Why Glioblastoma Cannot Be Completely Removed Surgically
Glioblastoma cannot be completely removed surgically due to its highly infiltrative nature, as tumor cells diffusely invade surrounding brain tissue beyond what is visible on imaging, making total resection impossible without damaging critical brain structures. 1
Biological Characteristics That Prevent Complete Resection
Glioblastomas diffusely infiltrate surrounding tissues and frequently cross the midline to involve the contralateral brain, making it impossible to distinguish tumor margins from normal brain tissue during surgery 1
Tumor cells have been found in the peritumoral edema, which corresponds to the T2-weighted MRI abnormalities, extending well beyond the contrast-enhancing portion visible on imaging 1
The extreme infiltrating capacity of tumor cells into the brain parenchyma makes complete surgical removal difficult, as tumor cells can be found centimeters away from the main tumor mass 2
Unlike oligodendrogliomas which are often well-demarcated, glioblastomas lack distinct tumor margins, making it impossible to identify all infiltrating cells during surgery 1
Imaging Limitations
It is difficult to accurately assess the full extent of glioblastoma using CT or MRI scans, as the visible contrast enhancement primarily reflects blood-brain barrier disruption rather than the true tumor boundaries 1
The extent of tumor infiltration often extends beyond what can be visualized with current imaging techniques, leading to residual tumor cells after what appears to be a "complete" resection 1
Surgical Challenges
While the goals of surgery include obtaining tissue for diagnosis, alleviating symptoms related to increased intracranial pressure, and increasing survival, the infiltrative nature of high-grade astrocytomas frequently renders gross total removal impossible 1
Attempting to remove all infiltrating tumor cells would require removing large volumes of functional brain tissue, resulting in unacceptable neurological deficits 1, 2
Even with aggressive surgical approaches, nearly all glioblastomas recur, with 90% of recurrences occurring within a few centimeters of the surgical resection cavity 3
Contrast with Other Brain Tumors
Unlike glioblastomas, total resection is often possible for oligodendrogliomas because they typically occur in the frontal lobes and have distinct tumor margins 1
Low-grade oligodendrogliomas appear well-demarcated radiographically, while glioblastomas have poorly defined borders with surrounding brain tissue 1
Clinical Implications
Because of the impossibility of complete surgical removal, the standard of care for glioblastoma involves multimodal treatment including maximal safe surgical resection followed by radiation therapy and chemotherapy 1
Surgical resection alone leads to median survivals of only 3 to 6 months due to the inevitable recurrence from residual infiltrating cells 1
The infiltrative nature of glioblastoma has led to research into novel approaches such as implantable scaffolds to trap residual tumor cells after surgery 3 and targeted radiolabeled therapies to address the infiltration zone 4
Innovative treatments targeting the invasive phenotype of glioblastoma are under development but no approved therapy specifically directed against this characteristic exists as of now 2, 5