Longer-term (≥2 years) survival in patients with glioblastoma in population-based studies pre- and post-2005: a systematic review and meta-analysis

Translation of survival benefits observed in glioblastoma clinical trials to populations and to longer-term survival remains uncertain. We aimed to assess if >= 2-year survival has changed in relation to the trial of radiotherapy plus concomitant and adjuvant temozolomide published in 2005. We searched MEDLINE and Embase for population-based studies with >= 50 patients published after 2002 reporting survival at >= 2 years following glioblastoma diagnosis. Primary endpoints were survival at 2-, 3- and 5-years stratified by recruitment period. We meta-analysed survival estimates using a random effects model stratified according to whether recruitment ended before 2005 (earlier) or started during or after 2005 (later). PROSPERO registration number CRD42019130035. Twenty-three populations from 63 potentially eligible studies contributed to the meta-analyses. Pooled 2-year overall survival estimates for the earlier and later study periods were 9% (95% confidence interval [CI] 6-12%; n/N=1,488/17,507) and 18% (95% CI 14-22%; n/N=5,670/32,390), respectively. Similarly, pooled 3-year survival estimates increased from 4% (95% CI 2-6%; n/N=325/10,556) to 11% (95% CI 9-14%; n/N=1900/16,397). One study with a within-population comparison showed similar improvement in survival among the older population. Pooled 5-year survival estimates were 3% (95% CI 1-5%; n/N=401/14,919) and 4% (95% CI 2-5%; n/N=1,291/28,748) for the earlier and later periods, respectively. Meta-analyses of real-world data suggested a doubling of 2- and 3-year survival in glioblastoma patients since 2005. However, 5-year survival remains poor with no apparent improvement. Detailed clinically annotated population-based data and further molecular characterization of longer-term survivors may explain the unchanged survival beyond 5 years.