Prognostic Evaluation of Surgical Re-Resection for Recurrent Glioblastoma Using the Novel RANO Classification for Extent of Resection by The RANO Resect Group

INTRODUCTION: The value of re-resection in recurrent glioblastoma remains unclear since leaving certain tumor deliberately behind appears ethically not justified. METHODS: The international RANO resect group retrospectively compiled an eight-center cohort of patients with first recurrence from a previously resected glioblastoma. The associations of re-resection and clinical factors with outcome were analyzed. Propensity score-matched analyses were constructed to minimize potential confounders when comparing the different RANO classes. RESULTS: We identified 681 patients with first recurrence of IDH-wildtype glioblastomas, including 310 patients who underwent re-resection. The use of re-resection was associated with prolonged survival also when stratifying for molecular and clinical confounders on multivariate analysis; and ≤ 1 cm3 residual CE tumor translated into improved survival compared to non-surgical management. Accordingly, ‘maximal resection’ (class 2) had superior survival compared to ‘submaximal resection’ (class 3). Adjuvant (radio-)chemotherapy further augmented the beneficial effects of lower residual CE tumor. Conversely, ‘supramaximal resection’ of non-CE tumor (class 1) was not associated with prolonged survival but frequently accompanied by post-operative deficits, hampering further treatment. The prognostic role of residual CE tumor was confirmed in propensity score analyses. CONCLUSIONS: Maximal extent of re-resection measured as residual CE tumor is highly prognostic in recurrent glioblastoma. The RANO classification serves to stratify patients accordingly. While the optimal adjuvant therapy awaits evaluation, our study supports that (radio-)chemotherapy consolidates the effects of re-resection.