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最新临床证据：肺癌高风险人群中，低剂量CT筛查与常规随访相比，对早期肺癌检出率、死亡率和假阳性风险的影响
根据最新临床证据，低剂量CT (LDCT) 筛查与常规随访（或胸部X光筛查）相比，对肺癌高风险人群的早期肺癌检出率、死亡率和假阳性风险有显著影响。以下是详细分析：
早期肺癌检出率的影响
LDCT筛查显著提高了早期肺癌的检出率。
- LDCT的优势：与胸部X光或无筛查组相比，LDCT筛查能发现更多肺癌病例（风险比 [RR] = 1.58, 95% CI = 1.25-1.99, P < 0.001），并且能显著提高I期肺癌的检出率（RR = 3.45, 95% CI = 2.08-5.72, P < 0.001）。LDCT筛查的主要优势在于其能够检测出早期、无症状的恶性病变，这对于肺癌的治愈性治疗至关重要。一项伞形回顾也证实，LDCT筛查显著增加了早期肺癌的检出（RR: 1.31, 95% CI: 1.18-1.45）。
- 分期诊断：在早期（I/II期）诊断时，治愈性治疗是可能的，但由于早期无症状，超过70%的病例在晚期（III/IV期）才被诊断，此时治疗很少能治愈。LDCT筛查有助于在可治愈阶段进行诊断，从而降低肺癌死亡率。
- 具体试验结果：
- 美国国家肺癌筛查试验（NLST）报告，与胸部X光相比，LDCT筛查可以将肺癌死亡率降低20%。
- 荷兰-比利时肺癌筛查研究（NELSON）进一步报告，与无筛查相比，LDCT筛查将男性肺癌死亡率降低了24%。NELSON试验的方案在资格标准、体积结节管理和增加筛查间隔方面有所不同，并显示出维持甚至提高早期CT敏感性和死亡率预防的可能性，同时减少不必要的随访。
- 一项包含8项试验的荟萃分析显示，LDCT筛查的肺癌相关死亡率降低了21%（RR 0.79, 95% CI 0.72至0.87）。另一项包含8项LDCT筛查研究的荟萃分析显示，肺癌死亡率相对降低了12%。总的来说，LDCT在肺癌相关死亡率方面优于胸部X光或常规护理。
- 检测敏感性：LDCT筛查具有高敏感性（0.97, 95% CI: 0.94-0.98）和特异性（0.87, 95% CI: 0.82-0.91）。NELSON筛查方案的建模研究发现，基线筛查时I期非小细胞肺癌（NSCLC）的敏感性为24.6%（其他NSCLC）至41.0%（腺癌），在重复筛查轮次中，I期腺癌的敏感性增加到70.9%。
- 筛查频率：年度LDCT筛查在发现更多肺癌方面更为敏感，并且可能比两年一次的筛查更能检测出更多早期肺癌病例。然而，也有研究提出，对于低风险个体延长筛查间隔可以降低成本和相关危害，并应采用个性化的筛查方法。
死亡率的影响
LDCT筛查在高风险人群中显著降低了肺癌相关死亡率。
- 肺癌特异性死亡率：LDCT筛查能够显著降低肺癌特异性死亡率。多项随机对照试验（RCTs）和荟萃分析证实，LDCT筛查能大幅降低肺癌死亡率。
- 美国预防服务工作组（USPSTF）的建议以及后续研究表明，LDCT筛查能通过早期发现降低肺癌死亡率。
- 一项包含11项试验的系统评价和荟萃分析发现，LDCT筛查与对照组（无筛查或胸部X光筛查）相比，肺癌相关死亡率降低了21%（RR 0.79, 95% CI 0.72至0.87）。
- 该荟萃分析还指出，女性在LDCT筛查中表现出比男性更大的肺癌相关死亡率益处。
- 总死亡率方面，LDCT筛查还导致全因死亡率（包括肺癌相关死亡）降低了5%（RR 0.95, 95% CI 0.91至0.99），但此项证据的确定性为中等。
- 另一项荟萃分析指出，LDCT筛查显著降低了肺癌特异性死亡率（RR=0.84, 95% CI=0.75-0.95, P=0.004），但对全因死亡率的降低不具统计学意义（RR=1.26, 95% CI=0.89-1.78, P=0.193）。而一项伞形回顾也指出，LDCT筛查将肺癌死亡率降低了18%（RR: 0.82, 95% CI: 0.75-0.90），但对全因死亡率的降低不具有统计学意义（RR: 0.91, 95% CI: 0.75-1.06）。
- 早期诊断与生存率：早期肺癌（如I期）的诊断可使5年生存率超过75%，而IV期诊断时则低于5%。因此，早期检测对于改善肺癌生存结果至关重要。
- 辐射风险与收益比：LDCT筛查的收益-辐射风险比非常有利。例如，对于美国国家肺癌筛查试验（NLST），仅考虑筛查剂量，收益-辐射风险比男性为12:1，女性为19:1，总体为16:1。即使包括筛查和估计的随访剂量，收益-辐射风险比男性为9:1，女性为13:1，总体为12:1。其他试验（ITALUNG和COSMOS）也显示出高收益-辐射风险比，强调了使用现代CT技术、保持低诊断随访率以及最小化筛查和诊断随访剂量的重要性。
假阳性风险的影响
LDCT筛查确实伴随着较高的假阳性结果和召回率，但这可以通过改进管理方案和技术来缓解。
- 假阳性率：LDCT筛查的假阳性率和召回率高于胸部X光筛查。一项系统回顾和荟萃分析显示，基线/单次筛查的假阳性估计中位数为25.53%，多次筛查的为23.28%。
- 过度诊断和侵入性检查：LDCT筛查的估计过度诊断率为18%（95% CI 0%至36%）。过度诊断是指发现的肺癌在患者的有生之年可能不会引起症状或导致死亡。在LDCT组中，侵入性检查发生频率更高（RR 2.60, 95% CI 2.41至2.80），例如，每1000名接受侵入性随访程序的患者中，有11.18例死亡和52.03例出现严重并发症。然而，术后60天死亡率在两组间无显著差异。
- 心理影响：LDCT筛查可能对患者造成负面心理影响，例如增加焦虑。不过，一项荟萃分析发现，LDCT筛查组的参与者报告的焦虑评分低于对照组。
- 缓解策略：
- 结节管理：通过使用基于体积的测量和随访，可以大大减少假阳性结果。例如，NELSON试验通过采用体积测量和增长时间来管理肺结节，成功地降低了不必要的随访和过度诊断的风险。国际肺癌研究协会（IASLC）的建议也包括制定偶然发现的肺结节追踪和管理协议，以补充程序性肺癌筛查。
- 风险预测模型：利用风险预测模型和更个性化的筛查方法可以提高筛查的效率和效益。例如，HUNT肺癌模型（HUNT LCM）在预测肺癌诊断方面比NELSON和2021年USPSTF标准更有效。
- 人工智能（AI）：将人工智能（AI）算法应用于LDCT扫描，可以实现更精确的分析，并有望增加对可疑CT筛查病变恶性程度的预测，以及标准化高质量的AI协议，从而大幅降低成本、资源利用率和放射科医师报告时间。
- 多学科团队：高质量的筛查项目需要多学科团队的参与，以平衡死亡率降低和避免假阳性结果、过度诊断、侵入性程序和辐射暴露等潜在危害。
实施和挑战
尽管有明确证据支持LDCT筛查的有效性，但其在全球范围内的实施仍面临挑战，包括筛查依从性低和不同群体间的差异。
- 筛查资格标准：美国癌症协会（ACS）建议对50-80岁、目前吸烟或曾吸烟且吸烟史≥20包年（pack-year）的无症状个体进行年度LDCT筛查。而USPSTF推荐对50-80岁、至少20包年吸烟史、目前吸烟或在过去15年内戒烟的成年人进行LDCT筛查。对于曾吸烟者，戒烟年限不再是开始或停止筛查的资格标准。
- 共享决策：在决定开始LDCT筛查之前，个体应与合格的卫生专业人员进行共享决策讨论。共享决策对提高筛查依从性至关重要。
- 戒烟咨询：目前吸烟的个体应接受戒烟咨询并获得戒烟资源。将戒烟计划纳入筛查项目具有重要价值。
- 质量指标与标准化：需要建立普遍的筛查项目质量指标，并开发证据支持对非吸烟但高风险个体进行筛查的标准，以及规范筛查间隔和对其他异常发现的管理。德国已基于强有力的科学证据，发布了针对高风险人群采用LDCT进行结构化肺癌筛查项目的建议，强调了对高风险人群的明确定义、个体风险评估、合格人员、诊断和治疗步骤验证、中央文件和质量保证以及整合戒烟计划等。
- 未吸烟人群的风险：国际肺癌研究协会的路线图包括建立基于证据的标准，以识别从未吸烟但患肺癌高风险的个体。男性、非洲裔和拉丁裔、受教育程度较低以及二手烟暴露与肺癌死亡风险增加相关。
- 全球实施：尽管有强有力的证据，但全球范围内LDCT筛查的普及率仍不理想。许多国家正在推进国家LDCT筛查计划，旨在通过风险模型扩大资格，并针对高风险的非吸烟者和轻度吸烟者，以提高效率和公平性。
综上所述，LDCT筛查在高风险人群中显著提高了早期肺癌的检出率和肺癌相关死亡率的降低。然而，它也带来了较高的假阳性风险和随之而来的侵入性检查。通过优化结节管理、采用风险预测模型、整合人工智能技术、加强多学科合作以及推行共享决策和戒烟咨询，可以最大程度地发挥LDCT筛查的益处并减轻其潜在危害，从而在全球范围内有效地减少肺癌的死亡率和痛苦。
References
1Screening for lung cancer: 2023 guideline update from the American Cancer Society.PubMed
Andrew M D Wolf, Kevin C Oeffinger, Tina Ya-Chen Shih, et al.
Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network-validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit-to-radiation-risk ratios from LCS and follow-up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50-80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low-dose computed tomography for asymptomatic individuals aged 50-80 years who currently smoke or formerly smoked and have a ≥20 pack-year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision-making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States.
2Impact of low-dose computed tomography (LDCT) screening on lung cancer-related mortality.PubMed
Asha Bonney, Reem Malouf, Corynne Marchal, et al.
BACKGROUND: Lung cancer is the most common cause of cancer-related death in the world, however lung cancer screening has not been implemented in most countries at a population level. A previous Cochrane Review found limited evidence for the effectiveness of lung cancer screening with chest radiography (CXR) or sputum cytology in reducing lung cancer-related mortality, however there has been increasing evidence supporting screening with low-dose computed tomography (LDCT). OBJECTIVES: To determine whether screening for lung cancer using LDCT of the chest reduces lung cancer-related mortality and to evaluate the possible harms of LDCT screening. SEARCH METHODS: We performed the search in collaboration with the Information Specialist of the Cochrane Lung Cancer Group and included the Cochrane Lung Cancer Group Trial Register, Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library, current issue), MEDLINE (accessed via PubMed) and Embase in our search. We also searched the clinical trial registries to identify unpublished and ongoing trials. We did not impose any restriction on language of publication. The search was performed up to 31 July 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs) of lung cancer screening using LDCT and reporting mortality or harm outcomes. DATA COLLECTION AND ANALYSIS: Two review authors were involved in independently assessing trials for eligibility, extraction of trial data and characteristics, and assessing risk of bias of the included trials using the Cochrane RoB 1 tool. We assessed the certainty of evidence using GRADE. Primary outcomes were lung cancer-related mortality and harms of screening. We performed a meta-analysis, where appropriate, for all outcomes using a random-effects model. We only included trials in the analysis of mortality outcomes if they had at least 5 years of follow-up. We reported risk ratios (RRs) and hazard ratios (HRs), with 95% confidence intervals (CIs) and used the I statistic to investigate heterogeneity. MAIN RESULTS: We included 11 trials in this review with a total of 94,445 participants. Trials were conducted in Europe and the USA in people aged 40 years or older, with most trials having an entry requirement of ≥ 20 pack-year smoking history (e.g. 1 pack of cigarettes/day for 20 years or 2 packs/day for 10 years etc.). One trial included male participants only. Eight trials were phase three RCTs, with two feasibility RCTs and one pilot RCT. Seven of the included trials had no screening as a comparison, and four trials had CXR screening as a comparator. Screening frequency included annual, biennial and incrementing intervals. The duration of screening ranged from 1 year to 10 years. Mortality follow-up was from 5 years to approximately 12 years. None of the included trials were at low risk of bias across all domains. The certainty of evidence was moderate to low across different outcomes, as assessed by GRADE. In the meta-analysis of trials assessing lung cancer-related mortality, we included eight trials (91,122 participants), and there was a reduction in mortality of 21% with LDCT screening compared to control groups of no screening or CXR screening (RR 0.79, 95% CI 0.72 to 0.87; 8 trials, 91,122 participants; moderate-certainty evidence). There were probably no differences in subgroups for analyses by control type, sex, geographical region, and nodule management algorithm. Females appeared to have a larger lung cancer-related mortality benefit compared to males with LDCT screening. There was also a reduction in all-cause mortality (including lung cancer-related) of 5% (RR 0.95, 95% CI 0.91 to 0.99; 8 trials, 91,107 participants; moderate-certainty evidence). Invasive tests occurred more frequently in the LDCT group (RR 2.60, 95% CI 2.41 to 2.80; 3 trials, 60,003 participants; moderate-certainty evidence). However, analysis of 60-day postoperative mortality was not significant between groups (RR 0.68, 95% CI 0.24 to 1.94; 2 trials, 409 participants; moderate-certainty evidence). False-positive results and recall rates were higher with LDCT screening compared to screening with CXR, however there was low-certainty evidence in the meta-analyses due to heterogeneity and risk of bias concerns. Estimated overdiagnosis with LDCT screening was 18%, however the 95% CI was 0 to 36% (risk difference (RD) 0.18, 95% CI -0.00 to 0.36; 5 trials, 28,656 participants; low-certainty evidence). Four trials compared different aspects of health-related quality of life (HRQoL) using various measures. Anxiety was pooled from three trials, with participants in LDCT screening reporting lower anxiety scores than in the control group (standardised mean difference (SMD) -0.43, 95% CI -0.59 to -0.27; 3 trials, 8153 participants; low-certainty evidence). There were insufficient data to comment on the impact of LDCT screening on smoking behaviour. AUTHORS' CONCLUSIONS: The current evidence supports a reduction in lung cancer-related mortality with the use of LDCT for lung cancer screening in high-risk populations (those over the age of 40 with a significant smoking exposure). However, there are limited data on harms and further trials are required to determine participant selection and optimal frequency and duration of screening, with potential for significant overdiagnosis of lung cancer. Trials are ongoing for lung cancer screening in non-smokers.
3Low-dose computed tomography lung cancer screening: Clinical evidence and implementation research.PubMed
Harriet L Lancaster, Marjolein A Heuvelmans, Matthijs Oudkerk
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.
4Lung Cancer Screening.PubMed
Humberto K Choi, Peter J Mazzone
Lung cancer screening with low-dose computed tomography (LDCT) reduces lung cancer deaths by early detection. The United States Preventive Services Task Force recommends lung cancer screening with LDCT in adults of age 50 years to 80 years who have at least a 20 pack-year smoking history and are currently smoking or have quit within the past 15 years. The implementation of a lung-cancer-screening program is complex. High-quality screening requires the involvement of a multidisciplinary team. The aim of a screening program is to find balance between mortality reduction and avoiding potential harms related to false-positive findings, overdiagnosis, invasive procedures, and radiation exposure. Components and processes of a high-quality lung-cancer-screening program include the identification of eligible individuals, shared decision-making, performing and reporting LDCT results, management of screen-detected lung nodules and non-nodule findings, smoking cessation, ensuring adherence, data collection, and quality improvement.
5Inadequate Uptake of USPSTF-Recommended Low Dose CT Lung Cancer Screening.PubMed
Steven Sorscher
In 2023, published the results of 4 outstanding studies in which investigators aimed to explore and improve clinician and eligible individuals' knowledge of the rationale for lung cancer screening (LCS). Their results highlighted the underutilization of LCS, particularly for certain high risk populations, and the continued disparities in screening seen between groups of eligible individuals. Here, key findings from those 2023 reports, along with salient findings of other recent LCS reports, are discussed. The bases for the United States Preventive Task Force (USPSTF) LCS recommendations, barriers primary care providers face, the perspective of eligible individuals, importance of shared decision-making (SDM) and disparities between groups in LCS are reviewed along with potential strategies to ensure that more eligible individuals are offered LCS.
6Current and Future Perspectives on Computed Tomography Screening for Lung Cancer: A Roadmap From 2023 to 2027 From the International Association for the Study of Lung Cancer.PubMed
Stephen Lam, Chunxue Bai, David R Baldwin, et al.
Low-dose computed tomography (LDCT) screening for lung cancer substantially reduces mortality from lung cancer, as revealed in randomized controlled trials and meta-analyses. This review is based on the ninth CT screening symposium of the International Association for the Study of Lung Cancer, which focuses on the major themes pertinent to the successful global implementation of LDCT screening and develops a strategy to further the implementation of lung cancer screening globally. These recommendations provide a 5-year roadmap to advance the implementation of LDCT screening globally, including the following: (1) establish universal screening program quality indicators; (2) establish evidence-based criteria to identify individuals who have never smoked but are at high-risk of developing lung cancer; (3) develop recommendations for incidentally detected lung nodule tracking and management protocols to complement programmatic lung cancer screening; (4) Integrate artificial intelligence and biomarkers to increase the prediction of malignancy in suspicious CT screen-detected lesions; and (5) standardize high-quality performance artificial intelligence protocols that lead to substantial reductions in costs, resource utilization and radiologist reporting time; (6) personalize CT screening intervals on the basis of an individual's lung cancer risk; (7) develop evidence to support clinical management and cost-effectiveness of other identified abnormalities on a lung cancer screening CT; (8) develop publicly accessible, easy-to-use geospatial tools to plan and monitor equitable access to screening services; and (9) establish a global shared education resource for lung cancer screening CT to ensure high-quality reading and reporting.
7Screening for lung cancer: A systematic review and meta-analysis.PubMed
Muhammad Usman Ali, John Miller, Leslea Peirson, et al.
OBJECTIVES: To examine evidence on benefits and harms of screening average to high-risk adults for lung cancer using chest radiology (CXR), sputum cytology (SC) and low-dose computed tomography (LDCT). METHODS: This systematic review was conducted to provide up to date evidence for Canadian Task Force on Preventive Health Care (CTFPHC) lung cancer screening guidelines. Four databases were searched to March 31, 2015 along with utilizing a previous Cochrane review search. Randomized trials reporting benefits were included; any design was included for harms. Meta-analyses were performed if possible. PROSPERO #CRD42014009984. RESULTS: Thirty-four studies were included. For lung cancer mortality there was no benefit of CXR screening, with or without SC. Pooled results from three small trials comparing LDCT to usual care found no significant benefits for lung cancer mortality. One large high quality trial showed statistically significant reductions of 20% in lung cancer mortality over a follow-up of 6.5years, for LDCT compared with CXR. LDCT screening was associated with: overdiagnosis of 10.99-25.83%; 11.18 deaths and 52.03 patients with major complications per 1000 undergoing invasive follow-up procedures; median estimate for false positives of 25.53% for baseline/once-only screening and 23.28% for multiple rounds; and 9.74 and 5.28 individuals per 1000 screened, with benign conditions underwent minor and major invasive follow-up procedures. CONCLUSION: The evidence does not support CXR screening with or without sputum cytology for lung cancer. High quality evidence showed that in selected high-risk individuals, LDCT screening significantly reduced lung cancer mortality and all-cause mortality. However, for its implementation at a population level, the current evidence warrants the development of standardized practices for screening with LDCT and follow-up invasive testing to maximize accuracy and reduce potential associated harms.
8Stage- and histology-specific sensitivity for the detection of lung cancer of the NELSON screening protocol-A modeling study.PubMed
Koen de Nijs, Kevin Ten Haaf, Juul Hubert, et al.
The Dutch-Belgian lung cancer (LC) screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) demonstrated low-dose computed tomography (CT) reduces LC mortality by 24% among men. The NELSON protocol differed from previous trials in the eligibility criteria, the use of volume-based nodule management, and increasing screening intervals. The early-stage sensitivity of the protocol is pivotal in determining the optimal screening strategy, such as the interval and age range. The MIcrosimulation SCreening ANalysis-Lung natural history model was used to reproduce LC incidence and mortality by detection method (clinical or screen-detected), sex, histology, and stage in the NELSON trial based on individual-level data. We evaluated screening effectiveness by stage and histology, accounting for population characteristics, trial design, and LC epidemiology. We find stage IA non-small cell LC (NSCLC) sensitivity of 24.6% (other NSCLC) to 41.0% (adenocarcinoma) at baseline screening. At repeat screening rounds, we find this increased to 70.9% for stage IA adenocarcinoma. For stage IB, the sensitivity by histology ranges from 26.4% to 77.1%; for stage II, 39.6%-81.9%. Upon detection, the probability of LC mortality prevention is estimated at 83% for stage IA. The sensitivity for detecting early-stage LC is found to depend on the histology of cancer and is increased for adenocarcinoma at repeat screenings. Despite a low rate of referral to follow-up screening in the NELSON trial, early-stage CT sensitivity and the probability of mortality prevention were similar to previous estimates from the National Lung cancer Screening Trial. Previously demonstrated screening effectiveness may be maintained when implementing new programs, while reducing unnecessary follow-up when considering NELSON evidence.
9Improving Lung Cancer Screening Selection: The HUNT Lung Cancer Risk Model for Ever-Smokers Versus the NELSON and 2021 United States Preventive Services Task Force Criteria in the Cohort of Norway: A Population-Based Prospective Study.PubMed
Olav Toai Duc Nguyen, Ioannis Fotopoulos, Maria Markaki, et al.
BACKGROUND: Improving the method for selecting participants for lung cancer (LC) screening is an urgent need. Here, we compared the performance of the Helseundersøkelsen i Nord-Trøndelag (HUNT) Lung Cancer Model (HUNT LCM) versus the Dutch-Belgian lung cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON)) and 2021 United States Preventive Services Task Force (USPSTF) criteria regarding LC risk prediction and efficiency. METHODS: We used linked data from 10 Norwegian prospective population-based cohorts, Cohort of Norway. The study included 44,831 ever-smokers, of which 686 (1.5%) patients developed LC; the median follow-up time was 11.6 years (0.01-20.8 years). RESULTS: Within 6 years, 222 (0.5%) individuals developed LC. The NELSON and 2021 USPSTF criteria predicted 37.4% and 59.5% of the LC cases, respectively. By considering the same number of individuals as the NELSON and 2021 USPSTF criteria selected, the HUNT LCM increased the LC prediction rate by 41.0% and 12.1%, respectively. The HUNT LCM significantly increased sensitivity ( < 0.001 and = 0.028), and reduced the number needed to predict one LC case (29 versus 40, < 0.001 and 36 versus 40, = 0.02), respectively. Applying the HUNT LCM 6-year 0.98% risk score as a cutoff (14.0% of ever-smokers) predicted 70.7% of all LC, increasing LC prediction rate with 89.2% and 18.9% versus the NELSON and 2021 USPSTF, respectively (both < 0.001). CONCLUSIONS: The HUNT LCM was significantly more efficient than the NELSON and 2021 USPSTF criteria, improving the prediction of LC diagnosis, and may be used as a validated clinical tool for screening selection.
10Primary care outreach and decision counseling for lung cancer screening.PubMed
Heather Bittner Fagan, Claudine Jurkovitz, Zugui Zhang, et al.
INTRODUCTION: Lung cancer screening rates are very low despite a level B recommendation from the United States Preventive Services Task Force since 2013 and clear evidence that lung cancer screening reduces mortality. The Center for Medicare and Medicaid Services requires shared decision-making (SDM) for lung cancer screening reimbursement. The objective of this study was to determine the effect of an SDM intervention on lung cancer screening in primary care. METHODS: The study design was a single-arm clinical trial design. The intervention included phone contact outside of a primary care visit and the use of the Decision Counseling Program ®, an online interactive decision aid focused on determining the factors which influence patients to screen or not screen, prioritizing those factors, and determining a decision preference score. The primary outcome was the completion of low-dose computed tomography scan (LDCT) 1 year after the SDM session compared in participants versus nonparticipants. RESULTS: From six practices, there were 1359 potentially eligible patients in electronic medical record data, and 336 were reached to assess eligibility criteria. A total of 80 patients consented to be in the study, 64 completed a decision counseling session and 16 did not complete a session. Among the 64 people who agreed to have decision counseling, 45% had LDCT, higher than typically seen in routine clinical practice. Although not a comparable group, among the 16 people who declined decision counseling, none had LDCT. CONCLUSIONS: Decision counseling is a promising intervention that might support SDM in the context of improving uptake of lung cancer screening in primary care. However, further, larger studies are needed.
11[Lung cancer screening among the smoker population].PubMed
Gaëlle Coureau, Fleur Delva
CONTEXT: Lung cancer is the most common cancer in men and the leading cause of cancer death worldwide. This cancer, often diagnosed at an advanced stage, mainly affects smokers and survival could increase with early detection. Screening by chest x-ray has not shown its effectiveness, then several randomized trials have been carried out about screening by thoracic low-dose computed tomography in smokers. METHODS: A systematic review of these trials was conducted according to the PRISMA criteria as well as a point of the difficulties of setting up screening following these trials. RESULTS: Among five trials that published mortality results, only the US one, the National Lung Screening Trial (NLST) was showed a 20% decrease in lung cancer mortality in smokers screened by low-dose computed tomography compared to chest x-ray. However, besides the lack of power of the other trials, a great heterogeneity of the methods makes the synthesis of the results difficult. While many expert groups are in favor of testing, only the United States has implemented a screening program, whose adherence remains low. CONCLUSION: Many persistent questions about the eligible population, the organization, the side effects, and finally the cost-benefit, need additional research around these issues.
12Benefit-to-radiation-risk of low-dose computed tomography lung cancer screening.PubMed
R Edward Hendrick, Robert A Smith
BACKGROUND: The US National Lung Screening Trial (NLST) and Dutch-Belgian NELSON randomized controlled trials have shown significant mortality reductions from low-dose computed tomography (CT) lung cancer screening (LCS). NLST, ITALUNG, and COSMOS trials have provided detailed dosimetry data for LCS. METHODS: LCS trial mortality benefit results, organ dose and effective dose data, and Biological Effects of Ionizing Radiation, Report VII (BEIR VII) organ dose-to-cancer-mortality risk data are used to estimate benefit-to-radiation-risk ratios of the NLST, ITALUNG, and COSMOS trials. Data from those trials also are used to estimate benefit-to-radiation-risk ratios for longer-term LCS corresponding to scenarios recommended by United States Preventive Services Task Force and the American Cancer Society. RESULTS: Including only screening doses, NLST benefit-to-radiation-risk ratios are 12:1 for males, 19:1 for females, and 16:1 overall. Including both screening and estimated follow-up doses, benefit-to-radiation-risk ratios for NLST are 9:1 for males, 13:1 for females, and 12:1 overall. For the ITALUNG trial, the benefit-to-radiation-risk ratio is 58-63:1. For the COSMOS trial, assuming sex-specific mortality benefits like those of the NELSON trial, the benefit-to-radiation-risk ratio is 23:1. Assuming a conservative 20% mortality benefit, annual screening in people 50-79 years old with a 20+ pack-year history of smoking has benefit-to-radiation-risk ratios of 23:1 (with follow-up doses adding 40% to screening doses) to 29:1 (with follow-up adding 10%) based on COSMOS dose data. CONCLUSIONS: Based on linear, no threshold BEIR VII dose-risk estimates, benefit-to-radiation-risk ratios for LCS are highly favorable. Results emphasize the importance of using modern CT technologies, maintaining low diagnostic follow-up rates, and minimizing both screening and diagnostic follow-up doses. PLAIN LANGUAGE SUMMARY: The benefits of lung cancer screening significantly outweigh estimates of future harms associated with exposure to radiation during screening and diagnostic follow-up examinations. Our findings emphasize the importance of lung cancer screening practices using state-of-the-art computed tomography scanners and specialized low-dose lung screening and diagnostic follow-up techniques.
13Hesitancy around low-dose CT screening for lung cancer.PubMed
J L Dickson, C Horst, A Nair, et al.
Lung cancer is the leading cause of cancer death worldwide. The absence of symptoms in early-stage (I/II) disease, when curative treatment is possible, results in >70% of cases being diagnosed at late stage (III/IV), when treatment is rarely curative. This contributes greatly to the poor prognosis of lung cancer, which sees only 16.2% of individuals diagnosed with the disease alive at 5 years. Early detection is key to improving lung cancer survival outcomes. As a result, there has been longstanding interest in finding a reliable screening test. After little success with chest radiography and sputum cytology, in 2011 the United States National Lung Screening Trial demonstrated that annual low-dose computed tomography (LDCT) screening reduced lung cancer-specific mortality by 20%, when compared with annual chest radiography. In 2020, the NELSON study demonstrated an even greater reduction in lung cancer-specific mortality for LDCT screening at 0, 1, 3 and 5.5 years of 24% in men, when compared to no screening. Despite these impressive results, a call to arms in the 2017 European position statement on lung cancer screening (LCS) and the widespread introduction across the United States, there was, until recently, no population-based European national screening programme in place. We address the potential barriers and outstanding concerns including common screening foes, such as false-positive tests, overdiagnosis and the negative psychological impact of screening, as well as others more unique to LDCT LCS, including appropriate risk stratification of potential participants, radiation exposure and incidental findings. In doing this, we conclude that whilst the evidence generated from ongoing work can be used to refine the screening process, for those risks which remain, appropriate and acceptable mitigations are available, and none should serve as barriers to the implementation of national unified LCS programmes across Europe and beyond.
14Identifying Populations at Risk for Lung Cancer Mortality from the National Health and Nutrition Examination Survey (2001-2018) Using the 2021 USPSTF Screening Guidelines.PubMed
Vivian Tieu, Samuel MacDowell, Sedra Tibi, et al.
Lung cancer (LC) is the leading cause of cancer mortality in the United States. To combat this predicament, early screening and critically assessing its risk factors remain crucial. The aim of this study was to identify the value of specific factors from the National Health and Nutrition Examination Survey (NHANES) from 2001-2018, as they relate to lung cancer mortality in the US Preventive Services Task Force (USPSTF)-eligible population. A total of 3545 adults who met USPSTF criteria were extracted from 81,595 NHANES participants. The LC Death Risk Assessment Tool was used to calculate the number of deaths per 1000 individuals. The Mann-Whitney U test and one-way ANOVA determined the statistical significance of the factors involved in LC mortality. Male sex, African and Hispanic ethnicity, lower education attainment, and secondhand exposure to cigarette smoke correlated with an increased risk of LC mortality. Additionally, the factor of emotional support from NHANES data was analyzed and did not show any benefit to reducing risk. By identifying individuals at high-risk, preventative measures can be maximized to produce the best possible outcome.
15[Lung cancer screening: new frontiers].PubMed
Rimma Kondrashova, Jens Vogel-Claussen
CLINICAL/METHODICAL ISSUE: Lung cancer is the leading cause of cancer-related deaths worldwide. In early, asymptomatic stages, curative treatment is possible, but the disease is often diagnosed too late. STANDARD RADIOLOGICAL METHODS: Lung cancer screening (LCS) using low-dose computed tomography (LDCT) helps to detect potentially malignant lesions in early stages and to reduce lung cancer mortality. METHODOLOGICAL INNOVATIONS: The application of artificial intelligence (AI) algorithms enables a more precise analysis of LDCT scans. PERFORMANCE: A meta-analysis of eight LCS studies revealed a statistically significant 12% relative reduction in lung cancer mortality. ACHIEVEMENTS: Based on strong scientific evidence, a recommendation for a structured lung cancer screening program using LDCT for the high-risk population in Germany was issued. PRACTICAL RECOMMENDATIONS: The holistic LCS program requires a clear definition of the high-risk population, individual risk assessment, qualified personnel for conducting and reading examinations, verification of all diagnostic and therapeutic steps, central documentation and quality assurance, as well as the integration of tobacco cessation programs.
16Low-dose CT screening can reduce cancer mortality: A meta-analysis.PubMed
Xue Tang, Guangbo Qu, Lingling Wang, et al.
OBJECTIVE: Lung cancer is the leading cause of cancer-related death. To reduce lung cancer mortality and detect lung cancer in early stages, low dose CT screening is required. A meta-analysis was conducted to verify whether screening could reduce lung cancer mortality and to determine the optimal screening program. METHODS: We searched PubMed, Web of Science, Cochrane library, ScienceDirect, and relevant Chinese databases. Randomized controlled trial studies with participants that were smokers older than 49 years (smoking >15 years or quit smoking 10 or 15 years ago) were included. RESULTS: Nine RCT studies met the criteria. LDCT screening could find more lung cancer cases (RR=1.58, 95%CI=1.25-1.99, P<0.001) and more stage I lung cancers (RR=3.45, 95%CI=2.08-5.72, P<0.001) compared to chest-X ray or the no screening group. This indicated a statistically significant reduction in lung-cancer-specific mortality (RR=0.84, 95%CI=0.75-0.95, P=0.004), but without a statistically reduction in mortality due to all causes (RR=1.26, 95%CI=0.89-1.78, P=0.193). Annually, LDCT screening was sensitive in finding more lung cancers. CONCLUSIONS: Low-dose CT screening is effective in finding more lung cancer cases and decreasing the deaths from lung cancer. Annual low-dose CT screening may be better than a biennial screening to detect more early-stage lung cancer cases.
17Low-dose computed tomography for lung cancer screening in high-risk populations: a systematic review and economic evaluation.PubMed
Tristan Snowsill, Huiqin Yang, Ed Griffin, et al.
BACKGROUND: Diagnosis of lung cancer frequently occurs in its later stages. Low-dose computed tomography (LDCT) could detect lung cancer early. OBJECTIVES: To estimate the clinical effectiveness and cost-effectiveness of LDCT lung cancer screening in high-risk populations. DATA SOURCES: Bibliographic sources included MEDLINE, EMBASE, Web of Science and The Cochrane Library. METHODS: 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. RESULTS: 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. LIMITATIONS: 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. CONCLUSIONS: 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. FUTURE WORK: 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]. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016048530. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
18Lung Cancer Screening: Evidence, Risks, and Opportunities for Implementation.PubMed
Giulia Tringali, Gianluca Milanese, Roberta Eufrasia Ledda, et al.
BACKGROUND: Lung cancer is the most common cause of cancer death worldwide. Several trials with different screening approaches have recognized the role of lung cancer screening with low-dose CT for reducing lung cancer mortality. The efficacy of lung cancer screening depends on many factors and implementation is still pending in most European countries. METHODS: This review aims to portray current evidence on lung cancer screening with a focus on the potential for opportunities for implementation strategies. Pillars of lung cancer screening practice will be discussed according to the most updated literature (PubMed search until November 16, 2020). RESULTS AND CONCLUSION: The NELSON trial showed reduction of lung cancer mortality, thus confirming previous results of independent European studies, notably by volume of lung nodules. Heterogeneity in patient recruitment could influence screening efficacy, hence the importance of risk models and community-based screening. Recruitment strategies develop and adapt continuously to address the specific needs of the heterogeneous population of potential participants, the most updated evidence comes from the UK. The future of lung cancer screening is a tailored approach with personalized continuous stratification of risk, aimed at reducing costs and risks. KEY POINTS: · Secondary prevention of lung cancer by low-dose computed tomography showed a reduction of lung cancer mortality.. · Semi-automated volume measurement and use of volume doubling time should be the reference method for optimization of risks, namely controlling measurement variability and the false-positive rate.. · A conservative approach with surveillance of subsolid nodules can be one of the strategies to reduce the risk of overdiagnosis and overtreatment.. · The goal of a tailored approach with personalized risk stratification aims to reduce costs and risks. A longer interval between rounds is one option for participants at lower risk.. CITATION FORMAT: · Tringali G, Milanese G, Ledda RE et al. Lung Cancer Screening: Evidence, Risks, and Opportunities for Implementation. Fortschr Röntgenstr 2021; 193: 1153 - 1161.
19Current evidence of low-dose CT screening benefit.PubMed
Rowena Yip, James L Mulshine, Matthijs Oudkerk, et al.
Lung cancer is the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis. Low-dose computed tomography (LDCT) screening has emerged as a powerful tool for early detection, enabling diagnosis at curable stages and reducing lung cancer mortality. Despite strong evidence, LDCT screening uptake remains suboptimal globally. This review synthesizes current evidence supporting LDCT screening, highlights ongoing global implementation efforts, and discusses key insights from the 1st AGILE conference. Lung cancer screening is gaining global momentum, with many countries advancing plans for national LDCT programs. Expanding eligibility through risk-based models and targeting high-risk never- and light-smokers are emerging strategies to improve efficiency and equity. Technological advancements, including AI-assisted interpretation and image-based biomarkers, are addressing concerns around false positives, overdiagnosis, and workforce burden. Integrating cardiac and smoking-related disease assessment within LDCT screening offers added preventive health benefits. To maximize global impact, screening strategies must be tailored to local health systems and populations. Efforts should focus on increasing awareness, standardizing protocols, optimizing screening intervals, and strengthening multidisciplinary care pathways. International collaboration and shared infrastructure can accelerate progress and ensure sustainability. LDCT screening represents a cost-effective opportunity to reduce lung cancer mortality and premature deaths.
20An umbrella review of systematic evidence on the Low Dose Computed Tomography (LDCT) for lung cancer screening.PubMed
Stany Mathew, Gowthaman Thangavel, Praveen Pujar, et al.
AIM: Despite lung cancer's high mortality rate, many countries still lack organized lung cancer screening programs. This review aims to evaluate the impact of low-dose computed tomography (LDCT) screening on lung cancer diagnosis, mortality, and overall clinical outcomes. MATERIALS AND METHODS: Following the Joanna Briggs Institute methodology for umbrella reviews, a comprehensive search was conducted in PubMed, Embase, and the Cochrane Library for reviews published between January 2013 and December 2023. Eligible meta-analyses included studies comparing LDCT screening with chest X-ray (CXR) or no screening, reporting outcomes such as sensitivity, specificity, and lung cancer mortality. The methodological quality of the included reviews was assessed using AMSTAR-2. RESULTS: Out of 801 citations, 14 meta-analyses met the inclusion criteria. LDCT demonstrated high sensitivity (0.97, 95% CI: 0.94-0.98) and specificity (0.87, 95% CI: 0.82-0.91). It significantly increased early-stage lung cancer detection (RR: 1.31, 95% CI: 1.18-1.45) and reduced lung cancer mortality by 18% (RR: 0.82, 95% CI: 0.75-0.90). However, the reduction in all-cause mortality (RR: 0.91, 95% CI: 0.75-1.06) was not statistically significant. Overdiagnosis and false positives remain essential challenges. CONCLUSION: This umbrella review confirms that LDCT screening effectively reduces lung cancer mortality, particularly in high-risk populations.