Prognostic impact of MGMT promoter methylation in glioblastoma - a systematic review

The aim of the present study was to analyze literature data on the correlation between MGMT promoter methylation and survival of glioblastoma (GBM) patients. MGMT promoter methylation is currently regarded as the main prognostic biomarker in GBM, yet some concerns remain about its actual impact on patients’ outcome. Reviewing recently published GBM cohorts, we found that only 19 out of 28 studies (68%) confirmed the prognostic value of MGMT promoter methylation and/or its role in predicting response to temozolomide. In studies demonstrating a prognostic/predictive value of MGMT promoter methylation, the patient population showed significantly lower rates of unfavorable prognosticators, including older age, poor performance status, and biopsy surgery as compared with studies where MGMT methylation was not prognostic/predictive of better outcome. In addition, studies demonstrating a better prognosis for MGMT methylated cases had significantly lower rates of deaths at 3 and 6 months. Multivariate analysis showed that the 3- and 6-month death rates are significant independent variables, and that the MGMT promoter methylation approaches statistical significance if modeled with the 6- but not with the 3-month mortality rate. These results suggest that a temporal threshold may be necessary in order to demonstrate any clinical benefit of MGMT promoter methylation, and that the paucity of short-term survivors may represent a bias in studies focusing on MGMT methylation and prognosis.