Maximum Resection in Glioblastoma Improves Survival

Liam Davenport

June 23, 2016

For patients with glioblastoma multiforme, an aggressive and often fatal form of brain tumor, the maximum possible resection yields the longest overall and progression-free survival, say US investigators.

A meta-analysis of data for more than 40,000 patients with glioblastoma found that gross total resection (GTR) was associated with a significant survival benefit in comparison with subtotal resection (STR).

In comparison with STR, GTR improved 1-year survival by approximately 61%; 2-year survival was improved by around 19%, the researchers found.

The finding should settle the ongoing controversy over the ideal extent of resection in glioblastoma, the investigators comment.

The research was published online June 16 in JAMA Oncology.

Senior author Michael Glantz, MD, of the Department of Neurosurgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, told Medscape Medical News that the study "provides a precise estimate of the benefit" of GTR in patients with glioblastoma, adding: "It means that gross total resection extends life in all patients."

However, he cautioned that the right clinical approach to treating the disease should be to perform the "most aggressive resection that is clinically safe; that's what most neurosurgeons would advocate now."

Dr Glantz explained, "You can operate on anything, but sometimes that's unwise; you can leave people devastated, and a longer life with a poor quality isn't a good trade-off."

Given the continued debate over the best approach to surgery for glioblastoma, Dr Glantz believes it is now "an issue of getting the message out there."

"There's been ongoing controversy at almost every neurosurgical meeting about this, but I think now that people have reliable estimates of benefit and they know the quality of the evidence, there aren't many other barriers [to adoption]," he said.

Details of the Meta-analysis

Although a number of studies have reported on survival following glioblastoma surgery, the association between the extent of tumor resection and outcomes had been unclear. The researchers therefore searched the PubMed, CINAHL, and Web of Science databases for studies involving adults with newly diagnosed supranatorial glioblastoma that examined extent of resection and included survival data.

Each article was graded using American Academy of Neurology level of evidence criteria. The body of evidence was evaluated in line with the Grading of Recommendations Assessment, Development, and Evaluation criteria and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

The team identified 37 studies published from 1966 through 2015 for inclusion in the meta-analysis, yielding a total of 41,117 unique patients.

The analysis revealed that GTR was associated with significantly improved survival in comparison with STR at 1 year, at a relative risk (RR) of 0.62 and a number needed to treat (NNT) of nine (P < .001); at 2 years, the RR was 0.84 and the NNT was 17 (P < .001).

Dr Glantz pointed out that the number needed to treat is valuable because it "is so easy to translate for patients into something that's meaningful."

The results also showed that STR was associated with a level of survival improvement similar to that for biopsy at 1 year, at an RR of 0.85 (P < .001). However, STR was not associated with a survival benefit in comparison with biopsy at 2 years.

Any resection was associated with a survival benefit compared with biopsy at 1 year, with an RR of 0.77 and an NNT of 21 (P < .001); at 2 years, the RR was 0.94 and the NNT was 593 (P = .04).

Among the eight studies that met the inclusion criteria for reporting progression-free survival (PFS), there was a nonsignificant improvement in PFS with GTR over STR at 6 months. However, the improvement in PFS significantly favored GTR at 1 year, with an RR of progression of 0.66 and an NNT of 26 (P < .001).

STR was associated with a significant reduction in progression in comparison with biopsy at 6 months (RR, 0.72; NNT, 321; P = .05), but the difference was no longer significant at 1 year.

The team reports that the quality of the body of evidence for overall survival was moderate; for all other measures, it was low.

They write: "Although the available studies are retrospective and mostly carry a high risk for bias and confounding, an overwhelming consistency of the evidence supports the superiority of GTR over STR and biopsy."

The researchers believe that further retrospective cohort studies "will not contribute additional useful data and should not be performed or published."

They note, however: "A high-quality, audited, prospective registry of patients with GBM [glioblastoma multiforme] represents a valuable alternative for identifying factors that affect patient outcomes such as EOR [extent of resection], adjuvant therapies, molecular data, preoperative and postoperative imaging, tumor size, topography, location, and medical comorbidities, and should be a critical priority for the neurosurgical and oncology communities."

The study received no funding. The authors have disclosed no relevant financial relationships.

JAMA Oncol. Published online June 16, 2016. Abstract

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