Abstract

Abstract BACKGROUND The role of re-resection in recurrent glioblastoma remains controversial since leaving certain tumor volumes deliberately behind cannot be ethically justified. We aimed to (I) analyze the prognostic value of re-resection using the novel RANO resect classification for quantification of residual tumor, and (II) explore factors that favorably consolidate the effects of re-resection on outcome. METHODS The RANO resect group retrospectively accumulated a global, 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 mimic randomized clinical trials comparing different residual tumor volumes. RESULTS We analyzed 681 patients with first recurrence of IDH-wildtype glioblastoma, including 310 patients who underwent re-resection at first recurrence. The use of re-resection was associated with prolonged survival also when stratifying for molecular and clinical confounders (HR:0.65, CI:0.5-0.8; p = 0.001). Smaller post-operative contrast-enhancing (CE) tumor volumes were favorably associated with outcome of re-resected patients (HR per cm3:1.04, CI:1.0-1.1; p = 0.009), 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) (mOS after recurrence: 12 vs. 9 months; p = 0.003). Adjuvant 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. CONCLUSION Residual CE tumor is highly prognostic in recurrent glioblastoma and the RANO resect classification serves to stratify patients accordingly. Chemotherapy may favorably contribute to the prognostic associations of re-resection. When pursuing re-resection of non-CE tumor, intraoperative mapping strategies to minimize the risk of post-operative deficits are recommended.

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