Prognosis of intracranial meningiomas with TERTp mutation: Systematic review with meta-analysis

Abstract Background Telomerase reverse transcriptase promoter (TERTp; C228T/C250T) mutations are incorporated into the World Health Organization 2021 classification of meningiomas (20%-30% in grade 3) as criteria for higher-grade designation, despite heterogeneous evidence regarding their independent prognostic value. Objectives To evaluate the association between TERTp mutations and overall survival (OS) and progression-free survival (PFS) in patients with intracranial meningiomas. Methods A systematic review and meta-analysis of clinical-pathological cohort studies comparing TERTp-mutated and wild-type meningiomas was conducted. Studies were identified through searches of PubMed, Embase, and Web of Science. Survival outcomes were synthesized using hazard ratios (HRs) and median survival estimates. Results Thirteen studies were included. Meta-analyses comprised 4 studies for PFS by HR, 5 for OS by HR, 5 for PFS by mean difference (MD) (8 comparisons), and 5 for OS by MD. Sensitivity analyses excluded Maas et al. (2021), Spiegl-Kreineck et al. (2018), and Mellai et al. (2021) from the PFS mean-difference, OS HR, and OS mean-difference models, respectively; no study was excluded from the PFS HR model. Conclusions Telomerase reverse transcriptase promoter mutations identify a biologically aggressive meningioma subgroup with markedly reduced survival, supporting their role as prognostic biomarkers. However, their isolated use for tumor reclassification should be interpreted cautiously and integrated with additional molecular features. Registration PROSPERO platform (No. CRD420251135452).