Early Resection Boosts Survival in Low-Grade Gliomas

Roxanne Nelson

October 25, 2012

Early surgical resection of low-grade gliomas might be a better option than watchful waiting, according to a new study.

The researchers compared results from 2 Norwegian hospitals. At one, the primary initial treatment strategy was early resection; at the other, it was a diagnostic biopsy followed by watchful waiting. The survival benefit seen at the early resection hospital remained, even after adjustment for validated prognostic factors.

The study was published online October 25 in JAMA: The Journal of the American Medical Association, to coincide with its presentation at the annual meeting of the European Association of Neurosurgical Societies.

After a median follow-up of about 7 years, overall survival was significantly better in patients treated at the early resection hospital (P = .01). At the watchful waiting hospital, median survival was 5.9 years (95% confidence interval [CI], 4.5 to 7.3); at the early resection hospital, it has not yet been reached.

The expected 5-year survival at the early resection hospital was 74% (95% CI, 64% to 84%) and at the watchful waiting hospital was 60% (95% CI, 48% to 72%). The expected 7-survival is similar: 68% (95% CI, 58% to 78%) and 44% (95% CI, 30% to 58%), respectively.

On adjusted multivariable analysis, the relative hazard ratio was 1.8 (95% CI, 1.1 to 2.9; P = .03) at the watchful waiting hospital.

Despite the survival benefit, intervention needs to be based on the individual patient, explained lead author Asgeir S. Jakola, MD, from St. Olavs University Hospital in Trondheim, Norway.

"Clinical judgment is still necessary, since survival benefits need to be weighed against risks in terms of the patient's age, comorbidity, functional status, tumor size, and tumor location," he told Medscape Medical News. "However, the study clearly indicates that early resection should be preferred in a great majority of patients," he noted.

Lack of Class I Evidence, But...

In an accompanying editorial, James M. Markert, MD, MPH, director of the division of neurosurgery at the University of Alabama at Birmingham, explains that an increasing number of studies support the idea of "maximizing the extent of resection in patients with glioma while maintaining neurologic function; however, no class I evidence exists for this approach."

Although 1 large review found no difference between treatment strategies (J Neurosurg. 2011;115:948-965), the vast majority of studies report increases in 5-year survival, 5-year progression-free survival, or both, after resection, he notes. In addition, other studies suggest that more aggressive surgery might reduce the rate of malignant transformation.

Despite the lack of class I evidence for surgical resection in this population, the National Comprehensive Cancer Center practice guidelines in oncology "support maximal safe resection as a feasible first line of treatment for low-grade gliomas.

Dr. Markert concludes that a follow-up of the cohorts examined by Dr. Jakola and colleagues, "allowing for more definitive measurement of survival and more rigorous assessment of complications, neurologic deterioration, and malignant degeneration, would be valuable."

Improved Survival Observed

Study participants were diagnosed with low-grade gliomas from 1998 to 2009, and follow-up ended April 11, 2011. Of the 153 patients, 87 were treated at the early resection hospital and 66 were treated at the watchful waiting hospital.

Lesions such as astrocytomas, oligodendrogliomas, and oligoastrocytomas were classified as low-grade lesions; because of diffuse infiltration in the brain, these tumors are not usually considered to be curable with surgery, Dr. Jakola and colleagues explain.

In addition, the effect of surgery on survival remains unclear because current evidence relies on uncontrolled surgical series alone," they add.

Of the patients treated with initial biopsy alone, 12 were from the early resection hospital and 47 were from the watchful waiting hospital (14% vs 71%; P < .001). There were no significant differences in clinical presentation or known prognostic factors in the populations at the 2 hospitals.

At the end of the follow-up period, 28 patients at the early resection hospital and 34 at the watchful waiting hospital had died (32% vs 52%), so overall survival was significantly longer at the early resection hospital (P = .01).

The survival advantage of early resection over watchful waiting increased over time.

Survival Advantage of Early Resection Over Time

Survival Early Resection
Hospital, %
Watchful Waiting
Hospital, %
1-Year 89 89
3-Year Expected 80 70
5-Year Expected 74 60
7-Year Expected 68 44

At the early resection and watchful waiting hospitals, there were no significant differences in surgical complications (8% vs 9%; P = .82) or in acquired deficits (21% vs 18%; P = .70). However, malignant transformation was less common with early resection as the initial management (37% vs 56%; P = .02).

Dr. Jakola pointed out that the study was not designed to determine differences in complications or neurologic deterioration. "However, we will address this in studies to come," he said. "With the somewhat crude measure of neurologic complications in our study, early resection guided with 3D-ultrasound was not associated with excess risk."

Other studies have shown that long-term survivors with low-grade gliomas have fairly good disease-specific quality of life. "Since most deaths from brain tumors are preceded by progressive symptoms, a possible early advantage of biopsy and watchful waiting for quality of life will be lost over time," Dr. Jakola noted.

"It is also unlikely that the survival difference observed in our study is the result of a synergistic effect of radiotherapy and radical surgery," he added. It has been demonstrated that early radiotherapy has no effect on survival, nor does a more intensive radiotherapy regimen. "Thus, this survival difference is best explained by the early and aggressive surgical treatment," he said.

The researchers note that the population of Norway is homogeneous, and that the socialized healthcare system leads to the equal distribution of resources and the uniform training and licensing of healthcare personnel. That aspect plus the blinded histopathologic review ensured comparable study populations.

The main limitation of this study is the retrospective assessment of baseline and treatment variables, the researchers write, but they add that survival is a robust end point that is unaffected by the retrospective collection of data.

Coauthor Geirmund Unsgård, MD, from St. Olavs University Hospital, reports owning stock in Sonowand, the company that makes the 3D-ultrasound-based intraoperative imaging system (SonoWand) used at the early resection hospital. Dr. Markert reports relationships with Catherex and Tocgen, and reports receiving a grant from the National Institutes of Health and the Department of Defense.

JAMA. Published online October 25, 2012. Abstract, Editorial