Nederlands-Leuvens Longkanker Screenings Onderzoek Research Articles

Lung Nodule Management in Low-Dose CT Screening for Lung Cancer: Lessons from the NELSON Trial.

Screening with low-dose CT (LDCT) in a high-risk population, as defined by age and smoking behavior, reduces lung cancer-related mortality. However, LDCT screening presents a major challenge. Numerous, mostly benign, nodules are seen in the lungs during screening. The question is how to distinguish the malignant from the benign nodules. Various studies use different protocols for nodule management. The Dutch-Belgian NELSON (Nederlands-Leuvens Longkanker Screenings Onderzoek) trial, the largest European lung cancer screening trial, used distinctions based on nodule volumetric assessment and growth rate. This review discusses key findings from the NELSON study regarding the characteristics of screening-detected nodules, including nodule size and its volumetric assessment, growth rate, subtype, and their associated malignancy risk. These results are compared with findings from other screening studies and current recommendations for lung nodule management. By examining differences in nodule management strategies and providing a comprehensive overview of outcomes specific to lung cancer screening, this review aims to contribute to the broader discussion on optimizing lung nodule management in screening programs.

The American Cancer Society National Lung Cancer Roundtable strategic plan: Implementation of high-quality lung cancer screening.

More than a decade has passed since researchers in the Early Lung Cancer Action Project and the National Lung Screening Trial demonstrated the ability to save lives of high-risk individuals from lung cancer through regular screening by low dose computed tomography scan. The emergence of the most recent findings in the Dutch-Belgian lung-cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) further strengthens and expands on this evidence. These studies demonstrate the benefit of integrating lung cancer screening into clinical practice, yet lung cancer continues to lead cancer mortality rates in the United States. Fewer than 20% of screen eligible individuals are enrolled in lung cancer screening, leaving millions of qualified individuals without the standard of care and benefit they deserve. This article, part of the American Cancer Society National Lung Cancer Roundtable (ACS NLCRT) strategic plan, examines the impediments to successful adoption, dissemination, and implementation of lung cancer screening. Proposed solutions identified by the ACS NLCRT Implementation Strategies Task Group and work currently underway to address these challenges to improve uptake of lung cancer screening are discussed. PLAIN LANGUAGE SUMMARY: The evidence supporting the benefit of lung cancer screening in adults who previously or currently smoke has led to widespread endorsement and coverage by health plans. Lung cancer screening programs should be designed to promote high uptake rates of screening among eligible adults, and to deliver high-quality screening and follow-up care.

Cost-effectiveness analysis of a lung cancer screening program in the Netherlands: a simulation based on NELSON and NLST study outcomes

Background In the Netherlands, lung cancer is the leading cause of cancer-related death, accounting for more than 10,000 annual deaths. Lung cancer screening (LCS) studies using low-dose computed tomography (LDCT) have demonstrated that early detection reduces lung cancer mortality. However, no LCS program has been implemented yet in the Netherlands. A national LCS program has the potential to enhance the health outcomes for lung cancer patients in the Netherlands. Objective and Methods This study evaluates the cost-effectiveness of LCS compared to no-screening in the Netherlands, by simulating the screening outcomes based on data from NEderlands–Leuvens Longkanker Screenings ONderzoek (NELSON) and National Lung Screening Trial (NLST). We simulated annual screening up to 74 years of age, using inclusion criteria from the respective studies. A decision tree and Markov model was used to predict the incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICERs) for the screening population. The analysis used a lifetime horizon and a societal perspective. Results Compared to no-screening, LCS resulted in an ICER of €5,169 per QALY for the NELSON simulation, and an ICER of €17,119 per QALY for the NLST simulation. The screening costs were highly impactful for the cost-effectiveness. The most influential parameter was the CT scan cost. Cost reduction for CT from €201 to €101 per scan would reduce the ICER to €2,335 using NELSON criteria. Additionally, LCS could prevent 15,115 and 12,611 premature lung cancer deaths, accompanied by 1.66 and 1.31 QALYs gained per lung cancer case for the NELSON and NLST simulations, respectively. Conclusion LCS was estimated to be cost-effective in the Netherlands for both simulations at a willingness-to-pay threshold of €20,000 per QALY. Using the NELSON criteria, less than €5,500 per QALY had to be spent. Lowering the cost per CT exam would lead to a further reduction of this amount.

Evaluation of risk prediction models to select lung cancer screening participants in Europe: a prospective cohort consortium analysis

Lung cancer risk prediction models might efficiently identify individuals who should be offered lung cancer screening. However, their performance has not been comprehensively evaluated in Europe. We aimed to externally validate and evaluate the performance of several risk prediction models that predict lung cancer incidence or mortality in prospective European cohorts. We analysed 240 137 participants aged 45-80 years with a current or former smoking history from nine European countries in four prospective cohorts from the pooled database of the Lung Cancer Cohort Consortium: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (Finland), the Nord-Trøndelag Health Study (Norway), CONSTANCES (France), and the European Prospective Investigation into Cancer and Nutrition (Denmark, Germany, Italy, Spain, Sweden, the Netherlands, and Norway). We evaluated ten lung cancer risk models, which comprised the Bach, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 2012 model (PLCOm2012), the Lung Cancer Risk Assessment Tool (LCRAT), the Lung Cancer Death Risk Assessment Tool (LCDRAT), the Nord-Trøndelag Health Study (HUNT), the Optimized Early Warning Model for Lung Cancer Risk (OWL), the University College London-Death (UCLD), the University College London-Incidence (UCLI), the Liverpool Lung Project version 2 (LLP version 2), and the Liverpool Lung Project version 3 (LLP version 3) models. We quantified model calibration as the ratio of expected to observed cases or deaths and discrimination using the area under the receiver operating characteristic curve (AUC). For each model, we also identified risk thresholds that would screen the same number of individuals as each of the US Preventive Services Task Force 2021 (USPSTF-2021), the US Preventive Services Task Force 2013 (USPSTF-2013), and the Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) criteria. Among the participants, 1734 lung cancer cases and 1072 lung cancer deaths occurred within five years of enrolment. Most models had reasonable calibration in most countries, although the LLP version 2 overpredicted risk by more than 50% in eight countries (expected to observed ≥1·50). The PLCOm2012, LCDRAT, LCRAT, Bach, HUNT, OWL, UCLD, and UCLI models showed similar discrimination in most countries, with AUCs ranging from 0·68 (95% CI 0·59-0·77) to 0·83 (0·78-0·89), whereas the LLP version 2 and LLP version 3 showed lower discrimination, with AUCs ranging from 0·64 (95% CI 0·57-0·72) to 0·78 (0·74-0·83). When pooling data from all countries (but excluding the HUNT cohort), 33·9% (73 313 of 216 387) of individuals were eligible by USPSTF-2021 criteria, which included 74·8% (1185) of lung cancers and 76·3% (730) of lung cancer deaths occurring over 5 years. Fewer individuals were selected by USPSTF-2013 and NELSON criteria. After applying thresholds to select a population of equal size to USPSTF-2021, the PLCOm2012, LCDRAT, LCRAT, Bach, HUNT, OWL, UCLD, and UCLI, models identified 77·6%-79·1% of future cases, although they selected slightly older individuals compared with USPSTF-2021 criteria. Results were similar for USPSTF-2013 and NELSON. Several lung cancer risk prediction models showed good performance in European countries and might improve the efficiency of lung cancer screening if used in place of categorical eligibility criteria. US National Cancer Institute, l'Institut National du Cancer, Cancer Research UK.

Shall We Screen Lung Cancer with Volume Computed Tomography in Austria? A Cost-Effectiveness Modelling Study.

This study assessed the cost-effectiveness of a lung cancer screening (LCS) program using low-dose computed tomography (LDCT) in Austria. An existing decision tree with an integrated Markov model was used to analyze the cost-effectiveness of LCS versus no screening from a healthcare payer perspective over a lifetime horizon. A simulation was conducted to model annual LCS for an asymptomatic high-risk population cohort aged 50-74 with a smoking history using the Dutch-Belgian Lung Cancer Screening Study (NEderlands-Leuvens Longkanker ScreeningsONderzoek, NELSON) screening outcomes. The principal measure utilized to assess cost-effectiveness was the incremental cost-effectiveness ratio (ICER). Sensitivity and scenario analyses were employed to determine uncertainties surrounding the key model inputs. At an uptake rate of 50%, 300,277 eligible individuals would participate in the LCS program, yielding 56,122 incremental quality-adjusted life years (QALYs) and 84,049 life years gained compared to no screening, with an ICER of EUR 24,627 per QALY gained or EUR 16,444 per life-year saved. Additionally, LCS led to the detection of 25,893 additional early-stage lung cancers and averted 11,906 premature lung cancer deaths. It was estimated that LCS would incur EUR 945 million additional screening costs and EUR 386 million additional treatment costs. These estimates were robust in sensitivity analyses. Implementation of annual LCS with LDCT for a high-risk population, using the NELSON screening outcomes, is cost-effective in Austria, at a threshold of EUR 50,000 per QALY.

Shall We Screen Lung Cancer With Low-Dose Computed Tomography? Cost-Effectiveness in Hungary

ObjectivesClinical data and cost-effectiveness analyses from several countries support the use of low-dose computed tomography (LDCT) to screen patients with high risk of lung cancer (LC). This study aimed to explore the economic value of screening LC with LDCT in Hungary. MethodsCohorts of screened and nonscreened subjects were simulated in a decision analytic model over their lifetime. Five steps in the patient trajectory were distinguished: no LC, nondiagnosed LC, screening, diagnosed LC, and post-treatment. Patient pathways were populated based on the Hungarian pilot study of screening, the Nederlands–Leuvens Longkanker Screenings Onderzoek (NELSON) LC screening trial, and local incidence and prevalence data. Healthcare costs were obtained from the National Health Insurance Fund. Utility data were obtained from international sources and adjusted to local tariffs. Scenarios according to screening frequency, age bands (50-74, 55-74 years), and smoking status were analyzed. ResultsAnnual LDCT-based screening compared with no screening for 55- to 74-year-old current smokers showed 0.031 quality-adjusted life-year (QALY) gains for an additional €137, which yields €5707 per QALY. Biennial screening for the same target population showed that purchasing 1 QALY would cost €10 203. The least cost-effective case was biennial screening of the general population aged 50 to 74 years, which yielded €37 931 per QALY. ConclusionsScreening LC with LDCT for a high-risk population could be cost-effective in Hungary. For the introduction of screening with LDCT, targeting the most vulnerable groups while having a long-term approach on costs and benefits is essential.

Updated cost-effectiveness analysis of lung cancer screening for Australia, capturing differences in the health economic impact of NELSON and NLST outcomes

BackgroundA national, lung cancer screening programme is under consideration in Australia, and we assessed cost-effectiveness using updated data and assumptions.MethodsWe estimated the cost-effectiveness of lung screening by applying screening parameters and outcomes from either the National Lung Screening Trial (NLST) or the NEderlands–Leuvens Longkanker Screenings ONderzoek (NELSON) to Australian data on lung cancer risk, mortality, health-system costs, and smoking trends using a deterministic, multi-cohort model. Incremental cost-effectiveness ratios (ICERs) were calculated for a lifetime horizon.ResultsThe ICER for lung screening compared to usual care in the NELSON-based scenario was AU$39,250 (95% CI $18,150–108,300) per quality-adjusted life year (QALY); lower than the NLST-based estimate (ICER = $76,300, 95% CI $41,750–236,500). In probabilistic sensitivity analyses, lung screening was cost-effective in 15%/60% of NELSON-like simulations, assuming a willingness-to-pay threshold of $30,000/$50,000 per QALY, respectively, compared to 0.5%/6.7% for the NLST. ICERs were most sensitive to assumptions regarding the screening-related lung cancer mortality benefit and duration of benefit over time. The cost of screening had a larger impact on ICERs than the cost of treatment, even after quadrupling the 2006–2016 healthcare costs of stage IV lung cancer.DiscussionLung screening could be cost-effective in Australia, contingent on translating trial-like lung cancer mortality benefits to the clinic.

SMOKING HISTORY DOCUMENTATION IN THE ELECTRONIC HEALTH RECORD: AN IMPORTANT CONTRIBUTOR TO RATES OF LUNG CANCER SCREENING

SMOKING HISTORY DOCUMENTATION IN THE ELECTRONIC HEALTH RECORD: AN IMPORTANT CONTRIBUTOR TO RATES OF LUNG CANCER SCREENING

The Journey for Lung Cancer Screening where we Stand Today.

Lung cancer remains a leading cause of cancer mortality worldwide with many patients presenting with advanced disease. We reviewed the available literature for lung cancer screening using low dose computed tomography (LDCT). We reviewed the National Lung Screening Trial (NLST), Early Lung Cancer Action Program (ELCAP) and the (Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) trials. We also look at different lung cancer risk prediction models that may aid in identifying target populations and also discuss the cost-effectiveness of LDCT screening in different groups of smokers and ex-smokers. Lastly, we discuss recent guideline changes that have occurred in line with new and emerging evidence on lung cancer screening. LDCT has been shown reduce lung cancer mortality in certain groups of current and former smokers and should be considered to help in the early diagnosis of lung cancer.

OA05.04 A Comparison of Stage- and Histology-Specific CT Sensitivity in the NELSON Trial and the NLST

The Dutch-Belgian lung cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) demonstrated a reduction in lung cancer mortality of 24%1 for screening with low-dose computed tomography (CT), compared to the 20%2 found in the National Lung Screening Trial (NLST). The NELSON and NLST differed in study population and trial design. Specifically, in contrast to the NLST, the NELSON trial employed a nodule management protocol that incorporated nodule volume and growth3 as opposed to nodule diameter only.

Advances in lung cancer screening and early detection.

Lung cancer is associated with a heavy cancer-related burden in terms of patients’ physical and mental health worldwide. Two randomized controlled trials, the US-National Lung Screening Trial (NLST) and Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON), indicated that low-dose CT (LDCT) screening results in a statistically significant decrease in mortality in patients with lung cancer, LDCT has become the standard approach for lung cancer screening. However, many issues in lung cancer screening remain unresolved, such as the screening criteria, high false-positive rate, and radiation exposure. This review first summarizes recent studies on lung cancer screening from the US, Europe, and Asia, and discusses risk-based selection for screening and the related issues. Second, an overview of novel techniques for the differential diagnosis of pulmonary nodules, including artificial intelligence and molecular biomarker-based screening, is presented. Third, current explorations of strategies for suspected malignancy are summarized. Overall, this review aims to help clinicians understand recent progress in lung cancer screening and alleviate the burden of lung cancer.

Low-dose computed tomography lung cancer screening: Clinical evidence and implementation research.

Lung cancer causes more deaths than breast, cervical, and colorectal cancer combined. Nevertheless, population‐based lung cancer screening is still not considered standard practice in most countries worldwide. Early lung cancer detection leads to better survival outcomes: patients diagnosed with stage 1A lung cancer have a >75% 5‐year survival rate, compared to <5% at stage 4. Low‐dose computed tomography (LDCT) thorax imaging for the secondary prevention of lung cancer has been studied at length, and has been shown to significantly reduce lung cancer mortality in high‐risk populations. The US National Lung Screening Trial reported a 20% overall reduction in lung cancer mortality when comparing LDCT to chest X‐ray, and the Nederlands‐Leuvens Longkanker Screenings Onderzoek (NELSON) trial more recently reported a 24% reduction when comparing LDCT to no screening. Hence, the focus has now shifted to implementation research. Consequently, the 4‐IN‐THE‐LUNG‐RUN consortium based in five European countries, has set up a large‐scale multicenter implementation trial. Successful implementation of and accessibility to LDCT lung cancer screening are dependent on many factors, not limited to population selection, recruitment strategy, computed tomography screening frequency, lung‐nodule management, participant compliance, and cost effectiveness. This review provides an overview of current evidence for LDCT lung cancer screening, and draws attention to major factors that need to be addressed to successfully implement standardized, effective, and accessible screening throughout Europe. Evidence shows that through the appropriate use of risk‐prediction models and a more personalized approach to screening, efficacy could be improved. Furthermore, extending the screening interval for low‐risk individuals to reduce costs and associated harms is a possibility, and through the use of volumetric‐based measurement and follow‐up, false positive results can be greatly reduced. Finally, smoking cessation programs could be a valuable addition to screening programs and artificial intelligence could offer a solution to the added workload pressures radiologists are facing.

Cancer Risk in Nodules Detected at Follow-Up Lung Cancer Screening CT.

BACKGROUND. Nodules may have different lung cancer risks when new on follow-up CT versus when present on previously performed CT (i.e., existing nodules). Diameter-based Lung-RADS and volume-based NELSON (Nederlands-Leuvens Longkanker Screenings ONderzoek trial) categories have shown variable performance in nodule risk assessment. OBJECTIVE. The purpose of this study was to assess Lung-RADS and NELSON classifications of nodules detected on follow-up lung cancer screening CT examinations. METHODS. This retrospective study included 185 patients (100 women and 85 men; median age, 66 years) who underwent a lung cancer screening CT examination for which a prior CT examination was available. Stratified random sampling was performed to enrich the sample with suspicious nodules, yielding 50, 45, 47, 30, and 13 nodules with Lung-RADS categories 2, 3, 4A, 4B, and 4X, respectively. Lung-RADS categories were recorded from clinical reports. The linear measurements of the nodules were extracted from clinical reports to generate Lung-RADS categories by use of strict criteria from Lung-RADS version 1.1. Two radiologists used a semiautomated tool to obtain nodule volumes, which were used to generate NELSON categories. Lung cancer risk was assessed. ROC analysis was performed. Percentages and AUCs were weighted on the basis of Lung-RADS category frequencies in the underlying screening cohort. RESULTS. Twenty-nine cancers were diagnosed. The weighted cancer risk was 5% for new nodules, 1% for stable existing nodules, and 44% for growing existing nodules. None of the clinical Lung-RADS category 2 nodules were cancer. With use of strict Lung-RADS version 1.1 criteria, 34 nodules, including seven cancers, were downgraded to category 2. The AUC for cancer was 0.96 for clinical Lung-RADS, 0.81 for strict Lung-RADS, 0.71-0.84 for the NELSON algorithm (two readers), and 0.89 for nodule diameter measurement. Clinical Lung-RADS achieved weighted sensitivity and specificity, respectively, of 100% and 85% for the entire sample, 100% and 41% for new nodules, and 100% and 94% for existing nodules. The optimal diameter threshold was 8 mm for existing nodules versus 6 mm for new nodules. CONCLUSION. Lung-RADS, as applied by radiologists in clinical practice, achieved excellent performance on follow-up screening examinations. Strict Lung-RADS resulted in the downgrading of some cancers to category 2. Volumetric assessments had weaker performance than clinical Lung-RADS. New nodules warrant smaller size thresholds than existing nodules. CLINICAL IMPACT. The findings of the present study provide insight into radiologists' management of nodules detected on follow-up screening examinations.

What is the balance of benefits and harms for lung cancer screening with low-dose computed tomography?

After the National Lung Screening Trial (NLST)1 demonstrated improved lung cancer mortality almost a decade ago, hopes have been raised that low-dose computed tomography could be used to detect lung cancer in asymptomatic populations and improve outcomes by reducing the number of people diagnosed with advanced disease. The publication of the long-awaited Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) trial last year2 has provided further evidence of a lung cancer mortality benefit and has provoked further calls to implement national population-based screening programmes, but the case for lung cancer screening remains controversial.

The promises and challenges of early non-small cell lung cancer detection: patient perceptions, low-dose CT screening, bronchoscopy and biomarkers.

Lung cancer survival statistics are sobering with survival ranking among the poorest of all cancers despite the addition of targeted therapies and immunotherapies. However, improvements in tools for early detection hold promise. The Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) trial recently corroborated the findings from the previous National Lung Screening Trial low-dose Computerised Tomography (NLST) screening trial in reducing lung cancer mortality. Biomarker research and development is increasing at pace as the molecular life histories of lung cancers become further unravelled. Low-dose CT screening (LDCT) is effective but targets only those at the highest risk and is burdensome on healthcare. An optimally designed CT screening programme at best will only detect a low proportion of overall lung cancers as only those at very high-risk meet screening criteria. Biomarkers that help risk stratify suitable patients for LDCT screening, and those that assist in determining which LDCT detected nodules are likely to represent malignant disease are needed. Some biomarkers have been proposed as standalone lung cancer diagnosis tools. Bronchoscopy technology is improving, with better capacity to identify and obtain samples from early lung cancers. Clinicians need to be aware of each early lung cancer detection method's inherent limitations. We anticipate that the future of early lung cancer diagnosis will involve a synergistic, multimodal approach, combining several early detection methods.

Lung cancer screening, what has changed after the latest evidence?

Lung cancer (LC) is still one of the most frequent cancers with a high related mortality. Their prognosis is directly proportional to the stage at the time of diagnosis. Seventy percent are currently diagnosed in advanced or locally advanced stage (higher than stage III), making a cure unlikely for the majority of patients. Developments in LC treatment are significant however they do not seem to be enough to reverse the current situation, at least, in a short period of time. Despite recent advances in treatment, primary prevention and early diagnosis appear to be the key to reduce the incidence and mortality of this disease. Many countries have developed LC screening programs based on the results of clinical trials published in recent years. The aim of this paper is to review the latest results of the NEderlands Leuvens Longkanker Screenings Onderzoek and compare them with the findings of the National Lung Screening Trial. We address the question whether it is necessary to continue discussing the evidence regarding LC screening. In both trials, there is a clear impact on LC mortality but, with a modest reduction in over all mortality. Undoubtedly, the benefit of screening can be expected to grow as low-dose computed tomographys are performed over longer periods of time.

Do we need to see to believe?-radiomics for lung nodule classification and lung cancer risk stratification.

Despite multiple recent advances, the diagnosis and management of lung cancer remain challenging and it continues to be the deadliest malignancy. In 2011, the National Lung Screening Trial (NLST) reported 20% reduction in lung cancer related mortality using annual low dose chest computed tomography (CT). These results led to the approval and nationwide establishment of lung cancer CT-based lung cancer screening programs. These findings have been further validated by the recently published Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) and Multicentric Italian Lung Detection (MILD) trials, the latter showing benefit of screening even beyond the 5 years. However, the implementation of lung cancer screening has been impeded by several challenges, including the differentiation between benign and malignant nodules, the large number of false positive studies and the detection of indolent, potentially clinically insignificant lung cancers (overdiagnosis). Hence, the development of non-invasive strategies to accurately classify and risk stratify screen-detected pulmonary nodules in order to individualize clinical management remains a high priority area of research. Radiomics is a recently coined term which refers to the process of imaging feature extraction and quantitative analysis of clinical diagnostic images to characterize the nodule phenotype beyond what is possible with conventional radiologist assessment. Even though it is still in early phase, several studies have already demonstrated that radiomics approaches are potentially useful for lung nodule classification, risk stratification, individualized management and prediction of overall prognosis. The goal of this review is to summarize the current literature regarding the radiomics of screen-detected lung nodules, highlight potential challenges and discuss its clinical application along with future goals and challenges.

Update on Lung Cancer Screening

Over the past 10 years, there has been substantial progress in the study and implementation of lung cancer screening using low-dose computed tomography (LDCT). The National Lung Screening Trial, the recently reported NELSON (NEderlands-Leuvens Longkanker Screenings ONderzoek) trial, and other European trials provide strong evidence for the efficacy of LDCT to reduce lung cancer mortality. This has resulted in the United State's Preventative Task Force and numerous professional medical societies adopting lung cancer screening recommendations. Despite the general acceptance of the positive effect of screening, low adoption and implementation rates remain nationally. In this article, the authors discuss the evolution and current state of the evidence for LDCT screening for lung cancer. The authors will also review the associated risks, cost, and challenges of implementation of an LDCT screening program.

ES08.01 Participation of the Target Population in Lung Cancer Screening

The two largest randomized controlled trials performed, The National Lung Screening Trial (NLST) and the Nederlands-Leuvens Longkanker ScreeningsONderzoek (NELSON) 1,2, proved that lung cancer screening using low dose CT scan, resulted in a significant reduction in lung cancer mortality. Following the results of the NLST trial, lung cancer screening was initiated in the United States and Canada. However, the uptake of lung cancer screening is poor, with only 3% to 4% of all eligible persons participating in the implemented screening program 3. Given more recent positive results of the NELSON study that were presented at the World Conference on Lung Cancer last year in Toronto, lung cancer screening is now considered in many countries across the globe. This low uptake of lung cancer screening is however a cause of concern. The reasons for the low participation rate are multi-factorial. The novelty of the lung cancer screening program is such a factor, resulting in lower uptake and might be the easiest one to address. The identification of the target population is more challenging due to the fact that the population to be screened is more defined than just age and sex. In addition, the lower socioeconomic status, which presents a significant portion of the to be screened population, and those who face barriers to care present a major challenge for implementing a successful screening program with a satisfactory uptake rate. Several strategies have been proposed to improve lung cancer screening uptake. In the socioeconomically deprived and heavy smoking communities, lung cancer is perceived as an uncontrollable disease 4, while cure rates in yearly screening programs lead to a cure in the majority of patients when lung cancer is detected 5,6. Therefore, public awareness of the curability of lung cancer when screening programs are implemented could boost the participation rate. Mobile lung cancer testing in supermarket car parks proved to be a successful pilot 7. This strategy avoids difficulties relating to the distance of travel, lack of public transport available, and the cost of either the journey itself or hospital parking. This strategy is currently explored in a larger cohort. One potential intervention that is being evaluated in clinical trials to improve the uptake and implementation of lung cancer screening is a patient navigator. A navigator can be a layperson, a medical assistant, or a nurse who will directly contact potential candidates for lung cancer screening for enrollment 3. The Accelerate, Coordinate, Evaluate (ACE) Programme, initiated in the United Kingdom, is an early diagnosis of cancer initiative focused on testing innovations that either identify individuals at high risk of cancer earlier 8. This program consists of several individual programs in different regions of the UK, of which The Liverpool Healthy Lung Programme is a participant. Among other goals, this initiative tries to improve uptake in the hard to reach cohort. They used general practitioners’ records to invite participants meeting the criteria to a ‘Lung Health Check’. This ‘Lung Health Check’ is a novel approach that may overcome or minimize the emotional barriers associate with the term “lung cancer screening”. This method resulted in an uptake level up to 40% 9. This initiative is an example that a higher uptake rate is indeed possible, even in the hard to reach population. At the IASLC World Conference on Lung Cancer in Barcelona, the issues regarding participation of the target population in lung cancer screening will be addressed and possible strategies will be discussed to overcome these challenges. As lung cancer screening is yet to be implemented in the majority of countries worldwide, we now have a unique opportunity to test and apply these strategies to successfully implement lung cancer screening in order to reduce lung cancer mortality.

Low-dose computed tomography for lung cancer screening in high-risk populations: a systematic review and economic evaluation.

Diagnosis of lung cancer frequently occurs in its later stages. Low-dose computed tomography (LDCT) could detect lung cancer early. To estimate the clinical effectiveness and cost-effectiveness of LDCT lung cancer screening in high-risk populations. Bibliographic sources included MEDLINE, EMBASE, Web of Science and The Cochrane Library. Clinical effectiveness - a systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programmes [such as chest X-ray (CXR)] was conducted. Bibliographic sources included MEDLINE, EMBASE, Web of Science and The Cochrane Library. Meta-analyses, including network meta-analyses, were performed. Cost-effectiveness - an independent economic model employing discrete event simulation and using a natural history model calibrated to results from a large RCT was developed. There were 12 different population eligibility criteria and four intervention frequencies [(1) single screen, (2) triple screen, (3) annual screening and (4) biennial screening] and a no-screening control arm. Clinical effectiveness - 12 RCTs were included, four of which currently contribute evidence on mortality. Meta-analysis of these demonstrated that LDCT, with ≤ 9.80 years of follow-up, was associated with a non-statistically significant decrease in lung cancer mortality (pooled relative risk 0.94, 95% confidence interval 0.74 to 1.19). The findings also showed that LDCT screening demonstrated a non-statistically significant increase in all-cause mortality. Given the considerable heterogeneity detected between studies for both outcomes, the results should be treated with caution. Network meta-analysis, including six RCTs, was performed to assess the relative clinical effectiveness of LDCT, CXR and usual care. The results showed that LDCT was ranked as the best screening strategy in terms of lung cancer mortality reduction. CXR had a 99.7% probability of being the worst intervention and usual care was ranked second. Cost-effectiveness - screening programmes are predicted to be more effective than no screening, reduce lung cancer mortality and result in more lung cancer diagnoses. Screening programmes also increase costs. Screening for lung cancer is unlikely to be cost-effective at a threshold of £20,000/quality-adjusted life-year (QALY), but may be cost-effective at a threshold of £30,000/QALY. The incremental cost-effectiveness ratio for a single screen in smokers aged 60-75 years with at least a 3% risk of lung cancer is £28,169 per QALY. Sensitivity and scenario analyses were conducted. Screening was only cost-effective at a threshold of £20,000/QALY in only a minority of analyses. Clinical effectiveness - the largest of the included RCTs compared LDCT with CXR screening rather than no screening. Cost-effectiveness - a representative cost to the NHS of lung cancer has not been recently estimated according to key variables such as stage at diagnosis. Certain costs associated with running a screening programme have not been included. LDCT screening may be clinically effective in reducing lung cancer mortality, but there is considerable uncertainty. There is evidence that a single round of screening could be considered cost-effective at conventional thresholds, but there is significant uncertainty about the effect on costs and the magnitude of benefits. Clinical effectiveness and cost-effectiveness estimates should be updated with the anticipated results from several ongoing RCTs [particularly the NEderlands Leuvens Longkanker Screenings ONderzoek (NELSON) screening trial]. This study is registered as PROSPERO CRD42016048530. The National Institute for Health Research Health Technology Assessment programme.