Is MGMT promoter methylation to be considered in the decision making for recurrent surgery in glioblastoma patients?

Abstract

Objectives: At present, there is no standard therapy approved for recurrent glioblastoma (rGB). In particular, the counselling of patients with an unmethylated O⁶-methylguanine-DNA methyltransferase (MGMT) promoter GB remains a challenge. Our aim was to compare the overall survival (OS) and progression free survival (PFS) in patients treated surgically and non-surgically at the time of GB recurrence. This was evaluated with particular reference to the impact of recurrent surgery for patients with unmethylated MGMT promoter rGB.

Patients and methods: The clinical and radiological data from 127 consecutive cases of rGB was retrospectively identified and evaluated. The PFS and OS from cohorts of surgically and non-surgically treated patients at time of GB recurrence were compared using Kaplan Meier estimations and Log-Rank tests. Multivariate Cox regression analysis included the major influencing variables (surgical resection, MGMT promoter methylation status, Karnofsky performance scale (KPS), age, eloquent tumor location) to analyze the survival benefit. Subgroup analysis of cases depending on the MGMT promoter methylation status was performed.

Results: Multiple Cox regression analysis revealed inferior OS (p = 0.029, OR = 1.731, CI 95% 1.059-2.829) of patients treated non-surgically (14 vs. 31 months). MGMT promoter methylation and age were related to longer OS (p < 0.001, OR 2.683, CI 95% 1.631-4.414 and p = 0.009, OR = 1.029, CI95% 1.007-0.052 respectively). Gross total resection (GTR) in comparison to subtotal resection (STR) lead to a median OS of 39 months vs. 22 months and a PFS of seven vs. four months respectively. In the subgroup of cases with unmethylated MGMT promoter rGB, those who underwent GTR survived significantly longer (OS: 31 months) than patients who underwent STR (OS: 15 months, p = 0.024). PFS was six vs. four months after GTR and STR respectively.

Conclusion: Surgical management for recurrent glioblastoma appears to be a safe procedure which results in longer OS in comparison to non-surgical management. GTR may be of particular benefit to patients with unmethylated MGMT promoter rGB.

Keywords: Gross total resection; MGMT; Overall survival; Progression free survival; Recurrent glioblastoma; Reoperation.