Abstract
Background: Glioblastoma remains the most aggressive and treatment-resistant primary brain tumor, with patient outcomes strongly associated with the extent of surgical resection. Tumor recurrence is largely driven by infiltrating glioma cells that extend beyond the contrast-enhancing margin, which has traditionally served as the boundary for surgical resection. Advances in pre- and intraoperative imaging, functional mapping, and fluorescence guidance have challenged the conventional definition of "maximal safe resection" and given rise to the concept of supramaximal resection (SMR). This technique, where surgical resection extends beyond the contrast-enhancing border, has garnered significant interest in recent years and shown promising preliminary survival outcomes. However, the lack of standardized definitions and methodological consistency has limited reproducibility and clinical adoption. Methods: A systematic literature search of PubMed/MEDLINE, Embase, and Web of Science was performed from database inception through March 2026 in accordance with PRISMA guidelines. Studies investigating resection beyond the contrast-enhancing tumor margin in adult glioblastoma patients were evaluated for inclusion. Results: A total of 1045 records were identified, with 37 studies meeting inclusion criteria. Across studies, SMR was frequently associated with improved progression-free and overall survival in selected patients, particularly following complete contrast-enhancing tumor resection. However, substantial heterogeneity exists in SMR definitions, and the current body of evidence is largely retrospective and derived from high-volume centers. Conclusions: SMR represents a promising extension of maximal safe resection targeting infiltrative tumor beyond conventional imaging boundaries. While emerging evidence suggests survival benefits, variability in methodology and patient-specific factors require cautious interpretation. Future standardization and prospective validation are needed to better define the role of SMR within multimodal glioblastoma treatment.