Extent of reoperation predicts survival in recurrent IDH-wildtype glioblastoma based on institutional data and individual patient data meta analysis

TL;DR

This study finds that the extent of tumor removal during reoperation significantly affects survival in patients with recurrent glioblastoma.

Contribution

The study provides the largest meta-analysis to date on recurrent IDH-wildtype glioblastoma, linking reoperation extent to survival outcomes.

Findings

Patients with residual tumor volume ≤1 cm³ after re-resection had significantly longer overall survival (14.4 months) compared to those with >1 cm³ (8.8 months).

Maximal safe resection during reoperation was significantly associated with improved overall survival.

Progression-free survival did not differ between the two groups despite differences in overall survival.

Abstract

Glioblastoma (GB) is the most aggressive brain tumor, characterized by rapid progression and poor prognosis. Despite initial multimodal treatment options, therapeutic options become more limited upon recurrence. Consequently, recurrent IDH-wildtype GB is associated with poor survival outcomes, with limited data to guide optimal therapeutic strategies. This study presents the largest meta-analysis to date, pooling institutional data with individual patient data (IPD), addressing progression-free survival (PFS) and overall survival (OS) from timepoint after re-resection.

Institutional data and data from literature (2016–2024) were analyzed to evaluate PFS and OS in relation to the extent of resection (EoR). Survival data from identified studies were extracted from Kaplan-Meier curves with the R package IPDfromKM. Additionally, a retrospective analysis of institutional data was conducted, assessing for PFS and OS in 53 patients. EoR was dichotomized as suggested by the RANO group into residual contrast-enhancing tumor volume (CE-RTV) ≤ 1 cm3 or > 1cm3.

A total of 442 IPD were included in this meta-analysis. Among them, 331 patients (74.9%) underwent neurosurgical treatment with CE-RTV ≤ 1cm3, while 111 patients (25.1%) had CE-RTV > 1 cm3. Pooled analysis indicated a significant reduction in OS after re-resection with CE-RTV > 1 cm3 compared to CE-RTV ≤ 1cm3 (HR: 1.731, 95% confidence interval (CI): 1.342–2.234, p < 0.0001). While re-resection with CE-RTV ≤ 1cm3 was associated with longer OS (14.4 months) compared to CE-RTV > 1 cm3 (8.8 months) (p < 0.0001), PFS did not differ between the two groups (CE-RTV ≤ 1 cm3: 7.2 months compared to CE-RTV > 1cm3: 5.8 months) (p = 0.76).

Across pooled IPD, maximal safe resection at re-resection operationalized as GTR or RANO class 1 and 2 was significantly associated with longer overall survival (OS). Where volumetric assessment is available, achieving a postoperative CE-RTV ≤ 1 cm3 may be a reasonable pragmatic target, however this threshold was not directly measured in all included cohorts and should be interpreted as hypothesis-generating.

The online version contains supplementary material available at 10.1007/s12672-025-03928-8.

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