Understanding the difference in symptoms and outcomes between glioblastoma patients diagnosed based on histological or molecular criteria: a retrospective cohort analysis from the Histo-Mol GBM collaborative

Purpose: Since the 2021 World Health Organisation (WHO) classification, glioblastoma could be diagnosed based on classical histological features (hGBM) or molecular criteria (mGBM). However, prior studies included patients who required reclassification as a mGBM, potentially biasing survival analyses. The Histo-Mol GBM collaborative performed an international multicentre retrospective real-world cohort study of glioblastoma patients diagnosed according to WHO CNS 5. Methods: We identified consecutive patients diagnosed in 2021 with IDH wildtype glioblastoma according to WHO CNS 5. Clinicopathological, treatment, and survival data were collected and compared between mGBM and hGBM. Results: 1828 patients diagnosed with glioblastoma were included. 75 mGBM patients (8.4% of tested patients) were identified, with no difference in age (median 61 vs 64, p=0.057), gender (p=0.937), or proportion with performance status 0-1 (82.7% vs 68.3%, p=0.052) compared to hGBM. mGBM patients had an extended interval from MRI to surgery (median 23 vs 14 days, p<0.001) and more frequently underwent biopsy (69.3% vs 30.3%, p<0.001), but equivalent proportions received oncological treatment (80.0% vs 78.7%, p=0.784). Overall survival (OS) from surgery was not different (p=0.063). However, OS from initial MRI, stratified by surgical extent, demonstrated improved OS for mGBM patients (hazard ratio (HR) 0.56, 95% confidence interval (CI): 0.43-0.73). Propensity score matching identified improved survival following resection (HR 0.48, 95% CI: 0.24-0.95; median OS: 26.0 versus 14.0 months, p=0.031) but not biopsy (HR 1.10, 95% CI: 0.71-1.72). Conclusion: In this large real-world cohort, mGBMs had longer OS than hGBMs following resection with implications for prognostication and clinical decision making.