Abstract
Objective:
Lung cancer screening with low-dose computed tomography (LDCT) partly reduces cancer-specific mortality. However, few data have described this specific population for screening in mainland China. Here, we conducted a population-based screening program in Anhui, China.
Methods:
9084 individuals were participating in the screening program for lung cancer in Anhui province from 1 June 2014 to 31 May 2017. LDCT was offered to all participants who joined the program.
Results:
Of 9084 individuals undergoing LDCT, we detected 54 lung cancers (0.594%). The age with the highest rate was 61–65 years (up to 1.016%), followed by 56–60 (0.784%). Most patients (98.1%, 53/54) were in stage I–II (early stage), and only one was in stage III (advanced stage). Adenocarcinoma, squamous cell carcinoma and small cell lung cancer accounted for 57.4% (31/54), 37% (20/54) and 5.6% (3/54) of the individuals, respectively. Notably, There were 4,102 never smokers in our study. The median age was 63 years. Males and females accounted for 53.4 and 46.6%, respectively. Among the 4102 never smokers, 96 participants had a positive family cancer history. Additionally, we detected 20 lung cancers (0.488%), slightly lower than the whole rate 0.594%. Finally, our data showed that age, smoking, family cancer history and features of nodules were risk factors for lung cancer.
Conclusion:
Our study qualified the efficiency of LDCT to detect early-stage lung cancers in Anhui, China. Further establishment of appropriate lung cancer screening methods specifically for individuals in China is warranted.
Advances in knowledge:
We evaluated the performance of lung cancer screening for asymptomatic populations using LDCT in Anhui, an eastern inland province of China. Our study qualified the efficiency of LDCT to detect early-stage lung cancers in Anhui, China.
Introduction
Lung cancer is the leading cause of cancer-related mortality worldwide for both males and females. 1,2 Despite recent advances in therapeutic approaches, the long-term survival of patients with lung cancer remains poor. 3 Because most lung cancers are diagnosed at advanced stages, the opportunity for potentially curative interventions is lost. Early detection and subsequent surgical resection remain the best options for the prevention and therapy of lung cancer. 4 Recently, the US National Lung Screening Trial (NLST) has shown that lung cancer screening of high-risk populations with low-dose CT (LDCT) reduced the mortality by more than 20%. 5 Following the publication of the NLST, several medical societies currently recommend screening programs. 6 However, few data are available concerning lung cancer screening in mainland China. In our study, the screening program greatly supported by the national cancer center was implemented in Anhui, an eastern inland province of China. It has a population of 61.4 million, and its social, cultural and economic background is representative of over 80% of the whole population in China. 7 Importantly, the incidence of lung cancer in Anhui is higher than that in other provinces, such as Shanxi and Gansu. 8
Herein, we designed the present study to fully address two main questions: (1) to find the overall detection rate of lung cancers using LDCT, compare the differences in the pathological findings, and analyze the risk factors for lung cancer in Anhui; (2) to preliminary evaluate the detection rate and distribution characteristics of lung cancers in never smoking participants.
Methods and materials
Participant selection
During the 3-year period from 1 June 2014 to 31 May 2017, we conducted a population-based screening program for lung cancer in Anhui province. The service was provided to inhabitants in Anhui and employees of Anhui Provincial Cancer Hospital. The participants were asymptomatic adults aged 40 years or older and had no cancer history. A smoking history was not necessary for entrance into the study. For each individual, relevant clinical notes, family cancer history and other risk factors for lung cancer were documented. All the participants were enrolled in the study only after providing written informed consent. The study was approved by the ethics committee of Anhui Provincial Cancer Hospital.
LDCT screening
LDCT was offered to all individuals who joined the program. All CT scans were performed on thin-sliced scanners from different manufacturers (General Electric Medical Systems, Milwaukee, WI, USA). All the scans were obtained using a low-dose regimen. The effective radiation dose ranged from 0.3 to 0.8 mSv. Detection was performed on axial, coronal and sagittal reconstructions with 1.25 mm slab thickness. All the CT images were interpreted on a dedicated workstation by one thoracic radiologist with ≥3 years of chest CT imaging experience.
We evaluated the attenuation and size of the nodules according to the longest perpendicular diameter. Baseline CT evaluations were defined as positive for non-calcified solid or part-solid nodules ≥ 5 mm or non-solid nodules ≥ 8 mm in diameter. All the individuals with positive findings were automatically referred to pulmonologists for expert evaluations.
Management recommendations, including follow-up LDCT scans and biopsy, were made by attending physicians. The most appropriate approach was selected to suit their practice routine based on the management algorithm of cancer early diagnosis and treatment program of China (Figure 1). All the individuals with detected lung cancers were traced, and the corresponding LDCT scans, clinical notes, and pathology reports were reviewed.
Figure 1.
Management of pulmonary nodules detected by LDCT. The recommendation was based on the size and attenuation of nodules.
Statistical analysis
Chi-squared test was used to investigate associations between the groups and various clinical features. Continuous variables were analyzed using Student’s t-test. Multivariate analysis was performed using a conditional logistic regression model by computing the odds ratio (OR) and corresponding 95% confidence intervals (CIs). The cut-off value for MIC-1 was expressed as the mean value plus two-point-five standard deviations of healthy individuals. Statistical activity was calculated using SPSS v.16.0. p < 0.05 was considered to be statistically significant.
Results
Clinicopathological features of participants and outcomes of lung cancer screening
During the 3-year period from 1 June 2014 to 31 May 2017, 9084 asymptomatic individuals attended our screening program. The median age was 55 years, ranging from 40 to 75 years. Slightly more males than females were included (57.2% vs 42.8%, respectively). There were 2365 (26.0%) former smokers, 2617 (28.8%) current smokers and 4102 (45.2%) never smokers. There were 157 (1.7%) participants with a positive family cancer history (Table 1). Following LDCT, solid nodules (SNs), part-solid nodules (PSNs), non-solid nodules (NSNs) and calcified nodules (CNs) numbered 1515 (16.7%), 81 (0.9%), 1071 (11.8%) and 671 (7.4%), respectively.
Table 1.
Characteristics of the whole 9084 populations
| Factor | Description | n | (%) |
|---|---|---|---|
| Sex | Male | 5199 | 57.2 |
| Female | 3885 | 42.8 | |
| Age | <=55 | 4927 | 54.2 |
| >55 | 4157 | 45.8 | |
| Smoking history | Never-smoker | 4102 | 45.2 |
| Former smokers | 2365 | 26.0 | |
| Current smoker | 2617 | 28.8 | |
| Family cancer history | Yes | 157 | 1.7 |
| No | 8927 | 98.3 | |
| Nodule | PSN | 81 | 0.9 |
| SN | 1515 | 16.7 | |
| NSN | 1071 | 11.8 | |
| CN | 671 | 7.4 | |
| None | 5746 | 63.2 |
CN, Calcified nodule; NSN, Non solid nodule; PSN, Part solid nodule; SN, Solid nodule.
Of 9084 individuals undergoing LDCT, we detected 54 lung cancers (0.594%). As shown in Table 2, the rate was 0.406% (20/4927) in the age group ≤55 years and 0.818% (34/4157) in the age group >55 years. The age with the highest rate was 61–65 years (up to 1.016%), followed by 56–60 (0.784%) and 45–50 years (0.666%). Additionally, there was a particularly high rate in the high-risk Group 7.6% (12/157) with a positive family cancer history (Table 3). Among the detected cancers, 37.0% (20/54) of patients were never smokers, 16.7% (9/54) were former smokers, and 46.3% (25/54) were current smokers. Furthermore, 37 patients presented with SNs, six with PSNs, and nine with NSNs. Histopathological data showed that the proportions of adenocarcinomas, squamous cell carcinomas and small cell lung cancers were 31 (57.4%), 20 (37%) and 3 (5.6%), respectively. Importantly, 98.1% (53/54) patients were in stage I–II (early stage) and only one was in stage III (advanced stage) (Table 3).
Table 2.
Positive rates of lung cancer in different age groups
| Age (years) | Number of lung cancers | Number of screening | Rate (%) |
|---|---|---|---|
| <=45 | 4 | 1169 | 0.342 |
| 45–50 | 9 | 1352 | 0.666 |
| 51–55 | 7 | 1391 | 0.503 |
| 56–60 | 10 | 1276 | 0.784 |
| 61–65 | 15 | 1477 | 1.016 |
| >=66 | 9 | 2419 | 0.372 |
| Total | 54 | 9084 | 0.594 |
Table 3.
Characteristics of the lung cancer
| Factor | Description | n | (%) |
|---|---|---|---|
| Sex | Male | 34 | 63 |
| Female | 20 | 37 | |
| Smoking history | Never-smoker | 20 | 37 |
| Former smokers | 9 | 16.7 | |
| Current smoker | 25 | 46.3 | |
| Stage | I-II | 53 | 98.1 |
| III | 1 | 1.9 | |
| Family cancer history | Yes | 12 | 22.2 |
| No | 42 | 77.8 | |
| Nodule | PSN | 6 | 11.1 |
| NSN | 9 | 16.7 | |
| SN | 37 | 68.5 | |
| None | 2 | 3.7 | |
| Histologic type | Squamous cell carcinoma | 20 | 37 |
| Adenocarcinoma | 31 | 57.4 | |
| Small cell lung cancer | 3 | 5.6 |
Clinicopathological features of never smoking participants
Consider the diversification of risk factors for lung cancer, smoking history was not a strict restriction on the populations selected for our screening program. There were 4102 never smokers in our study. The median age was 63 years. As shown in Table 4, males and females accounted for 53.4 and 46.6%, respectively. Following LDCT, solid nodules (SNs), part-solid nodules (PSNs), non-solid nodules (NSNs) and calcified nodules (CNs) numbered 1008 (24.6%), 57 (1.4%), 796 (19.4%) and 311 (7.6%), respectively. There were 96 participants with a positive family cancer history. Of 4102 never smokers, we detected 20 lung cancers (0.488%), slightly lower than the whole rate 0.594%. Histopathological data showed that the adenocarcinomas, squamous cell carcinomas and small cell lung cancers accounted for 15 (75.0%), 4 (20.0%) and 1 (5.0%), respectively. All patients in the group were in stage I–II (early stage).
Table 4.
Characteristics of the never smoker populations
| Factor | Description | n | (%) |
|---|---|---|---|
| Sex | Male | 2190 | 53.4 |
| Female | 1912 | 46.6 | |
| Age | <=55 | 589 | 14.4 |
| >55 | 3513 | 85.6 | |
| Family cancer history | Yes | 96 | 2.3 |
| No | 4006 | 97.7 | |
| Nodule | PSN | 57 | 1.4 |
| SN | 1008 | 24.6 | |
| NSN | 796 | 19.4 | |
| CN | 311 | 7.6 | |
| None | 1930 | 47.1 | |
| Lung cancer | Squamous cell carcinoma | 4 | 20.0 |
| Adenocarcinoma | 15 | 75.0 | |
| Small cell lung cancer | 1 | 5.0 | |
| Stage I-II | 20 | 100.0 |
Risk factors for the development of lung cancer
As shown in Table 5, according to univariate analysis, age (p = 0.011), smoking (p = 0.015) and family cancer history (p = 0.000) were significant risk factors for lung cancer. Moreover, the features of nodules (p = 0.000) indicated a significantly positive association with lung cancer. In multivariate analysis, age (p = 0.032), smoking (p = 0.038), family cancer history (p = 0.000) and features of nodules (p = 0.000) were also risk factors for lung cancer.
Table 5.
Risk factors for lung cancer
| Univariate analysis | Multivariate analysis | ||||
|---|---|---|---|---|---|
| Control (n, %) | Cancer (n, %) | p | OR (95% CI) | p | |
| Sex | 0.393 | ||||
| Male | 5165 | 34 | |||
| Female | 3865 | 20 | |||
| Age | 0.011 | 0.239 (0.125–0.456) | 0.032 | ||
| <=55 | 4907 | 20 | |||
| >55 | 4123 | 34 | |||
| Smoking history | 0.015 | 0.022 (0.001–0.806) | 0.038 | ||
| Never | 4082 | 20 | |||
| Former smokers | 2356 | 9 | |||
| Current smoker | 2592 | 25 | |||
| Family cancer history | 0.000 | 9.437 (3.336–−26.695) | 0.000 | ||
| Yes | 145 | 12 | |||
| No | 8885 | 42 | |||
| Nodule | 0.000 | 32.882 (6.108–176.999) | 0.000 | ||
| PSN | 75 | 6 | |||
| SN | 1478 | 37 | |||
| NSN | 1062 | 9 | |||
| None | 5744 | 2 | |||
Discussion
Recently, several studies have reported favorable efficiency for lung cancer screening using LDCT. 9 Additionally, more evidence from other ongoing randomized-controlled trials 10 has demonstrated benefits. However, most studies were generally conducted in western developed countries. 11 Few reports have described the specific population for screening in mainland China. Given the large population and high incidence of lung cancer in Anhui province, the National Cancer Center performed lung cancer screening using LDCT in the area. Regarding the management algorithm in our study, 54 asymptomatic individuals were diagnosed with lung cancer. The overall rate (0.594%) was lower than that in previous reports. 12 One possible reason was the lack of strict restrictions on the populations selected for the screening program, such as age and smoking history. In our study, 2763 (30.4%) individuals aged younger than 50 years and 4102 (45.2%) never-smokers might be considered as relatively low-risk participants. Consistent with this explanation, the detection rate was also lower in the Korean study. 13 Additionally, our data showed that the highest detection rate was 1.016% in the age Group 61–65 years, followed by 0.784% in the age Group 56–60 years. The data indicated that the populations over 55 years were a high-risk group for the development of lung cancer. Furthermore, histopathological data showed that 98.1% of patients were in stage I–II. These results revealed that our management algorithm provided a predictive value for the diagnosis of early-stage lung cancer.
Notably, we selected 4102 never smoking individuals in our study for several reasons. On the one hand, considering the diversification of risk factors and no unified high-risk population criteria in China for lung cancer, smoking history was not a strict restriction on the populations selected for the screening program. 14 Other factors, such as age and family history of cancers, were mainly used as the criteria for these populations. On the other hand, considering the high incidence of lung cancer in Anhui, we preliminary evaluated the detection rate using LDCT and distribution characteristics of lung cancers in never-smokers. Finally, the program was greatly supported by the national cancer center of China. One of the main aims was to benefit more people. Just as we expected, the detection rate was lower than the whole rate (0.488% vs 0.594%) among the never-smoking participants. Histopathological data showed that all patients were in stage I–II (early stage), including 15 adenocarcinomas, four squamous cell carcinomas and one small cell lung cancers.
We further investigated the risk factors for lung cancer. Our study demonstrated that age, smoking history and family history of cancers were significantly related to the development of lung cancer. Matakidou et al reported that family history of cancers was associated with risk of lung cancer and risk appeared to greater multiple affect family members. 15 Additionally, features of nodules indicated a significant positive association with lung cancer. These data played a major role in management of nodules detected on CT scans under the current practice.
In conclusion, our study qualified the efficiency of LDCT to detect early-stage lung cancer in Anhui, China. However, our study possessed some main limitations. First, some individuals with positive baseline CT findings received second opinions or diagnostic evaluations at other hospitals. Unavoidably, several patients were not included in our study. Second, there were still many debates over lung cancer screening with LDCT, including false-positive results, financial costs, and certain radiation hazards. 16 Similarly, there were certain defects for our screening management algorithm of lung cancer. For instance, there were inevitable over diagnosis for some participants, such as benign resections and minor harms from invasive testing. Hence, further establishment of appropriate lung cancer screening methods specifically for individuals in China, especially for low-risk people (such as never smokers), is warranted.
Footnotes
Acknowledgements: We wish to thank Feng Wang for technical assistance in the experimental analyses. We thank the cancer screening center of our hospital for helping to sort out the information. This work was supported by grants from the Key Research and Development Program of Anhui [grant number 1704a0802157] and the Fundamental Research Funds for the Central Universities [WK9110000025].
Contributor Information
Wulin Shan, Email: 350swl@sina.com.
Zhaowu Chen, Email: 104597893@qq.com.
Donghua Wei, Email: 330934652@qq.com.
Ming Li, Email: 18919685630@sina.cn.
Liting Qian, Email: money2004@sina.com.
REFERENCES
- 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018; 68: 7–30. doi: 10.3322/caac.21442 [DOI] [PubMed] [Google Scholar]
- 2. Teoh S, Fiorini F, George B, Vallis KA, Van den Heuvel F. Is an analytical dose engine sufficient for intensity modulated proton therapy in lung cancer? Br J Radiol 2020; 93: 20190583. doi: 10.1259/bjr.20190583 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Wang B-Y, Huang J-Y, Cheng C-Y, Lin C-H, Ko J-L, Liaw Y-P. Lung cancer and prognosis in Taiwan: a population-based cancer registry. J Thorac Oncol 2013; 8: 1128–35. doi: 10.1097/JTO.0b013e31829ceba4 [DOI] [PubMed] [Google Scholar]
- 4. Patz EF, Rossi S, Harpole DH, Herndon JE, Goodman PC. Correlation of tumor size and survival in patients with stage IA non-small cell lung cancer. Chest 2000; 117: 1568–71. doi: 10.1378/chest.117.6.1568 [DOI] [PubMed] [Google Scholar]
- 5. Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011; 365: 395–409. doi: 10.1056/NEJMoa1102873 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. van der Aalst CM, Ten Haaf K, de Koning HJ. Lung cancer screening: latest developments and unanswered questions. Lancet Respir Med 2016; 4: 749–61. doi: 10.1016/S2213-2600(16)30200-4 [DOI] [PubMed] [Google Scholar]
- 7. Shen X, Diao M, Lu M, Feng R, Zhang P, Jiang T, et al. Pathways and cost-effectiveness of routine lung cancer inpatient care in rural Anhui, China: a retrospective cohort study protocol. BMJ Open 2018; 8: e018519. doi: 10.1136/bmjopen-2017-018519 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Shi J-F, Wang L, Wu N, Li J-L, Hui Z-G, Liu S-M, et al. Clinical characteristics and medical service utilization of lung cancer in China, 2005-2014: overall design and results from a multicenter retrospective epidemiologic survey. Lung Cancer 2019; 128: 91–100. doi: 10.1016/j.lungcan.2018.11.031 [DOI] [PubMed] [Google Scholar]
- 9. Pinsky PF. Cost-Effectiveness of CT screening in the National lung screening trial. N Engl J Med 2015; 372: 387. doi: 10.1056/NEJMc1414726 [DOI] [PubMed] [Google Scholar]
- 10. Baldwin DR, Duffy SW, Wald NJ, Page R, Hansell DM, Field JK. Uk lung screen (UKLS) nodule management protocol: modelling of a single screen randomised controlled trial of low-dose CT screening for lung cancer. Thorax 2011; 66: 308–13. doi: 10.1136/thx.2010.152066 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Tammemägi MC, Katki HA, Hocking WG, Church TR, Caporaso N, Kvale PA, et al. Selection criteria for lung-cancer screening. N Engl J Med 2013; 368: 728–36. doi: 10.1056/NEJMoa1211776 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Chen C-Y, Chen C-H, Shen T-C, Cheng W-C, Hsu C-N, Liao C-H, et al. Lung cancer screening with low-dose computed tomography: experiences from a tertiary hospital in Taiwan. J Formos Med Assoc 2016; 115: 163–70. doi: 10.1016/j.jfma.2015.11.007 [DOI] [PubMed] [Google Scholar]
- 13. Chong S, Lee KS, Chung MJ, Kim TS, Kim H, Kwon OJ, et al. Lung cancer screening with low-dose helical CT in Korea: experiences at the Samsung medical center. J Korean Med Sci 2005; 20: 402–8. doi: 10.3346/jkms.2005.20.3.402 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Fan L, Wang Y, Zhou Y, Li Q, Yang W, Wang S, et al. Lung cancer screening with low-dose CT: baseline screening results in Shanghai. Acad Radiol 2019; 26: 1283–91. doi: 10.1016/j.acra.2018.12.002 [DOI] [PubMed] [Google Scholar]
- 15. Gu J, Hua F, Zhong D, Chen J, Liu H, Zhou Q. Systematic review of the relationship between family history of lung cancer and lung cancer risk. Zhongguo Fei Ai Za Zhi 2010; 13: 224–9. doi: 10.3779/j.issn.1009-3419.2010.03.07 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Field JK, Devaraj A, Duffy SW, Baldwin DR. CT screening for lung cancer: is the evidence strong enough? Lung Cancer 2016; 91: 29–35. doi: 10.1016/j.lungcan.2015.11.003 [DOI] [PubMed] [Google Scholar]