Grade-Dependent Prognostic Value of Classical Clinicopathological Factors in Glioma: A Single-Center Retrospective...

Background: The prognostic relevance of classical clinicopathological factors in glioma may vary across World Health Organization (WHO) grades. We examined whether anatomical location, Ki-67, and treatment-related variables show grade-dependent associations with survival. Methods: We retrospectively included 429 patients with glioma treated at a single center between 2012 and 2024. Patients were stratified into WHO grade 2-3 gliomas (n = 129) and WHO grade 4 gliomas (n = 300). Overall survival was evaluated using Kaplan-Meier analysis and Cox proportional hazards models. Additional exploratory analyses were performed in cases with known IDH status with adjustment for IDH and MGMT status. Results: Median overall survival for the full cohort was 29.93 months, and survival differed significantly across WHO grades. In grade 2-3 gliomas, higher Karnofsky Performance Status, non-deep location, and lower Ki-67 were associated with better survival; deep/midline location and Ki-67 ≥ 30% remained independently associated with worse overall survival. Within non-deep grade 2-3 tumors, temporal location was associated with worse survival. In grade 4 gliomas, female sex, non-deep location, and receipt of radiotherapy were independently associated with better survival, whereas Ki-67 was not prognostic. In exploratory molecularly adjusted analyses, deep/midline location remained associated with worse survival across grades, whereas the prognostic effect of Ki-67 became unstable. Longer chemotherapy duration showed a trend toward improved survival in grade 4 gliomas. Conclusions: Classical clinicopathological factors show substantial grade-dependent prognostic heterogeneity in glioma. Anatomical location appears to be a relatively stable adverse prognostic factor across grades, including after partial molecular adjustment. In contrast, the prognostic relevance of Ki-67 was less robust after adjustment for IDH and MGMT and should be interpreted cautiously as an exploratory, molecular-context-dependent marker.