Extent of resection and survival in IDH-wildtype glioblastoma: interaction with MGMT status and chemoradiation

PURPOSE: Whether gross total resection (GTR) remains associated with survival among MGMT-methylated IDH-wildtype glioblastoma patients receiving chemoradiation remains uncertain. We evaluated whether GTR versus less-than-GTR (< GTR) was associated with overall survival across MGMT promoter methylation and chemoradiation strata. METHODS: We retrospectively reviewed 261 patients undergoing biopsy or resection for newly diagnosed IDH-wildtype glioblastoma at a single institution from 2010 to 2024. Extent of resection was dichotomized as GTR versus < GTR, and chemoradiation was coded as receipt of postoperative radiation and temozolomide. Overall survival was assessed using Kaplan-Meier analysis and multivariable Cox models with prespecified EOR × MGMT × chemoradiation interaction testing, adjusted for age, KPS, tumor location, and mFI-5. RESULTS: GTR was associated with longer overall survival than < GTR in the overall cohort and within all four MGMT × chemoradiation strata. MGMT-methylated patients receiving chemoradiation had a median overall survival of 17.02 months after GTR versus 10.65 months after < GTR (log-rank p = 0.001), and the model-derived adjusted hazard ratio for < GTR versus GTR was 2.12 (95% CI 1.27-3.54; p = 0.004). The three-way EOR × MGMT × chemoradiation interaction was not significant (likelihood-ratio p = 0.309). In a 6-week sensitivity analysis, all survival associations remained, but EOR × chemoradiation was no longer significant. CONCLUSION: GTR was associated with longer survival across all MGMT and chemoradiation-defined subgroups, including MGMT-methylated patients receiving chemoradiation. These findings are consistent with maximal safe resection when feasible but should be interpreted cautiously because of small subgroups as well as treatment-selection and immortal-time biases.