Relevance of a complete re-resection of contrast enhancing tumor in MGMT promotor non-methylated versus methylated recurrent glioblastomas.

Introduction: Management of recurrent glioblastoma (rGB) requires an individualized approach, considering tumor location, functional status, and patient age. While lomustine chemotherapy remains the standard treatment for most patients, response is limited in MGMT non-methylated tumors. Research question: Does maximal surgical resection improve survival outcomes in recurrent glioblastoma patients with poor response to systemic therapy? Material and methods: We performed a retrospective analysis of rGB patients who underwent re-resection between January 2016 and December 2021. Clinical, radiological, and molecular data were collected. Extent of resection was defined by RANO criteria. Progression-free survival after re-resection (PFS2), reoperation survival (RS), and overall survival (OS) were analyzed using Kaplan-Meier and multivariate Cox regression models. Results: Maximal resection was achieved in 54% of patients. MGMT-methylated tumors were associated with longer OS than non-methylated cases (18.7 vs. 17.2 months; p = 0.012), while PFS2 did not differ significantly by MGMT status (4.1 vs. 3.4 months; p = 0.11). Maximal resection significantly improved PFS2 (6.27 vs. 3.02 months; p = 0.0064) and showed a trend toward better OS (p = 0.055). MGMT-methylated patients with maximal resection had the best outcomes (PFS2: 6.27 months; OS: 14.1 months). In multivariate analysis, submaximal resection predicted worse PFS2 (p < 0.001) and RS (p = 0.024), while ECOG ≥2 was associated with shorter PFS2 (p = 0.02). In non-methylated patients, resection extent and ECOG were not significant prognostic factors. Conclusion: MGMT methylation correlates with improved survival. In methylated rGB, submaximal resection and poor performance status predict worse outcomes, supporting maximal resection as a key prognostic factor.