Ahead of Print: Neurosurgical Management and Prognosis of Patients with Glioblastoma that Progress During Bevacizumab Treatment
BACKGROUND: The management and prognosis of glioblastoma patients after Stupp protocol treatment and progression during bevacizumab (BV) treatment remains undefined.
OBJECTIVE: We compared the morbidity and survival of patients whose glioblastomas progressed during bevacizumab treatment requiring craniotomy to non-bevacizumab-treated patients.
METHODS: We retrospectively reviewed patients who underwent craniotomy for recurrent glioblastoma from 2005-2009. Patients operated on for progression during bevacizumab (preoperative bevacizumab) were compared to patients receiving no bevacizumab or bevacizumab after surgery (postoperative bevacizumab). Preoperative bevacizumab patients were compared to those progressing on bevacizumab but not operated on (no surgery).
RESULTS: There were 23 preoperative bevacizumab patients, 135 no bevacizumab patients, 16 postoperative bevacizumab patients, and 25 no surgery patients. Pre-operative bevacizumab patients had worse postoperative overall survival (HR=3.1; p<0.001) and worse postoperative progression free survival (HR=3.4, p<0.001) than no bevacizumab patients. Preoperative bevacizumab patients had higher perioperative morbidity (44%) than patients not receiving pre-operative BV (21%) (p=0.02). Survival after diagnosis was comparable between groups (86-93 weeks, P=0.9), consistent with glioblastomas developing bevacizumab evasion being not intrinsically more aggressive, but possibly bevacizumab evasion conferring uniquely poor prognosis. No surgery patients had shorter overall survival after progression during bevacizumab compared to preoperative bevacizumab patients (HR=3.6, p<0.001).
CONCLUSION: Patients whose glioblastomas progress on bevacizumab leading to craniotomy exhibit shorter postoperative survival and more perioperative morbidity than non-bevacizumab-treated patients. While there may be benefits to surgical debulking, the decision to pursue repeat surgery in patients who have failed BV must be balanced against the increased risk of peri-operative complications.