BACKGROUND:Lung cancer screening is effective for people at higher risk of the disease, but there is no international consensus on eligibility criteria. Some programmes use risk factors; others use multivariable risk scores, which might target an older, more comorbid population and thus limit life years gained. In this study, we compare frailty, comorbidities and overall survival between different eligible populations. METHODS:Participants aged 55-74 years undergoing lung cancer risk assessment in the Yorkshire Lung Screening Trial were analysed, comparing those who met the US Preventive Services Task Force 2021 lung cancer screening criteria (USPSTF2021) criteria against established risk-based criteria currently used in screening protocols (Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial risk model (PLCOm2012) ≥1.51%, used internationally, and the Liverpool Lung Project risk model (version 2) (LLPv2) ≥2.5%, used in the UK), examining the number of individuals with frailty and comorbidities selected by each approach. In addition, risk score thresholds were set to select equivalent numbers of people screened compared with USPSTF2021. Data recorded in primary care prior to randomisation were retrospectively extracted to allow calculation of the electronic Frailty Index (eFI) and an overall comorbidity count. Frailty, comorbidity counts and 3-year overall survival were compared between these various populations. RESULTS:Of 11 994 individuals aged 55-74 undergoing risk assessment, 3502 were eligible by USPSTF2021, 3139 by PLCOm2012 ≥1.51% and 3957 by LLPv2 ≥2.5%. The proportion of individuals with moderate/severe frailty was lower for the USPSTF2021 population (10.6%) compared with PLCOm2012 ≥1.51% (13.1%, adjusted p=0.0777) and LLPv2 ≥2.5% (13.4%, adjusted p=0.0272). The USPSTF2021 identified significantly fewer individuals with multiple comorbidities (30.8%) than the PLCOm2012 (36.1%, adjusted p=0.0033) and the LLPv2 (37.3%, adjusted p=0.0001).When compared in equivalent populations, both PLCOm2012 with a threshold of 1.32%, and LLPv2 with a threshold of 2.92%, had a higher proportion of people both with moderate/severe frailty (12.6%, adjusted p=0.221 and 14.0%, adjusted p=0.0067 respectively) and multiple comorbidities (35.1%, adjusted p=0.0211 and 38.5%, adjusted p<0.0001 respectively) than USPSTF2021.There were no apparent differences in 3-year overall survival between the eligible populations overlapping 95% CIs across risk groups. CONCLUSION:These data suggest that currently used risk models identify populations with a small increase in moderate/severe frailty and multimorbidity compared to the USPSTF2021 criteria, but there is no evidence to suggest that this results in differences in 3-year overall survival.

BACKGROUND:Lung cancer (LC) is the most common cause of cancer death in the UK and worldwide, but screening with low-dose CT (LDCT) reduces LC deaths. The UK National Screening Committee has recommended nationwide roll-out of LDCT screening, but the optimal risk thresholds for eligibility remain uncertain. METHODS:We conducted a cost-effectiveness analysis in the Yorkshire Lung Screening Trial (YLST) population comparing three eligibility criteria: US Preventive Services Task Force (USPSTF)2013, Prostate Lung Colorectal and Ovarian study (PLCO)M2012 ≥1.51% and Liverpool Lung Project model (LLP)v2 ≥5%. A Markov model estimated a no-screening counterfactual. Scenario analyses assessed how increasing PLCOM2012 (1.51%-7%) and LLPv2 (5%-9%) thresholds affected LC detection, costs and quality-adjusted life years (QALYs). Payouts per detected LC were calculated using mortality and utility estimates from the literature and cost data from the trial. RESULTS:Incremental cost-effectiveness ratios (ICERs) versus no screening were £3949 (USPSTF2013), £3797 (LLPv2≥5%) and £4013 (PLCOM2012≥1.51%). PLCOM2012 yielded the largest numbers screened and LCs detected, most QALYs gained and highest incremental net monetary benefit. Raising LLPv2 and PLCOM2012 thresholds reduced both ICERs and QALYs gained. CONCLUSION:All three screening eligibility criteria are cost-effective according to the UK's willingness to pay threshold of £20 000/QALY. Within the range of thresholds observed in YLST, PLCOM2012 thresholds between ≥1.51% and ≥4% offered the most efficient cost-benefit trade-offs. Evidence suggests that lowering thresholds further would detect more LC cases while remaining cost-effective. These findings support the criteria implemented in YLST, but do not by themselves identify the optimal screening threshold for the wider UK population. TRIAL REGISTRATION NUMBER:ISRCTN42704678.

BACKGROUND:Lung cancer screening with low-dose computed tomography (LDCT) saves lives by detecting early-stage curable cancer and estimates of overdiagnosis in the previous randomised studies were generally low. Screening selection criteria vary, with some programmes only recommending screening for people who are surgical candidates, whereas others make no reference to fitness for surgery. Here we report clinical characteristics and outcomes for participants in the Yorkshire Lung Screening Trial with screen-detected clinical stage I lung cancer according to treatment modality. METHODS:Consecutive participants with screen-detected clinical stage I lung cancer were stratified according to curative treatment modality into surgical and SABR cohorts. Factors associated with overall survival and cancer-specific survival were assessed with a median follow-up of 3.6 years. RESULTS:Of 190 patients with stage I lung cancer studied, 31 % (n = 58) received SABR and 69 % (n = 132) surgery (55 lobectomy, 77 sub-lobar resection). Patients treated with SABR were older with worse performance status and fitness parameters. Cancer-specific survival was similar between the SABR and surgery cohorts (HR for death 1.19, 95 % CI 0.45-3.14, p = 0.72) but overall survival was worse following SABR compared to surgery (HR for death 2.61 95 % CI 1.45-4.69, p = 0.001), indicating that the worse overall survival was due to non-cancer deaths. In the SABR cohort 17 patients (29.3 %) died from non-cancer causes during the study follow-up period compared with 9 (6.8 %) in the surgery cohort. Three-year survival was 69.4 % in the SABR cohort and 92.4 % in the surgical cohort (p < 0.001). CONCLUSIONS:Cancer-specific survival was similar between the two groups, but overall survival following SABR for screen-detected stage I lung cancer is worse than surgery due to higher rates of non-cancer death within 5 years of treatment. Lung cancer sojourn time has been estimated at around 5 years, so it is likely that rates of overdiagnosis are higher in patients treated with SABR compared to surgery. Further research may be needed to optimise inclusion and exclusion criteria for lung cancer screening.

INTRODUCTION:Low-dose computed tomography screening for lung cancer reduces lung cancer mortality, but there is a lack of international consensus regarding the optimal eligibility criteria for screening. The Yorkshire Lung Screening Trial was designed to evaluate lung cancer screening (LCS) implementation, and a primary objective was prospective evaluation of three predefined eligibility criteria. METHODS:Individuals who had ever smoked, aged 55 to 80 years, who responded to written invitation, underwent telephone risk assessment and if eligible by at least one criterion (PLCOM2012 ≥ 1.51%, LLPv2 ≥ 5%, USPSTF2013) were offered biennial low-dose computed tomography screening. RESULTS:Of 44,957 individuals invited, 22,814 responded and underwent eligibility assessment, of whom a total of 7826 were eligible according to any of the three LCS criteria. Comparing PLCOM2012 ≥ 1.51%, LLPv2 ≥ 5%, and USPSTF2013, the proportions of responders eligible for screening were 28.0%, 20.5%, and 18.9%, respectively (p < 0.0001 for each comparison), and the proportion of all cancers detected 91.1%, 77.0%, and 62.8%, respectively (p ≤ 0.0002 for each comparison). When risk thresholds were selected to result in equivalent numbers of people eligible for screening, cancer detection proportions were higher for PLCOM2012 (74.5%) and LLPv2 (71.3%) than USPSTF2013 (62.8%) (p = 0.0002 and p = 0.032, respectively), but there was no significant difference between the two risk models. Reducing the LLPv2 risk threshold from 5% to 2.5% (as currently used in the English LCS program) and reducing the pack-year requirement for the USPSTF2021 versus the USPSTF2013 criteria increased the numbers eligible for screening, but subsequent cancer yield was not measured in this study. CONCLUSION:The PLCOM2012 ≥ 1.51% criteria identified more people eligible for screening in Yorkshire Lung Screening Trial and resulted in more screen-detected lung cancers than LLPv2 ≥ 5% or USPSTF2013. When compared in equivalent populations, there was no significant difference between risk models in terms of lung cancer detection and each appeared more efficient at screening population selection than USPSTF2013.

Background:Lower socioeconomic status, as measured by the Index of Multiple Deprivation (IMD), is associated with higher rates of smoking-related disease mortality, and with poor uptake of cancer screening. Here we explore whether socioeconomic status impacts the effectiveness of a single round of low-dose-CT screening, or impacts other causes of death, in the UKLS LDCT screening trial. Methods:IMD quintiles were defined according to UK-wide data, with the deprived group defined as the lower two quintiles (Q1-2) and the less deprived as Q3-5. Follow-up data was obtained for lung cancer diagnosis (median follow-up 9.1 years) and cause of death (median follow-up 9.9 years). Outcomes were compared based on IMD group and trial arm (CT or control). Findings:More deprived quintiles were less likely to respond to the questionnaire, but this population was more likely to be selected for screening by the LLP risk model. Lower IMD quintiles benefitted from low-dose-CT screening in terms of lung cancer survival (HR 1.89, 95% CI 1.16-3.08) to the same extent as upper quintiles (HR 1.87, 95% CI 1.07-3.26). However, there was a bigger impact on deaths due to COPD and emphysema in more deprived quintiles. Interpretation:Whilst LDCT screening benefit for lung cancer was similar, significant impact on the rates of death from other smoking-related diseases, notably COPD and emphysema, was seen primarily in lower socioeconomic groups. Future research is required to confirm how lung cancer screening benefits other disease outcomes. Funding:NIHR Health Technology Assessment Programme; NIHR Policy Research programme; Roy Castle Lung Cancer Foundation.

Introduction Lung cancer is the most common cause of cancer death globally. In 2022 the UK National Screening Committee recommended the implementation of a national targeted lung cancer screening programme, aiming to improve early diagnosis and survival rates. Research studies and services internationally consistently observe socioeconomic and smoking-related inequalities in screening uptake. Pathway navigation (PN) is a process through which a trained pathway navigator guides people to overcome barriers to accessing healthcare services, including screening. This nested randomised controlled trial aims to determine whether a PN intervention results in more individuals participating in lung cancer screening compared with the usual written invitation within a previous non-responder population as part of the Yorkshire Lung Screening Trial (YLST).Methods and analysis A two-arm randomised controlled trial and process evaluation nested within the YLST. Participants aged 55–80 (inclusive) who have not responded to previous postal invitations to screening will be randomised by household to receive PN or usual care (a further postal invitation to contact the screening service for a lung health check) between March 2023 and October 2024. The PN intervention includes a postal appointment notification and prearranged telephone appointment, during which a pathway navigator telephones the participant, following a four-step protocol to introduce the offer and conduct an initial risk assessment. If eligible, participants are invited to book a low-dose CT (LDCT) lung cancer screening scan. All pathway navigators receive training from behavioural psychologists on motivational interviewing and communication techniques to elicit barriers to screening attendance and offer solutions.Coprimary outcomes The number undergoing initial telephone assessment of lung cancer risk. The number undergoing an LDCT screening scan.Secondary outcomes include demographic, clinical and risk parameters of people undergoing telephone risk assessment; the number of people eligible for screening following telephone risk assessment; the number of screen-detected cancers diagnosed; costs and a mixed-methods process evaluation.Descriptive analyses will be used to present numbers, proportions and quantitative components of the process evaluation. Primary comparisons of differences between groups will be made using logistic regression. Applied thematic analysis will be used to interpret qualitative data within a conceptual framework based on the COM-B framework. A health economic analysis of the PN intervention will also be conducted.Ethics and dissemination The study is approved by the Greater Manchester West Research Ethics Committee (18-NW-0012) and the Health Research Authority following the Confidentiality Advisory Group review. Results will be shared through peer-reviewed scientific journals, conference presentations and on the YLST website.Trial registration numbers ISRCTN42704678 and NCT03750110.

Data from the ongoing Yorkshire Lung Screening Trial (YLST) indicate that 50% of people invited to a lung cancer screening risk-assessment do not take up the offer, with lowest uptake by people from less affluent areas and who currently smoke. Pathway Navigation (PN) helps individuals overcome barriers to accessing healthcare, particularly among populations disadvantaged by inequalities. This study tests whether PN improves uptake of lung cancer screening compared to normal written invitation within the YLST.

BACKGROUND:Population breast screening services in England were suspended in March 2020 due to the COVID-19 pandemic. Here, we estimate the number of breast cancers whose detection may be delayed because of the suspension, and the potential impact on cancer deaths over 10 years. METHODS:We estimated the number and length of screening delays from observed NHS Breast Screening System data. We then estimated additional breast cancer deaths from three routes: asymptomatic tumours progressing to symptomatically diagnosed disease, invasive tumours which remain screen-detected but at a later date, and ductal carcinoma in situ (DCIS) progressing to invasive disease by detection. We took progression rates, prognostic characteristics, and survival rates from published sources. RESULTS:We estimated that 1,489,237 women had screening delayed by around 2-7 months between July 2020 and June 2021, leaving 745,277 outstanding screens. Depending on how quickly this backlog is cleared, around 2500-4100 cancers would shift from screen-detected to symptomatic cancers, resulting in 148-452 additional breast cancer deaths. There would be an additional 164-222 screen-detected tumour deaths, and 71-97 deaths from DCIS that progresses to invasive cancer. CONCLUSIONS:An estimated 148-687 additional breast cancer deaths may occur as a result of the pandemic-related disruptions. The impact depends on how quickly screening services catch up with delays.

Objectives The NHS Breast Screening programme is recovering from the hiatus in screening in 2020 due to the COVID-19 pandemic. Currently, open rather than timed invitations are issued, which leads to lower uptake but more rapid coverage of the eligible population by invitation and therefore closer adherence to a round length of 3 years. We aimed to estimate the likely effect on numbers of cancers detected at incident screens of a range of round lengths and uptake rates. Methods We assumed exponential distributions of time to incidence of preclinical screen-detectable cancer and of time to progression thereafter to symptomatic clinical disease. We derived numerical values of these, along with screening sensitivity, from published research results and statistics from the NHS Breast Screening programme. These were used to calculate numbers of cancers detected at incident screens at ages 51-70 by round length and uptake rates. Results We found that in a homogeneous population of cancers, a 4-year round length with uptake of 62%, as observed with timed appointments in London before the pandemic, would result in 295 cancers screen detected per 10,000 invited, compared to 222 cancers with a 3-year round and uptake of 46%, as observed in London during the recovery period. Similar results were found when we posited two populations, one of rapidly progressing and one of slowly progressing cancers. Conclusions It may be more productive in terms of early detection to focus on uptake rather than round length in the programme's recovery from the pandemic.

Lower socioeconomic status, as measured by the Index of Multiple Deprivation (IMD), is associated with higher rates of smoking-related disease mortality, and with poor uptake in cancer screening. The UKLS low-dose-CT (LD-CT) screening trial for lung cancer was consistent with a lung cancer mortality benefit for CT screening [Field, et al. (2021) Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. Lancet Regional Health Europe, doi.org/10.1016/j.lanepe.2021.100179].

Background Early detection of lung cancer saves lives, as demonstrated by the two largest published low-dose CT screening trials. Optimal implementation depends on our ability to identify those most at risk. Methods Version 2 of the Liverpool Lung Project risk score (LLPv2) was developed from case-control data in Liverpool and further adapted when applied for selection of subjects for the UK Lung Screening Trial. The objective was to produce version 3 (LLPv3) of the model, by calibration to national figures for 2017. We validated both LLPv2 and LLPv3 using questionnaire data from 75 958 individuals, followed up for lung cancer over 5 years. We validated both discrimination, using receiver operating characteristic (ROC) analysis, and absolute incidence, by comparing deciles of predicted incidence with observed incidence. We calculated proportionate difference as the percentage excess or deficit of observed cancers compared with those predicted. We also carried out Hosmer-Lemeshow tests. Results There were 599 lung cancers diagnosed over 5 years. The discrimination of both LLPv2 and LLPv3 was significant with an area under the ROC curve of 0.81 (95% CI 0.79 to 0.82). However, LLPv2 overestimated absolute risk in the population. The proportionate difference was −58.3% (95% CI −61.6% to −54.8%), that is, the actual number of cancers was only 42% of the number predicted. In LLPv3, calibrated to national 2017 figures, the proportionate difference was −22.0% (95% CI −28.1% to −15.5%). Conclusions While LLPv2 and LLPv3 have the same discriminatory power, LLPv3 improves the absolute lung cancer risk prediction and should be considered for use in further UK implementation studies.

Background: The NLST reported a significant 20% reduction in lung cancer mortality with three annual low-dose CT (LDCT) screens and the Dutch-Belgian NELSON trial indicates a similar reduction. We present the results of the UKLS trial. Methods: From October 2011 to February 2013, we randomly allocated 4 055 participants to either a single invitation to screening with LDCT or to no screening (usual care). Eligible participants (aged 50-75) had a risk score (LLPv2) >= 4.5% of developing lung cancer over five years. Data were collected on lung cancer cases to 31 December 2019 and deaths to 29 February 2020 through linkage to national registries. The primary outcome was mortality due to lung cancer. We included our results in a random-effects meta-analysis to provide a synthesis of the latest randomised trial evidence. Findings: 1 987 participants in the intervention and 1 981 in the usual care arms were followed for a median of 7.3 years (IQR 7.1-7.6), 86 cancers were diagnosed in the LDCT arm and 75 in the control arm. 30 lung cancer deaths were reported in the screening arm, 46 in the control arm, (relative rate 0.65 [95% CI 0.41-1.02]; p=0.062). The meta-analysis indicated a significant reduction in lung cancer mortality with a pooled overall relative rate of 0.84 (95% CI 0.76-0.92) from nine eligible trials. Interpretation: The UKLS trial of single LDCT indicates a reduction of lung cancer death of similar magnitude to the NELSON and NLST trials and was included in a meta-analysis of nine randomised trials which provides unequivocal support for lung cancer screening in identified risk groups. (C) 2021 The Authors. Published by Elsevier Ltd.