Risk factors for pulmonary metastases in osteosarcoma: a systematic review and meta-analysis.

BACKGROUND: Pulmonary metastases are the leading cause of mortality in osteosarcoma patients. Identifying high-risk factors is essential for optimizing surveillance and treatment. To systematically review and analyze clinical and pathological risk factors associated with pulmonary metastases in osteosarcoma. METHODS: A systematic digital screening of PubMed, Scopus, and EMBASE was carried out without restrictions, supplemented by manual and grey literature searches. Observational studies reporting odds ratios (ORs) with 95% confidence intervals (CIs) for pulmonary metastases were included. A qualitative and quantitative analysis was carried out by pooling the effect estimates using forest plots. The quality of the studies was assessed by the Newcastle- Ottawa scale. RESULTS: Fifteen studies involving over 12,000 patients were included. In univariate analyses, larger tumor size, positive N stage, higher T stage, and treatment with radiation or chemotherapy were significantly associated with increased risk of lung metastasis, whereas surgery was associated with reduced risk. Patients aged 18–40 years showed a lower risk in univariate analysis, while gender and tumor location were not significantly associated. In multivariate analyses, tumor size greater than 10 cm, positive N stage, higher histologic grade (particularly Grades III and IV), and advanced T stage remained independent predictors of lung metastasis. Age and gender were not independently associated after adjustment. Surgery continued to demonstrate a protective association, whereas radiation and chemotherapy were associated with increased odds of lung metastasis. CONCLUSION: Tumor size, stage, nodal status, and histological grade are strong predictors of pulmonary metastases in osteosarcoma, while surgery is protective. These findings support the use of risk-stratified follow-up and further research on integrating molecular markers into prognostic models. PROSPERO REGISTRATION: CRD420251053452.