Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio As Biomarkers to Prognosticate Survival in Advanced Gastric Cancer Patients in the Era of Immunotherapy: a Systematic Review and Meta-analysis

Background: Gastric cancer (GC) remains an important global health concern with limited treatment options for advanced cases. Immunotherapy has shown promising results, but identifying predictive biomarkers for treatment efficacy is challenging. Novel inflammatory markers, such as the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), derived from complete blood count measurements, have gained attention as potential prognostic indicators. This systematic review and meta-analysis investigates the roles of the PLR and NLR as predictors of overall survival (OS) and progression-free survival (PFS) in advanced GC and gastroesophageal junction cancer (GEJC) patients treated with immunotherapy.

Methods: A comprehensive search of the literature was conducted through PubMed, Embase, and Cochrane Library to identify relevant studies. A total of 16 studies involving NLR and 8 studies involving PLR were included. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between high biomarker values and poor OS and PFS. Subgroup analyses were performed to explore potential sources of heterogeneity. Poor OS, PFS were defined by each study as statistically significant shorter survival.

Results: A high NLR was significantly associated with worse OS (HR: 2.11; 95% CI: 1.70-2.62) and PFS (HR: 1.76; 95% CI: 1.43-2.17). High PLR was also significantly associated with poorer OS (HR: 1.77; 95% CI: 1.44-2.17) and PFS (HR: 1.61; 95% CI: 1.33-1.96). Subgroup analyses and sensitivity analyses supported the robustness of these findings. Publication bias was noted in NLR analysis for OS but not for PFS. PLR analysis showed low publication bias.

Conclusions: Elevated NLR and PLR are associated with unfavorable OS and PFS outcomes in advanced GC/GEJC patients on immunotherapy. These findings imply the utility of these easily accessible biomarkers in prognostic assessment. However, standardized cutoff values and further research on interactions with the tumor microenvironment and comorbidities are needed. Additional prospective studies are warranted to validate these findings for both biomarkers.