To be or not to be: The dilemma over the prognostic role of epilepsy at presentation in patients with glioblastoma – a systematic review and meta-analysis

Despite some evidence of a possible link between epileptogenesis and tumorigenesis in glioblastoma, the prognostic value of epilepsy at presentation has been debated over the years. We performed a systematic review and meta-analysis to summarize all published data evaluating the prognostic significance of seizures as a presenting manifestation of glioblastoma. A comprehensive search of five databases from inception to December 2023 was conducted. Included studies underwent meta-analysis, with subgroup analyses performed to identify sources of heterogeneity. Fifteen studies were included in the analysis. Seizures were considered a favorable prognostic factor in seven studies, while eight studies found no differences in overall survival between patients with seizures and those with other presenting symptoms. Eleven studies were included in the meta-analysis. The overall pooled analysis indicated a potentially favorable prognostic impact of seizures at the clinical onset of glioblastoma (HR 0.73; 95% CI 0.61–0.87). However, subgroup analysis within studies focusing on IDH-wild type cases showed no discernible impact from preoperative seizures. Retrospective design, poor quality in reporting results, and heterogeneity in tumor characteristics and therapies are the main limitations of included studies. Future prospective studies on large, homogeneous cohorts of patients with IDH-wild type glioblastoma are warranted. Overall, these findings suggest that while seizures may hold some prognostic value, further research is essential to clarify their role. Understanding the true prognostic role of seizures at clinical onset may enhance our ability to predict patient outcomes and guide clinical decision-making.