Molecularly diagnosed glioblastoma: clinical presentation and outcomes.

BACKGROUND: The 2021 WHO classification permits diagnosis of glioblastoma in IDH-wildtype diffuse astrocytic tumors with TERT promoter mutation, EGFR amplification, or chromosome 7 gain/10 loss, even without necrosis or microvascular proliferation. The clinical behavior of these molecularly defined glioblastomas (molGBM) remains uncertain. METHODS: We retrospectively analyzed patients with molGBM treated at Hannover Medical School between 2017 and 2024. A contemporaneous histologically defined glioblastoma cohort (hisGBM) served as a control group in an approximately 1:3 ratio. MolGBM were stratified by histological grade and additionally compared with IDH-mutant astrocytomas of corresponding grade. Survival was assessed using Kaplan-Meier analysis, Cox regression, and propensity score matching. RESULTS: Thirty-four patients with molGBM and 103 with hisGBM were included. Compared with hisGBM, molGBM patients were younger (p < 0.001), had higher Karnofsky Performance Status (p < 0.001), and more often presented with seizures (p = 0.006), whereas focal neurological deficits were more frequent in hisGBM. MolGBM showed less contrast enhancement (p < 0.001) and lower Ki-67 indices (p < 0.001). Median overall survival was longer in molGBM (539 vs. 374 days; p = 0.032), but tumor group was not independently associated with survival after adjustment for age and KPS (HR 1.21, 95% CI 0.77-1.90; p = 0.411). In the matched cohort, overall survival did not differ significantly (517 vs. 468 days; p = 0.670). MolGBM had inferior survival to grade-corresponding IDH-mutant astrocytomas (p < 0.001). CONCLUSIONS: MolGBM shows a distinct clinical-radiological phenotype, while its apparent survival advantage over hisGBM is influenced by baseline clinical differences. CLINICAL TRIAL NUMBER: Not applicable.