Annual CT Screening Research Articles

Combination Diagnostics: Adding Blood-Based ctDNA Screening to Low-Dose CT Imaging for Early Detection of Lung Cancer.

Annual low-dose CT screening of individuals with a smoking history identifies early curable lung tumors and reduces cancer mortality by 20%, yet only a minority of eligible patients undergo such monitoring. Mazzone and colleagues apply a blood-based cfDNA fragmentomic assay as a high-sensitivity/low-specificity pre-screen to help stratify individuals who may benefit most from more definitive low-dose CT imaging. See related article by Mazzone et al., p. 2224.

P4.04D.04 Efficiency of the Annual CT Screening Interval for Those at a Lower Risk of Lung Cancer - A CISNET Comparative Modelling Study

P4.04D.04 Efficiency of the Annual CT Screening Interval for Those at a Lower Risk of Lung Cancer - A CISNET Comparative Modelling Study

Invitation strategies and participation in a community-based lung cancer screening programme located in areas of high socioeconomic deprivation

IntroductionAlthough lung cancer screening is being implemented in the UK, there is uncertainty about the optimal invitation strategy. Here, we report participation in a community screening programme following a population-based...

Comparative effectiveness of different hepatocellular carcinoma screening intervals or modalities: a systematic review and meta-analysis.

Current guidelines recommend hepatocellular carcinoma (HCC) screening in high-risk populations. However, the ideal HCC screening interval and screening modality have not been determined. This study aimed to compare the screening efficacy among different modalities with various intervals. PubMed and other nine databases were searched through June 30, 2021. Binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs). Survival rates were also pooled using RR with 95% CIs because most eligible studies only provided the number of survival patients instead of hazard ratio. In all, 13 studies were included. Two random controlled trials (RCTs) and six cohort studies compared screening intervals for ultrasonography (US) screening and found no significant differences between shorter (3- or 4-month) and longer (6- or 12-month) screening intervals in terms of early HCC proportion, HCC significant mortality, 1-year survival rate; screening at 6-month interval significantly increased the proportion of early HCC (RR = 1.17, 95% confidence interval [CI]: 1.08-1.26) and prolonged the 5-year survival rate (RR = 1.39, 95% CI: 1.07-1.82) relative to the 12-month interval results. Three other RCTs and two cohort studies compared different screening modalities in cirrhosis or chronic hepatitis B, which indicated no statistical differences in the proportion of early HCC (RR = 0.89, 95% CI: 0.40-1.96) and HCC mortality (RR = 0.69, 95% CI: 0.23-2.09) between the biannual US and annual computed tomography (CT screening). Biannual US screening showed a lower proportion of early HCC than biannual magnetic resonance imaging (MRI) (RR = 0.60, 95% CI: 0.37-0.97) and biannual US combined with annual CT (RR = 1.31, 95% CI: 1.13-1.51) screening. The proportion of early HCC in the contrast-enhanced US group was slightly higher than that in the B-mode US (RR = 1.08, 95% CI: 1.00-1.23) group. The evidence suggests that 6 months may be the best HCC screening interval for US screening. The effectiveness of CT and MRI is better than US during same screening intervals. However, MRI and CT are more expensive than US, and CT also can increase the risk of radiation exposure. The selection of CT or MRI instead of US should be carefully considered. No. CRD42020148258 at PROSPERO website ( https://www.crd.york.ac.uk/PROSPERO/ ).

EP01.04-006 Clinical Scores, Biomarkers and It Tools in Lung Cancer Screening - Can an Integrated Approach Overcome Current Challenges?

Lung cancer (LC) is the leading cause of cancer related mortality. One reason is that still more than two thirds of patients are diagnosed with advanced disease. Cigarette smoking is the most important risk factor (RF). Recent LC screening studies demonstrated that annual low dose chest CT (LDCT) screening can reduce LC related mortality. Challenges still exist with LDCT based LC screening like optimal selection of individuals for LC screening programs, personalization of screening intervals, specification of individualized follow up intervals for nodule management or the detection of incidental findings

Determining cost-effectiveness of lung cancer screening in urban Chinese populations using a state-transition Markov model

ObjectivesThis study analyses the cost-effectiveness of annual low-dose CT (LDCT) screening of high-risk cancer populations in Chinese urban areas.DesignWe used a Markov model to evaluate LDCT screening from a sociological...

Microsimulation modeling of extended annual CT screening among lung cancer cases in the National Lung Screening Trial

PurposeTo microsimulate the effects of three additional annual CT screening rounds on lung cancer (LC) survival in the National Lung Screening Trial (NLST). MethodsWe used multiple imputation to model the effect of additional screening in the full NLST cohort on the time to LC diagnosis and on LC death in those participants who were diagnosed with LC by the end of NLST. Nodule growth models were derived from a Dutch in-vivo study. Microsimulations were repeated 500 times. The method was validated by simulating three rounds of CT screening in the original chest radiography (CXR) cohort. The times up to which the simulations remained within the 95 % confidence bands of the CT cohort’s original results were used to estimate the validity of the results in the CT cohort with three additional simulated screening rounds. ResultsValidation of the simulation approach on the CXR cohort resulted in a LC mortality reduction which remained well within the 95 % confidence intervals of the original CT cohort up to 6.5 years after the start of simulations. Simulating additional CT screening in the CT cohort led to LCs being diagnosed earlier than originally, resulting in a relative risk reduction in LC mortality of 11 % (95 % confidence bands, 7 %–14 %) at 6.5 years. This is equivalent to preventing 71 % (48 %–94 %) more LC deaths than the original CT cohort achieved in comparison to the original CXR cohort. ConclusionThree additional annual CT screening rounds in the NLST may have led to substantial further LC mortality reduction.

Psychosocial consequences of a three-month follow-up after receiving an abnormal lung cancer CT-screening result: A longitudinal survey

BackgroundParticipation in lung cancer CT-screening can be associated with a need for follow-up procedures. The screening and waiting for test results introduce the risk of experiencing psychosocial consequences. Therefore, the aims of this study were: 1) To investigate if the psychosocial consequences changed from before an annual screening round to before a three-month follow-up CT-scan in participants with a positive screening result.2) To investigate potential differences in psychosocial consequences between false positives (FP) and true positives (TP). FP were defined as those where cancer was not confirmed in the follow-up CT-scan and TP where it was. Materials and Methods: This longitudinal study was based on data from the Danish Lung Cancer Screening Trial (DLCST). The Consequences of Screening – Lung cancer (COS-LC) questionnaire was used to measure psychosocial consequences among 130 participants who all received an abnormal CT-screening result at their annual screening round. Eligible participants completed the COS-LC before their annual CT-screening and before the three-month follow-up. ResultsWe found a statistically significant increase in negative psychosocial consequences between the annual lung cancer CT-screening and the three-month follow-up CT-scan in four of nine psychosocial scales; Sense of dejection, Self-blame, Focus on airway symptoms and Harm of smoking. Furthermore, an increase, however not statistically significant, was identified in all remaining scales, except for the scale Stigmatisation which was slightly decreased. We found no evidence of an association between psychosocial consequences and diagnostic groups, FP and TP.Conclusions: An increase in negative psychosocial consequences was observed between the annual lung cancer CT-screening and the three-month follow-up CT-scan. Since we found no statistically significant difference between the diagnostic groups, the increase in negative psychosocial consequences is interpreted as a nocebo effect of living three months in uncertainty not knowing if one’s positive CT-screening result was true or false.

The Incidence and Risk Analysis of Lung Cancer Development in Patients with Chronic Obstructive Pulmonary Disease: Possible Effectiveness of Annual CT-Screening.

PurposeLung cancer is a serious complication in patients with chronic obstructive pulmonary disease (COPD) and accounts for approximately 15% of deaths in patients with COPD. However, with the exception of emphysema, few reports to date have been published on the factors that predict lung cancer development in COPD patients. It has been reported that patients with COPD develop lung cancer at a rate of 0.8% - 1.7%/year, but the incidence may be higher in the Japanese population. Therefore, we investigated the incidence of lung cancer and the lung cancer mortality rate in Japanese COPD patients, as well as factors that are associated with the development of lung cancer in COPD patients.Patients and MethodsWe followed up 224 patients with stable COPD and performed CT examinations at least once per year. The incidence of lung cancer was recorded and data at enrollment were compared with data of the group that did not develop lung cancer.ResultsOver a median follow-up period of 4.58 years, lung cancer was newly diagnosed in 19 patients; the incidence of lung cancer in this population was 1.85%/year. Patients who developed lung cancer had more severe emphysema assessed by CT and GOLD classification and were more likely to be current smokers than those who did not develop lung cancer. No other significant differences were observed between these two groups. Mortality was significantly increased in patients who developed lung cancer compared with those who did not.ConclusionIn COPD patients, the incidence of lung cancer is higher and the development of lung cancer worsens the prognosis; however, lung cancer development is unpredictable and attention should be paid to all patients. Annual CT screening is important for early detection of lung cancer.

183. chlamydia Trachomatis Seroprevalence with a pgp3 Serologic Assay and Association with Pelvic Inflammatory Disease Among Women, United States, 2013–2016

Background Chlamydia trachomatis (CT) causes pelvic inflammatory disease (PID) and other sequelae; however, these associations are not fully characterized. CT serologic assays including Pgp3 ELISA may detect prior CT infection and may better elucidate these associations. We used a serologic Pgp3 multiplex bead array assay (Pgp3MBA) to measure CT seroprevalence in reproductive-age US women and assess the association with PID.MethodsWe performed CT Pgp3MBA on sera collected from women 18–39 years old during the 2013–2016 cycles of the National Health and Nutrition Examination Survey (NHANES) who had available urine CT nucleic acid amplification test results. Weighted Pgp3MBA CT seroprevalence and 95% confidence intervals (95% CI) were calculated. We also determined weighted prevalence ratios (PRs) and 95% CIs of self-reported lifetime PID among women with and without detectable Pgp3MBA and other characteristics to estimate these US national statistics.ResultsAmong 2,339 women, 1,725 (73.7%) had available sera. Of these women, 1,425 (or 93.4% of those with data) were sexually experienced and had a CT seroprevalence of 35.9% (95% CI 33.4–38.4). When weighted for US women, CT seroprevalence was 30.5% (95% CI 26.6–34.4%), ranging from 16.9% (95% CI 11.0–22.8%) among non-Hispanic Asian women to 70.2% (95% CI 62.4–78.0%) among non-Hispanic black women.PID was reported by 4.2% (95% CI 3.1–5.2) of 1,413 sexually-experienced women with PID data or an estimated 3.8% (95% CI 2.6–5.0) of US women. Among US women, estimated PID varied by Pgp3MBA status; 7.3% (95% CI 4.3–10.2) of Pgp3MBA-positive women were estimated to report PID versus 2.3% (95% CI 1.3–3.4) of Pgp3MBA-negative women (PR 3.1; 95% CI 1.7–5.9). PID prevalence did not vary by age, nor self-reported recent sexually transmitted disease among US women, but was higher among non-Hispanic black women compared to non-Hispanic white women (PR 2.2; 95% CI 1.4–3.5).ConclusionNearly one-third of US women have had CT by Pgp3MBA, with differences by race/ethnicity. Women with prior CT had three times the reported PID prevalence of women without CT. Further serologic research may refine the population-level impact of CT prevention activities, such as recommended annual CT screening, on PID incidence, particularly among non-Hispanic black women.Disclosures All Authors: No reported disclosures

Abstract 4609: TP53, PIK3CA, and BRAF somatic mutations in airway epithelial field of injury associated with lung cancer risk

Abstract Background: Lung cancer is the leading cause of cancer-related death in men and women, and cigarette smoking is the most significant preventable risk factor. Early detection through annual low dose CT screening reduces mortality but has low positive predictive value and specificity, in part due to low lung cancer incidence (<10%) among those who currently meet screening criteria. Thus, there is a need for biomarkers that reliably detect those at highest lung cancer risk, thereby enabling more effectivescreening. The purpose of this study was to test the hypothesis that high risk for lung cancer is characterized by high prevalence of low variant allele frequency (VAF) somatic mutations among known lung cancer driver genes in normal airway epithelial cells (AEC). Methods: Synthetic DNA internal standards (IS) were prepared for each of 11 lung cancer driver genes and mixed with each AEC genomic (g)DNA specimen prior to competitive multiplex PCR amplicon NGS library preparation. A custom Perl script was developed to separate IS reads and respective specimen gDNA reads from each target into separate files for parallel variant frequency analysis. This approach enabled reliable detection of mutations with VAF as low as 5 x 10-4 (0.05%). This method was then applied in a retrospective case-control study. Specifically, AEC specimens were collected by bronchoscopic brush biopsy from the normal airways of 19 subjects, including eleven lung cancer cases and eight non-cancer controls, and the association of lung cancer risk with AEC driver gene mutations was tested. Results: TP53 mutations with 0.05-1.0% VAF were more prevalent (p<0.005) and significantly more enriched for tobacco smoke and age-associated mutation signatures in AEC from lung cancer cases compared to non-cancer controls matched for smoking and age. Further, PIK3CA and BRAF mutations in this VAF range were identified in AEC from cases but not controls. Conclusions: Measurement of very low frequency mutations in the 0.05-1.0% VAF range enabled identification of an AEC somatic mutation field of injury associated with lung cancer risk. A biomarker comprising TP53, PIK3CA, and BRAF somatic mutations may better stratify individuals for optimal lung cancer screening and prevention outcomes. Citation Format: Daniel J. Craig, Thomas Morrison, Sadik Khuder, Erin L. Crawford, Leihong Wu, Joshua Xu, Thomas M. Blomquist, James C. Willey. TP53, PIK3CA, and BRAF somatic mutations in airway epithelial field of injury associated with lung cancer risk [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4609.

Predictors of Lung Cancer Screening Utilization in a Population-Based Survey.

Annual low-dose CT (LDCT) screening in high-risk individuals has been recommended to detect lung cancer earlier and reduce mortality. The objective of this study was to identify demographic, financial, and health care factors associated with screening uptake in a population-based survey. Data from the Lung Cancer Screening Module and core modules of the 2017 Behavioral Risk Factor Surveillance System, a population-based survey administered via cell phone and landline, were analyzed to examine demographic, health, and financial factors associated with screening uptake among the 10 states that administered the screening module. Weighted frequencies and confidence intervals (CIs) were produced, and weighted Wald χ2 tests were used to compare differences in screening utilization by patient characteristics. A multivariate logistic mixed-effects model was constructed, in which participant clustering by state was accounted for with a random intercept. The uninsured were less likely to undergo LDCT screening (odds ratio [OR], 0.28; 95% CI, 0.12-0.65). LDCT screening uptake was higher for participants with chronic respiratory conditions (OR, 4.14; 95% CI, 2.33-7.35); those who were divorced, separated, widowed, or refused to answer (OR, 1.41; 95% CI, 1.05-1.86); those who had previous cancer diagnoses (OR, 1.90; 95% CI, 1.40-2.56); and those aged 65 to 69 years (OR, 1.23; 95% CI, 1.06-1.44) or 70 to 74 years (OR, 1.17; 95% CI, 1.00-1.37). Utilization also varied significantly across states. Having a related health condition whereby participants were sensitized to the benefits of early screening (ie, another cancer diagnosis, presence of chronic respiratory conditions) and having insurance coverage were associated with higher LDCT screening uptake. Providers should engage LDCT-eligible patients through informed and shared decision making to increase preference-sensitive screening decisions.

Spirometry performed as part of the Manchester community-based lung cancer screening programme detects a high prevalence of airflow obstruction in individuals without a prior diagnosis of COPD

BackgroundCOPD is a major cause of morbidity and mortality in populations eligible for lung cancer screening. We investigated the role of spirometry in a community-based lung cancer screening programme.MethodsEver smokers,...

Extent of implementation of low-dose CT in lung cancer screening.

e19177 Background: Lung cancer is the leading cause of cancer deaths in the United States with only 15% alive 5 years after diagnosis. In 2013, USPSTF recommended annual screening for LDCT in high risk individuals. Studies had shown a 20% lower mortality (NELSON trial showed significantly lower lung cancer mortality) with LDCT screening. We aimed to assess the extent to which the guideline for lung cancer screening is being adopted in a community clinic. Methods: A retrospective review of electronic medical record of patients aged 55-80 years with no history of lung cancer who visited a primary care provider in a community clinic in New Jersey from October 2014- December 2019 was done. All records with any form of documentation of smoking were identified electronically. The records of those meeting the criteria (30 pack-year smoking history and currently smoking or have quit within the past 15 years) were reviewed manually to check 1) whether they are eligible for screening, 2) if eligible whether low dose CT has been recommended by the provider and 3) once recommended has it been done and followed by the patients. Results: 359 individuals with documented smoking history were identified. Of those 38.8 % (139/359) had a proper documentation (includes both PPD and number of years of smoking) of smoking history based on which high risk individuals could be identified. Of those 37 individuals met the criteria for lung cancer screening. 62% (23/37) had CT chest ordered at some point of time (16.2% for a different indication and the rest for lung cancer screening). Only 52.2% (12/23) of the patients followed the recommendations and got a LDCT done. Among those 50% (6/12) had follow up CT, 50 % (3/6) of those did it on a regular annual basis while the rest 50% (3/6) did it irregularly. 3 patients followed the annual CT screening for lung cancer. Conclusions: Based on these we note that almost half a decade since the recommendation has been established only a small proportion received the care and a still smaller minority followed it. It reflects the dearth of information regarding the guideline among providers and the lack of awareness of the need to follow among patients. This puts forward need for further interventions for implementation of the guidelines at all levels of care for lung cancer prevention. Measures include analyzing the areas of deficiency through questionnaires for patients and providers. Creating awareness on the need for accurate documentation of smoking history and the impact it can have on care delivered. Educating patients about the benefits in health outcome by following the recommendations.

Direct and indirect healthcare costs of lung cancer CT screening in Denmark: a registry study

IntroductionA study based on the Danish Randomised Controlled Lung Cancer Screening Trial (DLCST) calculated the healthcare costs of lung cancer screening by comparing costs in an intervention group with a...

Low-dose CT screening can reduce cancer mortality: A meta-analysis.

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. 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. 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. 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.

Attending community-based lung cancer screening influences smoking behaviour in deprived populations

ObjectivesThe impact of lung cancer screening on smoking is unclear, especially in deprived populations who are underrepresented in screening trials. The aim of this observational cohort study was to investigate whether a community-based lung cancer screening programme influenced smoking behaviour and smoking attitude in socio-economically deprived populations. Material and MethodsEver-smokers, age 55–74, registered at participating General Practices were invited to a community-based Lung Health Check (LHC). This included an assessment of respiratory symptoms, lung cancer risk (PLCOm2012), spirometry and signposting to stop smoking services. Those at high risk (PLCOM2012≥1.51%) were offered annual low-dose CT screening over two rounds. Self-reported smoking status and behaviour were recorded at the LHC and again 12 months later, when attitudes to smoking were also assessed. Results919 participants (51% women) were included in the analysis (77% of attendees); median deprivation rank in the lowest decile for England. At baseline 50.3% were current smokers. One-year quit rate was 10.2%, quitting was associated with increased baseline symptoms (adjOR 2.62, 95% CI 1.07–6.41; p = 0.035) but not demographics or screening results. 55% attributed quitting to the LHC. In current smokers, 44% reported the LHC had made them consider stopping, 29% it made them try to stop and 25% made them smoke less whilst only 1.7% and 0.7% said it made them worry less about smoking or think it acceptable to smoke. ConclusionsOur data suggest a community-based lung cancer screening programme in deprived areas positively impacts smoking behaviour, with no evidence of a ‘licence to smoke’ in those screened.

Program for lung cancer screening and tobacco cessation: Study protocol of a sequential, multiple assignment, randomized trial

PLUTO will conduct a sequential, multiple assignment, randomized trial to inform the choice and delivery of smoking cessation treatments for smokers in the setting of lung cancer screening, including for smokers who respond both incompletely (any smoking after quit date) and completely to first-line treatment (4 or 8 weeks of counseling with nicotine replacement therapy). Currently, there is little evidence to guide the development of adaptive interventions in tobacco cessation. SMART designs, such as the one we propose, are an ideal experimental design to assess different adaptive intervention strategies. Adaptive interventions for smoking cessation in the context of lung cancer screening have high potential for dissemination and impact. The USPSTF recommends annual low-dose CT screening for patients at high risk Recommendation (Grade B)4; private insurance coverage is mandated for USPSTF Grade A or B recommendations. The Affordable Care Act (ACA) mandates coverage of preventative services including smoking cessation treatment. The ACA requires coverage of at least 2 quit attempts/year, 4 counseling sessions of at least 10 minutes, and all Food and Drug Administration (FDA) approved tobacco cessation meds for a 90 day treatment regimen when prescribed by a health care provider (7 medications: 5 forms of NRT, bupropion, and varenicline).74 Effective smoking cessation treatment, delivered in the context of lung cancer screening programs, may augment the mortality benefit of imaging studies. The novel tobacco treatment system we plan – identification of smokers by using the EMR and proactive invitation to treatment coupled with lung cancer screening – is an opportunity to engage a new cohort of smokers with mechanisms in place to implement delivery of care. Thus, the PLUTO trial takes advantage of a new clinical practice development: recommendation for annual lung cancer screening based on age and smoking history. Strengths are an innovative study design and sequential random assignment of treatment conditions in addition to the main comparative effectiveness outcome that allows more rigorous measurement of effects than a standard randomized controlled trial would afford. The information about timing of assessment, optimal intervention components, and intensity of treatment are ripe for dissemination.

Lung cancer: Low-dose CT screening - determining the right interval.

Annual thoracic CT screening is currently recommended for individuals deemed to be at high risk of developing lung cancer; however, Patz and co-workers now raise the very important question of choosing the optimal interval between screening exams, in order to balance the potential benefits and harms associated with each round of CT. Herein, we present important considerations for determining such intervals.

Lung cancer incidence and mortality in National Lung Screening Trial participants who underwent low-dose CT prevalence screening: a retrospective cohort analysis of a randomised, multicentre, diagnostic screening trial

Annual low-dose CT screening for lung cancer has been recommended for high-risk individuals, but the necessity of yearly low-dose CT in all eligible individuals is uncertain. This study examined rates of lung cancer in National Lung Screening Trial (NLST) participants who had a negative prevalence (initial) low-dose CT screen to explore whether less frequent screening could be justified in some lower-risk subpopulations. We did a retrospective cohort analysis of data from the NLST, a randomised, multicentre screening trial comparing three annual low-dose CT assessments with three annual chest radiographs for the early detection of lung cancer in high-risk, eligible individuals (aged 55-74 years with at least a 30 pack-year history of cigarette smoking, and, if a former smoker, had quit within the past 15 years), recruited from US medical centres between Aug 5, 2002, and April 26, 2004. Participants were followed up for up to 5 years after their last annual screen. For the purposes of this analysis, our cohort consisted of all NLST participants who had received a low-dose CT prevalence (T0) screen. We determined the frequency, stage, histology, study year of diagnosis, and incidence of lung cancer, as well as overall and lung cancer-specific mortality, and whether lung cancers were detected as a result of screening or within 1 year of a negative screen. We also estimated the effect on mortality if the first annual (T1) screen in participants with a negative T0 screen had not been done. The NLST is registered with ClinicalTrials.gov, number NCT00047385. Our cohort consisted of 26 231 participants assigned to the low-dose CT screening group who had undergone their T0 screen. The 19 066 participants with a negative T0 screen had a lower incidence of lung cancer than did all 26 231 T0-screened participants (371·88 [95% CI 337·97-408·26] per 100 000 person-years vs 661·23 [622·07-702·21]) and had lower lung cancer-related mortality (185·82 [95% CI 162·17-211·93] per 100 000 person-years vs 277·20 [252·28-303·90]). The yield of lung cancer at the T1 screen among participants with a negative T0 screen was 0·34% (62 screen-detected cancers out of 18 121 screened participants), compared with a yield at the T0 screen among all T0-screened participants of 1·0% (267 of 26 231). We estimated that if the T1 screen had not been done in the T0 negative group, at most, an additional 28 participants in the T0 negative group would have died from lung cancer (a rise in mortality from 185·82 [95% CI 162·17-211·93] per 100 000 person-years to 212·14 [186·80-239·96]) over the course of the trial. Participants with a negative low-dose CT prevalence screen had a lower incidence of lung cancer and lung cancer-specific mortality than did all participants who underwent a prevalence screen. Because overly frequent screening has associated harms, increasing the interval between screens in participants with a negative low-dose CT prevalence screen might be warranted. None.