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Background: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy., Methods: LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell)., Results: 1568 participants were randomised during 2007-2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75-1.95) or 0.82 (95% CI 0.52-1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively., Conclusions: Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening., Competing Interests: Conflict of interest: S.G. Spiro has nothing to disclose. Conflict of interest: P.L. Shah has nothing to disclose. Conflict of interest: R.C. Rintoul has nothing to disclose. Conflict of interest: J. George has nothing to disclose. Conflict of interest: S. Janes reports personal fees for advisory board work from BARD1, Achilles Therapeutics and AstraZeneca, personal fees for conference travel from AstraZeneca, outside the submitted work. Conflict of interest: M. Callister has nothing to disclose. Conflict of interest: M. Novelli has nothing to disclose. Conflict of interest: P. Shaw has nothing to disclose. Conflict of interest: G. Kocjan has nothing to disclose. Conflict of interest: C. Griffiths has nothing to disclose. Conflict of interest: M. Falzon has nothing to disclose. Conflict of interest: R. Booton has nothing to disclose. Conflict of interest: N. Magee has nothing to disclose. Conflict of interest: M. Peake reports personal fees for lectures from Roche Products Ltd, grants and personal fees for lectures from MSD Ltd, personal fees for advisory board work from BMS and Pfizer Ltd, outside the submitted work. Conflict of interest: P. Dhillon has nothing to disclose. Conflict of interest: K. Sridharan has nothing to disclose. Conflict of interest: A.G. Nicholson has nothing to disclose. Conflict of interest: S. Padley has nothing to disclose. Conflict of interest: M.N. Taylor has nothing to disclose. Conflict of interest: A. Ahmed has nothing to disclose. Conflict of interest: J. Allen has nothing to disclose. Conflict of interest: Y. Ngai has nothing to disclose. Conflict of interest: N. Chinyanganya has nothing to disclose. Conflict of interest: V. Ashford-Turner has nothing to disclose. Conflict of interest: S. Lewis has nothing to disclose. Conflict of interest: D. Oukrif has nothing to disclose. Conflict of interest: P. Rabbits has nothing to disclose. Conflict of interest: N. Counsell has nothing to disclose. Conflict of interest: A. Hackshaw has nothing to disclose., (Copyright ©ERS 2019.)

Background: Earlier diagnosis of lung cancer is key to reducing mortality. New evidence suggests that smokers have negative attitudes to screening and participation in lung cancer screening trials is poor (<1 in 6 of those eligible). Understanding participation is important since uptake in screening trials is likely to predict uptake in screening programmes. A qualitative study of people accepting and declining participation in the Lung-SEARCH screening trial was conducted. Two questions were addressed: Are the screening methods offered acceptable to patients? Why do some people take part and others decline?, Methods: The qualitative study used semi-structured interviews with 60 respondents from three groups: (a) trial participants providing an annual sputum sample; (b) trial participants with a sputum sample showing abnormal cytology and thus undergoing annual CT scanning and bronchoscopy; and (c) those declining trial participation., Results: Most respondents (48/60, 80%) viewed sputum provision, CT scanning and bronchoscopy as largely acceptable. Those declining trial participation described fear of bronchoscopy, inconvenience of travelling to hospitals for screening investigations and perceived themselves as having low susceptibility to lung cancer or being too old to benefit. Patients declining participation discounted their risk from smoking and considered negative family histories and good health to be protective. Four typological behaviours emerged within those declining: 'too old to be bothered', 'worriers', 'fatalists' and 'avoiders'., Conclusion: Sputum provision, CT scanning and bronchoscopy are largely acceptable to those participating in a screening trial. However, the decision to participate or decline reflects a complex balance of factors including acceptability and convenience of screening methods, risk perception, altruism and self-interest. Improving practical and changing cognitive aspects of participation will be key to improving uptake of lung cancer screening.