Ghasem Yadegarfar

UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening

Background Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial. Methods The pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction. Results 247u2005354 individuals aged 50–75u2005years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50u2005mm3 or 5u2005mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50u2005mm3 at 12u2005months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12u2005569). Conclusions The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective—this needs to be confirmed using data on observed lung cancer mortality reduction. Trial registration ISRCTN 78513845.

The UK Lung Screen (UKLS): demographic profile of first 88,897 approaches provides recommendations for population screening.

The UK Lung Cancer Screening trial (UKLS) aims to evaluate low-dose computed tomography (LDCT) lung cancer population screening in the United Kingdom. In UKLS, a large population sample ages 50 to 75 years is approached with a questionnaire to determine lung cancer risk. Those with an estimated risk of at least 5% of developing lung cancer in the next 5 years (using the Liverpool Lung project risk model) are invited to participate in the trial. Here, we present demographic, risk, and response rate data from the first 88,897 individuals approached. Of note, 23,794 individuals (26.8% of all approached) responded positively to the initial questionnaire; 12% of these were high risk. Higher socioeconomic status correlated positively with response, but inversely with risk (P < 0.001). The 50- to 55-year age group was least likely to participate, and at lowest cancer risk. Only 5% of clinic attendees were ages ≤60 years (compared with 47% of all 88,897 approached); this has implications for cost effectiveness. Among positive responders, there were more ex-smokers than expected from population figures (40% vs. 33%), and fewer current smokers (14% vs. 17.5%). Of note, 32.7% of current smokers and 18.4% of ex-smokers were designated as high risk. Overall, 1,452 of 23,794 positive responders (6.1%) were deemed high risk and attended a recruitment clinic. UKLS is the first LDCT population screening trial, selecting high-risk subjects using a validated individual risk prediction model. Key findings: (i) better recruitment from ex- rather than current smokers, (ii) few clinic attendees ages early 50s, and (iii) representative number of socioeconomically deprived people recruited, despite lower response rates. Cancer Prev Res; 7(3); 362–71. ©2014 AACR.

The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer.

BACKGROUNDnLung cancer kills more people than any other cancer in the UK (5-year survival <u200913%). Early diagnosis can save lives. The USA-based National Lung Cancer Screening Trial reported a 20% relative reduction in lung cancer mortality and 6.7% all-cause mortality in low-dose computed tomography (LDCT)-screened subjects.nnnOBJECTIVESnTo (1) analyse LDCT lung cancer screening in a high-risk UK population, determine optimum recruitment, screening, reading and care pathway strategies; and (2) assess the psychological consequences and the health-economic implications of screening.nnnDESIGNnA pilot randomised controlled trial comparing intervention with usual care. A population-based risk questionnaire identified individuals who were at high risk of developing lung cancer (≥u20095% over 5 years).nnnSETTINGnThoracic centres with expertise in lung cancer imaging, respiratory medicine, pathology and surgery: Liverpool Heart & Chest Hospital, Merseyside, and Papworth Hospital, Cambridgeshire.nnnPARTICIPANTSnIndividuals aged 50-75 years, at high risk of lung cancer, in the primary care trusts adjacent to the centres.nnnINTERVENTIONSnA thoracic LDCT scan. Follow-up computed tomography (CT) scans as per protocol. Referral to multidisciplinary team clinics was determined by nodule size criteria.nnnMAIN OUTCOME MEASURESnPopulation-based recruitment based on risk stratification; management of the trial through web-based database; optimal characteristics of CT scan readers (radiologists vs. radiographers); characterisation of CT-detected nodules utilising volumetric analysis; prevalence of lung cancer at baseline; sociodemographic factors affecting participation; psychosocial measures (cancer distress, anxiety, depression, decision satisfaction); and cost-effectiveness modelling.nnnRESULTSnA total of 247,354 individuals were approached to take part in the trial; 30.7% responded positively to the screening invitation. Recruitment of participants resulted in 2028 in the CT arm and 2027 in the control arm. A total of 1994 participants underwent CT scanning: 42 participants (2.1%) were diagnosed with lung cancer; 36 out of 42 (85.7%) of the screen-detected cancers were identified as stage 1 or 2, and 35 (83.3%) underwent surgical resection as their primary treatment. Lung cancer was more common in the lowest socioeconomic group. Short-term adverse psychosocial consequences were observed in participants who were randomised to the intervention arm and in those who had a major lung abnormality detected, but these differences were modest and temporary. Rollout of screening as a service or design of a full trial would need to address issues of outreach. The health-economic analysis suggests that the intervention could be cost-effective but this needs to be confirmed using data on actual lung cancer mortality.nnnCONCLUSIONSnThe UK Lung Cancer Screening (UKLS) pilot was successfully undertaken with 4055 randomised individuals. The data from the UKLS provide evidence that adds to existing data to suggest that lung cancer screening in the UK could potentially be implemented in the 60-75 years age group, selected via the Liverpool Lung Project risk model version 2 and using CT volumetry-based management protocols.nnnFUTURE WORKnThe UKLS data will be pooled with the NELSON (Nederlands Leuvens Longkanker Screenings Onderzoek: Dutch-Belgian Randomised Lung Cancer Screening Trial) and other European Union trials in 2017 which will provide European mortality and cost-effectiveness data. For now, there is a clear need for mortality results from other trials and further research to identify optimal methods of implementation and delivery. Strategies for increasing uptake and providing support for underserved groups will be key to implementation.nnnTRIAL REGISTRATIONnCurrent Controlled Trials ISRCTN78513845.nnnFUNDINGnThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 40. See the NIHR Journals Library website for further project information.

Barriers to uptake among high-risk individuals declining participation in lung cancer screening: a mixed methods analysis of the UK Lung Cancer Screening (UKLS) trial

Objective The current study aimed to identify the barriers to participation among high-risk individuals in the UK Lung Cancer Screening (UKLS) pilot trial. Setting The UKLS pilot trial is a randomised controlled trial of low-dose CT (LDCT) screening that has recruited high-risk people using a population approach in the Cambridge and Liverpool areas. Participants High-risk individuals aged 50–75u2005years were invited to participate in UKLS. Individuals were excluded if a LDCT scan was performed within the last year, if they were unable to provide consent, or if LDCT screening was unable to be carried out due to coexisting comorbidities. Outcome measures Statistical associations between individual characteristics and UKLS uptake were examined using multivariable regression modelling. In those who completed a non-participation questionnaire (NPQ), thematic analysis of free-text data was undertaken to identify reasons for not taking part, with subsequent exploratory linkage of key themes to risk factors for non-uptake. Results Comparative data were available from 4061 high-risk individuals who consented to participate in the trial and 2756 who declined participation. Of those declining participation, 748 (27.1%) completed a NPQ. Factors associated with non-uptake included: female gender (OR=0.64, p<0.001), older age (OR=0.73, p<0.001), current smoking (OR=0.70, p<0.001), lower socioeconomic group (OR=0.56, p<0.001) and higher affective risk perception (OR=0.52, p<0.001). Among non-participants who provided a reason, two main themes emerged reflecting practical and emotional barriers. Smokers were more likely to report emotional barriers to participation. Conclusions A profile of risk factors for non-participation in lung screening has emerged, with underlying reasons largely relating to practical and emotional barriers. Strategies for engaging high-risk, hard-to-reach groups are critical for the equitable uptake of a potential future lung cancer screening programme. Trial registration number The UKLS trial was registered with the International Standard Randomised Controlled Trial Register under the reference 78513845.