Surgical resection versus watchful waiting in low-grade gliomas

Abstract

Background: Infiltrating low-grade gliomas (LGG; WHO grade 2) typically present with seizures in young adults. LGGs grow continuously and usually transform to higher grade of malignancy, eventually causing progressive disability and premature death. The effect of up-front surgery has been controversial and the impact of molecular biology on the effect of surgery is unknown. We now present long-term results of upfront surgical resection compared with watchful waiting in light of recently established molecular markers.

Materials and methods: Population-based parallel cohorts were followed from two Norwegian university hospitals with different surgical treatment strategies and defined geographical catchment regions. In region A watchful waiting was favored while early resection was favored in region B. Thus, the treatment strategy in individual patients depended on their residential address. The inclusion criteria were histopathological diagnosis of supratentorial LGG from 1998 through 2009 in patients 18 years or older. Follow-up ended 1 January 2016. Making regional comparisons, the primary end-point was overall survival.

Results: A total of 153 patients (66 from region A, 87 from region B) were included. Early resection was carried out in 19 (29%) patients in region A compared with 75 (86%) patients in region B. Overall survival was 5.8 years (95% CI 4.5-7.2) in region A compared with 14.4 years (95% CI 10.4-18.5) in region B (P < 0.01). The effect of surgical strategy remained after adjustment for molecular markers (P = 0.001).

Conclusion: In parallel population-based cohorts of LGGs, early surgical resection resulted in a clinical relevant survival benefit. The effect on survival persisted after adjustment for molecular markers.

Keywords: astrocytoma; brain neoplasm; low-grade glioma; population based; survival; treatment outcome.

Figure 1.

Flow chart of patient inclusion.

Figure 2.

Survival analysis comparing cohorts, where region A preferred biopsy while region B preferred early resection. In region A the median survival was 5.8 years (95% CI 4.5–7.2) compared with 14.4 years (95% CI 10.4–18.5) in region B.

Figure 3.

Survival in cohorts (A–C) with adjustment for molecular risk-group (log-rank test, P = 0.001). Results are presented stratified according to risk groups (A) low-risk (B) medium-risk and (C) high-risk group. (A) IDH mutated, 1p19 codeleted LGGs (n =43). Median survival was not reached. (B) IDH mutated, non-codeleted LGGs (n =61). Median survival in region A was 5.6 years (95% CI 3.5–7.6) compared with 10.2 year (95% CI 6.9–13.4) in region B. (C) IDH wild-type LGGs (n=41). Median survival in region A was 1.4 year (95% CI 0.6–2.2) compared with 5.3 year (95% CI 0.0–20.0) in region B.