2067 Background: Pseudoprogression (PsPD) refers to an increase in size or appearance of new areas of contrast enhancement on MRI scans, seen in about 30% of the patients with newly diagnosed glioblastoma soon after completing chemoradiation (chemoRT). It is distinguished from true progression by its improvement independent of treatment; however, timely diagnosis of PsPD to guide clinical decisions has been a challenge. Given that tissue sampling of the MRI changes, when initially seen, could potentially distinguish PsPD from true progression, we examined the utility of surgery in the diagnosis of PsPD and its impact on patient outcome. Methods: A retrospective review of data from adults with GBM between October 2006 and March 2009 identified 140 patients with MRI changes suggestive of progression within 3 months of chemoRT; of these, 34 underwent surgical resection for diagnostic purposes. Three subsets - progression, PsPD or mixed -were identified based on imaging characteristics in the nonsurgical group and by histology in the surgical group. TTP and OS were calculated using the Kaplan Meier method and log rank analysis for significance of differences. Results: The median TTP was 4.8, 5.8 and 7.5 months (p=0.69) for PsPD, progression and mixed in the surgical group respectively compared to 3.9, 4.1 and 6.2 months (p=0.67) in the nonsurgical group. The median OS was 14.4, 18.5 and 17.1 months (p=0.82) for PsPD, progression and mixed in the surgical group compared to 13.4, 11.6 and 14.5 months (p=0.12) in the nonsurgical group respectively. No significant differences in TTP or OS were seen. Conclusions: These findings suggest that routine surgical sampling and histologic review of MRI changes after chemoRT does not help identify differences in outcome compared to the nonsurgical group. Additionally, no significant differences in outcome were seen among the three categories in the surgical or nonsurgical groups. Refinement of the histological criteria, careful intraoperative selection of areas of interest and advances in imaging studies are critically needed to permit early differentiation of PsPD versus progression to allow appropriate clinical management and formulate prospective studies.