Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis

Abstract

Importance: 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.

Data sources: 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.

Study selection: 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.

Data extraction and synthesis: 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.

Main outcome and measures: 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.

Conclusion and relevance: 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.

Figure 1.

PRISMA Flow Diagram ALA indicates 5-aminolevulinic acid; GBM, glioblastoma multiforme.

Figure 2.

Relative Risk (RR) for 1-Year Mortality for Gross Total Resection (GTR) vs Subtotal Resection (STR) Forest plots depict RRs (random Mantel-Haenszel test) at 1 year. Twenty-five studies were included in this analysis of 20 769 patients. Overall RR at 1 year is 0.62 (95%CI, 0.56–0.69; P < .001), favoring GTR over STR. Removal of Surveillance, Epidemiology, and End Results (SEER) data produced an RR of 0.60 (95%CI, 0.53–0.67; P < .001). Removal of the SEER and Radiation Therapy Oncology Group data produced an RR of 0.59 (95%CI, 0.53–0.65; P < .001). Marker size indicates the relative weight of the study as it contributes to the results of the overall comparison.

Figure 3.

Relative Risk (RR) for 2-Year Mortality for Gross Total Resection (GTR) vs Subtotal Resection (STR) Forest plots depict RRs (random Mantel-Haenszel test) at 2 years. Twenty-three studies were included in this analysis of 20 699 patients. Overall RR for death at 2 years was 0.84 (95%CI, 0.79–0.89; P < .001), favoring GTR over STR. Removal of the Surveillance, Epidemiology, and End Results (SEER) data produced an RR of 0.83 (95%CI, 0.77–0.89; P < .001). Removal of the SEER and Radiation Therapy Oncology Group data produced an RR of 0.83 (95%CI, 0.77–0.89; P < .001). Marker size indicates the relative weight of the study as it contributes to the results of the overall comparison.

Figure 4.

Relative Risk (RR) for Mortality for Subtotal Resection (STR) vs Biopsy Forest plots depict RRs (random Mantel-Haenszel test) at 1 and 2 years. A, Twenty studies were included in this analysis of 14 136 patients. The RR of mortality at 1 year with STR is 0.85 (95%CI, 0.80–0.91; P < .001). Removal of the Surveillance, Epidemiology, and End Results (SEER) data produced an RR of 0.85 (95%CI, 0.78–0.92; P < .001) compared with biopsy. B, Sixteen studies were included in this analysis of 13 811 patients. The RR of mortality at 2 years did not significantly differ between STR and biopsy in this analysis (RR, 0.99; 95%CI, 0.97–1.00; P = .09).We hypothesized that the narrower differences between STR and biopsy result from the wide percentages of resections that constitute STR in the primary literature and perhaps some overlap between biopsy and STR, particularly in the setting of smaller tumors. Marker size indicates the relative weight of the study as it contributes to the results of the overall comparison.