Glioblastoma inevitably recurs, but no standard regimen has been established for treating this recurrent disease. Several reports claim that reoperative surgery can improve survival, but the effects of reoperation timing on survival have rarely been investigated. We, therefore, evaluated the relationship between reoperation timing and survival in recurrent GBM. A consecutive cohort of unselected patients (real-world data) from three neuro-oncology cancer centers was analyzed (a total of 109 patients). All patients underwent initial maximal safe resection followed by treatment according to the Stupp protocol. Those meeting the following criteria during progression were indicated for reoperation and were further analyzed in this study: (1) The tumor volume increased by >20-30% or a tumor was rediscovered after radiological disappearance; (2) The patient's clinical status was satisfactory (KS ≥ 70% and PS WHO ≤ gr. 2); (3) The tumor was localized without multifocality; (4) The minimum expected tumor volume reduction was above 80%. A univariate Cox regression analysis of postsurgical survival (PSS) revealed a statistically significant effect of reoperation on PSS from a threshold of 16 months after the first surgery. Cox regression models that stratified the Karnofsky score with age adjustment confirmed a statistically significant improvement in PSS for time-to-progression (TTP) thresholds of 22 and 24 months. The patient groups exhibiting the first recurrence at 22 and 24 months had better survival rates than those exhibiting earlier recurrences. For the 22-month group, the HR was 0.5 with a 95% CI of (0.27, 0.96) and a p-value of 0.036. For the 24-month group, the HR was 0.5 with a 95% CI of (0.25, 0.96) and a p-value of 0.039. Patients with the longest survival were also the best candidates for repeated surgery. Later recurrence of glioblastoma was associated with higher survival rates after reoperation.

Department of Health Care Science Faculty of Humanities T Bata University in Zlin Stefanikova 5670 760 01 Zlín Czech Republic

Department of Neurosurgery Faculty of Medicine and Dentistry Palacky University in Olomouc University Hospital Olomouc Zdravotníků 248 7 779 00 Olomouc Czech Republic

Department of Neurosurgery Faculty of Medicine Masaryk University St Anne's University Hospital in Brno Pekarska 664 53 602 00 Brno Czech Republic

Department of Neurosurgery Faculty of Medicine Masaryk University University Hospital Brno Jihlavská 20 625 00 Brno Czech Republic

Department of Neurosurgery Faculty of Medicine University of Ostrava University Hospital Ostrava 17 Listopadu 1790 5 708 52 Ostrava Czech Republic

Department of Radiation Oncology Faculty of Medicine Masaryk University Masaryk Memorial Cancer Institute Zluty Kopec 7 656 53 Brno Czech Republic

Institute of Molecular and Translate Medicine Faculty of Medicine and Dentistry Palacky University in Olomouc Hnevotinska 133 5 779 00 Olomouc Czech Republic

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