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Surgery May Not Improve Survival After First Documented Progression of Glioblastoma

Key findings

  • Multivariate analysis in this retrospective study suggested that resection of progressive glioblastoma was not associated with improved post-progression survival
  • Chemotherapy, with or without bevacizumab is a reasonable alternative to resection for managing progressive glioblastoma
  • Besides extending life, there are other reasons for resection at progression, including minimizing steroid dependence, debulking tumor mass or palliating symptoms

Resection is now performed on 20-30% of patients at first documented progression of glioblastoma. Most studies suggest a survival benefit of such surgeries, and greater extent of resection has been linked to increasing benefit. However, many of the patients included in these studies were treated prior to the current widespread availability of bevacizumab and effective chemotherapy for progression.

By reviewing a large contemporary series of glioblastoma patients at Massachusetts General Hospital, neurosurgeons William T. Curry, MDGanesh Shankar, MD, PhD, and colleagues found that resection at the first sign of progression does not seem to improve post-progression survival. Their report appears in the Journal of Clinical Neuroscience.

Dr. Curry's group identified 368 patients who had craniotomy with confirmed postoperative pathologic diagnosis of progressive glioblastoma between January 1, 2008, and December 31, 2015. Of these:

  • 32% underwent gross total resection at initial surgery
  • 49.5% underwent subtotal resection
  • 18.5% underwent biopsy

The median follow-up period was 16.7 months. The vast majority of patients (96%) underwent subsequent treatment with radiotherapy and temozolomide. The use of bevacizumab at progression was more widespread (76%) than in any previous study of this issue. An equal number of patients were treated with chemotherapy at first recurrence.

Median overall survival was 19.5 months (95% CI, 17.6–21.2 months). Median post-progression survival was 8.1 months (95% CI, 7.16–8.74 months).

In multivariate analysis, factors significantly associated with improved post-progression survival were:

  • Karnofsky Performance Status ≥ 70 at first progression
  • Use of bevacizumab at first progression
  • Use of chemotherapy at first progression

Variables not significantly associated with improved post-progression survival were the extent of resection achieved at initial operation, whether a patient underwent resection at the time of progression, the extent of resection at the time of surgery for progression and the number of post-progression resections.

The value of chemotherapy in this setting is consistent with the most recently published multicenter phase 3 studies.

Obtaining gross total resection at first recurrence came close to significance, though, and the researchers comment that if total resection is a reasonable goal of surgery, there may be a benefit.

The team concludes that resection for progressive glioblastoma may not be life-extending and that medical therapy is a reasonable alternative. The researchers do note that there are other reasons for resection at progression such as to palliate symptoms, minimize steroid dependence or acquire tissue for molecular analysis and allow for enrollment in clinical trials.

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