Introduction: So where exactly does this "king" earn its title? Not from incidence — lung cancer, liver cancer, and colorectal cancer far outnumber GBM. It earns the title in four words: currently without a cure.

The pathology report comes back: IDH-wildtype glioblastoma, WHO Grade 4. The family asks how much time is left. Every neurosurgeon has answered this question many times over. It never gets easier. Median overall survival is 14 to 16 months — a figure drawn from large-scale clinical data established after the Stupp protocol became standard of care, representing a population median.

Under the microscope, GBM is a study in chaos. Nuclear size varies wildly; nuclear atypia is striking; mitotic figures crowd every high-power field; microvascular proliferation coils into dense, disorganized networks. The image most familiar to neuropathologists is a ring of tumor cells arranged in an orderly palisade around a central zone of necrosis — pseudopalisading necrosis, as it is known in the literature — a finding present on virtually every GBM H&E section without exception. The Ki-67 proliferation index frequently climbs to 20–30%; by comparison, low-grade astrocytoma runs at 1–3%, and benign pituitary adenoma may be below 1%. The cell doubling rate locks in the timeline for postoperative recurrence before the patient has even left the operating room.

So where exactly does this "king" earn its title? Not from incidence — lung cancer, liver cancer, and colorectal cancer far outnumber GBM in absolute case volume. It earns the title in four words: currently without a cure. Maximal safe resection is performed, concurrent temozolomide chemoradiotherapy is initiated, the standard six-week regimen is endured — and the tumor essentially always comes back. Recurrence most often arises within a two-centimeter margin around the original resection cavity; the band of postoperative signal change visible on FLAIR is its preferred territory for return. Distant recurrence also occurs — contralateral across the corpus callosum, periventricular, or even leptomeningeal dissemination, with tumor cells traveling through the cerebrospinal fluid (CSF) down into the spinal canal. Intracranial MRI may still look acceptable, but the patient reports back pain and leg numbness; a contrast-enhanced spinal MRI reveals disease already established in the spinal canal — at that stage, the available treatment options are few.

GBM recurrence is not an accident. It is the biological destiny of a tumor defined by infiltrative growth. The ring of contrast enhancement on the preoperative T1 represents only the region where the blood-brain barrier is most severely disrupted — not the true boundary of the tumor. Within the broad zone of FLAIR hyperintensity surrounding it, individual tumor cells have already migrated outward along white matter fiber tracts and perivascular spaces — traveling farther than any imaging sequence can detect. What surgery removes is the enhancing lesion. It does not excise the full extent of the disease. This is not a reflection of surgical technique; it is an irreducible gap between the infiltrative extent of GBM and the spatial resolution limits of neuroimaging.

MGMT promoter methylation is the first major prognostic watershed. In patients with a methylated MGMT promoter, temozolomide is effective, and median survival can be extended to beyond 23 months, with a five-year survival rate of approximately 10%. In those without methylation, temozolomide contributes relatively little, and median survival curves begin their decline just past 12 months. The same GBM diagnosis carries substantially different trajectories depending on MGMT methylation status — the two survival curves diverge widely. IDH-mutant glioblastoma represents yet another category: median survival can reach 31 months. But IDH-mutant GBM is uncommon; the vast majority of GBMs present as IDH-wildtype from the outset.

Exceptions do exist. GBMs arising at the frontal pole or temporal pole — remote from the motor cortex and language centers — allow for en bloc resection of both the enhancing lesion and the surrounding T2-hyperintense zone when anatomy permits a genuinely supramaximal resection. Patients in these favorable locations who complete adjuvant chemoradiotherapy occasionally return to clinic three or five years later with a clean scan. Ask them what they have been up to: still working, raising children. This is not a miracle — it is anatomy providing the surgeon an opportunity to extend the resection margin. And in GBM, every additional volume of tumor removed translates directly into additional time.

The first month after surgery is the critical window for initiating adjuvant therapy. The concurrent chemoradiotherapy phase — six weeks in duration — must not be interrupted. Even when the leukocyte count bottoms out, it has to be pushed through. Some patients develop wound healing complications or intracranial infection after surgery, delaying the start of radiotherapy by two or three weeks — and once that schedule slips, everything downstream is disrupted. The end of surgery is not the finish line; it is the moment the baton is passed to radiation oncology, and that handoff cannot be dropped. Surgery determines the parameters of the playing field. How steadily every subsequent step is executed within those parameters is equally a variable in how long the patient lives.

Reference: https://www.incsg.com/jiaozhiliu/8496.html