Prognostic value of the immune-inflammatory indices in osteosarcoma: a systematic review and meta-analysis

Systemic inflammation plays an important role in driving tumor progression. Several inflammation-related indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and the systemic immune-inflammation index (SII), have been proposed as prognostic biomarkers across various cancers. Nevertheless, their prognostic utility in osteosarcoma remains uncertain. This systematic review and meta-analysis was conducted to evaluate the associations between these indices and survival outcomes in patients with osteosarcoma. We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library for articles published through 30 June 2025 that assessed the relationship between pretreatment NLR, PLR, LMR, or SII and osteosarcoma patient overall survival (OS), progression-free survival (PFS), and/or event-free survival (EFS). A random-effects model was used to pool summary hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses were also conducted, along with publication-bias assessments. A total of 22 studies incorporating 57 cohort comparisons met the inclusion criteria for this meta-analysis. High NLR values were significantly associated with worse OS (HR = 1.52; 95% CI, 1.29–1.78; p < 0.0001). Similarly, high SII values were correlated with reduced OS (HR = 1.84; 95% CI, 1.05–3.21; p = 0.03), and high PLR values predicted poorer OS (HR = 1.21; 95% CI, 1.07–1.37; p = 0.002). In contrast, LMR was not significantly associated with OS (HR = 1.13; 95% CI, 0.91–1.39; p = 0.26). Of the evaluated progression endpoints, only NLR was significantly associated with shorter PFS (HR = 1.84; 95% CI, 1.04–3.25; p = 0.03). Pretreatment immune-inflammatory indices may have prognostic relevance in osteosarcoma, with NLR showing the most consistent association with adverse survival outcomes. Although PLR and SII were associated with poorer OS in pooled analyses, these findings should be interpreted cautiously because of substantial heterogeneity, limited study numbers, potential small-study effects, and sensitivity instability, particularly for SII. Large-scale prospective multicenter studies with standardized cut-off values are required before these indices can be incorporated into routine clinical prognostic evaluation.