The relationship between repeat resection and overall survival in patients with glioblastoma: a time-dependent analysis

OBJECTIVE Previous studies assessed the relationship between repeat resection and overall survival ( OS) in patients with glioblastoma, but ignoring the timing of repeat resection may have led to biased conclusions. Statistical methods that take time into account are well established and applied consistently in other medical fields. The goal of this study was to illustrate the change in the effect of repeat resection on OS in patients with glioblastoma once timing of resection is incorporated. METHODS The authors conducted a retrospective study of patients initially diagnosed with glioblastoma between January 2005 and December 2014 who were treated at Memorial Sloan Kettering Cancer Center. Patients underwent at least 1 craniotomy with both pre-and postoperative MRI data available. The effect of repeat resection on OS was assessed with time-dependent extended Cox regression controlling for extent of resection, initial Karnofsky Performance Scale score, sex, age, multifocal status, eloquent status, and postoperative treatment. RESULTS Eighty-nine ( 55%) of 163 patients underwent repeat resection with a median time between resections of 7.7 months ( range 0.5-50.8 months). Median OS was 18.8 months ( 95% confidence interval [CI] 16.3-20.5 months) from initial resection. When timing of repeat resection was ignored, repeat resection was associated with a lower risk of death ( hazard ratio [HR] 0.62, 95% CI 0.43-0.90, p = 0.01); however, when timing was taken into account, repeat resection was associated with a higher risk of death ( HR 2.19, 95% CI 1.47-3.28, p < 0.001). CONCLUSIONS In this study, accounting for timing of repeat resection reversed its protective effect on OS, suggesting repeat resection may not benefit OS in all patients. These findings establish a foundation for future work by accounting for timing of repeat resection using time-dependent methods in the evaluation of repeat resection on OS. Additional recommendations include improved data capture that includes mutational data, development of algorithms for determining eligibility for repeat resection, more rigorous statistical analyses, and the assessment of additional benefits of repeat resection, such as reduction of symptom burden and enhanced quality of life.