Determinants of survival after re-resection for recurrent glioblastoma: a meta-analysis

TL;DR

This study identifies factors affecting survival after re-surgery for recurring glioblastoma, finding that complete tumor removal and MGMT gene methylation are linked to better outcomes.

Contribution

The study provides a meta-analysis of prognostic factors for survival after re-resection in recurrent glioblastoma, highlighting the importance of gross total resection and MGMT promoter methylation.

Findings

Gross total resection and methylated MGMT promoter status are strongly associated with improved survival.

Age and preoperative KPS < 70 are modestly associated with worse survival.

Adjuvant chemotherapy and timing of re-resection show inconsistent survival benefits.

Abstract

Glioblastoma (GBM) inevitably recurs despite maximal safe resection and standard chemoradiotherapy. The factors influencing survival after first recurrence and re-resection remain controversial.

What are the prognostic factors influencing survival following re-resection of glioblastoma?

A systematic search of major databases was conducted for original studies reporting on survival outcomes. Data on hazard ratios (HR) for overall survival and key prognostic factors were extracted, followed by meta-analyses of univariate and multivariate Cox models. Study quality and risk of bias were assessed.

A total of 30 studies were included. Gross total resection and methylated MGMT promoter status were significantly associated with improved survival, with pooled HRs of 0.52 (95% CI: 0.36–0.76, p < 0.001) and 0.58 (95% CI: 0.45–0.75, p < 0.001), respectively. In contrast, age was modestly associated with worse survival (HR: 1.02, 95% CI: 1.01–1.03, p < 0.001). Preoperative Karnofsky Performance Status (KPS) < 70 was associated with worse survival (HR: 2.25, 95% CI: 1.59–3.19, p < 0.001). Adjuvant chemotherapy (HR: 0.69, 95% CI: 0.33–1.45, p = 0.33) and time to re-resection (HR: 0.69, 95% CI: 0.41–1.16, p = 0.16) failed to show consistent survival benefits.

Our findings suggest gross total resection of contrast-enhancing tumour and MGMT promoter methylation are strongly associated with improved survival following first recurrence of glioblastoma. Conversely, age, preoperative KPS, adjuvant chemotherapy, and timing of re-resection showed inconsistent or non-significant associations, emphasizing the need for prospective studies to refine prognostic assessments and guide individualized treatment strategies in recurrent glioblastoma.

The online version contains supplementary material available at 10.1007/s00701-025-06755-6.

Re-resection should be considered where gross total re-resection is feasible.Methylated MGMT promoter status indicates effectiveness of alkylating agents in recurrent glioblastoma.More congruence in study design and outcome reporting on KPS and time to re-resection is required to conclude on their prognostic influence.

Re-resection should be considered where gross total re-resection is feasible.

Methylated MGMT promoter status indicates effectiveness of alkylating agents in recurrent glioblastoma.

More congruence in study design and outcome reporting on KPS and time to re-resection is required to conclude on their prognostic influence.

The online version contains supplementary material available at 10.1007/s00701-025-06755-6.

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