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. 2024 May 31;13(5):1047-1060.
doi: 10.21037/tlcr-23-816. Epub 2024 May 29.

Race, age at diagnosis and histological characteristics of lung cancer in never-smokers (LCINS) and ever-smokers in low-dose computed tomography (LDCT) screening: a systematic review and meta-analysis

Natthaya Triphuridet  1 , Misako Nagasaka  2   3 , Elaine Shum  4 , Sai-Hong Ignatius Ou  2   3
Affiliations

Race, age at diagnosis and histological characteristics of lung cancer in never-smokers (LCINS) and ever-smokers in low-dose computed tomography (LDCT) screening: a systematic review and meta-analysis

Natthaya Triphuridet et al. Transl Lung Cancer Res. .

Abstract

Background: We previously demonstrated in a meta-analysis there was no difference in risk ratio (RR) of lung cancer detected by low-dose computed tomography (LDCT) screening among female never-smokers (NS) and male ever-smokers (ES) in Asia. LDCT screening significantly decreased lung cancer death among Asian NS compared to Asian ES (RR =0.27, P<0.001).

Methods: We investigated if race, age at diagnosis, and histology further differentiate lung cancer diagnosed by LDCT among in NS and ES using the 14 studies from our previous meta-analysis.

Results: Twelve publications reported relevant data utilized in this study. From five Asian and one international studies, Asian ES had similar risk of lung cancer diagnosed at baseline screening as Asian NS [RR =0.96; 95% confidence interval (CI): 0.74-1.24] but among non-Asian ES had a 4.56 times significantly higher risk than non-Asian NS (RR =4.56; 95% CI: 2.85-7.28). The baseline incidence of lung cancer in never-smoker (LCINS) was approximately 2.3 times higher among Asian NS than non-Asian NS (0.62% vs. 0.27%, P=0.001). Asian ES had about half the baseline incidence of lung cancer diagnosed as non-Asian ES (0.65% vs. 1.26%). LCINS was diagnosed at 1.98 years younger than ES (95% CI: -3.38 to -0.58) (four studies) and exhibited a higher proportion of adenocarcinoma (ADC) (96.58% vs. 70.37%).

Conclusions: Among normal-risk individuals, LCINS had a significantly higher likelihood of being diagnosed among Asians than non-Asians, predominantly manifesting as ADC and diagnosed approximately 2 years younger than ES suggesting that the age limit to initiate lung cancer screening in NS may be set lower compared to LDCT lung cancer screening among ES.

Keywords: Meta-analysis; low-dose computed tomography screening (LDCT screening); lung cancer in never-smokers (LCINS).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-816/coif). S.H.I.O. serves as an Associate Editor-in-Chief of Translational Lung Cancer Research from August 2023 to July 2025. N.T. got payment or honoraria for lectures or presentations from AstraZeneca, Roche, and Thoracic Society of Thailand under Royal Patronage (TST) in the past 36 months; got support for attending meetings from AstraZeneca, Roche, TST, IASLC, and I-ELCAP in the past 36 months. M.N. received consulting fees from Pfizer, Lilly, Novartis, Jassen, Daiichi Sankyo, BMS, AnHeart Therapeutics, J Inst Bio and BluePrint Medicines within the past 36 months; got payment or honoraria for lectures or presentations from Pfizer, Janssen, Dava Oncology LLP, EMD Sereno, OncLive, Takeda, Caris Life Science and Mirati within the past 36 months; got support for attending meetings from AnHeart Therapeutics within the past 36 months; and has stock ownership in MBrace Therapeutics within the past 36 months. E.S. received research grant from Delfi Diganostics within the last 36 months; received consulting fees from Astra Zeneca, Boerhinger Ingelheim, Janssen, and Genentech within the last 36 months; and received lecture fees from OncLive within the past 36 months. S.H.I.O. received consulting fees from Pfizer, Lilly, Jassen, Daiichi Sankyo, BMS, AnHeart Therapeutics, J Inst Bio, and Bayer within the past 36 months; got payment or honoraria for lectures or presentations from Pfizer, Janssen, Dava Oncology LLP, Caris Life Science and OncLive within the past 36 months; has received payment for scientific advisory board from Elevation Oncology within the past 36 months; and has stock ownership in MBrace Therapeutics, BlossomHill Therapeutics, Nuvalent, Lilly, Turning Point Therapeutics, and Elevation Oncology within the past 36 months. The authors have no other conflicts of interest to declare.

Figures

Figure 1
Figure 1
PRISMA diagram of studies analyzed and included in the meta-analysis (8-11,13-16,18-20,22). IASLC, International Association for the Study of Lung Cancer.
Figure 2
Figure 2
Forest plots of meta-analysis of RR and the proportion of lung cancer diagnosed at baseline screening in ES and NS according to race. (A) Forest plot of meta-analysis of RR of lung cancer diagnosed at baseline screening in ES and NS among Asians and non-Asians. (B) Forest plot of metaprop of the proportion of ES with lung cancer diagnosed at baseline screening to total screened ES according to race (Asian and non-Asian). (C) Forest plot of metaprop of the proportion of NS with lung cancer diagnosed at baseline screening to total screened NS according to race (Asian and non-Asian). LC, lung cancer; CI, confidence interval; REML, restricted maximum likelihood; RR, risk ratio; ES, ever-smokers; NS, never-smokers; metaprop, proportional meta-analysis.
Figure 3
Figure 3
Prevalence of lung cancer by age and forest plot of meta-analysis of mean difference in age at lung cancer diagnosis. (A) Prevalence of lung cancer per 100,000 participants by age. (B) Forest plot of meta-analysis of mean difference in age at lung cancer diagnosis in NS and ES. SD, standard deviation; diff., difference; CI, confidence interval; REML, restricted maximum likelihood; NS, never-smokers; ES, ever-smokers.
Figure 4
Figure 4
Forest plots of meta-analysis of RR and the proportion of patients with lung cancer according to histology. (A) Forest plot of metaprop of the proportion of patients with ADC lung cancer to total lung cancer diagnosed in NS and ES. (B) Forest plot of meta-analysis of RR of patients with ADC lung cancer in NS and ES. (C) Forest plot of metaprop of the proportion of patients with SqCC lung cancer to total lung cancer diagnosed in NS and ES. (D) Forest plot of meta-analysis of RR of patients with SqCC lung cancer in NS and ES. (E) Forest plot of metaprop of the proportion of patients with SCLC to total lung cancer diagnosed in NS and ES. (F) Forest plot of meta-analysis of RR of patients with SCLC in NS and ES. ADC, adenocarcinoma; LC, lung cancer; CI, confidence interval; REML, restricted maximum likelihood; SqCC, squamous cell carcinoma; SCLC, small cell lung carcinoma; RR, risk ratio; NS, never-smokers; ES, ever-smokers; metaprop, proportional meta-analysis.
Figure 5
Figure 5
Forest plots of meta-analysis of RR and the proportion of lung cancer lesions according to histology. (A) Forest plot of metaprop of the proportion of ADC lesions diagnosed to total lung cancer lesions diagnosed in NS and ES. (B) Forest plot of meta-analysis of RR ADC lung cancer lesions diagnosed in NS and ES. (C) Forest plot of metaprop of the proportion of SqCC lesions to total lung cancer lesions in NS and ES. (D) Forest plot of meta-analysis of RR of SqCC lesions diagnosed in NS and ES. (E) Forest plot of metaprop of the proportion of SCLC lesions diagnosed to total lung cancer lesions diagnosed in NS and ES. (F) Forest plot of meta-analysis of RR of SCLC lesions diagnosed in NS and ES. ADC, adenocarcinoma; CI, confidence interval; LC, lung cancer; REML, restricted maximum likelihood; SqCC, squamous cell carcinoma; SCLC, small cell lung carcinoma; RR, risk ratio; NS, never-smokers; ES, ever-smokers; metaprop, proportional meta-analysis.
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