Prognostic Validation of the RANO-Resect Classification and Non–Contrast-Enhancing Tumor Resection: A Meta-Science Study in Glioblastoma Surgery

BACKGROUND AND OBJECTIVES: Maximal safe resection correlates with improved overall survival (OS) and progression-free survival (PFS) in patients with glioblastoma (GBM). However, standardized classifications-particularly for resections extending beyond the contrast-enhancing (CE) tumor-remain inconsistent. The Response Assessment in Neuro-Oncology (RANO)-resect volumetric classification has demonstrated prognostic value in GBM, yet comparative validation across the literature remains limited. We aim to evaluate the prognostic performance of the RANO-resect classification for extent of resection (EOR) and compare its reproducibility in survival estimation relative to alternative, nonstandardized definitions of resection beyond the CE region. METHODS: A search was conducted on May 23, 2024, identifying studies on GBM surgery that categorized EOR using the RANO-resect classification, as well as studies evaluating resection of non-CE tumor. RESULTS: Seventeen articles were included (n = 2606). Higher RANO-resect volumetric classes were associated with improved OS (P ≤ .0001) and PFS (P ≤ .0001): Class 1 (Supramaximal): OS 24.6 months, PFS 13.6 months; Class 2 (Maximal): OS 18 months, PFS 9.2 months; Class 3 (Submaximal): OS 13.5 months, PFS 8.2 months; and Class 4 (Biopsy): OS 8.2 months, PFS 4.8 months. Resection of non-CE tumor was associated with improved OS (MD = 6.4 months; 95% CI: 4.25-8.68; P ≤ .0001) and PFS (MD = 5.2 months; 95% CI: 3.4-6.6; P ≤ .0001) over complete CE tumor resection alone. Several different nonstandardized terminologies for non-CE tumor resection were identified. When applying the Class 1 RANO-resect definition, heterogeneity in OS outcomes was I2 = 0%, compared with 40% to 74% with alternative definitions. CONCLUSION: Maximal volumetric resection of non-CE tumor correlates with improved survival in patients with newly diagnosed GBM. We present the first direct comparison of the prognostic reproducibility between the RANO-resect framework for EOR compared with alternative nonstandardized definitions. Notably, the use of the RANO-resect volumetric classification was associated with more homogeneous survival estimates and greater OS predictability across studies, supporting its potential implementation in future clinical trials.