Inflammatory and Nutritional Biomarkers for Overall Survival in Gastric Adenocarcinoma: Comparative Performance and Exploratory Temporal Patterns

Background: Inflammatory and nutritional biomarkers are associated with survival in gastric cancer; however, their incremental prognostic value beyond routinely available clinical factors and the stability of their associations over time remain uncertain. We compared six routinely available biomarkers within a common clinically adjusted framework and evaluated their associations with overall survival (OS), model performance, temporal variation, and internal robustness. Methods: This retrospective single-center cohort study included 255 patients with gastric adenocarcinoma. A prespecified parsimonious Cox model comprising age, sex, Eastern Cooperative Oncology Group performance status, and metastatic disease at diagnosis served as the clinical reference model. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), and hemoglobin–albumin–lymphocyte–platelet (HALP) score were added separately. Model fit and discrimination, multiple-testing-adjusted associations, time-varying effects, bootstrap internal validation, and influence-diagnostic sensitivity analyses were assessed. Results: During follow-up, 227 patients (89.0%) died. Median OS was 11.66 months (95% confidence interval [CI], 9.63–13.47), and reverse Kaplan–Meier median follow-up was 88.51 months (95% CI, 69.72–110.59). After adjustment for the prespecified clinical factors, higher NLR, PLR, and SII were associated with increased mortality, whereas higher LMR, PNI, and HALP were associated with lower mortality; all associations remained significant after Benjamini–Hochberg correction (q ≤ 0.007). The clinical model had a C-index of 0.678. Biomarker addition yielded C-indices ranging from 0.682 to 0.695, with the largest numerical increase observed for PNI (ΔC-index, +0.017). The HALP-extended model yielded the numerically lowest Akaike information criterion. Exploratory time-specific estimates suggested stronger biomarker–mortality associations during early follow-up, although the interaction tests did not remain significant after multiplicity correction. Bootstrap-corrected C-indices were 0.689 for PNI, 0.686 for HALP, and 0.682 for SII, with low optimism and successful convergence of all 1000 resamples. Influence-diagnostic sensitivity analyses preserved the direction and statistical significance of these associations. Conclusions: Inflammatory and nutritional biomarkers provided additional prognostic information beyond the prespecified clinical factors. Although all six biomarkers remained associated with OS when evaluated separately, their incremental contribution to overall discrimination was modest. PNI and HALP yielded the most favorable numerical model-performance estimates; however, the absolute differences were modest, and formal paired bootstrap comparisons identified no significant differences between the biomarker-extended models. External and longitudinal validation is required before routine prognostic implementation.