The Trial


Patients with glioblastoma face a grim prognosis. Despite recent advancement in neurosurgical technology and neuro-oncology glioblastomas almost invariably progress or recur after a median of 4-8 months. The strategy to repeat tumor resection at recurrence in order to minimize tumor load and thus to facilitate subsequent second-line therapy has been shown to be feasible and safe.

However, evidence for a survival benefit of surgery for recurrent glioblastoma is scarce and relies entirely on retrospective analyses. While most retrospective analyses report an apparent survival benefit, an EORTC meta-Analysis on second-line therapies found no survival difference in patients with or without surgery at recurrence. With regard to the risks and costs inherent to surgery for glioblastoma, a randomized controlled trial is required.


The primary objective of this randomized trial is to compare survival outcome after surgery followed by adjuvant second-line therapy to no surgery followed by second-line therapy in recurrent glioblastoma. An auxiliary objective to primary objective is to compare the survival outcomes of operated patients to control in the subgroups stratified by extent of resection: incomplete resection (non-CRET) vs complete resection (CRET).

Secondary objectives are: assessment of recruitment for all screened patients, comparison of progression-free survival between Treatment arms, evaluation of crossover and comparison of patient quality of life between treatment arms.

Safety objectives are: to assess neurological deficits, local infections and morbidity associated to surgery and hospital stay after surgery and during follow-up.

Inclusion Criteria

  1. Informed consent
  2. ≥18 years of age
  3. Prior resection of glioblastoma confirmed by histology
  4. Glioblastoma pretreated with standard radiotherapy without or with temozolomide
  5. First progression according to RANO criteria
  6. First progression not within 3 months after completion of radiation therapy
  7. Complete removal of contrast-enhancing lesion considered feasible without significant risk ofpermanent speech or motor function according to MRI as confirmed by study eligibilitycommittee after screening and prior to recruitment
  8. No encroachment of the M1 or A1 segments of the medial and anterior cerebral artery on MRI
  9. No contrast enhancement in presumed speech and primary motor areas on MRI
  10. No midlineshift on MRI
  11. No contrast enhancing ventricular spread, multifocal recurrence, meningeosis carcinomatosaor infiltration of the contra-lateral hemisphere on MRI
  12. No contra-indication for surgery
  13. Good functional status (KPS ≥ 70)