Background: Tumor resection is a prerequisite in many studies of new glioblastoma therapeutics; however, no clear parameters for "resectability" exist. We evaluated inter-rater variability in assessing tumor resectability and potential associations between resectability and survival in a trial cohort of glioblastoma recurrence.
Methods: DIRECTOR (NCT00941460; 9/2009-6/2012) evaluated two dose-dense temozolomide regimens for first recurrent glioblastoma, yielding similar outcomes between arms. Re-resection was allowed before initiation of systemic therapy by institutional decision. Eleven surgical neuro-oncologists (blinded to final outcomes) rated whether a 'meaningful resection' was achievable for each recurrent IDH-wildtype glioblastoma based on imaging and clinical data.
Results: MRI scans from 69 patients were available (median age:58.2 ± 1.1 years, median survival:10.0 months). 40 patients underwent re-resection (median age:56.4 ± 1.7 years, median survival:10.8 months). Surgical decision-making markedly varied between raters, ranging from 30-58 of 69 cases being classified as 'resectable' (κ = 0.405). In patients who received re-resection, a 'meaningful resection' was deemed feasible by > 80% of raters in 30/40 cases (75.0%). For patients without re-resection, unanimous agreement on non-resectability occurred in only 3/29 cases (10.4%); and 5/29 tumors (17.2%) were considered resectable by > 80% of raters. Knowledge of additional clinical factors virtually never changed MRI-based judgments. While patients who had a complete resection of contrast-enhancing tumor had favorable outcomes, a consensus on resectability by > 80% of raters was not associated with prolonged overall survival.
Discussion: Feasibility assessment for re-resection is heterogenous among neurosurgeons, challenging single-surgeon evaluation of "resectability". Those findings are limited by the number of surgical raters and the size of the DIRECTOR cohort.
Keywords: extent of resection; glioblastoma; heterogeneity; resectability; surgery.
We asked whether neurosurgeons agree on which recurring brain tumors (“glioblastoma”) can be safely removed, and whether this matters for survival. This is important because many studies require surgery, yet “resectability” is not clearly defined. We analyzed MRIs from 69 patients from a prior trial. Eleven experienced neurosurgeons independently judged if meaningful tumor removal was possible. We found that opinions varied widely, even among experts. Adding clinical details rarely changed decisions. Importantly, agreement on resectability did not predict survival, but the amount of tumor left after surgery did. This suggests we need standardized tools to guide surgical decisions and trials.
© The Author(s) 2026. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.