Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 18;23(1):238.
doi: 10.1186/s12957-025-03892-1.

Risk factors and clinical risk stratification of distant metastasis in early-stage lung cancer in never smokers

Dongsheng Wu #  1 , Xiaohu Hao #  1 , Zhipeng Gong #  1 , Ruichen Cui  1 , Liang Xia  1 , Lunxu Liu  2
Affiliations

Risk factors and clinical risk stratification of distant metastasis in early-stage lung cancer in never smokers

Dongsheng Wu et al. World J Surg Oncol. .

Abstract

Background: Risk factors for distant metastasis in early-stage lung cancer in never smokers (LCINS) remain poorly understood. This study aimed to identify key risk factors and to develop a clinical risk stratification model for early-stage LCINS.

Methods: We retrospectively analyzed patients diagnosed with early-stage LCINS at West China Hospital, Sichuan University, from 2015 to 2020. Univariable and multivariable Cox regression analyses were performed to identify independent risk factors for distant metastasis. A predictive model was developed and internally validated using bootstrap resampling, with performance assessed by the concordance index (C-index), area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis.

Results: A total of 1,406 patients with pathological stage I-II LCINS were included, among whom 76 (5.41%) developed distant metastasis during follow-up. Multivariable Cox regression analysis revealed that independent risk factors included advanced pathological T and N stages, higher consolidation-to-tumor ratio, and histologic subtype, particularly solid/micropapillary predominant adenocarcinoma. Based on these predictors, a predictive model was developed, demonstrating strong discrimination with a C-index of 0.799 and AUC values of 0.809, 0.791, and 0.783 for predicting 1-, 2-, and 3-year distant metastasis, respectively. Calibration and decision curve analyses confirmed the reliability and clinical utility of the model.

Conclusions: This study identified risk factors and developed a clinical risk stratification model for distant metastasis in early-stage LCINS. This validated model enables risk stratification and personalized monitoring to facilitate early detection of distant recurrence in LCINS.

Keywords: Distant metastasis; Lung cancer in never smokers; Predictive model; Risk factors.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: This is an observational study. The Institutional Review Board of West China Hospital, Sichuan University has confirmed that no ethical approval is required. Consent for publication: All authors gave consent for the publication of this study. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart illustrating the patient selection process. Abbreviations: NSCLC, non-small cell lung cancer; LCINS, lung cancer in never smokers; C-index, Harrell concordance index; ROC, receiver operating characteristic curves; AUC, area under the curve; DCA, decision curve analysis
Fig. 2
Fig. 2
Nomogram model for predicting distant metastasis in patients with early-stage LCINS. The patient #6 is illustrated in the nomogram by mapping its values to the covariate scales. The probability of distant metastasis in 1-, 2-, and 3-year follow-up are estimated to be 3.16%, 6.27%, and 9.56%, respectively. Abbreviation: LCINS, lung cancer in never smokers
Fig. 3
Fig. 3
A-C Time-dependent ROC curves for predicting the probability of distant metastasis at 1, 2, and 3 years, respectively. D-F Calibration curves showing predicted versus observed probabilities of distant metastasis at 1, 2, and 3 years, respectively. G-I DCA illustrating the clinical utility of the model at 1, 2, and 3 years, respectively
Fig. 4
Fig. 4
Kaplan–Meier curves comparing distant metastasis outcomes between low- and high-risk groups for early-stage LCINS. Abbreviation: LCINS, lung cancer in never smokers
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63. - PubMed
    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49. - PubMed
    1. Kelsey CR, Marks LB, Hollis D, Hubbs JL, Ready NE, D’Amico TA, et al. Local recurrence after surgery for early stage lung cancer: an 11-year experience with 975 patients. Cancer. 2009;115(22):5218–27. - PubMed
    1. Wang T, Wang Z, Zhou J, Jie H, Liao H, Mei J, et al. A nomogram predicting the risk of extrathoracic metastasis at initial diagnosis of T(≤3cm)N(0) lung cancer. Transl Lung Cancer Res. 2024;13(8):1841–50. - PMC - PubMed
    1. Zhou J, Wu D, Zheng Q, Wang T, Mei J. Development of a predictive model to predict postoperative bone metastasis in pathological I-II non-small cell lung cancer. Transl Lung Cancer Res. 2024;13(5):998–1009. - PMC - PubMed

LinkOut - more resources