Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis.
OBJECTIVE
Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies.


OBJECTIVE
To determine whether greater EOR is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients with GBM.


METHODS
Pubmed, CINAHL, and Web of Science (January 1, 1966, to December 1, 2015) were systematically reviewed with librarian guidance. Additional articles were included after consultation with experts and evaluation of bibliographies. Articles were collected from January 15 to December 1, 2015.


METHODS
Studies of adult patients with newly diagnosed supratentorial GBM comparing various EOR and presenting objective overall or progression-free survival data were included. Pediatric studies were excluded.


METHODS
Data were extracted from the text of articles or the Kaplan-Meier curves independently by investigators who were blinded to each other's results. Data were analyzed to assess mortality after gross total resection (GTR), subtotal resection (STR), and biopsy. The body of evidence was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and PRISMA guidelines.


METHODS
Relative risk (RR) for mortality at 1 and 2 years and progression at 6 months and 1 year.


RESULTS
The search produced 37 studies suitable for inclusion (41 117 unique patients). The meta-analysis revealed decreased mortality for GTR compared with STR at 1 year (RR, 0.62; 95% CI, 0.56-0.69; P < .001; number needed to treat [NNT], 9) and 2 years (RR, 0.84; 95% CI, 0.79-0.89; P < .001; NNT, 17). The 1-year risk for mortality for STR compared with biopsy was reduced significantly (RR, 0.85; 95% CI, 0.80-0.91; P < .001). The risk for mortality was similarly decreased for any resection compared with biopsy at 1 year (RR, 0.77; 95% CI, 0.71-0.84; P < .001; NNT, 21) and 2 years (RR, 0.94; 95% CI, 0.89-1.00; P = .04; NNT, 593). The likelihood of disease progression was decreased with GTR compared with STR at 6 months (RR, 0.72; 95% CI, 0.48-1.09; P = .12; NNT, 14) and 1 year (RR, 0.66; 95% CI, 0.43-0.99; P < .001; NNT, 26). The quality of the body of evidence by the GRADE criteria was moderate to low.


CONCLUSIONS
This analysis represents the largest systematic review and only quantitative systematic review to date performed on this subject. Compared with STR, GTR substantially improves overall and progression-free survival, but the quality of the supporting evidence is moderate to low.
Department of Medicine, University of Texas Southwestern Medical Center, Dallas.
Timothy J
TJ
Brown
Ann Barshinger Cancer Center, Lancaster General Health, Lancaster, Pennsylvania.
Matthew C
MC
Brennan
Department of Neurosurgery, University of Rochester Medical Center, Pittsford, New York.
Michael
M
Li
Department of Neurosurgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
Ephraim W
EW
Church
Department of Neurosurgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
Nicholas J
NJ
Brandmeir
Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
Kevin L
KL
Rakszawski
Department of Neurosurgery, Swedish Cerebrovascular Institute, Seattle, Washington.
Akshal S
AS
Patel
Department of Neurosurgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
Elias B
EB
Rizk
Division of Surgery, Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston.
Dima
D
Suki
Division of Surgery, Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston.
Raymond
R
Sawaya
Department of Neurosurgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
Michael
M
Glantz
D001921:Brain / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000401:mortality / Q000601:surgery*; D018572:Disease-Free Survival; D005909:Glioblastoma / Q000401:mortality / Q000601:surgery*; D006801:Humans; D012306:Risk; D016896:Treatment Outcome