Natural history models for lung Cancer: A scoping review

Lung Cancer. 2025 May:203:108495. doi: 10.1016/j.lungcan.2025.108495. Epub 2025 Mar 26.

Abstract

Introduction: Natural history models (NHMs) of lung cancer (LC) simulate the disease's natural progression providing a baseline for assessing the impact of interventions. NHMs have been increasingly used to inform public health policies, highlighting their utility. The objective of this scoping review was to summarize existing LC NHMs, identify their limitations, and propose a framework for future NHM development.

Methods: We searched MEDLINE, Embase, Web of Science, and IEEE Xplore from their inception to October 5, 2023, for peer-reviewed, full-length articles with an LC NHM. Model characteristics, their applications, data sources used, and limitations were extracted and narratively synthesized.

Results: From 238 publications, 69 publications were included in our review, corresponding to 22 original LC NHMs and 47 model applications. The majority of the models (n = 15, 68 %) used a microsimulation approach. NHM parameters were predominately informed by cancer registries, trial and institutional data, and literature. Model quality and performance were evaluated in 8 (36 %) models. Twenty (91 %) models included at least one carcinogenesis risk factor-primarily age, sex, and smoking history. Three (14 %) LC NHMs modeled progression in never-smokers; one (5 %) addressed recurrence. Non-tobacco smoking, nodule type, and biomarker expression were not considered in existing NHMs. Based on our findings, we proposed a framework for future LC NHM development which incorporates recurrence, nodule type differentiation, biomarker expression levels, biological factors, and non-smoking-related risk factors.

Conclusion: Regular updating and future research are warranted to address limitations in existing NHMs thereby ensuring relevance and accuracy of modeling approaches in the evolving LC landscape.

Keywords: Lung cancer; Natural history; Simulation modeling.

Publication types

  • Scoping Review

MeSH terms

  • Disease Progression
  • Humans
  • Lung Neoplasms* / epidemiology
  • Lung Neoplasms* / etiology
  • Lung Neoplasms* / pathology
  • Risk Factors