Lung cancer screening using low-dose CT: The current national landscape

<p>Supplementary Table S1. Leading causes of death among females worldwide, 2012 Number of deaths for top ten causes of death among females worldwide Supplementary Table S2. Leading causes of death among females by world region, 2012 Number of deaths for top ten causes of death among females by world region Supplementary Table S3. Estimated number of new cancer cases and deaths among females by world area, 2012 Number of cancer cases and deaths for all cancer sites combined among females by world region Supplementary Figure S1. Female breast cancer incidence and mortality rates, age-standardized rate (world), 2012 Two world maps: age-standardized breast cancer incidence rates among females and age-standardized breast cancer mortality rates among females Supplementary Figure S2. Female breast cancer incidence trends, age-standardized rate (world), select countries, 1973-2012 Observed age-standardized female breast cancer incidence rates, select countries, all ages, 1973-2012 Supplementary Figure S3. Female breast cancer survivors diagnosed in last five years (through 2012 or latest available) World map: number of breast cancer survivors diagnosed within the last five years, per 100,000 population Supplementary Figure S4. Cervical cancer incidence and mortality rates, age-standardized rate (world), 2012 Two world maps: age-standardized cervical cancer incidence rates and age-standardized cervical cancer mortality rates Supplementary Figure S5. Prevalence (%) of cervical HPV infection among women by region, all types combined, 1995-2009 World map of HPV prevalence (%) among women by world region Supplementary Table S6. Cervical cancer incidence trends, age-standardized rate (world), select countries, 1975-2007 Observed age-standardized cervical cancer incidence rates with a five-year moving average, select countries, all ages, 1975-2007 Supplementary Figure S7. Cervical cancer survivors diagnosed in last five years (through 2012 or latest available) World map: number of cervical cancer survivors diagnosed within the last five years, per 100,000 population Supplementary Figure S8. Uterine corpus cancer incidence and mortality rates, females, age-standardized rate (world), 2012 Two world maps: age-standardized uterine corpus cancer incidence rates and age-standardized uterine corpus cancer mortality rates Supplementary Figure S9. Uterine corpus cancer mortality trends, age-standardized rate (world), select countries, 1990-2014 Observed age-standardized uterine corpus cancer mortality rates with a five-year moving average, select countries, all ages, 1990-2014 Supplementary Figure S10. Ovarian cancer incidence and mortality rates, females, age-standardized rate (world), 2012 Two world maps: age-standardized ovarian cancer incidence rates and age-standardized ovarian cancer mortality rates Supplementary Figure S11. Ovarian cancer mortality trends, age-standardized rate (world), select countries, 1980-2014 Observed age-standardized ovarian cancer mortality rates with a five-year moving average, select countries, all ages, 1980-2014 Supplementary Figure S12. Colorectal cancer incidence and mortality rates, females, age-standardized rate (world), 2012 Two world maps: age-standardized liver cancer incidence rates among females and age-standardized liver cancer mortality rates among females Supplementary Figure S13. Colorectal cancer incidence trends, females, select countries, 1980-2014 Observed age-standardized colorectal cancer incidence rates among females with a five-year moving average, select countries, all ages, 1980-2014 Supplementary Figure S14. Colorectal cancer mortality trends, females, age-standardized rate (world), select countries, 1975-2014 Observed age-standardized colorectal cancer mortality rates among females with a five-year moving average, select countries, all ages, 1975-2014 Supplementary Figure S15. Lung cancer incidence and mortality rates, females, age-standardized rate (world), 2012 Two world maps: age-standardized lung cancer incidence rates among females and age-standardized lung cancer mortality rates among females Supplementary Figure S16. Population using solid fuels for heating and/or cooking, 2013 World map: percent of the population using solid fuels by country Supplementary Figure S17. Adult female smoking prevalence, age 15+ years, 2013 World map: percent of adult females (age 15+ years) who smoke by country, 2013 Supplementary Figure S18. Female youth smoking prevalence, age 13-15 years, 2011 or latest available data World map: percent of female youth (age 13-15 years) who smoke by country, 2011 or latest available data Supplementary Figure S19. Liver cancer incidence and mortality rates, females, age-standardized rate (world), 2012 Two world maps: age-standardized liver cancer incidence rates among females and age-standardized liver cancer mortality rates among females Supplementary Figure S20. Hepatitis B virus prevalence, both sexes, from systematic review of studies 1957-2013 World map of HBV prevalence (%) among both sexes combined by country Supplementary Figure S21. Estimated hepatitis C virus prevalence, both sexes, 2005 World map of HCV prevalence (%) among both sexes combined by country Supplementary Figure S22. Liver cancer mortality trends, females, age-standardized rate (world), select countries, 1995-2014 Observed age-standardized liver cancer mortality rates among females with a five-year moving average, select countries, all ages, 1995-2014</p>

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.

Informing Patient Surveillance for the Growing Number of Survivors of Lung Cancer

Background: Studies on outcomes of lung cancer screening and smoking cessation programs among underserved and ethnic minority populations are scarce. These patients, however, have the greatest potential to benefit from these services. African Americans have the highest incidence and mortality rates for lung cancer, often as a result of multiple factors including factors related to disparities in access to quality care. The aim of this study was to determine clinic utilization rates and smoking cessation practices among underserved and ethnic minority patients referred for paired lung cancer screening and smoking cessation services at a community cancer program. Methods: The Dana-Farber Cancer Institute (DFCI)'s Cancer Care Equity Program (CCEP) added lung cancer screening to the established tobacco treatment arm of its community cancer program, housed in a neighborhood Federally Qualified Community Health Center (FQHC) in 2014. Nearly half (46%) of patients, aged 55 to 77 years who received care at the center in 2015 did not have a recorded smoking history. The paired intervention was offered at no cost to patients. Prospective data approved by the IRB was collected on a secured REDcap database that was designed for the CCEP. Patients referred by primary care providers at the health center had a low-dose computed tomography (LDCT) scan scheduled if they met the U.S. Preventive Services Task Force (USPSTF) criteria for lung cancer screening at their first visit. Concurrently, and at subsequent follow-up visits to review results of LDCT scans, patients who had not quit smoking were encouraged to enroll in the tobacco treatment program (TTP), which is individualized, one-on-one and available in both English and Spanish. A yearly surveillance LDCT plan was established for all participants who had negative scans while those with positive scans (based on American College of Radiology Lung-RADs risk stratification system) received further care at DFCI's main campus. Study outcomes include clinic show rates, smoking status, recommendations for LDCT, attendance at LDCT appointments, willingness to enroll in the TTP, and TTP participation rates. Descriptive statistical analysis on data collected between September 2014 and May 2016 was performed using JMP Pro (version 11, SAS Institute Inc., Cary, NC). Results: Fifty two out of 70 patients referred for lung cancer screening and tobacco treatment presented to the clinic, indicating a no show rate of 26%. Of the 52, 46 (88%) were current smokers. Among 47 (90%) participants who consented to research, mean age was 59.8 years (SD±5.8), 49 % were men, 74% were African American/Black, and 89% were current smokers. Most participants (87%) met the USPSTF criteria and were recommended for LDCT. Of these, 93% attended their appointments and were screened. None of the participants had a positive screen. While 83% of current smokers were screened and 87% initially expressed willingness to enroll in the TTP, only a third (33%) participated in the TTP. Conclusion: Compared to a high percentage of attendance at LDCT screenings, study participants had a low attendance at the TTP despite having expressed willingness to participate in the program. Further studies are needed to elucidate the causative factors for this difference. Additionally, the impressive utilization of a free LDCT service by patients who were referred when compared to the much larger number of patients who would fit into the criteria who were not referred, underscores the importance of mitigating health disparities by improving access to care. Efforts should be made to improve smoking-history taking in order to identify and appropriately refer eligible underserved candidates who might benefit from lung cancer screening and tobacco treatment. Citation Format: Ruth N. Akindele, Ludmila A. Svoboda, Sabrina G. Gonzalez, Christopher S. Lathan. Clinic utilization and smoking cessation practices among ethnic minority patients referred for paired lung cancer screening and tobacco treatment services at a community cancer program. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C52.

Low-dose computed tomography (CT) screening was shown to reduce lung cancer-specific mortality in a large randomized trial of a high-risk population. The decision to pursue CT screening for lung cancer is a timely question raised by individuals at risk of lung cancer and by their health care practitioners. To discuss the evidence for use of chest x-rays and low-dose CT in screening for lung cancer; to describe potential benefits, harms, and uncertainties of CT screening; and to review current guidelines for CT screening. MEDLINE and the Cochrane Library were searched from 1984 to 2012. Additional citations were obtained from lists of references from select research and review articles on this topic. Evidence was graded using the American Hospital Association level of evidence guidelines. Low-dose CT screening has been associated with a 20% reduction in lung cancer mortality in a large randomized controlled trial (National Lung Screening Trial [NLST]) of a high-risk population. Mortality data have not yet been reported for 5 other randomized controlled trials, and the sample sizes were too small to detect a meaningful difference in 2 other completed trials. A major risk of CT screening is a high false-positive rate, with associated risks and costs associated with follow-up CT scans and the potential for more invasive diagnostic procedures. Published guidelines for screening indicate a consensus that screening may be indicated for individuals who meet entry criteria for the NLST, but some guidelines expand their recommendations for screening beyond these criteria. Individuals at high risk of lung cancer who meet the criteria for CT screening in published guidelines should participate in an informed and shared decision-making process by discussing the potential benefits, harms, and uncertainties of screening with their physicians.

Since the publication of the National Lung Screening Trial (NLST) in 2011 demonstrating a 20% reduction in lung cancer-specific mortality by annual low-dose CT (LDCT),1 implementation of screening has continued apace in the USA. Other developed nations, perhaps mindful of the potential cost implications of national screening programmes, have been more reticent, with many awaiting the final outcome data from the largest European randomised trial—the Dutch-Belgian Lung Cancer Screening trial (NELSON) study which remains in follow-up.2 Despite the convincing mortality reduction in NLST, questions remain about implementation of LDCT screening for lung cancer. Unresolved issues include how to best identify high-risk individuals for screening, what is the most appropriate screening interval to achieve an optimal balance between mortality reduction and cost-effectiveness and how to minimise possible harms associated with screening—particularly overdiagnosis. This issue of Thorax includes two papers which provide important additions to accumulating evidence in this field. Paci and colleagues3 report lung cancer incidence and mortality rates from the Italian Lung Cancer Screening Trial (ITALUNG) randomised lung cancer screening trial conducted in Tuscany, Italy, commencing in 2004. From an invited population of over 71 232 subjects aged 55–69 years, 1613 were randomised to four rounds of annual LDCT screening and 1593 to usual care. Like many of the other European screening studies, ITALUNG was not powered to demonstrate mortality reduction in isolation, and pooled analysis with other similarly designed randomised trials is planned. As expected, lung cancer incidence was higher in the intervention group during the 4-year screening period (55% excess diagnoses vs usual care group). However, this was followed by a compensatory reduction in diagnoses during the 5-year follow-up period, such that there was no significant difference in incidence rates between the groups at the end of the study. After a median follow-up of 9 years, the authors report …

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

COMPUTED TOMOGRAPHY (CT) SCANNING, WHICH WAS introduced for imaging the head in 1972 and became widely available for imaging the rest of the body by the early 1980s, has revolutionized the practice of medicine and surgery. This technology, for which the Nobel Prize was awarded in 1979, has been used to diagnose and guide the management of diseases affecting every part of the body, improving quality of life and saving countless lives. Two articles in this issue of JAMA, however, point out the complexities involved in deciding whether to extend the use of CT scanning from diagnosis to screening and in determining whether the current use of CT scanning is appropriate or excessive. As the value of CT scanning as a diagnostic tool became clear, it was natural to consider a potential role for this technology to screen for subclinical disease amenable to early intervention. The potential benefits of such screening must, of course, be weighed against the risks and costs. The risk that the ionizing radiation exposure from medical diagnostic tests will cause cancer appears to be small but not zero. Ionizing radiation causes DNA double-strand breaks that are repaired imperfectly, potentially leading to mutations and consequent cancers. An analysis of data from 15 countries has led to the estimate that from 0.6% to 3.2% of cancer diagnosed to age 75 years may be attributable to diagnostic x-rays, including CT scans, although these calculations involved assumptions subject to considerable uncertainty. Another risk of screening is the occurrence of falsepositive findings that may lead to adverse psychological effects on patients as well as physical harm caused by diagnostic procedures undertaken to investigate the findings. Moreover, CT scans are expensive, as are the diagnostic procedures performed to evaluate abnormalities detected. In this issue of JAMA, Bach and colleagues report the results of their systematic review of randomized clinical trials (RCTs) and cohort studies addressing the benefits and risks of screening for early-stage lung cancer using low-dose CT (LDCT) scans. The authors focus on lung cancer–specific and all-cause mortality outcomes in RCTs, avoiding the mistaken inferences that can result from lead-time bias, lengthbiased sampling, and overdiagnosis with other outcomes and designs. Their review yielded only 3 RCTs from which valid inferences can be drawn concerning the effect of LDCT screening for lung cancer among current or former smokers aged 50 years or older. Of these 3 studies, the National Cancer Institute’s National Lung Screening Trial (NLST) was by far the largest and most persuasive, driving the authors’ conclusion that lung cancer mortality is reduced by LDCT screening of adults meeting the NLST entry criteria: age 55 to 74 years, current or former smokers, 30 or more pack-years, and still smoking or having done so within the past 15 years. The good news of a mortality benefit is tempered by some of the specifics. In the NLST, the number needed to screen to prevent 1 lung cancer death was 320 persons undergoing 3 annual LDCTs. Across all studies reviewed, the average rate of detecting nodules per round of screening was 20%, and more than 90% of these nodules turned out to be benign, leading to substantial follow-up testing including invasive procedures. Combining screening and follow-up diagnostic scans, the estimated mean 3-year radiation exposure of NLST participants in the screening group was 8 mSv, which Bach et al estimate would cause 1 cancer death per 2500 persons screened, although this death would likely occur many years later. The heterogeneity in nodule detection rate both among NLST sites and among the other studies reviewed by Bach et al, and the inconsistent mortality results of the 2 smaller RCTs, add a measure of uncertainty to the estimated benefit that would be obtained from broad application of LDCT screening. Nevertheless, the estimates of the benefits and risks of LDCT screening for lung cancer derived from the NLST are the best information currently available. The American College of Chest Physicians, the American Society of Clinical Oncology, and the American Thoracic Society have endorsed an evidence-based practice guideline, included as an online appendix to the article by Bach et al, rec-

The last 5 years have been a busy time for lung cancer screening. In 2010, results from the National Lung Screening Trial were announced: the trial demonstrated that annual screening with low dose computed tomography (LDCT) led to a 20% reduction in lung cancer mortality for individuals aged 55 to 74 years who had a smoking history of at least 30 pack-years, and if former smokers, had quit within 15 years of enrollment (1). And in 2011, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial reported no reduction in lung cancer mortality with annual single view chest X-ray screening in either ever or never smokers (2). The results of the trials are generally accepted to have definitively answered two questions that had the subject of much debate over the years. When it comes to lung cancer screening, chest X-ray doesn’t work, but LDCT does.

The National Lung Screening Trial (NLST) demonstrated a reduction in lung cancer and all-cause mortality with low-dose CT (LDCT) screening. The aim of our study was to examine the time to diagnosis (TTD) of lung cancer in the LDCT arm of the NLST and assess its relationship with cancer characteristics and survival. The subjects (N = 462) with a positive baseline screen and subsequent lung cancer diagnosis within 3years were evaluated by data and image review to confirm the baseline abnormality. The cases were analysed for the relationship between TTD and imaging features, cancer type, stage and survival for 7years from baseline screen. Cancer was judged to be present at baseline in 397/462 cases. The factors that showed significant association (p value trend less than 0.05) with longer TTD included smaller nodule size, pure ground glass nodules (GGNs), smooth/lobulated margins, stages I/II, adenocarcinoma, and decreasing lung cancer mortality. The logistic regression model for lung cancer death showed significant inverse relationships with size less than 20mm (OR = 0.32), pure GGNs (OR = 0.24), adenocarcinoma (OR = 0.57) and direct relationship with age (OR = 1.4). TTD after a positive LDCT screen in the NLST showed a strong association with imaging features, stage and mortality. • NLST observed variable time to lung cancer diagnosis from positive baseline screen. • Time to diagnosis was associated with imaging features, cancer type and stage. • In univariate but not multivariate analysis, longer TTD correlated with decreased mortality.

Context: Lung cancer is the leading cause of cancer death. Most patients are diagnosed with advanced disease, resulting in a very low 5-year survival. Screening may reduce the risk of death from lung cancer. Objective: To conduct a systematic review of the evidence regarding the benefits and harms of lung cancer screening using low-dose computed tomography (LDCT). A multisociety collaborative initiative (involving the American Cancer Society, American College of Chest Physicians, American Society of Clinical Oncology, and National Comprehensive Cancer Network) was undertaken to create the foundation for development of an evidence-based clinical guideline. Data Sources: MEDLINE (Ovid: January 1996 to April 2012), EMBASE (Ovid: January 1996 to April 2012), and the Cochrane Library (April 2012). Study Selection: Of 591 citations identified and reviewed, 8 randomized trials and 13 cohort studies of LDCT screening met criteria for inclusion. Primary outcomes were lung cancer mortality and all-cause mortality, and secondary outcomes included nodule detection, invasive procedures, follow-up tests, and smoking cessation. Data Extraction: Critical appraisal using predefined criteria was conducted on individual studies and the overall body of evidence. Differences in data extracted by reviewers were adjudicated by consensus. Results: Three randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality, of which the National Lung Screening Trial was the most informative, demonstrating that among 53 454 participants enrolled, screening resulted in significantly fewer lung cancer deaths (356 vs 443 deaths; lung cancer−specific mortality, 274 vs 309 events per 100 000 person-years for LDCT and control groups, respectively; relative risk, 0.80; 95% CI, 0.73-0.93; absolute risk reduction, 0.33%; P = .004). The other 2 smaller studies showed no such benefit. In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20% of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1% had lung cancer. There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions. Major complications in those with benign conditions were rare. Conclusion: Low-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results.

The National Lung Screening Trial (NLST) demonstrated that screening with low-dose computed tomography (LDCT) is associated with a 20% reduction in lung cancer mortality. One potential limitation of LDCT screening is overdiagnosis of slow growing and indolent cancers. In this study, peritumoral and intratumoral radiomics was used to identify a vulnerable subset of lung patients associated with poor survival outcomes. Incident lung cancer patients from the NLST were split into training and test cohorts and an external cohort of non-screen detected adenocarcinomas was used for further validation. After removing redundant and non-reproducible radiomics features, backward elimination analyses identified a single model which was subjected to Classification and Regression Tree to stratify patients into three risk-groups based on two radiomics features (NGTDM Busyness and Statistical Root Mean Square [RMS]). The final model was validated in the test cohort and the cohort of non-screen detected adenocarcinomas. Using a radio-genomics dataset, Statistical RMS was significantly associated with FOXF2 gene by both correlation and two-group analyses. Our rigorous approach generated a novel radiomics model that identified a vulnerable high-risk group of early stage patients associated with poor outcomes. These patients may require aggressive follow-up and/or adjuvant therapy to mitigate their poor outcomes.

PURPOSE:The National Lung Screening Trial demonstrated a 20% relative reduction in lung cancer mortality with low-dose computed tomography screening, leading to implementation of lung cancer screening across the United States. The Centers for Medicare and Medicaid Services approved coverage, but questions remained about effectiveness of community-based screening. To assess screening implementation during the first full year of CMS coverage, we surveyed a nationwide network of lung cancer screening centers, comparing results from academic and nonacademic centers.METHODS:One hundred sixty-five lung cancer screening centers that have been designated Screening Centers of Excellence responded to a survey about their 2016 program data and practices. The survey included 21 pretested, closed- and open-ended quantitative and qualitative questions covering implementation, workflow, numbers of screening tests completed, and cancers diagnosed.RESULTS:Centers were predominantly community based (62%), with broad geographic distribution. In both community and academic centers, more than half of lung cancers were diagnosed at stage I or limited stage, demonstrating a clear stage shift compared with historical data. Lung-RADS results were also comparable. There are wide variations in the ways centers address Centers for Medicare and Medicaid Services requirements. The most significant barriers to screening implementation were insurance and billing issues, lack of provider referral, lack of patient awareness, and internal workflow challenges.CONCLUSION:These data validate that responsible screening can take place in a community setting and that lung cancers detected by low-dose computed tomography screening are often diagnosed at an early, more treatable stage. Lung cancer screening programs have developed different ways to address requirements, but many implementation challenges remain.

Introduction: Low-dose computed tomography (LDCT) screening can reduce lung cancer (LC)-related mortality, but questions remain about the duration of this effect and differences by sex and tumor histology. Methods: Extended follow-up data from the ITALUNG and LUSI trials were pooled to examine screening-related tumor stage-shifts and to estimate relative hazards for LC-related mortality, by sex and histology. Findings were compared to, and additionally combined with, those from the US National Lung Screening Trial (NLST). Results: In ITALUNG-LUSI, screening yielded a 30% reduction of overall LC mortality up to 8 years after final screening (dilution-adjusted HR=0.70[0.51-0.96]). This reduction, however, was more pronounced for women (HR=0.49[0.25-0.96]) than men (HR=0.78[0.54-1.11]), which was confirmed in combined data of ITALUNG-LUSI plus NLST (6 years post-screening, women: HR=0.74[0.61-0.90], men: HR=0.93[0.80-1.06]; pheterogeneity=0.06). Analyses of stage-shifts and relative mortality hazards suggested that screening reduced mortality by non-small cell and non-squamous tumors in both sexes. In women (18-20%), more than among men (5-9%), screening also resulted in frequent detection of adenocarcinomas with lepidic growth. Finally, in both ITALUNG-LUSI and NLST, LDCT screening reduced the incidence and mortality for small-cell lung cancer (SCLC) among women (HR=0.63[0.43-0.94], all trials combined) but not among men (pheterogeneity=0.04). Conclusion: LC-related mortality reduction by LDCT screening may last until 8 or more years after cessation, and appears to be stronger for women than men, due to reduced incidence and mortality of SCLC in women only. The latter might be caused by removal of (likely EGFR-mutated, and slowly growing) adenomatous precursor lesions that over time would transform into SCLC (lineage plasticity). These findings may have major implications for the optimization of screening programs in terms of eligibility criteria and screening intervals Citation Format: Rudolf Kaaks, Francisco O. Cortès-Ibañez, Stefan Delorme, Erna Motsch, Verena Katzke, Claus-Peter Heussel, Hans-Ulrich Kauczor, Giulia Picozzi, Giuseppe Gorini, Francesca Maria Carozzi, Laura Carrozzi, Eugenio Paci, Donella Puliti, Mario Mascalchi. Effectiveness of lung cancer screening by sex and tumor histology: Extended, pooled analysis of the ITALUNG and LUSI trials, with comparison to findings in the NLST [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7409.

Lung cancer is the leading cause of cancer-related deaths in Europe, with low survival rates primarily due to late-stage diagnosis. Early detection can significantly improve survival rates, but lung cancer screening is not currently implemented in Italy. Many countries have implemented lung cancer screening programs for high-risk populations, with studies showing a reduction in mortality. This review aimed to identify key areas for establishing a lung cancer screening program in Italy. A literature search was conducted in October 2022, using the PubMed and Scopus databases. Items of interest included updated evidence, approaches used in other countries, enrollment and eligibility criteria, models, cost-effectiveness studies, and smoking cessation programs. A literature search yielded 61 scientific papers, highlighting the effectiveness of low-dose computed tomography (LDCT) screening in reducing mortality among high-risk populations. The National Lung Screening Trial (NLST) in the United States demonstrated a 20% reduction in lung cancer mortality with LDCT, and other trials confirmed its potential to reduce mortality by up to 39% and detect early-stage cancers. However, false-positive results and associated harm were concerns. Economic evaluations generally supported the cost-effectiveness of LDCT screening, especially when combined with smoking cessation interventions for individuals aged 55 to 75 with a significant smoking history. Implementing a screening program in Italy requires the careful consideration of optimal strategies, population selection, result management, and the integration of smoking cessation. Resource limitations and tailored interventions for subpopulations with low-risk perception and non-adherence rates should be addressed with multidisciplinary expertise.