More Extensive Resection of Low-Grade Glioma Linked to Longer Survival

Patients with diffuse low-grade glioma (LGG) had longer overall survival (OS) if they underwent more extensive resection of the tumor compared with subtotal resection, a 20-year retrospective cohort study showed.

Among 392 patients with IDH-mutant grade 2 glioma, OS was not reached in those with oligodendroglioma with preoperative tumor volume (TV) ≤43.1 mL and postoperative TV ≤4.6 mL, as well as those with astrocytoma with smaller preoperative and residual TV who did not receive chemotherapy, reported Annette Molinaro, PhD, of the University of California San Francisco, and colleagues in the Journal of Clinical Oncology.

“Across both subtypes of LGG, EOR [extent of resection] beginning at 75% improves OS while beginning at 80% improves progression-free survival,” they wrote. “Nonetheless, maximal resection with preservation of neurological function remains the treatment goal. Our findings have implications for surgical strategies for LGGs, particularly oligodendroglioma.”

OS was shortest in astrocytoma patients with postoperative TV >4.6 mL and those with preoperative TV >43.1 mL and postoperative TV ≤4.6 mL (median 9.0 years, 95% CI 7.9-10.6), while intermediate OS was seen for subsets of both LGG subtypes (median 19.9 years, 95% CI 16 to not available), including astrocytoma patients treated with chemotherapy with smaller preoperative and residual TV, as well as oligodendroglioma patients with either larger preoperative and smaller residual TV, or just larger residual TV.

In initiating this study, Molinaro and colleagues noted that some studies have supported the notion that more extensive tumor resection is associated with longer OS for all LGGs, while others have suggested that complete surgical resection does not offer a survival advantage for patients with oligodendroglioma due to their relatively favorable prognosis and better response to chemoradiation. Thus, “these discrepancies have created controversy and confusion among both providers and patients,” they added.

The researchers tested two hypotheses: that OS is longer after more extensive resection (gross total resection [GTR]) than after subtotal resection, regardless of tumor subtype, and that GTR+ (beyond the imaging-defined tumor margins) influences survival outcomes.

Molinaro told MedPage Today that “this study really changes the approach to surgery for these lower-grade patients because we did have this longer follow-up and showed that gross total resection for these oligodendrogliomas or GTR+ for these astrocytomas is important, if it can be safely done.”

Considering that smaller postoperative TV was associated with longer OS in both LGG subtypes, the researchers also evaluated the effects of GTR+ compared with GTR and GTR- (resection ≤100%).

OS was longest in patients who underwent GTR+ (median not reached) and “was significantly different” than GTR and GTR- (P=0.001 and P=0.0004, respectively), they reported. The survival advantage with GTR+ compared with the other two methods persisted among patients with astrocytoma (P<0.001).

For patients with oligodendroglioma, median OS was longer after GTR+ and GTR (median not reached) compared with GTR- (median 22.2 years).

Using propensity score matching at extent of resection cutoffs between 60% and 100%, Molinaro and colleagues found that as extent increased, the hazard ratio increased, and that when it hit 75%, the effect of extent of resection was significant in improving OS. They also found that extent of resection had a similar effect on progression-free survival at a threshold of 80%, and malignant transformation-free survival at a threshold of 70%.

“One of the points we are trying to make here is that there have been studies that have said — for oligodendroglioma, in particular — you don’t need to take it all out,” Molinaro said. “However, these were single-institution studies, they were small, and their median follow-up was somewhere around 6 or 7 years. We were able to follow our patients a lot longer, and the interesting thing we see is that the difference really occurs after 7 to 10 years. That’s when you start to see that separation in survival.”

For this study, Molinaro and team included 392 patients with IDH-mutant grade 2 glioma. Median age at diagnosis was 38.2 years, and 56% were men.

OS results were validated in two external cohorts (n=365). Propensity score analysis of the combined cohorts was used to mimic a randomized trial with varying levels of extent of resection.