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Low-dose computed tomography (LDCT) screening is effective in reducing lung cancer mortality in smokers; however, the evidence in nonsmokers is scarce.
This study aimed to evaluate the participant rate and effectiveness of one-off LDCT screening for lung cancer among smokers and nonsmokers.
A population-based prospective cohort study was performed to enroll participants aged between 40 and 74 years from 2013 to 2019 from 4 cities in Zhejiang Province, China. Participants who were evaluated as having a high risk of lung cancer from an established risk score model were recommended to undergo LDCT screening. Follow-up outcomes were retrieved on June 30, 2020. The uptake rate of LDCT screening for evaluated high-risk participants and the detection rate of early-stage lung cancer (stage 0-I) were calculated. The lung cancer incidence, lung cancer mortality, and all-cause mortality were compared between the screened and nonscreened groups.
At baseline, 62.56% (18,818/30,079) of smokers and 6% (5483/91,455) of nonsmokers were identified as high risk (
LDCT screening effectively reduces lung cancer and all-cause mortality among high-risk smokers. Further efforts to define high-risk populations and explore adequate lung cancer screening modalities for nonsmokers are needed.
Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer-related death worldwide; in 2020, there were an estimated 2.2 million new cases and 1.8 million deaths [
Screening with low-dose computed tomography (LDCT) is effective in reducing lung cancer mortality in rigorously randomized controlled trials such as the National Lung Screening Trial (NLST) and the Dutch-Belgian lung cancer screening trial (Nederlands Leuvens Screening Onderzoek [NELSON]); however, such trials have high LDCT uptake rates exceeding 90% [
The Cancer Screening Program in Urban China (a large public health service project) conducted in 2012 included both smokers and nonsmokers and targeted 5 types of cancer (lung cancer, female breast cancer, esophageal and gastric cancer, colorectal cancer, and liver cancer) [
We performed a population-based prospective study using the framework of the Cancer Screening Program in Urban China [
We used data from lung cancer screening conducted between October 2013 and September 2019 in Zhejiang Province, which covered 4 cities (Hangzhou, Ningbo, Quzhou, and Jinhua). Overall, 121,534 eligible individuals participated in the lung cancer screening program (
Flow diagram of the study population. LDCT: low-dose computed tomography.
The study was approved by the ethics committee of the Chinese Academy of Medical Sciences’s Cancer Hospital (approval number 15-070/997) and Zhejiang Cancer Hospital (approval number IRB-2022-271).
Eligible participants completed a cancer-related risk assessment questionnaire designed by the Cancer Screening Program in Urban China before LDCT that included questions regarding cigarette smoking history, occupational exposure to hazardous substances, frequent exercise, chronic respiratory diseases, family history of lung cancer, dietary intake of fresh vegetables in the previous year, and passive smoking. We adopted the sex-specific risk score systems derived from the Harvard Cancer Risk Index to evaluate the risk of lung cancer [
Individuals labeled as being at high risk for lung cancer were recommended to undergo a free LDCT scan with ≥16 slices at a tertiary-level hospital designated by the program. These participants then underwent a process of shared decision-making that included information about the potential benefits and harms of screening with LDCT to ensure that their decisions on LDCT scans were based on their free will.
To account for potential immortal time bias, where individuals in the screened group had to survive (be alive and event free) until the LDCT scan was conducted, the cohort entry date was defined as the date of screening in the screened group. For individuals in the nonscreened 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 of the nonscreened group. Time to lung cancer occurrence was calculated from the cohort entry date until the earliest occurrence of lung cancer, death, or administrative censoring (June 30, 2020). Accordingly, time to lung cancer death or all-cause death was calculated from the cohort entry date until death or administrative censoring, whichever occurred first.
The primary outcomes of interest were incidence of lung cancer, lung cancer mortality, and all-cause mortality. The secondary outcomes were the proportion of early-stage lung cancer (stage 0-I) and the participation rate of LDCT. Lung cancer was defined according to the International Classification of Diseases (10th revision) and was coded as C34. Outcome data were retrieved from national linkages, including the cancer registry system and death surveillance system, every 6 months.
Paper-based standardized documentation forms (epidemiological questionnaire and LDCT report) were collected from trained staff and physicians. Form validity was checked and entered into the data management system by trained study staff. A consistency check was performed, and if inconsistencies were identified, errors were corrected by retrieving the original records. Each participant had a unique identification number that was used to track all individual-related documentation forms. All data were transmitted to the Central Data Management Team of the National Cancer Center of China, where databases were constructed and analyzed.
Covariates from the baseline survey included demographic characteristics (age: 40-54 years and 55-74 years; sex; education level: low [primary school or below], medium [primary school to high school], and high [high school or above]; and BMI), lifestyle factors (smoking status, passive smoking, occupational exposure to hazardous substances, and frequent exercise), family history of lung cancer, and baseline comorbidities (chronic respiratory diseases, digestive diseases, hepatobiliary diseases, hypertension, diabetes, and hyperlipidemia). Passive smoking referred to involuntary inhalation of tobacco smoke. Occupational exposure to hazardous substances included occupational exposure to asbestos, rubber, dust, pesticides, radiation, beryllium, uranium, and radon for at least 1 year. Frequent exercises were defined as exercises conducted at least 3 times per week for ≥30 minutes each. Respiratory diseases included pulmonary tuberculosis, chronic bronchitis, emphysema, asthmatic bronchiectasis, silicosis, and pneumoconiosis.
Baseline study population characteristics were summarized using frequencies and percentages for categorical variables and arithmetic means and SDs for continuous variables. Baseline factors were compared between the nonsmoker and smoker groups using a 2-tailed Student
In total, 121,534 participants aged 40-74 years who were enrolled in the program were included in this study; of them, 75.3% (n=91,453) were nonsmokers and 24.7% (n=30,079) were smokers. Compared with nonsmokers, smokers were older; were more likely to be male; were more likely to have medium and high educational levels; were more overweight and obese; and had more occupational exposure to hazardous substances, passive smoking, family history of lung cancer, chronic respiratory diseases, digestive diseases, hepatobiliary diseases, hypertension, hyperlipidemia, and diabetes but were less likely to exercise frequently (
Baseline characteristics of the study population (N=121,534).
Characteristics | Overalla (N=121,534) | Nonsmoker groupb (n=91,455) | Smoker groupc (n=30,079) | ||||||||
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|||||||||||
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|
56.5 (8.3) | 56.4 (8.4) | 56.8 (8.0) | <.001 | ||||||
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|
40-54, n (%) | 49,948 (41.10) | 38,166 (41.73) | 11,782 (39.17) |
|
|||||
|
|
55-74, n (%) | 71,586 (58.90) | 53,289 (58.27) | 18,297 (60.83) |
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|
<.001 | |||||||||
|
|
Male | 51,623 (42.48) | 22,499 (24.60) | 29,124 (96.83) |
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|
Female | 69,911 (57.52) | 68,956 (75.40) | 955 (3.17) |
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<.001 | |||||||||
|
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Low | 36,691 (30.19) | 28,925 (31.63) | 7766 (25.82) |
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|||||
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Medium | 70,489 (58.00) | 51,977 (56.83) | 18,512 (61.54) |
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|
High | 14,354 (11.81) | 10,553 (11.54) | 3801 (12.64) |
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<.001 | |||||||||
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<18.5 | 3294 (2.71) | 2645 (2.90) | 649 (2.16) |
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|
18. 5-24 | 68,948 (56.82) | 52,997 (58.05) | 15,951 (53.12) |
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24-28 | 40,842 (33.66) | 29,630 (32.45) | 11,212 (37.33) |
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≥28 | 8250 (6.80) | 6031 (6.61) | 2219 (7.39) |
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<.001 | |||||||||
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No | 106,361 (87.52) | 82,044 (89.71) | 24,317 (80.84) |
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|||||
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|
Yes | 15,173 (12.48) | 9411 (10.29) | 5762 (19.16) |
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<.001 | |||||||||
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No | 74,087 (61.11) | 63,153 (69.15) | 10,934 (36.55) |
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|||||
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Yes | 47,158 (38.89) | 28,173 (30.85) | 18,985 (63.45) |
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<.001 | |||||||||
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No | 64,019 (52.68) | 45,355 (49.59) | 18,664 (62.05) |
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|||||
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Yes | 57,515 (47.32) | 46,100 (50.41) | 11,415 (37.95) |
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<.001 | |||||||||
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No | 98,370 (88.69) | 74,851 (90.17) | 23,519 (84.30) |
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Yes | 12,539 (11.31) | 8159 (9.83) | 4380 (15.70) |
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|||||||||||
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<.001 | |||||||||
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No | 105,151 (86.52) | 81,371 (88.97) | 23,780 (79.06) |
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|||||
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|
Yes | 16,383 (13.48) | 10,084 (11.03) | 6299 (20.94) |
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<.001 | |||||||||
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No | 90,832 (74.74) | 70,115 (76.71) | 20,717 (68.88) |
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|||||
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|
Yes | 30,702 (25.26) | 21,340 (23.29) | 9362 (31.12) |
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<.001 | |||||||||
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No | 90,549 (74.51) | 70,159 (76.71) | 20,390 (67.79) |
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|||||
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|
Yes | 30,985 (25.49) | 21,296 (23.29) | 9689 (32.21) |
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<.001 | |||||||||
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No | 78,772 (71.20) | 60,271 (72.72) | 18,501 (66.66) |
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|||||
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Yes | 31,858 (28.80) | 22,605 (27.28) | 9253 (33.34) |
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<.001 | |||||||||
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No | 91,603 (82.81) | 69,381 (83.72) | 22,222 (80.07) |
|
|||||
|
|
Yes | 19,018 (17.19) | 13,487 (16.28) | 5531 (19.93) |
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|||||
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<.001 | |||||||||
|
|
No | 101,246 (91.52) | 76,417 (92.21) | 24,829 (89.46) |
|
|||||
|
|
Yes | 9379 (8.48) | 6455 (7.79) | 2924 (10.54) |
|
aOverall: 200 participants without information on BMI, 289 participants without information on passive smoking, 10,625 participants without information on family history of lung cancer, 10,904 participants without information on hypertension, 10,913 participants without information on hyperlipidemia, and 10,909 participants without information on diabetes.
bNonsmokers: 152 participants without information on BMI, 129 participants without information on passive smoking, 8445 participants without information on family history of lung cancer, 8579 participants without information on hypertension, 8587 participants without information on hyperlipidemia, and 8583 participants without information on diabetes.
cSmokers: 48 participants without information on BMI, 160 participants without information on passive smoking, 2180 participants without information on family history of lung cancer, 2325 participants without information on hypertension, 2326 participants without information on hyperlipidemia, and 2326 participants without information on diabetes.
d
Among smokers, 62.56% (18,818/30,079) were identified as being at high risk for lung cancer, which was significantly higher than 5.8% (5483/94,455) among nonsmokers (
Participation rates of low-dose computed tomography (LDCT) screening for high-risk population by smoking status (n =24,301).
Characteristics | Nonsmoker groupa | Smoker groupb | ||||||||||
|
Participants at high risk, n | Underwent LDCT, n (%) | ORd (95% CI) | Participants at high risk, n | Underwent LDCT, n (%) | ORd (95% CI) | ||||||
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||||||||||||
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|
.005 |
|
<.001 |
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|||||||
|
|
40-54 | 2374 | 1623 (68.37) |
|
—e | 7217 | 2779 (38.51) |
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Reference | ||
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55-74 | 3109 | 2013 (64.75) |
|
— | 11,601 | 5106 (44.01) |
|
1.24 (1.16-1.33) | ||
|
|
— |
|
<.001 |
|
|||||||
|
|
Male | 0 | 0 (0) |
|
— | 18,178 | 7524 (41.39) |
|
Reference | ||
|
|
Female | 5483 | 3636 (66.31) |
|
— | 640 | 361 (56.41) |
|
1.33 (1.11-1.58) | ||
|
|
.65 |
|
.48 |
|
|||||||
|
|
Low | 1889 | 1261 (66.75) |
|
— | 5304 | 2247 (42.36) |
|
— | ||
|
|
Medium | 3054 | 2026 (66.34) |
|
— | 11,540 | 4833 (41.88) |
|
— | ||
|
|
High | 540 | 349 (64.63) |
|
— | 1974 | 805 (40.78) |
|
— | ||
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|
.42 |
|
<.001 |
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|||||||
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<18.5 | 187 | 114 (60.96) |
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— | 445 | 174 (39.10) |
|
— | ||
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18.5-24 | 3156 | 2107 (66.76) |
|
— | 10,066 | 4089 (40.62) |
|
— | ||
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|
24-28 | 1736 | 1153 (66.42) |
|
— | 6882 | 2978 (43.27) |
|
— | ||
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|
≥28 | 393 | 257 (65.39) |
|
— | 1393 | 634 (45.51) |
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— | ||
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||||||||||||
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|
<.001 |
|
<.001 |
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|||||||
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No | 3716 | 2338 (62.92) |
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Reference | 14,712 | 5668 (38.53) |
|
Reference | ||
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Yes | 1767 | 1298 (73.46) |
|
1.37 (1.19-1.58) | 4106 | 2217 (53.99) |
|
1.50 (1.38-1.62) | ||
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|
.001 |
|
|
|
<.001 |
|
|||||
|
|
No | 949 | 586 (61.75) |
|
Reference | 5735 | 2140 (37.31) |
|
— | ||
|
|
Yes | 4463 | 2998 (67.17) |
|
1.22 (1.04-1.44) | 12,935 | 5649 (43.67) |
|
— | ||
|
|
.76 |
|
.41 |
|
|||||||
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|
No | 4205 | 2784 (66.21) |
|
— | 13,486 | 5676 (42.09) |
|
— | ||
|
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Yes | 1278 | 852 (66.67) |
|
— | 5332 | 2209 (41.43) |
|
— | ||
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|
<.001 |
|
<.001 |
|
|||||||
|
|
No | 2098 | 1238 (59.01) |
|
Reference | 13,583 | 5213 (38.38) |
|
Reference | ||
|
|
Yes | 3200 | 2305 (72.03) |
|
1.83 (1.62-2.08) | 3764 | 2255 (59.91) |
|
1.74 (1.60-1.90) | ||
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||||||||||||
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|
.12 |
|
<.001 |
|
|||||||
|
|
No | 333 | 234 (70.27) |
|
— | 13,440 | 4875 (36.27) |
|
Reference | ||
|
|
Yes | 5150 | 3402 (66.06) |
|
— | 5378 | 3010 (55.97) |
|
1.40 (1.29-1.51) | ||
|
|
.03 |
|
<.001 |
|
|||||||
|
|
No | 2158 | 1394 (64.60) |
|
— | 12,246 | 4519 (36.90) |
|
Reference | ||
|
|
Yes | 3325 | 2242 (67.40) |
|
— | 6572 | 3366 (51.22) |
|
1.24 (1.16-1.33) | ||
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|
<.001 |
|
<.001 |
|
|||||||
|
|
No | 2233 | 1355 (60.7) |
|
Reference | 12,186 | 4361 (35.79) |
|
Reference | ||
|
|
Yes | 3250 | 2281 (70.2) |
|
1.37 (1.21-1.56) | 6632 | 3524 (53.14) |
|
1.35 (1.25-1.45) | ||
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|
.80 |
|
<.001 |
|
|||||||
|
|
No | 3254 | 2162 (66.44) |
|
— | 11,319 | 4630 (40.90) |
|
— | ||
|
|
Yes | 1506 | 995 (66.07) |
|
— | 5736 | 2612 (45.54) |
|
— | ||
|
|
— |
|
<.001 |
|
|||||||
|
|
No | 3174 | 2068 (65.15) |
|
— | 13,458 | 5367 (39.88) |
|
Reference | ||
|
|
Yes | 1583 | 1086 (68.60) |
|
— | 3596 | 1873 (52.09) |
|
1.19 (1.10-1.30) | ||
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|
.21 |
|
<.001 |
|
|||||||
|
|
No | 4301 | 2864 (66.59) |
|
— | 15,225 | 6356 (41.75) |
|
Reference | ||
|
|
Yes | 457 | 291 (63.68) |
|
— | 1829 | 885 (48.39) |
|
1.16 (1.04-1.29) |
aNonsmokers: 11 participants without information on BMI, 71 participants without information on passive smoking, 185 participants without information on family history of lung cancer, 723 participants without information on hypertension, 726 participants without information on hyperlipidemia, and 725 participants without information on diabetes.
bSmokers: 32 participants without information on BMI, 148 participants without information on passive smoking, 1471 participants without information on family history of lung cancer, 1763 participants without information on hypertension, 1764 participants without information on hyperlipidemia, and 1764 participants without information on diabetes.
c
dOR: odds ratio. ORs are presented for variables with significance in the multivariate logistic regression.
eThe variable is excluded from the final model and OR is not available.
fAll nonsmokers were female .
After a median follow-up time of 5.1 years (IQR 3.1-5.9 years), 377 lung cancer cases, 202 all-cause death cases, and 67 lung cancer death cases were observed among smokers, and 733 lung cancer cases, 254 all-cause death cases, and 49 lung cancer death cases were observed among nonsmokers (
Lung cancer incidence cases and deaths among all participants (N=121,534).
|
Nonsmokera | Smokerb | |||||||||
|
All (n=91,455) | Low risk (n=85,972) | Nonscreened (n=1847) | Screened (n=3636) | All (n=30,379) | Low risk (n=11,261) | Nonscreened (n=10,933) | Screened (n=7885) | |||
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|
All cases | 733 | 662 | 17 | 54 | 377 | 86 | 148 | 143 | ||
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|
||||||||||
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|
0-I | 476 (80.3) | 424 (79) | 10 (83.3) | 42 (95.5) | 173 (60.3) | 45 (67.2) | 56 (49.1) | 72 (67.9) | |
|
|
II | 24 (4.1) | 23 (4.2) | 1 (8.3) | 0 (0) | 19 (6.6) | 3 (4.5) | 8 (7) | 8 (7) | |
|
|
III | 32 (5.4) | 31 (5.8) | 1 (8.3) | 0 (0) | 47 (16.4) | 8 (11.9) | 22 (19.3) | 17 (15) | |
|
|
IV | 61 (10.3) | 59 (11) | 0 (0) | 2 (4.5) | 48 (16.7) | 11 (16.4) | 28 (24.6) | 9 (8.5) | |
|
|
||||||||||
|
|
Adenocarcinoma | 607 (90.2) | 546 (89.1) | 16 (94.1) | 45 (93.8) | 194 (61.2) | 54 (71.1) | 59 (48.4) | 81 (68.1) | |
|
|
Squamous cell carcinoma | 34 (5.1) | 33 (5.4) | 0 (0) | 1 (2.1) | 79 (24.9) | 16 (21.1) | 39 (32) | 24 (20.2) | |
|
|
Small-cell carcinoma | 13 (1.9) | 13 (2.1) | 0 (0) | 0 (0) | 31 (9.8) | 4 (5.3) | 18 (14.8) | 8 (7.6) | |
|
|
Others | 19 (2.8) | 21 (3.4) | 1 (5.9) | 2 (4.2) | 13 (4.1) | 2 (2.6) | 6 (4.9) | 5 (4.2) | |
|
|||||||||||
|
All-cause death cases | 254 | 246 | 3 | 5 | 202 | 64 | 102 | 36 | ||
|
Lung cancer death cases | 49 | 48 | 1 | 0 | 67 | 13 | 40 | 14 |
aNonsmokers: 140 lung cancer cases without information on stage and 60 lung cancer cases without information on histological type.
bSmokers: 90 lung cancer cases without information on stage and 60 lung cancer cases without information on the histological type.
Lung cancer incidence density and mortality rate by subgroups.
|
Nonsmoker | Smoker | |||||||||||||||||||||||||
|
Cases, n | Crude ratea (95% CI) | Adjusted ratea,b (95% CI) | Cases, n | Crude ratea (95% CI) | Adjusted ratea,b (95% CI) | |||||||||||||||||||||
|
|||||||||||||||||||||||||||
|
Overall | 733 | 178.51 (166.05-191.92) | 179.78 (166.14-194.54) | N/Ad | 377 | 277.57 (250.92-307.05) | 219.86 (157.77-306.40) | N/A | ||||||||||||||||||
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|
<.001c |
|
<.001c | |||||||||||||||||||||||
|
|
Low-risk group | 662 | 170.23 (157.74-183.70) | 173.28 (159.64-188.08) | N/A | 86 | 157.80 (127.74-194.94) | 144.60 (67.76-308.57) | N/A | |||||||||||||||||
|
|
Nonscreened group | 17 | 223.72 (139.08-359.88) | 129.32 (80.39-208.03) | .06e | 148 | 306.10 (260.55-359.61) | 132.65 (112.91-155.84) | <.001 | |||||||||||||||||
|
|
Screened group | 54 | 382.33 (292.82-499.21) | 223.37 (171.03-291.72) | N/A | 143 | 433.71 (368.14-510.96) | 389.49 (249.18-608.81) | N/A | |||||||||||||||||
|
|||||||||||||||||||||||||||
|
Overall | 254 | 61.63 (54.50-69.69) | 72.62 (63.54-83.01) | N/A | 202 | 147.89 (128.84-169.76) | 74.83 (54.98-103.73) | N/A | ||||||||||||||||||
|
|
.29c |
|
<.001c | |||||||||||||||||||||||
|
|
Low-risk group | 246 | 63.04 (55.63-71.43) | 73.09 (63.92-83.58) | N/A | 64 | 117.10 (91.65-149.61) | 84.83 (37.31-192.89) | N/A | |||||||||||||||||
|
|
Nonscreened group | 3 | 39.29 (12.67-121.81) | 22.56 (7.28-69.95) | .89e | 102 | 210.0 (172.9-255.0) | 91.03 (74.97-110.53) | <.001e | |||||||||||||||||
|
|
Screened group | 5 | 35.02 (14.57-84.13) | 20.74 (8.63-49.86) | N/A | 36 | 107.93 (77.86-149.63) | 46.03 (33.16-63.88) | N/A | |||||||||||||||||
|
|||||||||||||||||||||||||||
|
Overall | 49 | 11.89 (8.99-15.73) | 15.98 (11.85-21.55) | N/A | 67 | 49.05 (38.61-62.33) | 32.4 (15.75-66.64) | N/A | ||||||||||||||||||
|
|
.43c |
|
<.001c | |||||||||||||||||||||||
|
|
Low-risk group | 48 | 12.3 (9.3-16.3) | 23.2 (18.6-29.1) | N/A | 13 | 25.7 (16.0-41.3) | 23.8 (13.8-41.0) | N/A | |||||||||||||||||
|
|
Nonscreened group | 1 | 13.1 (1.8-93.0) | 7.5 (1.1-53.4) | .17e | 40 | 82.3 (60.4-112.3) | 35.7 (26.2-48.6) | <.001e | |||||||||||||||||
|
|
Screened group | 0f | 0f | 0f | N/A | 14 | 41.97 (24.86-70.87) | 17.7 (10.47-29.94) | N/A |
aRate is the number of cases per 100,000 person-year.
bRate is adjusted by age group and gender.
c
dN/A: not applicable.
e
fNo lung cancer death cases were reported for the group.
For smokers, the crude lung cancer incidence densities in the low-risk, nonscreened, and screened groups were 157.80 (95% CI 127.74-194.94) per 100,000 person-year, 306.10 (95% CI 260.55-359.61) per 100,000 person-year, and 433.71 (95% CI 368.14-510.96) per 100,000 person-year, respectively (
(A) Cumulative intensity of lung cancer incidence, (B) cumulative lung cancer mortality, and (C) cumulative all-cause mortality in smokers.
For nonsmokers, lung cancer incidence densities in the low-risk, nonscreened, and screened groups were 170.23 (95% CI 157.74-183.70) per 100,000 person-year, 223.72 (95% CI 139.08-359.88) per 100,000 person-year, and 382.33 (95% CI 292.82-499.21) per 100,000 person-year, respectively. No significant differences were detected in lung cancer intensity (
(A) Cumulative intensity of lung cancer incidence, (B) cumulative lung cancer mortality, and (C) cumulative all-cause mortality in nonsmokers.
In this multicenter-based prospective cohort study involving ≥120,000 participants, we found a higher participation rate of LDCT screening among nonsmokers than among smokers (3636/5483, 66.31% vs 7885/18,818, 41.9%). Statistically significant reduced lung cancer mortality and all-cause mortality were observed among smokers in the screened group compared with those in the nonscreened group, with a higher proportion of early-stage lung cancer (72/106, 67.9% in the screened group and 56/114, 49.1% in the nonscreened group). However, we failed to find a significant mortality reduction among screened nonsmokers, relative to nonscreened nonsmokers.
The LDCT screening participation rate for nonsmokers was higher than that for smokers, as reported in other studies [
As expected, a higher lung cancer incidence density was detected in the high-risk and screened groups, and most lung cancers among the nonsmoker participants were detected in the early stages (476/593, 80.3% were in stage 0-I), in contrast to those among smokers (173/287, 60.3% were in stage 0-I). Moreover, our study showed that the proportion of early-stage lung cancer was also high in the nonscreened group (10/12, 83% vs 56/114, 49.1%). A multicenter hospital-based study in China reported that the proportion of patients with stage I lung cancer was only 19% [
In our study, the most frequent histological type was adenocarcinoma, with a proportion of 90.2% (607/673) among nonsmokers and 61.2% (194/317) among smokers. East Asian female never-smokers tend to develop adenocarcinoma, with the majority developing from oncogenic mutations [
Over a median follow-up time of 5.1 years, among smokers who were evaluated as high risk, we found a remarkable 48% lung cancer mortality reduction by screening with LDCT. LDCT screening has high potential benefit in decreasing lung cancer mortality worldwide, as shown in the NLST, NELSON, and the German Lung Cancer Screening Intervention Trial studies, which demonstrated that LDCT screening reduced lung cancer mortality by 20%, 24%, and 26%, respectively [
The promising effects of the LDCT screening program observed in this study may be because of sufficient medical resources and health care infrastructure in Zhejiang. Zhejiang is a coastal province with a relatively high economy level in China, of which the gross domestic product per capita was US $14,600 in 2020, which was 1.40 times that of the national average and 1.45 times that of the global average. Due to its rapidly growing economy and a well-developed medical system, cancer screening has been well received and undertaken since the 1970s [
We observed a significant 53% reduction in all-cause mortality following LDCT screening among smokers, which was higher than that reported by the NLST (6.7%); however, several European randomized controlled trials, such as the detection and screening of early lung cancer with novel imaging technology and NELSON trials [
We did not observe a significant reduction in either lung cancer mortality or all-cause mortality by screening for nonsmokers. This may be because (1) a high proportion of early-stage lung cancers might lead to a favorable prognosis and a limited number of deaths; (2) considering the inadequate sample size as well as the limited follow-up time, no lung cancer deaths were traced in the follow-up period of this study among nonsmokers; or (3) we lacked accurate risk stratification strategies of nonsmokers for lung cancer screening. In East Asia, approximately one-third of lung cancers are unrelated to smoking [
Our study had some limitations. First, this study may not be representative of the entire general population of China, but it can provide a scientific basis for other regions with similar socioeconomic status. Second, this was a real-world study rather than a randomized controlled trial, which might have led to residual confounders. We admit that a health volunteer effect existed in our study. Our program increased the health awareness of all participants involved in the program, including those in the screened, nonscreened, and low-risk groups. This can explain why the early-stage distributions were higher among all groups than in the general population. These findings suggest that screening programs involving health education may also increase the early detection of lung cancer and potentially decrease disease-specific mortality. Third, the median follow-up of 5.1 years in this study might be insufficient to trace cases and achieve consistent findings. Therefore, additional studies with extended follow-up times should be conducted to further evaluate the screening effects. Fourth, the smoker group was not categorized into heavy and light smokers because of the limited number of cases, and male participants without available information on smoking history were excluded. Passive smoking was only considered for women, which potentially induced gender disparity in smokers and nonsmokers. Finally, the outcome data presented here were obtained from the cancer registry and death surveillance systems, which might have resulted in a misclassification bias. Nevertheless, the cancer registry data in Zhejiang definitively met the requirements of the International Agency for Research on Cancer and the International Association of Cancer Registries, and the data were included in
In conclusion, our findings suggest effective reduction of all-cause and lung cancer mortality among smokers following LDCT screening, whereas evidence of LDCT screening effectiveness for nonsmokers is still insufficient. It is important to not only target smokers but also identify nonsmokers at high risk of developing lung cancer to implement lung cancer screening programs and maximize screening benefits in China. Our study has significant health service implications, thus providing promising evidence to support the implementation of a national lung cancer screening program and to define optimal guidelines for lung cancer screening in China.
Baseline characteristics of the study population of nonsmokers.
Baseline characteristics of the study population of smokers.
Effects of risk evaluation and low-dose computed tomography screening on lung cancer incidence, lung cancer mortality, and all-cause mortality among smokers.
hazard ratio
low-dose computed tomography
Nederlands Leuvens Screening Onderzoek
National Lung Screening Trial
odds ratio
This study was funded by the Science and Technology Service Network Initiative of the Chinese Academy of Sciences (grant KFJ-STS-QYZD-2021-08-001), the National Natural Science Foundation of China (grant 82273700), and the nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (grant 2019PT320027).
LD and NL contributed equally as the corresponding authors. LD, NL, LW, YW, and FW contributed to the conception and design of the study. LD, NL, LW, HL, CZ, and YW did the data curation; LW and FW performed formal data analysis; LD and NL did the funding acquisition and project administration; YG, ZF, WG, HL, CZ, YC, and LS performed the field investigation and supervision; LW, YW, and FW drafted the paper; and YG, ZF, WG, HL, CZ, YC, LS, LD, and NL interpreted the results. All authors contributed to data interpretation and rewriting of the paper. All authors reviewed and approved the final version. All authors had full access to all the data and were responsible for the decision to submit the manuscript. The corresponding author had full access to all the data in the study and had responsibility for the decision to submit for publication.
None declared.