Background: Clinical outcomes in isocitrate dehydrogenase (IDH)-wildtype grade 4 diffuse glioma remain highly heterogeneous despite standard multimodal therapy. We evaluated the prognostic significance of pretreatment platelet-to-albumin ratio (PAR) and compared its performance with established inflammatory biomarkers. Methods: This retrospective cohort study included 166 patients with histopathologically confirmed IDH-wildtype grade 4 diffuse glioma treated between 2017 and 2025. Pretreatment PAR, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), pan-immune inflammation value (PIV), C-reactive protein-to-albumin ratio (CAR), and lactate dehydrogenase-to-albumin ratio (LAR) were evaluated. Discriminative performance was assessed using classical and inverse probability of censoring weighting (IPCW)-adjusted time-dependent receiver operating characteristic (ROC) analyses. Survival outcomes were evaluated using Kaplan–Meier analyses and predefined baseline-adjusted multivariable Cox proportional hazards regression models. Internal validation was performed using 1000 bootstrap resampling iterations. Results: PAR demonstrated the highest discriminative performance for 12-month overall survival (OS), with an area under the curve of 0.853. Using an optimal cutoff value of 79.459, patients with elevated PAR experienced significantly shorter OS (median, 6.2 vs. 16.7 months; p < 0.001) and progression-free survival (PFS) (median, 5.9 vs. 12.3 months; p < 0.001). In baseline-adjusted multivariable analyses, elevated pretreatment PAR remained independently associated with inferior OS (hazard ratio [HR], 3.287; 95% confidence interval [CI], 2.196–4.921; p < 0.001) and PFS (HR, 3.791; 95% CI, 2.501–5.749; p < 0.001). These findings were supported by sensitivity analyses and bootstrap internal validation. Conclusions: Pretreatment PAR was independently associated with survival outcomes and demonstrated favorable discriminative performance relative to other inflammatory biomarkers. PAR may represent an accessible biomarker reflecting tumor–host interactions in IDH-wildtype grade 4 diffuse glioma. The proposed PAR cutoff should be considered exploratory and requires external validation before routine clinical application.

Background and Objectives: Clinical outcomes remain markedly heterogeneous in glioblastoma, isocitrate dehydrogenase (IDH)-wildtype, despite contemporary molecular classification and established clinicopathological risk factors. We investigated whether the pretreatment lactate dehydrogenase-to-albumin ratio (LAR), an accessible circulating index integrating systemic disease- and host-related information, provides complementary prognostic information. Materials and Methods: We retrospectively evaluated 134 patients with glioblastoma, IDH-wildtype, central nervous system (CNS) World Health Organization (WHO) grade 4. An exploratory, cohort-specific LAR threshold was derived for 12-month overall survival (OS) and retained without re-optimization across subsequent analyses. Associations with OS and progression-free survival (PFS) were evaluated using Cox regression, and incremental prognostic performance was assessed against a baseline clinicopathological model. Temporal and continuous associations with survival, internal model validation, and the relationship between LAR and treatment response during adjuvant temozolomide therapy were also examined. Results: The cohort-derived LAR threshold was 5.718. High pretreatment LAR was associated with shorter median OS (5.5 vs. 16.0 months) and PFS (5.2 vs. 10.6 months; both p < 0.001) and remained independently associated with OS (adjusted hazard ratio [HR], 4.51; 95% CI, 2.84–7.18) and PFS (adjusted HR, 3.60; 95% CI, 2.33–5.56). Adding LAR to the clinicopathological model increased Harrell’s C-index from 0.699 to 0.760 for OS and from 0.690 to 0.759 for PFS (both likelihood ratios, p < 0.001), with optimism-corrected C-indices of 0.743 and 0.742, respectively. Prognostic discrimination and adjusted effect estimates were greatest early in the follow-up period and attenuated over time, whereas continuous LAR showed nonlinear associations with both endpoints. Among the 104 patients who received adjuvant temozolomide, a high LAR was independently associated with progressive disease (adjusted odds ratio, 3.72; 95% CI, 1.28–10.81). Conclusions: Pretreatment LAR identified patients with IDH-wildtype glioblastoma who experienced poorer survival, and the prognostic effect was concentrated predominantly in the early disease course. Its incremental contribution beyond conventional clinicopathological characteristics supports the further evaluation of LAR as an accessible component of baseline risk characterization. However, independent external validation is required before clinical application.