Historical Perspective on Surgery and Survival with Glioblastoma: How Far Have We Come?

Background: Glioblastoma multiforme remains a therapeutic challenge. We offer a historical review of the outcomes of patients with glioblastoma from the earliest report of surgery for this lesion through the introduction of modern chemotherapeutics and aggressive approaches to tumor resection. Methods: We reviewed all major surgical series of patients with glioblastoma from the introduction of craniotomy for glioma (1884) to 2020. Results: The earliest reported craniotomy for glioblastoma resulted in the patient's death less than a month after surgery. Improved intracranial pressure management resulted in improved outcomes, reducing early postoperative mortality from 50% to 6% in Harvey Cushing's series. In the first major surgical series (1912), the mean survival was 10.1 months. This figure did not improve until the introduction of radiotherapy in the 1950s, which doubled survival relative to those who had surgery alone. The most recent significant advance, chemotherapy with the alkylating agent temozolomide, extended survival by 2.5 months compared with surgery and radiotherapy alone (14.6 and 12.1 months, respectively). This protocol remains the standard regimen for newly diagnosed glioblastoma. The innovative treatments being investigated have yet to show a survival benefit. Conclusions: With advancements in localization, imaging, anesthesia, surgical technique, control of cerebral edema, and adjuvant therapies, outcomes in glioblastoma improved incrementally from Cushing's time until the introduction of magnetic resonance imaging enabled better degrees of resection in the 1990s. Modest improvements came with the advent of biomarker-driven targeted chemotherapy in the first decade of the current century.