Stages of neuroblastoma

Staging describes or classifies a cancer based on how much cancer there is in the body and where it is when first diagnosed. This is often called the extent of cancer. Information from tests is used to find out the size of the tumour, which parts of the body have cancer, whether the cancer has spread from where it first started and where the cancer has spread. Generally, the higher the stage number, the larger the cancer is or the more the cancer has spread.

There are different staging systems used to stage neuroblastoma. The healthcare team may use more than one staging system when talking about your child's treatment. Neuroblastoma is classified into risk groups based on stage, age, and other prognostic factors. The healthcare team uses the stage along with the risk group to plan treatment and estimate your child's outcome (prognosis). Talk to your child's doctor if you have questions about staging.

International Neuroblastoma Risk Group Staging System

International Neuroblastoma Staging System

Risk groups for neuroblastoma

International Neuroblastoma Risk Group Staging System (INRGSS)

The newest staging system for neuroblastoma is the International Neuroblastoma Risk Group Staging System (INRGSS). The INRGSS is based on the results of imaging tests and sometimes other tests done before surgery. If image-defined risk factors (IDRFs) can be seen on the imaging tests, it may mean that the tumour will be harder to remove. IDRFs are when the cancer looks like it has spread to nearby important structures. The INRGSS divides neuroblastoma into 4 stages.

Stage L1 - The tumour is only in one area of the body where it started (such as the neck, chest, abdomen or pelvis) and there are no IDRFs.

Stage L2 - The tumour has spread to a nearby area and there are 1 or more IDRFs.

Stage M - The cancer has spread to distant parts of the body (called distant metastasis) but doesn't include tumours that are stage MS.

Stage MS - Stage MS is only used for children younger than 18 months with distant metastasis. The cancer has only spread to the skin, liver or bone marrow. If it has spread to the bone marrow, less than 10% of the cells in the bone marrow are cancer cells. An MIBG scan doesn't show cancer in the bone or bone marrow.

International Neuroblastoma Staging System (INSS)

The older staging system for neuroblastoma is the International Neuroblastoma Staging System (INSS). The INSS is based on the results of surgery to remove the tumour and has now mainly been replaced by the INRG Staging System. Each stage is given a number from 1 to 4.

Stage 1 - The tumour is only in the area where it started and is on only the right side or the left side of the body. It can be completely removed with surgery.

Stage 2A - The tumour is only in the area where it started and is on only one side of the body, but it can't be completely removed with surgery.

Stage 2B - The cancer is on only one side of the body and it may be completely removed with surgery. The cancer has spread to nearby lymph nodes on the same side of the body as the tumour (called ipsilateral lymph nodes).

Stage 3 - The cancer can't be completely removed with surgery and one of the following applies:

  • The tumour has grown across the midline of the body (defined as the spine) and the cancer may also have spread to nearby lymph nodes.

  • The main tumour is on one side of the body, but the cancer has spread to nearby lymph nodes on the other side of the body.

  • The tumour is growing on the midline of the body and the cancer has spread to lymph nodes or tissues on both sides of the body.

Stage 4 - The cancer has spread to other parts of the body (called distant metastasis), such as to distant lymph nodes, bone, bone marrow, liver, skin or other organs. This is also called metastatic neuroblastoma. Stage 4 doesn't include tumours that are stage 4S.

Stage 4S - This stage is only used for children younger than 1 year old. The main tumour is only in the area where it started and is classified as stage 1, 2A or 2B. But the cancer has spread to the liver, skin or bone marrow. If it has spread to the bone marrow, less than 10% of the cells in the bone marrow are cancer cells.

Recurrent neuroblastoma

Recurrent neuroblastoma means that the cancer has come back (recurred) after it has been treated. If it comes back in the same place that the cancer first started, it's called local recurrence. If it comes back in tissues or lymph nodes close to where it first started, it's called regional recurrence. It can also recur in another part of the body. This is called distant metastasis or distant recurrence.

Refractory neuroblastoma

Refractory neuroblastoma means that the cancer has not responded to initial treatment and additional treatment options will likely need to be considered.

Risk groups for neuroblastoma

Neuroblastoma grows differently and responds differently to treatment in different people depending on many different factors. The management of neuroblastoma is particularly complicated because its behaviour can be so varied. The Children's Oncology Group (COG) classifies neuroblastoma into risk groups based on stage and certain prognostic factors. Treatments are planned according to the risk group or how aggressive a tumour might be. Low-risk neuroblastoma (generally small, localised tumours and those without MYCN amplification) responds well to treatment and is often treated with surgery alone or, in certain cases, watchful waiting (observation). High-risk neuroblastoma (typically patients older than 18 months with metastatic disease, or those with tumours with MYCN amplification) often requires complex and intensive treatment including chemotherapy, radiotherapy and immunotherapy. Risk grouping can be very complicated and your child's doctor will discuss with you what they think is best in any particular situation based on the age, stage and other prognostic factors.

Low-risk neuroblastoma includes:

  • stage 1
  • stage 2A or 2B with no extra copies of the MYCN gene (a gene that causes cancer)
  • stage 4S in children younger than 12 months with favourable histology, excess DNA (called hyperdiploid) and no extra copies of the MYCN gene

Intermediate-risk neuroblastoma includes:

  • stage 3 in children younger than 18 months with no extra copies of the MYCN gene
  • stage 3 in children 18 months or older with no extra copies of the MYCN gene and favourable histology
  • stage 4 in children younger than 12 months with no extra copies of the MYCN gene
  • stage 4 in children older than 12 months and younger than 18 months with no extra copies of the MYCN gene, excess DNA (hyperdiploid) and favourable histology
  • stage 4S in children younger than 12 months with no extra copies of the MYCN gene and unfavourable histology
  • stage 4S in children younger than 12 months with no extra copies of the MYCN gene and normal DNA (diploid)

High-risk neuroblastoma includes:

  • stage 2A or 2B in children with extra copies of the MYCN gene
  • stage 3 with extra copies of the MYCN gene
  • stage 3 in children older than 18 months with no extra copies of the MYCN gene and unfavourable histology
  • stage 4 in children younger than 12 months with extra copies of the MYCN gene
  • stage 4 in children older than 12 months and younger than 18 months with extra copies of the MYCN gene
  • stage 4 in children older than 12 months and younger than 18 months with normal DNA (diploid)
  • stage 4 in children older than 12 months and younger than 18 months with unfavourable histology
  • stage 4 in children older than 18 months
  • stage 4S in children younger than 12 months with extra copies of the MYCN gene

Expert review and references