Research advances in the recurrence patterns of glioblastoma.

Glioblastoma (GBM) is the most aggressive type of primary brain tumor, and recurrence remains virtually inevitable despite standard treatment. The prevention of recurrence represents a critical unmet need. However, the evolutionary characteristics of GBM recurrence patterns and their determinants are incompletely understood, limiting improvements in multimodal treatment. We systematically reviewed studies on GBM recurrence patterns from 1980 onward. Recurrence patterns were harmonized using two classification systems-anatomical distance and radiation isodose overlap-and dichotomized into local versus nonlocal recurrence for a pooled analysis. Although local recurrence predominates, nonlocal recurrence has steadily increased and correlates with therapeutic advances (e.g., extended resection, precision chemoradiotherapy, and tumor treatment fields). MGMT promoter methylation, EGFR aberrations, and the involvement of the cortex or cerebellum promote nonlocal recurrence. Oligodendroglial progenitor cell-like, neuron-like, neural progenitor cell-like, and mesenchymal-like GBM cells undergo distal invasion along white matter tracts through multiple mechanisms. Distant recurrence, a representative nonlocal subtype, only prolongs progression-free survival without prolonging overall survival. Current therapies remain insufficient to prevent distant dissemination, and the underlying mechanisms require further elucidation. Therefore, building a multiparametric recurrence risk stratification system and developing targeted adjuvant strategies are essential for improving the long-term survival of patients with GBM.