Risk vs. Stage: What’s the Difference in Neuroblastoma?

Insights from Dr. Susan Cohn | February, 2025 Neuroblastoma Series Webinar

For families navigating a neuroblastoma diagnosis, one of the most confusing aspects is understanding the difference between stage and risk classification. Many assume that all Stage 4 neuroblastoma cases are the same, but the reality is much more complex—and personal.

What’s the Difference Between Stage and Risk?

• Staging describes where the tumor is located and whether it has spread.

• Risk classification predicts how aggressive the cancer is and how likely it is to respond to treatment.

“Survival differs very much according to the age the patient is at the time of diagnosis, their stage, histology of the tumor, as well as some tumor-specific genomic markers. And modern therapy is tailored according to the predicted risk of relapse, which is based on clinical and biologic markers.” – Dr. Susan Cohn, University of Chicago

This means two children with the same stage may need different treatment plans.

How Is Neuroblastoma Risk Determined?

Doctors use a mix of clinical and biological factors to determine a child's risk level:

✔ Age at diagnosis – Infants often have better outcomes. ✔ MYCN amplification – A key genetic marker linked to aggressive disease. ✔ Tumor histology – How cancer cells appear under a microscope. ✔ Ploidy – The number of chromosomes in a tumor cell. ✔ Chromosomal changes – Loss of regions like 1p, 11q, or 17q can affect outcomes.

“Stage and age have been around since the 70’s. Since the 80’s, we've known that MYCN amplification was prognostic. Tumor ploidy, histology, and chromosomal markers like 1p and 11q deletions have been studied for decades.” – Dr. Cohn

Risk Classification Is Always Evolving

As science improves, so does our ability to assess risk more precisely.

“As technology has changed, we've identified numerous other ways to evaluate genomic markers that have prognostic significance. But these haven’t quite made it into our current classification systems.” – Dr. Cohn

She also emphasized newer advances—including the use of telomerase maintenance mechanisms, RNA expression signatures, and liquid biopsy (circulating tumor DNA)—which are under study and could play a major role in future risk systems.

Why It Matters

A child diagnosed with Stage 4 neuroblastoma might be considered intermediate risk rather than high-risk, depending on their age and tumor biology. That difference can lead to:

• Less intensive treatment

• Fewer long-term side effects

• Similar survival outcomes
  

“We want to avoid overtreatment in kids who don’t need it. At the same time, we need to find better strategies for those who truly need more aggressive care.” – Dr. Cohn

Looking Ahead

Shir for Life is committed to supporting research that refines and advances risk classification tools. That includes funding a Liquid Biopsy ct-DNA study at Children’s Hospital of Philadelphia (CHOP), helping to unlock better, more personalized therapies.

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