What Is the Standard of Care for Glioblastoma?

When someone is diagnosed with glioblastoma multiforme (GBM), one of the first questions asked is: what treatment will I receive? For most newly diagnosed patients with GBM, the answer is a regimen known as the Stupp protocol — named after neuro-oncologist Roger Stupp, whose landmark 2005 trial established it as the global standard.

Understanding what this protocol involves, why it works, and what its limitations are can help patients and caregivers engage more meaningfully with their care team.

The Three Phases of the Stupp Protocol

  1. Surgery (Resection): The first step is typically maximal safe surgical resection — removing as much tumor as possible without causing unacceptable neurological damage. The extent of resection is associated with outcomes, but complete removal is rarely achievable due to GBM's infiltrative nature.
  2. Concurrent Chemoradiation: Following surgery, patients receive radiation therapy (typically 60 Gy in 30 fractions over 6 weeks) combined with daily oral temozolomide (TMZ), a chemotherapy agent that crosses the blood-brain barrier.
  3. Adjuvant Chemotherapy: After chemoradiation concludes, patients continue with 6 cycles of temozolomide on a 5-days-on, 23-days-off schedule.

The Role of MGMT Methylation

A key biomarker in GBM treatment is the methylation status of the MGMT promoter. MGMT is a DNA repair enzyme; when its promoter is methylated, the gene is silenced, meaning cancer cells cannot as effectively repair the DNA damage caused by temozolomide.

  • Patients with MGMT-methylated tumors tend to respond better to TMZ and often have longer survival.
  • Patients with unmethylated MGMT may receive less benefit from TMZ, and their care team may discuss alternative or additional approaches.

This is why MGMT testing is now a routine part of initial tumor profiling at most major cancer centers.

Tumor Treating Fields (TTFields)

Since the original Stupp protocol, one significant addition to standard care has been Tumor Treating Fields (TTFields), delivered by the Optune device (Novocure). TTFields use low-intensity, alternating electric fields to disrupt tumor cell division. A 2017 study published in JAMA showed that adding TTFields to maintenance TMZ improved median overall survival modestly but statistically significantly. TTFields are now included in NCCN guidelines for newly diagnosed GBM.

What Happens After Initial Treatment?

Unfortunately, GBM almost universally recurs. At recurrence, there is no single agreed-upon standard of care. Options may include:

  • Re-resection (if feasible)
  • Bevacizumab (Avastin), an anti-angiogenic agent
  • Re-irradiation in select cases
  • Enrollment in a clinical trial
  • Lomustine (CCNU) or other salvage chemotherapies

Questions to Ask Your Neuro-Oncologist

Armed with this background, patients can have more productive conversations with their care team. Consider asking:

  • What is my MGMT methylation status?
  • Am I a candidate for TTFields, and is it covered by my insurance?
  • What clinical trials are available for my tumor profile?
  • What are the most likely side effects of each phase of treatment?

The Stupp protocol is a starting point, not a ceiling. Advances in molecular profiling, immunotherapy, and targeted therapy are actively reshaping what GBM treatment may look like in the years ahead.