCT] conducted in the US) reported a 20% (95% CI 6.8% – 26.7%; P=0.004) relative reduction in mortality among long-term heavy smokers over three rounds of annual screening. High-risk eligibility criteria was defined as people aged 55–74 years with a smoking history of ≥30 pack-years (years in which a smoker has consumed 20-plus cigarettes each day) and, for former smokers, ≥30 pack-years and have quit within the past 15 years.(5) All-cause mortality was reduced by 6.7% (95% CI, 1.2% – 13.6%; P=0.02). Initial data from the second landmark RCT, the NEderlands-Leuvens Longkanker Screenings ONderzoek (known as the NELSON trial), have found an even greater reduction of 26% (95% CI, 9% – 41%) in lung cancer mortality, with full trial results yet to be published.(6, 7) Pooled analyses, including several smaller-scale European LDCT screening trials insufficiently powered in their own right, collectively demonstrate a statistically significant reduction in lung cancer mortality (RR 0.82, 95% CI 0.73–0.91).(8) Despite the reduction in all-cause mortality found in the NLST, pooled analyses of seven trials found no statistically significant difference in all-cause mortality (RR 0.95, 95% CI 0.90–1.00).(8) However, cancer-specific mortality is currently the most relevant outcome in cancer screening trials. These seven trials demonstrated a significantly greater proportion of early stage cancers in LDCT groups compared with controls (RR 2.08, 95% CI 1.43–3.03). Thus, when considering results across mortality outcomes and early stage cancers diagnosed, LDCT screening is considered to be clinically effective. Question 2: What is the evidence of potential harms from lung cancer screening for higher-risk individuals? The harms of LDCT lung cancer screening include false positive tests and the consequences of unnecessary invasive follow-up procedures for conditions that are eventually diagnosed as benign. While LDCT screening leads to an increased frequency of invasive procedures, it does not result in greater mortality soon after an invasive procedure (in trial settings when compared with the control arm).(8) Overdiagnosis, exposure to radiation, psychological distress and an impact on quality of life are other known harms. Systematic review evidence indicates the benefits of LDCT screening are likely to outweigh the harms. The potential harms are likely to be reduced as refinements are made to LDCT screening protocols through: i) the application of risk predication models (e.g. the PLCOm2012), which enable a more accurate selection of the high-risk population through the use of specific criteria (beyond age and smoking history); ii) the use of nodule management algorithms (e.g. Lung-RADS, PanCan), which assist in the diagnostic evaluation of screen-detected nodules and cancers (e.g. more precise volumetric assessment of nodules); and, iii) more judicious selection of patients for invasive procedures. Recent evidence suggests a positive LDCT result may transiently increase psychological distress but does not have long-term adverse effects on psychological distress or health-related quality of life (HRQoL). With regards to smoking cessation, there is no evidence to suggest screening participation invokes a false sense of assurance in smokers, nor a reduction in motivation to quit. The NELSON and Danish trials found no difference in smoking cessation rates between LDCT screening and control groups. Higher net cessation rates, compared with general population, suggest those who participate in screening trials may already be motivated to quit. Question 3: What are the main components of recent major lung cancer screening programs or trials? There are no systematic reviews that capture the main components of recent major lung cancer screening trials and programs. We extracted evidence from original studies and clinical guidance documents and organised this into key groups to form a concise set of components for potential implementation of a national lung cancer screening program in Australia: 1. Identifying the high-risk population: recruitment, eligibility, selection and referral 2. Educating the public, people at high risk and healthcare providers; this includes creating awareness of lung cancer, the benefits and harms of LDCT screening, and shared decision-making 3. Components necessary for health services to deliver a screening program: a. Planning phase: e.g. human resources to coordinate the program, electronic data systems that integrate medical records information and link to an established national registry b. Implementation phase: e.g. human and technological resources required to conduct LDCT examinations, interpretation of reports and communication of results to participants c. Monitoring and evaluation phase: e.g. monitoring outcomes across patients, radiological reporting, compliance with established standards and a quality assurance program 4. Data reporting and research, e.g. audit and feedback to multidisciplinary teams, reporting outcomes to enhance international research into LDCT screening 5. Incorporation of smoking cessation interventions, e.g. specific programs designed for LDCT screening or referral to existing community or hospital-based services that deliver cessation interventions. Most original studies are single-institution evaluations that contain descriptive data about the processes required to establish and implement a high-risk population-based screening program. Across all studies there is a consistent message as to the challenges and complexities of establishing LDCT screening programs to attract people at high risk who will receive the greatest benefits from participation. With regards to smoking cessation, evidence from one systematic review indicates the optimal strategy for incorporating smoking cessation interventions into a LDCT screening program is unclear. There is widespread agreement that LDCT screening attendance presents a ‘teachable moment’ for cessation advice, especially among those people who receive a positive scan result. Smoking cessation is an area of significant research investment; for instance, eight US-based clinical trials are now underway that aim to address how best to design and deliver cessation programs within large-scale LDCT screening programs.(9) Question 4: What is the cost-effectiveness of lung cancer screening programs (include studies of cost–utility)? Assessing the value or cost-effectiveness of LDCT screening involves a complex interplay of factors including data on effectiveness and costs, and institutional context. A key input is data about the effectiveness of potential and current screening programs with respect to case detection, and the likely outcomes of treating those cases sooner (in the presence of LDCT screening) as opposed to later (in the absence of LDCT screening). Evidence about the cost-effectiveness of LDCT screening programs has been summarised in two systematic reviews. We identified a further 13 studies—five modelling studies, one discrete choice experiment and seven articles—that used a variety of methods to assess cost-effectiveness. Three modelling studies indicated LDCT screening was cost-effective in the settings of the US and Europe. Two studies—one from Australia and one from New Zealand—reported LDCT screening would not be cost-effective using NLST-like protocols. We anticipate that, following the full publication of the NELSON trial, cost-effectiveness studies will likely be updated with new data that reduce uncertainty about factors that influence modelling outcomes, including the findings of indeterminate nodules. Gaps in the evidence There is a large and accessible body of evidence as to the effectiveness (Q1) and harms (Q2) of LDCT screening for lung cancer. N

Lung cancer is currently the leading cause of cancer-related death in China and western countries for both men and women. Overall, the five-year survival rate of lung cancer is approximately 15%, whereas the five-year survival for patients with surgically resected early-stage disease is 60–80%. Screening is conceptually a good strategy for reducing the mortality rate of lung cancer. Randomized controlled trials in the 1960s and 1970s found that chest radiographic screening did not result in a reduction in mortality for high-risk individuals. Recently published data from the National Lung Screening Trial (NLST) showed a 20% reduction in lung cancer mortality in subjects who underwent low-dose computed tomography (LDCT) screening compared to those randomized to conventional chest X-ray. The encouraging results of the NLST, however, could not be confirmed by the preliminary results of ongoing European trials. More results from European randomized controlled trials are expected in the next few years. Recently, a number of lung cancer screening studies using LDCT have been initiated in China. This article briefly summarizes the results of the current and previous lung cancer screening trials worldwide, and focuses on the current status of LDCT lung cancer screening in China.

WITHIN THE SPACE OF SEVERAL MONTHS, 2 VERY large randomized trials of screening for lung cancer have reported their findings, which fortunately complement one another. The National Lung Screening Study (NLST) found that annual lowdose computed tomography (CT) reduced lung cancer mortality by 20% relative to annual chest radiography. In this issue of JAMA, investigators from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Randomized Trial report that annual screening chest radiography does not reduce lung cancer mortality relative to no screening. Should clinicians infer that screening with low-dose CT reduces lung cancer mortality by 20% relative to no screening? This editorial addresses that question and several other aspects of the PLCO trial. Why would the National Cancer Institute sponsor a large trial of screening for lung cancer with chest radiography? Although 6 randomized trials, most of them published in the 1980s, found no evidence that screening radiography reduced lung cancer mortality, the control group received screening chest radiography in all but the Mayo Lung Project. This study had important protocol deviations and was relatively small (9211 participants randomized; 366 cancers detected). So the body of evidence was inconclusive according to the investigators who designed the PLCO trial. The PLCO trial measured the effect of a package of screening interventions aimed at preventing death from 4 cancers. Patients were individually randomized to a usual care group or to an intervention group that was screened periodically for prostate, lung, colorectal, and ovarian cancer for 3 years and then monitored for PLCO cancers (a stop-screen design). Recruiting targeted the US general population aged 55 through 74 years. The study was designed to have a 90% probability of detecting a 10% reduction in lung cancer mortality. Over 8 years, 77 445 participants were randomized to screening and 77 456 to usual care. Half of the participants were ever-smokers; 10% were current smokers. Lung cancer mortality, the primary end point, was 14.0 per 10 000 person-years of follow-up in the intervention group and 14.2 in the control group (rate ratio, 0.99; 95% CI, 0.87 to 1.22). In high-risk patients who met the NLST eligibility criteria, the outcome was similar except for higher lung cancer mortality rates. The PLCO trial shows that a short-term chest radiography screening program has no effect on lung cancer mortality. The only potential concern about the validity of this conclusion is the reporting of follow-up contact with the trial participants. The authors’ diagram of the flow of participants through the trial (Figure 1) does not state the number of participants in the usual care group that the authors were unable to contact during follow-up. Differential ascertainment of lung cancer mortality and, especially, incidence could occur if follow-up rates were unequal in the screening and usual care groups for reasons linked to lung cancer incidence and mortality. Most of the 1696 cancers were interval cancers (n=198), arose in patients who were never screened (n=193), or arose in patients who had completed 3 rounds of screening (n=998). These far outnumbered the screen-detected cancers (n=307). The large number of deaths from cancers diagnosed after screening is a reminder of the transitory benefit from a short-term program of screening for lung cancer. The best test of lung cancer screening in high-risk individuals would be a trial of lifelong screening. With a stop-screen design, the true effect of screening is unclear because of uncertainty about how long to monitor patients after screening. At one extreme, stopping right after the last screen will miss cancers that screening did not detect but that would have been diagnosed if monitoring had been extended into the postscreening period. Stopping monitoring too soon, therefore, may overestimate the effect of screening by covering up some of its failures. At the other extreme, extending the period of monitoring long past the time when the last cancer missed by screening would have been diagnosed will underestimate the

The potential to achieve greater reductions in lung cancer mortality than originally estimated by the National Lung Screening Trial with the inclusion of more Black participants stresses the importance of improving access to lung cancer screening for Black current and former smokers, a population presently with the highest lung cancer morbidity and mortality. To estimate lung cancer and all-cause mortality reductions achievable with lung cancer screening via low-dose computed tomography (LDCT) of the chest in populations with greater proportions of Black screening participants than seen in the original NLST cohort. This cohort study was conducted as a secondary analysis of existing data from the National Lung Screening Trial, a large national randomized clinical trial conducted from 2002 through 2009. NLST participants were current or former smokers, aged between 55 and 74 years, with at least 30 pack-years of smoking history and less than 15 years since quitting. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% CIs of lung cancer mortality and all-cause mortality according to LDCT screening compared with chest radiograph screening. Using a transportability formula, we estimated outcomes for LDCT screening among hypothetical populations by varying the distributions of Black individuals, women, and current smokers. Data were analyzed between September 2020 and March 2021. Lung screening with LDCT of the chest compared with chest radiography. Lung cancer mortality and all-cause mortality. This study included a total of 53 452 participants enrolled in the NLST. Of 2376 Black individuals and 51 076 non-Black individuals, 21 922 (41.0%) were women and the mean (SD) age was 61.4 (5.0) years. Over a median (interquartile range) follow-up of 6.7 (6.2-7.0) years, LDCT screening among the synthesized population with a higher proportion of Black individuals (13.4%, mirroring US Census data) was associated with a greater relative reduction of lung cancer mortality (eg, Black individuals: HR, 0.82; 95% CI, 0.72-0.92; vs entire NLST cohort: HR, 0.84; 95% CI, 0.76-0.96). Further reductions in lung cancer mortality by LDCT screening were found among a hypothetical population with a higher proportion of men or current smokers, along with a higher proportion of Black individuals (ie, 60% Black participants; 20% to 40% women) (HR, 0.68; 95% CI, 0.48-0.97). The potential to achieve greater reductions in lung cancer mortality than originally estimated by the NLST with the inclusion of more Black participants stresses the critical importance of improving access to lung cancer screening for Black current and former smokers.

Commentary: The role of low-dose computed tomography for lung cancer screening among the nonsmoking Asian population

Low-dose computed tomography (LDCT) screening is effective in reducing lung cancer mortality in smokers; however, the evidence in nonsmokers is scarce. This study aimed to evaluate the participant rate and effectiveness of one-off LDCT screening for lung cancer among smokers and nonsmokers. A population-based prospective cohort study was performed to enroll participants aged between 40 and 74 years from 2013 to 2019 from 4 cities in Zhejiang Province, China. Participants who were evaluated as having a high risk of lung cancer from an established risk score model were recommended to undergo LDCT screening. Follow-up outcomes were retrieved on June 30, 2020. The uptake rate of LDCT screening for evaluated high-risk participants and the detection rate of early-stage lung cancer (stage 0-I) were calculated. The lung cancer incidence, lung cancer mortality, and all-cause mortality were compared between the screened and nonscreened groups. At baseline, 62.56% (18,818/30,079) of smokers and 6% (5483/91,455) of nonsmokers were identified as high risk (P<.001), of whom 41.9% (7885/18,818) and 66.31% (3636/5483) underwent LDCT screening (P<.001), respectively. After a median follow-up of 5.1 years, 1100 lung cancer cases and 456 all-cause death cases (116 lung cancer death cases) were traced. The proportion of early-stage lung cancer among smokers was 60.3% (173/287), which was lower than the proportion of 80.3% (476/593) among nonsmokers (P<.001). Among smokers, a higher proportion was found in the screened group (72/106, 67.9%) than the nonscreened group (56/114, 49.1%; P=.005), whereas no significance was found (42/44, 96% vs 10/12, 83%; P=.20) among nonsmokers. Compared with participants who were not screened, LDCT screening in smokers significantly increased lung cancer incidence (hazard ratio [HR] 1.39, 95% CI 1.09-1.76; P=.007) but reduced lung cancer mortality (HR 0.52, 95% CI 0.28-0.96; P=.04) and all-cause mortality (HR 0.47, 95% CI 0.32-0.69; P<.001). Among nonsmokers, no significant results were found for lung cancer incidence (P=.06), all-cause mortality (P=.89), and lung cancer mortality (P=.17). LDCT screening effectively reduces lung cancer and all-cause mortality among high-risk smokers. Further efforts to define high-risk populations and explore adequate lung cancer screening modalities for nonsmokers are needed.

Incidental Lymphadenopathy at CT Lung Cancer Screening.