Rapid early progression (REP) of glioblastoma is an independent negative prognostic factor: Results from a systematic review and meta-analysis

Background In patients with newly diagnosed glioblastoma, rapid early progression (REP) refers to tumor regrowth between surgery and postoperative chemoradiotherapy. This systematic review and meta-analysis appraised previously published data on REP to better characterize and understand it. Methods Systematic searches of MEDLINE, EMBASE and the Cochrane database from inception to October 21, 2021. Studies describing the incidence of REP-tumor growth between the postoperative MRI scan and pre-radiotherapy MRI scan in newly diagnosed glioblastoma were included. The primary outcome was REP incidence. Results From 1590 search results, 9 studies were included with 716 patients. The median age was 56.9 years (IQR 54.0-58.8 y). There was a male predominance with a median male-to-female ratio of 1.4 (IQR 1.1-1.5). The median number of days between MRI scans was 34 days (IQR 18-45 days). The mean incidence rate of REP was 45.9% (range 19.3%-72.0%) and significantly lower in studies employing functional imaging to define REP (P<.001). REP/non-REP groups were comparable with respect to age (P=.99), gender (P=.33) and time between scans (P=.81). REP was associated with shortened overall survival (HR 1.78, 95% CI 1.30-2.43, P<.001), shortened progression-free survival (HR 1.78, 95% CI 1.30-2.43, P<.001), subtotal resection (OR 6.96, 95% CI 4.51-10.73, P<.001) and IDH wild-type versus mutant tumors (OR 0.20, 95% CI 0.02-0.38, P=.03). MGMT promoter methylation was not associated with REP (OR 1.29, 95% CI 0.72-2.28, P=.39). Conclusions REP occurs in almost half of patients with newly diagnosed glioblastoma and has a strongly negative prognostic effect. Future studies should investigate its biology and effective treatment strategies.