Survival Impact of Isocitrate Dehydrogenase (IDH)-Wildtype Histological Versus Molecular Glioblastoma: A Propensity Score-Matched Analysis

Introduction Glioblastoma (GBM) is a highly aggressive brain tumor with a poor prognosis. Molecular classification has redefined GBM subtypes, but survival differences between histological GBM (h-GBM) and molecular GBM (mol-GBM) remain underexplored. This study uses propensity score matching (PSM) to compare survival outcomes, accounting for clinical confounders. Methods A retrospective cohort of isocitrate dehydrogenase (IDH)-wildtype GBM patients was analyzed using 1:1 nearest-neighbor PSM, balancing age (<64 or ≥64 years), O6-methylguanine-DNA methyltransferase (MGMT) methylation status, and radiotherapy (RT) dose. Kaplan-Meier estimates and log-rank tests were used to compare the overall survival (OS) and progression-free survival (PFS) between h-GBM and mol-GBM. Results The matched cohort included 26 h-GBM and 26 mol-GBM patients. Median OS was 15.2 months for mol-GBM vs. 14.2 months for h-GBM (p=0.238). Mol-GBM showed significantly longer PFS (11.8 vs. 8.0 months, p=0.005). In MGMT-unmethylated patients, mol-GBM had superior OS (15.2 vs. 12.7 months, p=0.030) and PFS (13.1 vs. 7.8 months, p<0.001). Higher RT dose (60 Gy/30 fractions) improved OS (22.1 vs. 13.3 months, p=0.010) and PFS (10.8 vs. 8.7 months, p=0.020) in mol-GBM. Conclusion Molecular classification significantly influences GBM prognosis, with mol-GBM demonstrating better PFS and selective OS benefits in MGMT-unmethylated patients. Higher RT doses enhance outcomes, supporting personalized treatment strategies. Validation in larger cohorts is needed.