Articles
One-off low-dose CT for lung cancer screening in China:
Lancet Respir Med 2022;
10: 378–91
Published Online
March 8, 2022
https://doi.org/10.1016/
S2213-2600(21)00560-9
See Comment page 320
For the Chinese translation of the
abstract see Online for
appendix 1
*Contributed equally to this
work
†Group members are listed at the
end of the paper
Office of Cancer Screening
(Prof N Li PhD, Prof W Chen PhD,
Prof M Dai PhD, F Wang PhD,
J Li PhD, Y Yu MPH, W Cao PhD,
Y XU PhD, C Qin PhD, L Zhao BS,
Z Wu BS, Z Yang BS, Y Zheng BS,
H Chen PhD), Department of
Thoracic Surgery (F Tan PhD,
Prof J He PhD), Department of
Diagnostic Radiology
(W Tang MD, Prof N Wu MD),
and PET-CT Center (Prof N Wu),
National Cancer Center/
National Clinical Research
Center for Cancer/Cancer
Hospital, Chinese Academy of
Medical Sciences and Peking
Union Medical College, Beijing,
China; Key Laboratory of
Cancer Data Science, Chinese
Academy of Medical Sciences
and Peking Union Medical
College, Beijing, China
(Prof N Li, Prof W Chen, J Li);
Department of Epidemiology,
Center for Global Health,
School of Public Health
(S Shen PhD, M Zhu PhD,
Prof H Shen PhD) and Jiangsu
Key Lab of Cancer Biomarkers,
Prevention and Treatment,
Collaborative Innovation
Center for Cancer Personalized
Medicine (S Shen, M Zhu,
Prof H Shen), Nanjing Medical
University, Nanjing, China;
Henan Office for Cancer Control
and Research (L Guo PhD) and
Department of Cancer
Epidemiology (S Zhang PhD),
Affiliated Cancer Hospital of
Zhengzhou University, Henan
Cancer Hospital, Zhengzhou,
378
a multicentre, population-based, prospective cohort study
Ni Li*, Fengwei Tan*, Wanqing Chen*, Min Dai*, Fei Wang, Sipeng Shen, Wei Tang, Jiang Li, Yiwen Yu, Wei Cao, Yongjie Xu, Chao Qin, Liang Zhao,
Meng Zhu, Lanwei Guo, Zheng Wu, Zhuoyu Yang, Yadi Zheng, Hongda Chen, Yunyong Liu, Donghua Wei, Dong Dong, Ji Cao, Shaokai Zhang,
Shipeng Yan, Ning Wang, Lingbin Du, Hongbing Shen, Ning Wu, Jie He, for the National Lung Cancer Screening programme group†
Summary
Background Lung cancer is the leading cause of cancer death worldwide. Data on the effectiveness of one-off low-dose
CT (LDCT) in reducing lung cancer mortality and all-cause mortality are needed to inform screening programmes in
countries with limited medical resources. We aimed to evaluate the effectiveness of one-off LDCT screening in the
early detection of lung cancer in China.
Methods A multicentre, population-based, prospective cohort study was done in 12 cities of eight provinces across China,
recruiting individuals aged 40–74 years who were asymptomatic for lung cancer with no lung cancer history. Participants
were classified as at high risk or low risk of lung cancer using a sex-specific risk score that incorporated cigarette smoking,
level of physical activity, occupational exposures, history of chronic respiratory diseases, family history of lung cancer,
diet, and passive smoking (women only). Participants at high risk were invited for a one-off LDCT scan and were classified
into screened and non-screened groups on the basis of whether or not they had the scan. Lung cancer incidence density,
lung cancer mortality, and all-cause mortality were calculated for the screened and non-screened groups. The effectiveness
of a one-off LDCT scan was evaluated by a comparison of the screened and non-screened groups in terms of lung cancer
mortality and all-cause mortality in the period from cohort entry until administrative censoring (June 20, 2020). Inverse
probability weighting was adopted to account for potential imbalanced factors between the two groups and Cox
proportional hazards model was used to estimate the weighted associations between mortality and one-off LDCT scans.
Findings Between Feb 19, 2013, and Oct 31, 2018, 1 032 639 individuals were assessed for eligibility. 1 016 740 participants
were enrolled in the study, of whom 3581 had a lung cancer diagnosis after a median follow-up of 3·6 years
(IQR 2·8–5·1). Among the 223 302 participants at high risk, 79 581 (35·6%) had an LDCT scan (screened group) and
143 721 (64·4%) did not (non-screened group). After inverse probability weighting, lung cancer incidence density
was 47·0% higher (hazard ratio 1·47 [95% CI 1·27–1·70]; p<0·0001), lung cancer mortality was 31·0% lower (0·69
[95% CI 0·53–0·92]; p=0·010) and all-cause mortality was 32·0% lower (0·68 [0·57–0·82]; p<0·0001) for participants
in the screened group compared with those in the non-screened group.
Interpretation One-off LDCT screening was associated with significantly lower lung cancer mortality and all-cause
mortality in a large population in China. Our results point to the promise of one-off LDCT screening in countries with
limited medical resources. Further studies are needed to explore interactions by subgroup—including sex, age,
smoking status, and economic status—to develop population-specific screening strategies.
Funding Ministry of Finance and National Health Commission of the People’s Republic of China.
Copyright © 2022 Elsevier Ltd. All rights reserved.
Introduction and burden. Studies from the Early Lung Cancer Action
Lung cancer is one of the most common cancers and the Project and the International Early Lung Cancer Action
leading cause of cancer-related deaths worldwide, Project found that screening with LDCT could help to
accounting for 11·4% of the total cancer incidence and detect lung cancer at an earlier stage, with diagnosis of
18·0% of all cancer-related deaths.1 In 2020, more than more than 80% of lung cancers at clinical stage I.4–6
one-third of all newly diagnosed lung cancers and Randomised controlled trials such as the US National
associated deaths worldwide occurred in China, according Lung Screening Trial (NLST), the Dutch–Belgian Lung
to a report from the International Agency for Research on Cancer Screening Trial (NELSON), and the German Lung
Cancer.2 Lung cancer accounts for 23·8% of all cancer Cancer Screening Intervention (LUSI) found that
deaths in China,2 and is one of the five leading causes of LDCT screening was associated with 20%, 24%, and
years of life lost,3 posing a heavy economic burden for 26% reductions in lung cancer mortality, respectively.7–9
patients, families, and the country. These findings have contributed to the development of
Evidence suggests that screening with low-dose CT evidence-based health policies on LDCT screening to
(LDCT) is an effective way to reduce lung cancer mortality reduce the lung cancer burden worldwide.
www.thelancet.com/respiratory Vol 10 April 2022
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China; Liaoning Office for

Research in context Cancer Control and Research,
Cancer Hospital of China
Evidence before this study non-smokers, and in participants living in high-income areas but Medical University, Liaoning
We searched PubMed and the China National Knowledge not in those from low-income and middle-income areas. Cancer Hospital and Institute,
Infrastructure databases for articles published in English or However, further studies are needed to establish whether or not Shenyang, China (Y Liu MPH);
Office for Cancer Prevention
Chinese about the effectiveness of low-dose CT (LDCT) these differences between subgroups are significant.
and Control, Anhui Provincial
screening on lung cancer published before Feb 1, 2021. Cancer Hospital, Hefei, China
Implications of all the available evidence
Our search terms were “lung cancer”, “screening”, and (D Wei MD); Office of Cancer
Our study provides support for a one-off LDCT screening Prevention and Treatment,
“low-dose computed tomography” or “LDCT”. We identified
strategy for lung cancer. Importantly, it indicates the feasibility Xuzhou Cancer Hospital,
40 population-based studies (published between
of implementing one-off LDCT screening in countries with Xuzhou, China (D Dong MD);
2001 and 2021) targeting repeated or one-off LDCT screening. Cancer Prevention and Control
limited resources. Evidence for the effectiveness of
Three randomised controlled trials have reported the Office, Cancer Hospital,
LDCT screening in subgroups delineated by sex, age, smoking Guangxi Medical University,
effectiveness of repeated LDCT screening in reducing lung
status, and economic status points to the potential of one-off Nanning, China (Prof J Cao MD);
cancer mortality. However, to our knowledge, there have been
LDCT screening in subpopulations at high risk; however, Department of Cancer
no previous population-based studies of one-off LDCT Prevention and Control, Hunan
further studies are needed to refine the criteria for identifying
screening. Therefore, evidence is scare regarding the Cancer Hospital and The
individuals at high risk and to inform the development of Affiliated Cancer Hospital of
effectiveness of one-off LDCT screening in reducing lung cancer
population-specific screening strategies, taking the Xiangya School of Medicine,
mortality and all-cause mortality in population-based studies. Central South University,
demographic profile of the screening population, awareness in
Changsha, China (S Yan PhD);
Added value of this study society of the benefit of screening, and local resources and
Key Laboratory of
To our knowledge, this is the first study to evaluate the facilities into consideration. On the basis of our data, people Carcinogenesis and
effectiveness of a one-off LDCT screening strategy in a with a smoking history of 20 or more pack-years and other risk Translational Research,
population-based cohort; our study was large, with more than factors should be considered as the priority for screening. Ministry of Education Beijing,
Beijing Office for Cancer
1 million eligible participants. The results show the effectiveness These findings from the National Lung Cancer Screening Prevention and Control, Peking
of one-off LDCT screening in reducing lung cancer mortality and programme in China could contribute to a global roadmap for University Cancer Hospital and
all-cause mortality for a population at high risk of lung cancer. effective prevention and control of lung cancer. In the context Institute, Beijing, China
Both lung cancer mortality and all-cause mortality reductions of the COVID-19 pandemic, with people paying greater (N Wang MPH); Department of
Cancer Prevention, The Cancer
were statistically significant in men but not in women, in attention to lung health, our study could prompt other Hospital of the University of
individuals aged 55–74 years but not in those aged 40–54 years, countries with limited resources to formulate lung cancer Chinese Academy of Sciences,
in people with a smoking history of 20 or more pack-years but screening strategies and subsequently contribute to global Zhejiang Cancer Hospital,
not in those with a history of less than 20 pack-years or in cancer control in the long run. Institute of Basic Medicine and
Cancer, Chinese Academy of
Sciences, Hangzhou, China
The Healthy China 2030 programme is the country’s considerations for policy makers in the development of (L Du MPH)
signature national domestic health policy, which sets screening policies. Correspondence to:
Prof Jie He, Department of
population health as the primary goal of economic In light of these knowledge gaps, we aimed to evaluate
Thoracic Surgery, National
development and health-care reform.10,11 One of the targets the effectiveness of one-off LDCT screening in a large Cancer Center/National Clinical
of the programme is to improve cancer survival via population-based cohort in China in allowing the early Research Center for Cancer/
screening. At present, there is no nationwide screening detection of lung cancer and a subsequent reduction in Cancer Hospital, Chinese
Academy of Medical Sciences
programme available and only a small portion of the lung cancer mortality and all-cause mortality.
and Peking Union Medical
population benefits from organised non-profit screening College, Beijing, 100021, China
projects.12 Results from rigorous randomised controlled Methods hejie@cicams.ac.cn
trials have shown the efficacy of repeated LDCT screening Study design and population
for mortality reduction.7–9 However, implementing This was a multicentre, population-based, prospective
national LDCT screening for lung cancer in China now cohort study completed as part of the National Lung
would be premature because of insufficient reliable data Cancer Screening programme, a non-profit programme
to support the effectiveness of LDCT screening strategies funded by the Ministry of Finance and the National
in reducing mortality in China and the variation in the Health Commission of China. 12 cities in eight provinces
supply of medical resources in different areas. Most in China were selected based on whether they had
existing lung cancer screening programmes include more (1) complete cancer registration data, (2) vital statistics
than one LDCT scan.7–9,13–15 Repeated examinations might data for all patients in registries, and (3) a relatively stable
ensure the beneficial effect of LDCT screening, but might population with limited migration. Cities were excluded
not be feasible due to high cost and low practicability in if the information on lung cancer diagnoses from the
countries such as China, given its large population and cancer registry system could not be cross-referenced to
high disease burden. Finding a more efficient way to medical records from hospital information systems
implement lung cancer screening with limited resources (appendix 2 p 1). See Online for appendix 2
is of utmost importance. Moreover, evidence from a 458 communities were selected across the 12 cities,
population-based screening study could highlight practical where television broadcasts, brochures, and websites were

www.thelancet.com/respiratory Vol 10 April 2022 379

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used to publicise cancer screening programmes, including
the National Lung Cancer Screening programme. We used
the household registration system in local communities to
identify eligible permanent residents who were aged
40–74 years and asymptomatic for lung cancer with no
history of cancer diagnosis. Individuals who were unable
to give informed consent, had a medical disability and
were unlikely to complete curative lung cancer surgery,
had a history of lung cancer, had received treatment for or
had evidence of any cancer within the past 5 years (with
the exception of non-melanoma skin cancer and most
in-situ carcinomas), or had symptoms suggestive of
lung cancer (including unexplained weight loss of >15 lb
within the past 12 months, or unexplained haemoptysis)
were not eligible to participate. Community-based
telephone calls or home visits were done to reach and
inform the maximum number of eligible residents. All
participants provided written informed consent. The
study was approved by the ethics committees of China
National Cancer Center/Cancer Hospital, Chinese
Academy of Medical Sciences, and Peking Union Medical
College (approval number 15-070/997).
Procedures
Eligible participants were interviewed by trained staff to
collect information about their exposure to risk factors
for lung cancer. A sex-specific scoring system derived
from the Harvard Cancer Risk Index were used to
evaluate the risk of lung cancer for men and women.16
The score included cigarette smoking, self-reported
exposure to ambient particulate matter in the past
10 years, level of physical activity, history of chronic
respiratory diseases, family history of lung cancer, dietary
intake of fresh vegetables in the past 10 years, and history
of passive smoking (women only). Men without smoking
history were excluded from the high-risk group. Detailed
information on the risk assessment score is given in
appendix 2 (p 2). Individuals categorised as being at high
risk of lung cancer were advised to have a free LDCT scan
with 16 or more slices at a tertiary-level hospital
designated by the programme. These participants then
completed a process of shared decision making that
included information about the potential benefits and
harms of screening with LDCT to ensure that their
decision on whether to have a LDCT scan was well
informed. Participants categorised as high risk who had
LDCT screening were included in the screened group,
and those categorised as high risk but who did not have
LDCT screening were included in the non-screened
group. Detailed information regarding the LDCT scan
protocol and the management of nodules is shown in
appendix 2 (pp 2–3).
The follow-up period for all events was calculated
from the cohort entry date. To account for potential
immortal time bias arising from the fact that individuals
in the screened group had to survive (be alive and event
free) until the LDCT scan was done,17 the cohort entry
380
date was defined as the date of screening in the
screened group. For individuals in the non-screened
group, the cohort entry date was estimated based on the
screening date of the individual in the screened group
whose risk assessment date was closest to that in the
non-screened group. Time to lung cancer occurrence
was calculated from the cohort entry date until the
earliest occurrence of lung cancer, death, or adminis­
trative censoring (June 20, 2020). Time to lung cancer
death or all-cause death was calculated from the cohort
entry date until death or administrative censoring,
whichever came first.
Covariates from the baseline survey included
demographic characteristics (age, sex, education level
[low: primary school or below; medium: primary school to
high school; high: high school or above], and body-mass
index), lifestyle factors (smoking status, passive smoking,
occupational exposure to hazardous substances, and
frequent exercise), a family history of lung cancer, and
baseline comorbidities (chronic respiratory diseases,
digestive diseases, hepatobiliary diseases, hypertension,
diabetes, and hyperlipidaemia). Smokers were defined as
those who had previously smoked or were currently
smoking tobacco more than once per day for at least
6 months. Participants were classified as non-smokers,
light smokers (<20 pack-year smoking history), and heavy
smokers (≥20 pack-year smoking history),18 where a
smoking pack-year is equal to one packet of 20 cigarettes
every day for 1 year. Passive smoking referred to the
involuntary inhalation of other people’s tobacco smoke
(eg, in the home or work environment) and was measured
only among women. Occupational exposure to hazardous
substances referred to occupational exposures to asbestos,
rubber, dust, pesticide, radiation, beryllium, uranium, and
radon for at least 1 year. Frequent exercise was defined as
exercise done at least three times per week, with each
exercise session lasting more than 30 min. Respiratory
diseases included pulmonary tuberculosis, chronic
bronchitis, emphysema, asthmatic bronchiectasis, and
silicosis or pneumoconiosis.
For quality control, each involved institution was
required to document the participants’ screening-related
information, including the risk assessment and LDCT
scan images, results, or both, as well as information about
any subsequent procedures, where applicable. All the data
were transmitted to the coordinating centre at the China
National Cancer Center (NCC) through a web-based
management system belonging to the National Cancer
Prevention and Control Network (NCPCN) for double-
checking and central reading.
Approximately 1·5% of all LDCT images transmitted to
the NCPCN were randomly reviewed annually by at least
two radiologists from the China NCC. Central reading of
the images from the eight provinces showed consistency
rates for the diagnostic results of the images ranging
from 85·9% to 95·4%, indicating acceptable quality of
our image data.
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Outcomes
The primary outcomes were lung cancer incidence,
lung cancer mortality, and all-cause mortality. The main
secondary outcome was the proportion of participants
with early-stage lung cancer (stage 0–I). All outcomes
were assessed in the screened, non-screened, and low-
risk groups. The prespecified secondary outcomes of
compliance rate, quality of life, and cost analysis were
not included in this analysis and will be reported
elsewhere. The International Classification of Diseases
(10th revision) was used throughout, in which lung cancer
is coded as C34. Outcome data were retrieved from
national linkages, including the cancer registry system
and death surveillance system, every 6 months. Data
from the two national linkages have been extensively
used to assess the disease burden both regionally and
nationally in China and globally,12,19–21 as well as for other
research purposes.22,23
For participants diagnosed with lung cancer who had
no information on the cancer stage or histological type in
the cancer registry system, cross-referencing with the
medical insurance system or hospital information
system was done to acquire the information.24 Overall,
the proportion of participants with lung cancer with
known stage at diagnosis increased from 18·3% to 67·9%
after cross-referencing. A clinical expert committee was
formed consisting of thoracic surgeons, radiologists, and
pathologists from the China NCC and provincial
hospitals to ascertain the disease stages and histological
types. Information on the disease stage for approximately
4% of cases and information on the histological type for
approximately 2% of the cases were modified.
The primary and secondary outcomes were also analysed
in subgroups prespecified in the statistical analysis plan
based on age (40–54 years and 55–74 years), sex, economic
status (high-income areas and low-income and middle-
income areas), and smoking status (non-smokers, light
smokers, and heavy smokers). Economic status was
determined based on each province’s gross domestic
product values in 2018 and classified as high-income areas
(Beijing, Zhejiang, and Jiangsu Provinces) or low-income
and middle-income areas (Anhui, Hunan, Liaoning,
Guangxi, and Henan Provinces).25
Safety data were collected including any unfavourable
and unintended symptom, or disease temporally
associated with the use of LDCT.
Statistical analysis
The baseline characteristics of the study population were
described as frequency (n) with proportion (%) for
categorical variables and mean with SD or median with
IQR for continuous variables. We compared the screened
and non-screened groups using standardised differences,
calculated as the difference in means or proportions
divided by a pooled estimate of the SD.26,27 This method is
not sensitive to sample size and is useful in identifying
meaningful differences.28 Standardised differences
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Articles
1 032 639 residents participated in the screening
programme risk assessment
15 899 excluded
847 died before cohort entry
256 had existing lung cancer
before cohort entry
14 796 had invalid data*
1 016 740 participants included in the study
223 302 in the high-risk group 793 438 in the low-risk group
invited for a one-off
LDCT scan
79 581 in the screened group 143 721 in the non-screened
group
531 with lung cancer at 663 with lung cancer during 2387 with lung cancer during
screening and during follow-up follow-up
follow-up
Figure 1: Study profile
Individuals were assessed for eligibility between Feb 19, 2013, and Oct 31, 2018. Lung cancer occurrence was
recorded from the cohort entry date until administrative censoring (June 20, 2020). LDCT=low-dose CT.
*Invalid data included those who did not meet the high-risk criteria but were classified as high-risk individuals;
those who were actually at high risk but were misclassified as being at low risk; and those who were at low risk but
had the free LDCT scan.
greater than 0·1 are considered to be meaningful.26 The
distribution of categorical variables between groups were
also evaluated by χ2 test.
To describe observed outcomes, we compared the
unadjusted cumulative incidence of each outcome after
cohort entry between the screened and non-screened
groups. For the lung cancer incidence outcome, we
treated death as a competing risk: cumulative incidence
was estimated using the cumulative incidence function,
accounting for the competing risk of mortality. For the
lung cancer mortality outcome, we treated death from
other causes as a competing risk: lung cancer mortality
was estimated using the cumulative incidence function,
accounting for the competing risk of death from other
causes. Gray tests were used to assess differences
between groups. For all-cause mortality, the Kaplan-
Meier method was used to estimate cumulative incidence
and log-rank tests were used to assess differences
between groups.
To account for potential imbalanced factors between
the screened and non-screened group, we used the
inverse probability weighting (IPW) method.29 Two
steps were taken. First, we did multivariable logistic
regression analysis in the population at high risk, with
having an LDCT scan as the dependent variable and the
afore­mentioned baseline characteristics (including
demo­graphic variables, lifestyle factors, a family history
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of lung cancer, and baseline comor­ bidities) as
independent variables. We were then able to predict a
participant’s probability of having an LDCT scan. Next,
the weights for each individual were calculated as the
inverse of the probability of receiving the LDCT scan
for the participants in the screened group who actually
had an LDCT scan, and the inverse of the probability of
not receiving the LDCT scan in the non-screened
group. After weighting, we assessed the balance of
baseline characteristics between the screened and
non-screened groups by calculating the standardised
difference.
To estimate the association of LDCT screening with
each outcome, we used a Cox proportional hazards

Overall High-risk group Low-risk group* Standardised

(n=1 016 740) (n=793 438) difference
(total high-
risk vs low-
risk)†
Total high-risk Screened‡ Non-screened§ Standardised
group (n=79 581) (n=143 721) difference
(n=223 302) (screened vs
non-
screened)¶
Demographic characteristics
Age ·· ·· ·· ·· 0·031 ·· 0·015
Mean (SD) 56·0 (8·8) 55·9 (8·2) 56·1 (8·0) 55·8 (8·3) ·· 56·0 (8·9) ··
40–54 years 460 622 (45·3%) 99 844 (44·7%) 34 795 (43·7%) 65 049 (45·3%) ·· 360 778 (45·5%) ··
55–74 years 556 118 (54·7%) 123 458 (55·3%) 44 786 (56·3%) 78 672 (54·7%) ·· 432 660 (54·5%) ··
Sex ·· ·· ·· ·· 0·218 ·· 0·323
Male 446 027 (43·9%) 125 750 (56·3%) 39 286 (49·4%) 86 464 (60·2%) ·· 320 277 (40·4%) ··
Female 570 713 (56·1%) 97 552 (43·7%) 40 295 (50·6%) 57 257 (39·8%) ·· 473 161 (59·6%) ··
Education ·· ·· ·· ·· 0·033 ·· 0·080
Low 180 881 (17·8%) 34 636 (15·5%) 12 940 (16·3%) 21 696 (15·1%) ·· 146 245 (18·4%) ··
Medium 665 857 (65·5%) 149 094 (66·8%) 52 793 (66·3%) 96 301 (67·0%) ·· 516 763 (65·1%) ··
High 169 996 (16·7%) 39 572 (17·7%) 13 848 (17·4%) 25 724 (17·9%) ·· 130 424 (16·4%) ··
Body-mass index, kg/m² ·· ·· ·· ·· 0·038 ·· 0·097
<18·5 18 913 (1·9%) 4272 (1·9%) 1507 (1·9%) 2765 (1·9%) ·· 14 641 (1·8%) ··
18·5 to <24 533 331 (52·5%) 109 747 (49·2%) 38 205 (48·1%) 71 542 (49·8%) ·· 423 584 (53·5%) ··
24 to <28 381 236 (37·5%) 87 509 (39·2%) 31 780 (40·0%) 55 729 (38·8%) ·· 293 727 (37·1%) ··
≥28 81 937 (8·1%) 21 489 (9·6%) 8007 (10·1%) 13 482 (9·4%) ·· 60 448 (7·6%) ··
Lifestyle factors
Smoking status ·· ·· ·· ·· 0·183 ·· 1·578
Non-smoker 794 345 (78·1%) 77 246 (34·6%) 31 991 (40·2%) 45 255 (31·5%) ·· 717 099 (90·4%) ··
Light smoker 108 876 (10·7%) 32 537 (14·6%) 10 308 (13·0%) 22 229 (15·5%) ·· 76 339 (9·6%) ··
Heavy smoker 113 519 (11·2%) 113 519 (50·8%) 37 282 (46·8%) 76 237 (53·0%) ·· 0|| ··
Occupational exposure to ·· ·· ·· ·· 0·207 ·· 0·653
hazardous substances
No 850 880 (83·7%) 140 851 (63·1%) 45 061 (56·6%) 95 790 (66·6%) ·· 710 029 (89·5%) ··
Yes 165 853 (16·3%) 82 451 (36·9%) 34 520 (43·4%) 47 931 (33·4%) ·· 83 402 (10·5%) ··
Passive smoking ·· ·· ·· ·· 0·147 ·· 1·406
No 638 974 (62·9%) 42 873 (19·3%) 12 565 (15·9%) 30 308 (21·2%) ·· 596 101 (75·2%) ··
0–19 years 96 133 (9·5%) 28 233 (12·7%) 9734 (12·3%) 18 499 (12·9%) ·· 67 900 (8·6%) ··
20–39 years 226 804 (22·3%) 114 971 (51·7%) 42 542 (53·8%) 72 429 (50·6%) ·· 111 833 (14·1%) ··
≥40 years 53 555 (5·3%) 36 244 (16·3%) 14 264 (18·0%) 21 980 (15·3%) ·· 17 311 (2·2%) ··
Frequent exercise ·· ·· ·· ·· 0·046 ·· 0·429
No 561 762 (55·3%) 159 062 (71·2%) 57 747 (72·6%) 101 315 (70·5%) ·· 402 700 (50·8%) ··
Yes 454 974 (44·7%) 64 240 (28·8%) 21 834 (27·4%) 42 406 (29·5%) ·· 390 734 (49·2%) ··
Family history of lung ·· ·· ·· ·· 0·399 ·· 1·047
cancer
No 799 931 (86·4%) 118 993 (55·8%) 33 452 (43·4%) 85 541 (62·9%) ·· 680 938 (95·6%) ··
Yes 125 439 (13·6%) 94 108 (44·2%) 43 659 (56·6%) 50 449 (37·1%) ·· 31 331 (4·4%) ··
(Table 1 continues on next page)

382 www.thelancet.com/respiratory Vol 10 April 2022

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Overall High-risk group Low-risk group* Standardised

(n=1 016 740) (n=793 438) difference
(total high-
risk vs low-
risk)†
Total high-risk Screened‡ Non-screened§ Standardised
group (n=79 581) (n=143 721) difference
(n=223 302) (screened vs
non-
screened)¶
(Continued from previous page)
Baseline comorbidity
Chronic respiratory ·· ·· ·· ·· 0·286 ·· 1·631
diseases
No 809 224 (79·6%) 71 074 (31·8%) 18 691 (23·5%) 52 383 (36·4%) ·· 738 150 (93·0%) ··
Yes 207 504 (20·4%) 152 227 (68·2%) 60 890 (76·5%) 91 337 (63·6%) ·· 55 277 (7·0%) ··
Digestive diseases ·· ·· ·· ·· 0·196 ·· 0·713
No 766 036 (75·3%) 112 991 (50·6%) 35 273 (44·3%) 77 718 (54·1%) ·· 653 045 (82·3%) ··
Yes 250 704 (24·7%) 110 311 (49·4%) 44 308 (55·7%) 66 003 (45·9%) ·· 140 393 (17·7%) ··
Hepatobiliary diseases ·· ·· ·· ·· 0·238 ·· 0·881
No 751 847 (73·9%) 97 333 (43·6%) 28 709 (36·1%) 68 624 (47·7%) ·· 654 514 (82·5%) ··
Yes 264 879 (26·1%) 125 968 (56·4%) 50 872 (63·9%) 75 096 (52·3%) ·· 138 911 (17·5%) ··
Hypertension ·· ·· ·· ·· 0·006 ·· 0·335
No 733 301 (79·4%) 141 697 (68·4%) 50 617 (68·2%) 91 080 (68·5%) ·· 591 604 (82·6%) ··
Yes 190 194 (20·6%) 65 474 (31·6%) 23 599 (31·8%) 41 875 (31·5%) ·· 124 720 (17·4%) ··
Hyperlipidaemia ·· ·· ·· ·· 0·127 ·· 0·434
No 773 203 (83·7%) 145 698 (70·3%) 49 411 (66·6%) 96 287 (72·4%) ·· 627 505 (87·6%) ··
Yes 150 244 (16·3%) 61 461 (29·7%) 24 793 (33·4%) 36 668 (27·6%) ·· 88 783 (12·4%) ··
Diabetes ·· ·· ·· ·· 0·049 ·· 0·177
No 857 442 (92·9%) 184 431 (89·0%) 65 326 (88·0%) 119 105 (89·6%) ·· 673 011 (94·0%) ··
Yes 66 008 (7·1%) 22 727 (11·0%) 8881 (12·0%) 13 846 (10·4%) ·· 43 281 (6·0%) ··
Data are n (%) unless otherwise specified. p values from the χ² test for differences between the high-risk and low-risk groups were all <0·0001. p values from the χ² test for
differences between the screened and non-screened groups were all <0·0001. *In the low-risk group, there were six participants without information on education,
1038 participants without information on body-mass index, 293 participants without information on passive smoking years, 81 169 participants without information on
family history of lung cancer, 11 participants without information on history of chronic respiratory diseases, seven participants without information on occupational
exposure to hazardous substances, four participants without information on frequent exercise, 13 participants without information on hepatobiliary diseases,
77 114 participants without information on hypertension, 77 150 participants without information on hyperlipidaemia, and 77 146 participants without information on
diabetes. †Standardised differences greater than 0·1 were considered meaningful. ‡In the screened group, there were 82 participants without information on body-mass
index, 476 participants without information on passive smoking years, 2470 participants without information on family history of lung cancer, 5365 participants without
information on hypertension, 5377 participants without information on hyperlipidaemia, and 5374 participants without information on diabetes. §In the non-screened
group, there were 203 participants without information on body-mass index, 505 participants without information on passive smoking years, 7731 participants without
information on family history of lung cancer, one participant without information on history of chronic respiratory diseases, one participant without information on
hepatobiliary diseases, 10 766 participants without information on hypertension, 10 766 participants without information on hyperlipidaemia, and 10 770 participants
without information on diabetes. ¶Standardised differences greater than 0·1 were considered meaningful. ||No heavy smokers were included in the low-risk group.

Table 1: Baseline characteristics of the study population

model and applied the individual weights in models to
estimate the weighted association between LDCT scans
and outcomes. Significance tests and CIs for estimates
were based on robust SEs to account for the clustering of
individuals by community. Hazard ratios (HRs) and
95% CIs are reported.
In addition to estimating overall effects, we also
estimated the associations of LDCT scans with each
outcome in the prespecified subgroups by using IPW
and running Cox models across each subgroup.
The WHO classification of lung tumours that was
released in 2021 excluded stage 0 lung cancers from
malignant cancers.30 We therefore did post-hoc sensitivity
analyses excluding patients with stage 0 cancer from
lung cancer cases. In the main analyses, a cutoff age of
55 years was used to categorise age groups because
studies have shown that the lung cancer incidence
dramatically increases after age 55 years (100·45 per
100 000 for people aged 55–60 years compared with
54·44 per 100 000 for people aged 50–55 years).31
Sensitivity analysis was done at a cutoff age of 50 years to
verify whether different cutoff ages could potentially
affect the main findings.
All statistical analyses were done using the statistical
software R (version 3.5.1). All tests were two-sided and
p<0·05 was considered statistically significant.

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diseases, hypertension, hyperlipidaemia, or diabetes

Overall High-risk group
(n=1 016 740) (p<0·0001 and standardised difference more than 0·1
for each). Sex-specific baseline characteristics are
Screened Non-
(n=79 581) screened shown in appendix 2 (pp 4–7).
(n=143 721) 531 (0·7%) participants in the screened group received
Lung cancer incidence a lung cancer diagnosis and there were 176 (0·2%)
Total 3581 (0·4%) 531 (0·7%) 663 (0·5%) all-cause deaths and 76 (0·1%) lung cancer deaths
Stage* (table 2). In the non-screened group, 663 (0·5%)
0–I 1318 (54·2%) 244 (62·7%) 186 (41·5%)
participants received a lung cancer diagnosis and there
II 159 (6·5%) 27 (6·9%) 41 (9·2%)
were 515 (0·4%) all-cause deaths and 218 (0·2%) lung
III 329 (13·5%) 59 (15·2%) 85 (19·0%)
cancer deaths (table 2). In the low-risk group,
2387 (0·3%) participants received a lung cancer diagnosis
IV 625 (25·7%) 59 (15·2%) 136 (30·4%)
and there were 2025 (0·3%) all-cause deaths and
Histological type†
473 (0·1%) lung cancer deaths.
Adenocarcinoma 2188 (74·3%) 330 (72·5%) 316 (59·2%)
The crude lung cancer incidence density was 187·3 per
Squamous cell 498 (16·9%) 81 (17·8%) 140 (26·2%)
carcinoma 100 000 person-years (95% CI 172·0–203·9) in the
Small-cell carcinoma 184 (6·2%) 28 (6·2%) 60 (11·2%) screened group and 132·4 per 100 000 person-years
Others 77 (2·6%) 16 (3·5%) 18 (3·4%)
(122·7–142·9) in the non-screened group (table 3),
Deaths
resulting in a crude rate ratio (RR) of 1·41 (95% CI
All-cause deaths 2716 (0·3%) 176 (0·2%) 515 (0·4%)
1·40–1·42; appendix 2 p 10) and a crude rate difference
Lung cancer-specific 767 (0·1%) 76 (0·1%) 218 (0·2%)
(RD) of 54·8 (95% CI 36·0–73·7; appendix 2 p 11).
deaths Significantly lower lung cancer mortality (26·7 [95% CI
*1150 lung cancer cases without information on stage: 142 in the screened group,
21·3 to 33·5] vs 43·5 [38·1 to 49·7] deaths per
215 in the non-screened group, and 793 in the low-risk group. †634 lung cancer 100 000 person-years) and all-cause mortality (61·9
cases without information on histological type: 76 in the screened group, 129 in [53·4 to 71·7] vs 102·9 [94·4 to 112·1] deaths per
the non-screened group, and 429 in the low-risk group. 100 000 person-years) was observed in the screened
Table 2: Lung cancer incidence and mortality group compared with the non-screened group, with
crude RRs of 0·61 (95% CI 0·58 to 0·65) for lung cancer
mortality and 0·60 (0·59 to 0·62) for all-cause mortality
Role of the funding source (appendix 2 p 10), and crude RDs of –16·8 (95% CI
The funder of the study had no role in study design, data –25·2 to –8·5) for lung cancer mortality and –41·0
collection, data analysis, data interpretation, or writing of (–53·7 to –28·2) for all-cause mortality (appendix 2 p 11).
the report. Throughout follow-up, the cumulative incidence of
lung cancer was highest in the screened group, followed
Results by the non-screened group, then the low-risk group
Between Feb 19, 2013, and Oct 31, 2018, 1 032 639 eligible (figure 2A). The cumulative lung cancer mortality was
residents participated in the risk assessment of the highest in the non-screened group, followed by the
lung cancer screening programme for this study screened group, then the low-risk group (figure 2B).
(figure 1). 1 016 740 eligible participants were included in All-cause cumulative mortality was highest in the
the final analyses, 3581 of whom had a lung cancer non-screened group, followed by the low-risk group, then
diagnosis after a median follow-up of 3·6 years (IQR the screened group (figure 2C).
2·8–5·1). 793 438 (78·0%) of the participants were The proportion of individuals in the high-risk group
classified as having a low risk of lung cancer. The who chose to have the LDCT scan was 79 581 (35·6%)
remaining 223 302 (22·0%) participants were at high of 223 302. Women were more likely to have the scan
risk of lung cancer and were invited to have LDCT scans. than men (40 295 [41·3%] vs 39 286 [31·2%]; appendix 2
In the high-risk group, 79 581 (35·6%) participants pp 8–9). Participants with hazardous substance exposure,
adhered to the LDCT scan (figure 1). a family history of lung cancer, or a history of chronic
The baseline characteristics of participants in the respiratory diseases, digestive diseases, hepatobiliary
high-risk (screened and non-screened) and low-risk disease, or hyperlipidaemia, were more likely to adhere
groups are shown in table 1. Mean age was 56·0 years to the assigned LDCT scan (standardised difference
(SD 8·8) across the entire population. Compared with more than 0·1; appendix 2 pp 8–9). However, heavy and
those in the low-risk group, participants in the high- light smokers were less likely to have the LDCT scan
risk group were more likely to be male, a smoker or than non-smokers (37 282 [32·8%] and 10 308 [31·7%] vs
passive smoker, or exposed to hazardous substances, 31 991 [41·4%]). After IPW, the standardised differences
and to have low levels of physical activity, a family were less than 0·1 for all confounders, suggesting that
history of lung cancer, or a medical history of chronic the screened and non-screened groups were well
respiratory diseases, digestive diseases, hepato­ biliary balanced (appendix 2 pp 8–9).

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High-risk group Low-risk group

Screened Non-screened
Number Incidence density* Number Incidence density* Number Incidence density*
(95% CI) (95% CI) (95% CI)
Lung cancer incidence
Total 531 (0·7%) 187·3 (172·0–203·9) 663 (0·5%) 132·4 (122·7–142·9) 2387 (0·3%) 81·1 (77·9–84·5)
Sex
Male 330 (62·2%) 231·7 (208·0–258·1) 522 (78·7%) 167·3 (153·6–182·3) 1130 (47·3%) 96·2 (90·7–101·9)
Female 201 (37·9%) 142·5 (124·1–163·6) 141 (21·3%) 74·7 (63·4–88·2) 1257 (52·7%) 71·1 (67·3–75·2)
Age group, years
40–54 125 (23·5%) 99·5 (83·5–118·6) 98 (14·8%) 43·1 (35·4–52·5) 478 (20·0%) 35·0 (32·0–38·3)
55–74 406 (76·5%) 257·1 (233·3–283·4) 565 (85·2%) 206·8 (190·4–224·5) 1909 (80·0%) 121·1 (115·8–126·7)
Economic status
Low-income and middle- 200 (37·7%) 123·6 (107·6–141·9) 315 (47·5%) 107·3 (96·1–119·9) 981 (41·1%) 58·2 (54·7–62·0)
income area
High-income area 331 (62·3%) 272·0 (244·2–303·0) 348 (52·5%) 168·0 (151·2–186·6) 1406 (58·9%) 111·8 (106·1–117·8)
Smoking status
Non-smoker 161 (30·3%) 141·4 (121·2–165·0) 111 (16·7%) 74·1 (61·5–89·3) 2115 (88·6%) 80·2 (76·8–83·7)
Light smoker 44 (8·3%) 125·6 (93·5–168·8) 67 (10·1%) 89·5 (70·4–113·7) 272 (11·4%) 89·6 (79·6–100·9)
Heavy smoker 326 (61·4%) 242·1 (217·2–269·9) 485 (73·2%) 175·8 (160·8–192·1) ··† ··†
Lung cancer mortality
Total 76 (0·1%) 26·7 (21·3–33·5) 218 (0·2%) 43·5 (38·1–49·7) 473 (0·1%) 16·1 (14·7–17·6)
Sex
Male 69 (90·8%) 48·3 (38·1–61·1) 204 (93·6%) 65·4 (57·0–75·0) 332 (70·2%) 28·3 (25·4–31·5)
Female 7 (9·2%) 4·9 (2·4–10·4) 14 (6·4%) 7·4 (4·4–12·5) 141 (29·8%) 8·0 (6·8–9·4)
Age group, years
40–54 9 (11·8%) 7·2 (3·7–13·7) 23 (10·6%) 10·1 (6·7–15·2) 77 (16·3%) 5·6 (4·5–7·0)
55–74 67 (88·2%) 42·3 (33·3–53·7) 195 (89·5%) 71·3 (62·0–82·1) 396 (83·7%) 25·1 (22·8–27·7)
Economic status
Low-income and middle- 34 (44·7%) 21·0 (15·0–29·4) 101 (46·3%) 34·4 (28·3–41·8) 167 (35·3%) 9·9 (8·5–11·5)
income area
High-income area 42 (55·3%) 34·3 (25·4–46·5) 117 (53·7%) 56·5 (47·1–67·7) 306 (64·7%) 24·3 (21·7–27·2)
Smoking status
Non-smoker 5 (6·6%) 4·4 (1·8–10·5) 6 (2·8%) 4·0 (1·8–8·9) 407 (86·1%) 15·4 (14·0–17·0)
Light smoker 8 (10·5%) 22·8 (11·4–45·6) 19 (8·7%) 25·4 (16·2–39·8) 66 (14·0%) 21·8 (17·1–27·7)
Heavy smoker 63 (82·9%) 46·6 (36·4–59·7) 193 (88·5%) 70·0 (60·8–80·6) ··† ··†
All-cause mortality
Total 176 (0·2%) 61·9 (53·4–71·7) 515 (0·4%) 102·9 (94·4–112·1) 2025 (0·3%) 68·8 (65·9–71·9)
Sex
Male 137 (77·8%) 95·8 (81·1–113·3) 447 (86·8%) 143·3 (130·6–157·2) 1280 (63·2%) 109·0 (103·2–115·1)
Female 39 (22·2%) 27·6 (20·1–37·7) 68 (13·2%) 36·0 (28·4–45·7) 745 (36·8%) 42·2 (39·2–45·3)
Age group, years
40–54 28 (15·9%) 22·2 (15·4–32·2) 78 (15·2%) 34·3 (27·5–42·8) 403 (19·9%) 29·5 (26·8–32·5)
55–74 148 (84·1%) 93·4 (79·5–109·7) 437 (84·9%) 159·9 (145·6–175·6) 1622 (80·1%) 102·9 (98·0–108·1)
Economic status
Low-income and middle- 87 (49·4%) 53·7 (43·5–66·2) 265 (51·5%) 90·3 (80·1–101·9) 1030 (50·9%) 61·2 (57·6–65·0)
income area
High-income area 89 (50·6%) 72·8 (59·1–89·6) 250 (48·5%) 120·6 (106·6–136·6) 995 (49·1%) 79·1 (74·3–84·2)
Smoking status
Non-smoker 35 (19·9%) 30·7 (22·0–42·7) 46 (8·9%) 30·7 (23·0–41·0) 1758 (86·8%) 66·6 (63·6–69·8)
Light smoker 19 (10·8%) 54·2 (34·5–84·9) 58 (11·3%) 77·5 (59·9–100·2) 267 (13·2%) 88·0 (78·1–99·2)
Heavy smoker 122 (69·3%) 90·3 (75·6–107·8) 411 (79·8%) 149·0 (135·3–164·1) ··† ··†
*Incidence density was the number of cases per 100 000 person-years; all incidence densities are crude rates. †No heavy smokers were categorised as low risk.

Table 3: Crude lung cancer incidence density and mortality by subgroup

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lower lung cancer mortality and all-cause mortality risks

A
1000 Screened
in the screened group compared with the non-screened
Cumulative lung cancer incidence
Non-screened group were statistically significant in men but not in
Low-risk women (figure 3). Reductions of 34·0% in lung cancer
750 High-risk
mortality (HR 0·66 [95% CI 0·49–0·88]) and 36·0% in
(per 100 000)

500 all-cause mortality (0·64 [0·53–0·78]) were observed in

the subgroup of participants aged 55–74 years in the
250 screened group compared with the non-screened group,
Gray test p<0·0001 but no significant reductions were observed in
0
0 2 4 6 8 participants aged 40–54 years (figure 3). Significant
Number at risk lung cancer mortality reductions were observed in high-
Screened 79 581 65 039 28 986 3052 income areas, but not in low-income and middle-
Non-screened 143 721 109 895 49 176 5641
Low-risk 793 438 643 906 324 237 39 332 income areas, in the screened group compared with the
High-risk 223 302 174 934 78 162 8693 non-screened group (figure 3). Compared with the
non-screened group, lung cancer mortality significantly
B
400
decreased among heavy smokers in the screened group,
Cumulative lung cancer mortality

whereas no significant lung cancer mortality reduction

300 was observed among light smokers or non-smokers.
Sex-specific HRs for the associations between LDCT
(per 100 000)

200 screening and lung cancer incidence, lung cancer

mortality, and all-cause mortality are shown in
100 appendix 2 (pp 12–13). Significant reductions in both
Gray test p<0·0001 lung cancer mortality and all-cause mortality were
0
0 2 4 6 8
observed among men in the screened group compared
Number at risk with the non-screened group. There were no significant
Screened 79 581 65 293 29 159 3106 reductions in lung cancer mortality or all-cause mortality
Non-screened 143 721 110 104 49 343 5679
Low-risk 793 438 644 660 324 961 39 577
among women in the screened group compared with the
High-risk 223 302 175 397 78 502 8785 non-screened group, despite there being significantly
more lung cancer cases detected in the screened women
C compared with the non-screened women (appendix 2
700
pp 12–13).
Cumulative all−cause mortality

600
The proportion of lung cancers that were stage 0–I was
500
highest in the screened group (244 [62·7%] of 389),
(per 100 000)

400
followed by the low-risk group (888 [55·7%] of 1594), then
300 the non-screened group (186 [41·5%] of 448). More
200 adenocarcinomas were detected in the low-risk group
100 (1542 [78·8%] of 1958) and the screened group (330 [72·5%]
Log-rank test p<0·0001
0 of 455) than in the non-screened group (316 [59·2%]
0 2 4 6 8
Follow-up (years)
of 534).
Number at risk Sensitivity analyses excluding individuals with stage 0
Screened 79 581 65 293 29 159 3106
Non-screened 143 721 110 104 49 343 5679 lung cancer from lung cancer cases showed insignificant
Low-risk 793 438 644 660 324 961 39 577 alteration of the findings from the main analysis
High-risk 223 302 175 397 78 502 8785
(appendix 2 p 14). Results were also similar when analysed
Figure 2: Cumulative lung cancer incidence (A), lung cancer mortality (B), with a cutoff age of 50 years (appendix 2 p 15).
and all-cause mortality (C)
p values are for the comparison between screened, non-screened, and low-risk Discussion
groups.
To our knowledge, this is the largest population-based,
prospective study evaluating the effectiveness of LDCT
Adjusted HRs for the association between LDCT screening in reducing the burden of lung cancer. With
screening and each outcome (lung cancer incidence, more than 1 million eligible participants recruited, we
lung cancer mortality, and all-cause mortality) from found that one-off LDCT screening was associated with a
weighted Cox regression models after IPW are shown in significant reduction in lung cancer mortality and all-cause
figure 3. The screened group had significantly higher mortality for the population assessed to be at high risk of
lung cancer incidence density (47·0% higher), lung cancer. Further studies are needed to explore
significantly lower lung cancer mortality (31·0% lower) interactions by subgroup to develop population-specific
and significantly lower all-cause mortality (32·0% screening strategies. Our results strongly support the
lower) than the non-screened group (figure 3). The feasibility of promoting one-off LDCT screening in

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populations at high risk of lung cancer, considering the

A HR (95%CI) p value
population’s demographic charac­teristics and local medical
facilities, especially in low-income and middle-income Sex
Male 1·33 (1·13–1·57) 0·0003
countries with limited medical resources. To promote
Female 1·91 (1·50–2·42) <0·0001
public health-care equity, prioritising a national lung cancer
Age, years
screening programme with one-off LDCT in such
40–54 2·28 (1·72–3·01) <0·0001
countries might be more beneficial—reaching more 1·30 (1·11–1·51)
55–74 0·0009
people—than maximising benefits among a small group Economic status
of people with repeated screenings. Low income and middle income 1·23 (1·01–1·51) 0·039
Our study adds important evidence to the area of High income 1·69 (1·41–2·02) <0·0001
LDCT screening. First, our study is the first and largest Smoking status
population-based, prospective study evaluating mortality Non–smoker 1·90 (1·45–2·49) <0·0001
reduction associated with one-off LDCT screening. The Light smoker 1·39 (0·96–2·00) 0·081
incidence densities of lung cancer in our study Heavy smoker 1·35 (1·14–1·60) 0·0003
(187·3 per 100 000 person-years [95% CI 172·0–203·9] Overall 1·47 (1·27–1·70) <0·0001
in the screened group and 132·4 per 100 000 person- 0·5 1·0 1·5 2·0 2·5 3·0 3·5
years [122·7–142·9] in the non-screened group) were
lower than those reported in randomised controlled B
trials such as the NLST trial (645 per 100 000 person- Sex
years) and the NELSON trial (558 per 100 000 person- Male 0·69 (0·51–0·92) 0·012
years).7,9 These lower incidence densities are not Female 0·73 (0·25–2·13) 0·56
surprising because the lung cancer incidence in China Age, years
(56·3 per 100 000) is systematically lower than that in 40–54 0·82 (0·37–1·83) 0·63

the USA (68·8 per 100 000), where the NLST trial was 55–74 0·66 (0·49–0·88) 0·0043
Economic status
done, or the Netherlands (78·8 per 100 000), where the
Low income and middle income 0·76 (0·51–1·14) 0·19
NELSON trial was done.2 Moreover, we included
High income 0·64 (0·44–0·93) 0·019
participants aged between 40–74 years in our study,
Smoking status
which is younger than the participants in NLST Non–smoker 1·11 (0·34–3·67) 0·87
(55–74 years) and NELSON (50–75 years).7,9 Additionally, Light smoker 1·00 (0·44–2·29) 0·99
our high-risk population included not only smokers, but Heavy smoker 0·65 (0·48–0·87) 0·0031
also non-smokers with remarkably lower lung cancer Overall 0·69 (0·53–0·92) 0·010
incidence than the smokers.32 Building on the results
0 1·0 2·0 3·0 4·0
from randomised controlled trials and considering
the limited resources in China, findings from our C
population-based screening study suggest that one-off
Sex
LDCT screening could substantially reduce lung cancer
Male 0·64 (0·52–0·79) <0·0001
mortality and all-cause mortality. In our study, the Female 0·85 (0·57–1·26) 0·41
reduction in lung cancer mortality associated with Age, years
screening (31·0%) was similar to that reported in NLST 40–54 0·80 (0·50–1·28) 0·35
and NELSON; however, the reduction in all-cause 55–74 0·64 (0·53–0·78) <0·0001
mortality associated with screening (32·0%) was Economic status
substantially higher than that reported in NLST (6·7%) Low income and middle income 0·74 (0·57–0·95) 0·016
and NELSON (the reduction reported in NELSON was High income 0·64 (0·49–0·84) 0·0012
not statistically significant).7,9 This reduction in all-cause Smoking status
mortality is considered to be an additional benefit of Non–smoker 1·10 (0·73–1·67) 0·64

screening, as previous studies have reported that Light smoker 0·72 (0·42–1·26) 0·25
Heavy smoker 0·62 (0·50–0·76) <0·0001
LDCT screening could result in other incidental clinical
Overall 0·68 (0·57–0·82) <0·0001
findings, particularly the early detection of cardio­
vascular33,34 and respiratory diseases,35 which are 0 0·5 1·0 1·5
two leading causes of years of life lost in China.3 A
Figure 3: Forest plot of the adjusted HRs for the association between an LDCT scan and lung cancer incidence
beneficial effect on all-cause mortality is likely to be density (A), lung cancer mortality (B), and all-cause mortality (C)
more noticeable in countries with limited medical Adjusted HRs are from weighted Cox regression models after inverse probability weighting. Comparisons are
resources and fewer diagnostic opportunities than in between the screened group and the non-screened group. HR=hazard ratio. LDCT=low-dose CT.
countries with enough medical supplies. Additionally,
compared with participants in the screened group and LDCT scan) might be more likely to have poor health
the low-risk group, the non-screened group awareness and less likely to seek medical assistance. We
(ie, participants at high risk who did not have an found that the cumulative all-cause mortality was

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highest in the non-screened group, followed by the
low-risk group and the screened group.
Second, our finding that mortality reductions associated
with one-off LDCT screening were statistically significant
only among smokers who had a 20 or more pack-year
smoking history with other lung cancer risk factors
warrants further investigation. This finding is consistent
with the recently released National Comprehensive
Cancer Network guidelines recom­ mending LDCT
screening for those with a 20 or more pack-year smoking
history.18 We did not find a significant lung cancer
mortality reduction in the screened group compared with
the non-screened group for light smokers (<20 pack-year
smoking history) or non-smokers, despite the fact that
more lung cancer cases were detected in the screened
group. Studies have repeatedly shown that lung cancer in
non-smokers differs from that in smokers with regard to
causes, treatment methods, and survival rates.36,37 A
prospective study of patients with lung cancer in the USA
found that compared with non-smokers, the adjusted HR
of all-cause deaths was 39% higher in current or recent
smokers than in non-smokers (HR 1·39 [95% CI
1·16–1·67]).38 Bryant and colleagues39 reported that overall
survival is better in non-smokers than in smokers, and the
difference is most apparent for those who are diagnosed at
an early stage of the disease. The underlying molecular
mechanisms of the difference in lung cancer between
smokers and non-smokers require further exploration.
We did not observe a significant difference in lung
cancer mortality among women in the screened and
non-screened groups. This finding differs from results of
the NELSON trial,9 which reported greater effects on
lung cancer mortality in women (RR 0·67 [95% CI
0·38–1·14]; not statistically significant) than in the entire
population (0·76 [0·61–0·94]). A possible explanation is
that most women in the NELSON trial were heavy
smokers,9 but 31 994 [79·4%] of the screened women in
our study were non-smokers. Strategies to select eligible
partici­pants for screening using other indices such as
polygenic risk scores, with lung cancer deaths as the
endpoint, are recommended in future studies to refine
the existing screening strategy for non-smokers and
women. The number of lung cancer deaths in non-
smokers and women was small, resulting in limited
statistical power to detect a significant association.
Further studies with a larger group of non-smokers and
women enrolled should be done to verify the effect of
one-off LDCT screening on mortality reductions. It
should be noted that in our study, the assessment
procedure for identifying the high-risk population
differed for men and women, which resulted in 65% of
the low-risk group being male non-smokers, with no
male non-smokers in the high-risk group. For non-
smokers, the higher proportion of men might be an
important reason for the higher all-cause mortality in the
low-risk group (66·6 per 100 000 person-years) than in
the high-risk group (30·7 per 100 000 person-years). This
388
finding is consistent with previous studies in which
all-cause mortality was higher in men than in women.40
We observed significant reductions in lung cancer
mortality in high-income areas, but not in low-income
and middle-income areas. The lower proportion of lung
cancer cases at stage 0–I in the screened group
(108 [54·2%] in low-income and middle-income areas vs
225 [67·9%] in high-income areas), limited access to
advanced medical services, and strained medical
facilities in low-income and middle-income areas might
impede patients with lung cancer from receiving timely
treatment. Previous studies have shown that the 5-year
survival rate for patients with lung cancer in high-
income areas is much higher than that in low-income
and middle-income areas.41 Area-specific screening
strategies, rather than a uniform strategy, should be
considered by lung cancer screening programmes.
Similarly, our findings did not suggest that lung cancer
screening should be done among individuals younger
than 55 years in the current screening setting. More data
are needed to develop an evidence-based screening
strategy to benefit this population. Policies targeting
heavy smokers, men, and those older than 55 years for
one-off LDCT screening should be initiated to maximise
the use of scarce medical services.
Last, the proportion of lung cancers at stage 0–I in the
non-screened group (186 [41·5%]) and the low-risk group
(888 [55·7%]) was much higher than that reported by
hospital-based analyses (19·0%).42 Our findings suggest
that even without the provision of a free LDCT scan,
screening programmes involving health education might
also increase the early detection of lung cancer and
potentially decrease disease-specific mortality. This
education could serve as a first step to promote health in
areas where it is not practicable to implement
LDCT screening. Our results are in line with the Healthy
China Initiative Implementation Plan for Cancer
Prevention and Treatment (2019–22),43 recently published
by the National Health Commission, which highlights
the importance of raising people’s awareness of cancer
and to promote lung cancer screening.
Lung cancer is the leading cause of cancer-related
morbidity and mortality in China.44 It is estimated that
there were 787 000 newly diagnosed lung cancer cases
in 2015, corresponding to more than 2100 new lung cancer
diagnoses each day. Moreover, there were an estimated
630 500 lung cancer deaths in China in 2015, equivalent
to an average of more than 1700 deaths each day.44 In 2018,
China accounted for more than one-third of lung cancer
cases and deaths in the world.2 In the past few years,
China has become one of the active advocates of health
promotion in Asia. The success of lung cancer screening
in China could help in the implementation of a global
roadmap towards effective control of lung cancer. As
such, the Chinese government has issued a series of
cancer control policies, including the Cancer Prevention
and Control Three-year Action Plan (2015–17)45 and
www.thelancet.com/respiratory Vol 10 April 2022

Medium-to-Long-Term Plan for Prevention and Control
of Chronic Diseases (2017–25).46 These policies share the
common goal of initiating integrated cancer control
programmes and reducing cancer mortality. In the
context of these policies, our finding that one-off
LDCT screening is effective in reducing the lung cancer
burden provides timely evidence for policy makers to
make evidence-based decisions on appropriate lung
cancer screening strategies, and could substantially
influence health-care reform in China.
A number of limitations should be acknowledged. First,
our study did not use representative sampling because it
was not possible in the context of rapid, large-scale
recruitment. However, we did consider economic and
geographical variations of the selected provinces. Second, a
median follow-up of 3·6 years (IQR 2·8–5·1) in the current
study might be insufficient to monitor long-term
outcomes. Our findings support the effectiveness of
one-off LDCT screening in reducing mortality in the short-
term, leaving long-term effective­ness to be investigated in
the future with extended follow-up. Third, outcome data
were obtained from the cancer registry system and death
surveillance system. China has endeavoured to improve
the coverage, accuracy, and timeliness of cancer registration
data and death surveillance data. Recently, local data from
several cancer registries from all eight provinces were
accepted and used to estimate the country-specific cancer
burden in China in GLOBOCAN 2020.47 The data quality
obtained from these provinces is reliable.12,48 Nevertheless,
there is a potential risk of missing or mis-stated cases in
practice. In 2012, a report indicated that 2·73% of causes of
death from the death surveillance system in China were
coded inaccurately.49 However, because any misclassi­
fication of data would be similar in the screened and
non-screened groups, this issue should not have influenced
our main findings to any great degree. Fourth, our study
has a 35·6% compliance rate for LDCT scans, which is
lower than that reported in randomised controlled trials
such as NLST (98·5%) and NELSON (90·0%).7,9 Studies
investigating factors that might be associated with
compliance should be considered in the future, and health
education should be initiated across the entire country.
Fifth, residual confounding is likely to exist given that
variables such as distance to medical services and
participants’ mobility might influence LDCT scan uptake.
These variables were not available in the current study, nor
in most other cohort studies. However, we did IPW
accounting for participants’ demographics, lifestyle factors,
and baseline comorbidity. Moreover, we reasonably
assumed that if the participants were able to participate in
the risk assessment, they should also be able to participate
in LDCT screening. Thus, the exclusion of these variables
should not have had a substantial effect on the results.
Despite this, we are currently collecting these data and will
assess their added value in future studies. Finally, although
we found that mortality reductions were statistically
significant in men but not in women, in individuals aged
www.thelancet.com/respiratory Vol 10 April 2022
Articles
55–74 years but not in those aged 40–54 years, in people
with a smoking history of 20 or more pack-years but not in
those with a history of less than 20 pack-years or in
non-smokers, and participants living in high-income areas
but not in low-income and middle-income areas, our
data—with considerable overlap of 95% CIs (figure 3 and
table 3)—do not provide evidence of significant differences
between these subgroups. Further studies powered for
these subgroup analyses will be needed to inform
population-specific screening strategies.
In conclusion, our results support the implementation
of one-off LDCT screening in China, and could contribute
to lung cancer control and improvements in the health of
the Chinese population. In the context of the COVID-19
pandemic, with people paying greater attention to lung
health, a high compliance rate for LDCT screening might
lead to better health outcomes. Our study provides
evidence for policy makers and public health practitioners
to shape current lung cancer screening guidelines and
develop public health strategies, not only in China but
also in other countries—an important step towards
global cancer control in the long run.
Contributors
JH conceived the National Lung Cancer Screening project and took
responsibility for its all aspects. NL and FT designed the study and
conceived this manuscript, with further contributions from HS and
WCh. NL, FT, WCh, and MD led the data collection supported by LZ, LG,
HC, YL, DW, DD, JC, SZ, SY, NWa, and LD. NWu, FT and WT led the
quality control by medical records reviews. NL, FT, WCh, FW, and YY
wrote the manuscript, with further contributions from JL, ZY, YZ, YX,
and CQ. NL, SS, and FT verified the underlying data, and completed all
the statistical analysis supported by FW, WCa, ZW, and MZ. All authors
interpreted data, contributed to critical revisions, and approved the final
version of the article. The corresponding author had full access to all the
data in the study and had final responsibility for the decision to submit
for publication. No author was prevented from accessing any data.
The National Lung Cancer Screening programme group
Group members are listed in alphabetical order; affiliations are provided
in appendix 2 (p 27–30). Ji Cao, Sumei Cao, Wei Cao, Hongda Chen,
Wanqing Chen, Ying Cheng, Hong Cui, Min Dai, Dong Dong,
Hua Dong, Xuesi Dong, Lingbin Du, Lianying Ge, Jiyong Gong,
Lanwei Guo, Jie He, Mei He, Yutong He, Limin Huang, Yao Huang,
Yubei Huang, Yunchao Huang, Jing Jiang, Shengyan Jin, Yunxin Kong,
Fang Li, Jiang Li, Jibin Li, Ni Li, Xin Li, Xianzhen Liao, Yunyong Liu,
Yuqin Liu, Zilin Luo, Zhangyan Lv, Hongxia Ma, Yanling Ma, Liang Qiao,
Chao Qin, Jiansong Ren, Hongbing Shen, Sipeng Shen, Jufang Shi,
Benhua Song, Bingbing Song, Shuming Song, Kai Su, Gang Sun,
Fengwei Tan, Wei Tang, Fei Wang, Le Wang, Ning Wang, Donghua Wei,
Luopei Wei, Qingfeng Wei, Yan Wen, Ning Wu, Zheng Wu, Yunfeng Xi,
Yongjie Xu, Shipeng Yan, Lei Yang, Zhuoyu Yang, Zhihua Yin,
Lianzheng Yu, Xinyang Yu, Yiwen Yu, Min Zhang, Shaokai Zhang,
Yongzhen Zhang, Liang Zhao, Yadi Zheng, Baosen Zhou, Jinyi Zhou,
Chen Zhu, Meng Zhu, and Kaiyong Zou.
Declaration of interests
We declare no competing interests.
Data sharing
The analysed datasets in the study cannot be shared with third parties
due to the relevant regulations of the Ministry of Industry and
Information Technology of China. Data sharing is only possible after
reaching a consensus agreement with the Ministry.
Acknowledgments
Funding for this study was provided by the Ministry of Finance and
National Health Commission of the People’s Republic of China, National
389
 Articles
Key Research and Development Program of China (grant number
2018YFC1315000/2018YFC1315001), the non-profit Central Research
Institute Fund of the Chinese Academy of Medical Sciences (grant
numbers 2019PT320027 and 2020PT330001), the Chinese Academy of
Medical Sciences Innovation Fund for Medical Science (grant number
2019-I2M-2-002), the Sanming Project of Medicine in Shenzhen (grant
number SZSM201911015), the National Natural Science Foundation of
China (grant number 81871885), and the Beijing Science and Technology
Project (grant number Z181100001718212).
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