Risk factors for exclusive lung metastasis in colorectal cancer: a comprehensive narrative review

Colorectal cancer (CRC) ranks among the leading causes of cancer-related mortality worldwide, with metastatic spread representing the primary determinant of patient prognosis. Exclusive lung metastasis (ELM) constitutes a distinct metastatic pattern characterized by pulmonary involvement without concurrent extrapulmonary disease, necessitating surveillance and therapeutic approaches that differ from those employed for liver-predominant or multi-organ metastatic disease. This narrative review synthesizes contemporary evidence regarding risk factors associated with ELM development in CRC patients, with the aim of facilitating early detection and enabling risk-stratified surveillance protocols. A comprehensive literature search was conducted across PubMed/MEDLINE, Web of Science, and Google Scholar from database inception through April 24, 2024. English-language human studies investigating clinicopathological, molecular, biomarker, and imaging predictors of CRC lung metastasis were eligible for inclusion, with particular emphasis on ELM. Current evidence demonstrates that ELM risk is multifactorial in nature. Demographic and socioeconomic determinants include advanced age, smoking history, African ancestry, and unmarried or uninsured status. Primary tumor characteristics encompass rectal location, advanced T/N stage, and poor histologic differentiation. At the molecular level, consensus molecular subtype 4 (CMS4) and specific gene alterations confer increased susceptibility. Circulating biomarkers-namely elevated carcinoembryonic antigen (CEA), elevated neutrophil-to-lymphocyte ratio (NLR), and elevated platelet-to-lymphocyte ratio (PLR)-further stratify risk. Select computed tomography (CT) imaging features, including pleural tags, spiculated margins, and radiomic signatures, provide additional predictive value. Integration of these diverse parameters may enhance identification of patients at elevated risk for isolated pulmonary metastatic spread. Comprehensive assessment of clinical, pathological, and molecular characteristics enables informed risk stratification and tailored surveillance strategies. Future investigations should prioritize development and prospective validation of integrated predictive models to guide personalized follow-up protocols and optimize clinical decision-making.