TABLE 1.

Contributions of single-arm studies and smaller randomised trials

	Design	Implication of findings
Randomised trials
LSS [9]	Age 55–74 years, ≥30 pack-years, smoked within 10 years LDCT versus CXR Baseline and year 1 screen n=3136	High screening uptake, low crossover contamination and good adherence demonstrated feasibility to conduct RCT
DEPISCAN [10]	Age 50–75 years, ≥15 cigarettes·day−1 for ≥20 years; smoked within 15 year LDCT versus CXR One screen n=621	Poor GP participation rate (41%) and high rate of noncompliant patients (19%) point to the need to improve GP participation and patient adherence
DANTE [11]	Men, age ≥60–75 years, ≥20 pack-years, smoked within 10 years Baseline CXR + sputum cytology, then LDCT at baseline + 4 annual screens versus usual care n=2450	Excellent adherence rate in community hospitals, suggesting that community implementation is possible
ITALUNG [12]	Age 55–69 years; ≥20 pack-years; smoked within 10 years LDCT versus usual care Baseline plus 4 annual screens n=3206	Modest response rate of 23.9% from direct mailing to at-risk individuals based on age group with letter signed by participating GP and screening centre. Surgery for benign lesions may be minimised by adherence to nodule management protocol
MILD [13]	Age 49–75 years; ≥20 pack-years; smoked within 10 years LDCT versus usual care 7 annual LDCT or 4 biennial LDCT n=4099	1) Prolonged screening beyond 5 years is needed to show a lung cancer mortality reduction benefit 2) Biennial screening achieved comparable lung cancer mortality reduction to annual screen in subjects with a negative baseline screen and potentially saved 44% of follow-up LDCTs
LUSI [5]	Age 50–69 years; ≥15 cigarettes·day−1 for >25 years or ≥10 cigarettes·day−1 for >30 years; smoked within 10 years LDCT versus usual care Baseline + 4 annual screens n=4052	Secondary analysis suggests that women, but not men, benefit from LDCT screening
UKLS [14]	Age 50–75 years; 5-year lung cancer risk ≥5% (LLPv2) LDCT versus usual care Single screen n=4055	Feasible to use primary care trust records to access general population to recruit eligible individuals for LDCT screening using risk assessment tool. However, 60% of people contacted with mass mail-out did not reply and only 3.3% met screening criteria. Barriers for nonparticipation found to be related to practical and emotional factors
AME [15]	Age 45–70 years; ever-smokers ≥20 pack-years, smoked within 15 years or family history of cancer, long history of passive smoking, cooking oil fumes or occupational exposure LDCT versus usual care; baseline LDCT and one repeat screen at 24 months n=6657	Only 7.1% met NLST criteria with 2.4% found to have lung cancer by LDCT compared to 1.3% cancer among those who did not meet NLST criteria, suggesting that nonsmoking risk factors need to be included as screening selection criteria for the Chinese population
Single-arm studies
ELCAP [16], I-ELCAP [17]	Age ≥60 years, ≥10 pack-years Baseline screening in 31 567 subjects Annual repeat screenings in 27 456 subjects	First demonstration that the majority (85%) of screen-detected lung cancers are stage I and potentially curable with an estimated 10-year survival of 80% for all participants
COSMOS [18]	Age >50 years; >20 pack-years Annual LDCT for 10 years n=1035	Stable lung cancer detection rate and stable proportion of early lung cancers suggest that screening should continue beyond 10 years, especially in current smokers
PanCan [19]	Age 50–74 years; 6-year lung cancer risk ≥2% (PLCOm2007) Screening at baseline, years 1 and 4 n=2537	1) Risk prediction tool identified a relatively high number of individuals who developed lung cancers relative to NLST age and pack-years criteria and a large proportion of the cancers (66%) were stage I 2) The web-based risk prediction tool in English and French was found to be a user-friendly and efficient means of determining eligibility and scheduling enrolment 3) Risk-based screening is cost-effective
Manchester Lung Health Check [20]	Age 55–74 years. 6-year; lung cancer risk ≥1.51% (PLCOm2012)	1) Use of “lung health check” instead of “lung cancer screening” may avoid cancer stigma to improve participation 2) Deployment of mobile CT scanner in convenient retail locations to deliver lung cancer screening to socioeconomically disadvantaged communities may be an effective means to engage underserved populations. This strategy may reduce inequalities and improve adherence in deprived areas 3) Cost-effective
Lung Screen Uptake Trial [21]	Age 60–75 years, smoker within 7 years, ≥30 pack-years, smoked within 15 years or 6-year lung cancer risk ≥1.51% (PLCOm2012) or Liverpool Lung project score ≥2.5% n=768	Lung Health Check approach with pre-invitation letter; invitation letter signed by primary care physician offering pre-scheduled appointment; and reminder re-invitation. 52.6% screening uptake rate. Stepped approach using a low-burden information invitation leaflet may reduce social gradient in areas of highest socioeconomic deprivation
ILST [22]	Age 55–80 years, ≥30 pack-years, smoked within 15 years or 6-year lung cancer risk ≥1.51% (PLCOm2012) Baseline LDCT and one repeat in 1–2 years n=4000	1) Preliminary results comparing USPSTF versus PLCOm2012 selection criteria suggest that PLCO m2012 is more efficient in identifying high-risk individuals with lung cancer 2) PanCan nodule management protocol for baseline scan may reduce healthcare resource utilisation by triaging very low risk individuals to biennial instead of annual screen 3) Randomised trial of CAD as first reader suggests that CAD may save radiologist reading time

LSS: Lung Screening Study; DANTE: Detection and Screening of Early Lung Cancer with Novel Imaging Technology; ITALUNG: Italian Lung Cancer Screening Trial; MILD: Multicentric Italian Lung Detection trial; LUSI: Lung Cancer Screening Intervention; UKLS: UK Lung Cancer Screening Trial; ELCAP: Early Lung Cancer Action Project; PanCan: Pan-Canadian Early Detection of Lung Cancer Study; ILST: International Lung Screening Trial; LDCT: low-dose computed tomography; CXR: chest radiography; RCT: randomised controlled trial; GP: general practitioner; LLPv2: Liverpool Lung Project criteria; NLST: National Lung Screening Trial; CT: computed tomography; PLCO: Prostate Lung Colorectal and Ovarian study models; USPSTF: US Preventive Services Task Force; CAD: computer-assisted diagnosis.