Efficacy and Safety of Reoperation Versus Alternative Interventions in Recurrent Glioblastoma: A 11,009 patient Meta-Analysis

Introduction: Glioblastoma (GBM) has a high rate of recurrence and poor overall survival despite maximal-safe resection and adjuvant radiation and chemotherapy. However, most of the clinical data has been limited to observational studies, and only one available trial. Current evidence does not conclusively show superiority of reoperation over radiation or chemotherapy alone. An updated meta-analysis comparing the efficacy of reoperation with non-reoperation, taking into consideration chemotherapy with or without radiotherapy, gamma knife surgery (GKS), and reirradiation has not been performed.

Methods: Databases were searched until August 24th, 2023 identifying clinical trials and observational cohort studies comparing the impact of reoperation to no-reoperation. The latter group included chemotherapy with/without radiotherapy, and radiation-based therapies (RBT) which included GKS, and reirradiation. Relevant outcomes included: overall survival (OS); post-recurrence survival (PRS), and complications.

Results: We included 36 studies with 11009 patients, of whom 3566 (50.5%) underwent repeat resection. OS mean difference (MD) favored reoperation group chemotherapy alone (MD=5.8 months[3.82,7.78], p= < 0.00001) or in combination with radiotherapy (MD=6.5 months[6.31,6.69], p= < 0.00001). Reoperation had a similar OS with radiation-based therapies (MD=1.07 months[-2.23,4.36], p=0.53). PRS favored the reoperation group over chemotherapy +/- radiotherapy (MD=3.35 months[1.51,5.20], p= < 0.00001). Complications were similar among both groups (Risk Ratio=0.81[0.66,1.01],p=0.06).

Conclusion : In the present study, reoperation seems to provide superior outcomes with a similar safety profile to non-reoperation interventions. Unfortunately, only one clinical trial was identified to support this. Reoperation did not demonstrate superiority to RBT. This study highlights the need for high-quality clinical trials to elucidate these findings.