Staging is the process of finding out how far a cancer has spread. The outlook (prognosis) for people with cancer depends, to a large extent, on the cancer's stage. The stage of a cancer is one of the most important factors in choosing treatment.

The stage of the neuroblastoma is based on results of imaging tests and biopsies of the main tumor and other tissues, which were described in the section "How is neuroblastoma diagnosed?"

For neuroblastoma, several other factors also affect prognosis, including a child's age and certain tests of blood and tumor specimens. While these prognostic factors are not included in determining the stage of the cancer, they are used along with the stage to determine which risk group a child falls into. These prognostic factors and risk groups are also described below.

International neuroblastoma staging system

A staging system is a standardized way for the cancer care team to describe the extent of the cancer. Since the mid-1990s, most cancer centers have used the International Neuroblastoma Staging System (INSS) to stage neuroblastoma. In simplified form, the stages are:

Stage 1: The cancer is still in the area where it started. It is on one side of the body (right or left). All visible tumor can be totally removed by surgery (although looking at the tumor's edges under the microscope may show some cancer cells). Lymph nodes enclosed within the tumor may contain neuroblastoma cells, but lymph nodes outside of the tumor should be free of cancer.

Stage 2A: The cancer is still in the area where it started and on one side of the body, but not all of the visible tumor can be removed by surgery. Lymph nodes enclosed within the tumor may contain neuroblastoma cells, but lymph nodes outside of the tumor should be free of cancer.

Stage 2B: The cancer is on one side of the body, and may or may not be able to be totally removed by surgery. Nearby lymph nodes outside the tumor contain neuroblastoma cells, but the cancer has not spread to lymph nodes on the other side of the body or elsewhere.

Stage 3: The cancer has not spread to distant parts of the body, but one of the following is true:

• The cancer cannot be completely removed by surgery and it has crossed the midline (defined as the spine) to the other side of the body. It may or may not have spread to nearby lymph nodes

• The cancer is still in the area where it started and is on one side of the body. It has spread to lymph nodes that are relatively nearby but on the other side of the body.

• The cancer is in the middle of the body and growing toward both sides (either directly or by spreading to nearby lymph nodes) and cannot be completely removed by surgery.

Stage 4: The cancer has spread to distant sites such as distant lymph nodes, bone, liver, skin, bone marrow, or other organs (but the child does not meet the criteria for stage 4S).

Stage 4S (also called "special" neuroblastoma): The child is younger than 1 year old. The cancer is on one side of the body. It may have spread to lymph nodes on the same side of the body but not to nodes on the other side. The neuroblastoma has spread to the liver, skin, and/or the bone marrow. However, no more than 10% of marrow cells may be cancerous, and imaging studies do not show spread to the bones.

Recurrent: This term is used to describe cancer that has come back (recurred) after it has been treated. It may come back in the area where it first started or in another part of the body.

Prognostic markers

Prognostic markers are specific features that help predict whether the child's outlook for cure is better or worse than would be predicted by the stage alone. The following markers are used to help determine a child's prognosis.

Age

Younger children (under 12-18 months) are more likely to be cured than older children.

Tumor histology

Tumor histology is based on how the neuroblastoma cells look under the microscope. Tumors that contain more normal-looking cells and tissues tend to have a better prognosis and are said to have a "favorable histology." Tumors whose cells and tissues look more abnormal under a microscope tend to have a poorer prognosis and are labeled as having an "unfavorable histology."

DNA ploidy

The amount of DNA in each cell, known as ploidy, can be measured by special lab techniques, such as flow cytometry or imaging cytometry. Neuroblastoma cells with about the same amount of DNA as normal cells are classified as diploid. Cells with increased amounts of DNA are termed hyperdiploid.

In infants, hyperdiploid cells tend to be associated with earlier stages of disease, respond better to chemotherapy, and usually predict a more favorable prognosis (outcome) than diploid cells.

MYCN gene amplifications

MYCN is an oncogene, a gene that is important in regulating growth of cells. Alterations of those genes can make cells grow and divide too quickly, as with cancer cells.

Researchers have found that neuroblastomas with too many copies (amplification) of the MYCN oncogene tend to grow more rapidly and mature less. Children whose neuroblastomas have this feature tend to have a worse prognosis than other children with neuroblastoma.

Other markers

These markers are not used to help determine risk groups (see below), but they are still important and may influence a doctor's decision on how to treat a patient with neuroblastoma.

Cytogenetics: In this lab test, the number of chromosomes in each cell is counted under a microscope, and the abnormalities of any chromosome are described. Normal cells have 46 chromosomes (2 sets of 23), which are made of DNA and protein. Neuroblastomas with normal chromosome numbers tend to be more aggressive than those with extra chromosomes.

Cells that are missing certain parts of chromosomes 1 or 11 (known as "1p deletions" or "11q deletions") may also predict a less favorable prognosis. It is thought that these chromosome parts -- missing in many neuroblastoma patients -- may contain important tumor suppressor genes, but more studies are needed to verify this. Having an extra part of chromosome 17 (17 q gain) is also linked with a worse prognosis; this probably means that there is an oncogene in this part of chromosome 17. Understanding the importance of chromosome deletions/gains is an active area of neuroblastoma research.

Neurotrophin (nerve growth factor) receptors: These are substances on the surface of normal nerve cells and on some neuroblastoma cells. They normally allow the cells to recognize neurotrophins -- hormone-like chemicals that help the nerve cells to mature.

Neuroblastomas with more neurotrophin receptors, especially the nerve growth factor receptor called TrkA, may have a more favorable prognosis.

Serum markers: Serum (blood) levels of certain substances can be used to help predict prognosis.

Neuroblastoma cells release ferritin, a chemical that is an important part of the body's normal iron metabolism, into the blood. Patients with high ferritin levels tend to have a worse prognosis.

Neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) are produced by several types of normal cells as well as by neuroblastoma cells. Increased levels of NSE and LDH in the blood predict a worse outlook for children with neuroblastoma.

A substance on the surface of many nerve cells known as ganglioside GD2 is often increased in the blood of neuroblastoma patients. Although the usefulness of GD2 in predicting prognosis is unknown, it may turn out to be more useful in treating neuroblastoma (see "What's New in Neuroblastoma Research and Treatment?").

Risk groups

The major prognostic factors above are combined with the stage of the disease to form 3 different risk groups: low, intermediate, and high. These risk groups are used to help predict how likely a child can be cured. For example, a child in a low-risk group would usually be cured with simple treatment, often surgery alone. With children in higher risk groups, the chance of cure is not as high, so more intensive treatment is often needed.

The risk groups are based on what is currently known about clinical and biologic features of neuroblastoma and how it is treated. As new research provides more information, these risk groups may change over time.

Low risk

• all children who are Stage 1

• any child who is Stage 2A or 2B and younger than age 1

• any child who is Stage 2A or 2B, older than age 1, whose cancer has no extra copies of the MYCN gene

• any child who is Stage 2A or 2B, older than age 1, whose cancer has extra copies of the MYCN gene but has a favorable histology (appearance under the microscope)

• any child who is Stage 4S (younger than age 1), whose cancer has favorable histology, is hyperdiploid (excess DNA) and has no MYCN amplification

Intermediate risk

• any child who is Stage 3, younger than age 1, whose cancer has no extra copies of the MYCN gene

• any child who is Stage 3, older than age 1, whose cancer has no extra copies of the MYCN gene and has favorable histology (appearance under the microscope)

• any child who is Stage 4, younger than 18 months, whose cancer has no extra copies of the MYCN gene

• any child who is Stage 4S (younger than age 1), whose cancer has no extra copies of the MYCN gene and has normal DNA ploidy (number of chromosomes) and/or has unfavorable histology

High risk

• any child who is Stage 2A or 2B, older than age 1, whose cancer has extra copies of the MYCN gene and unfavorable histology (appearance under the microscope)

• any child who is Stage 3, younger than age 1, whose cancer has extra copies of the MYCN gene

• any child who is Stage 3, older than age 1, whose cancer has no extra copies of the MYCN gene but has unfavorable histology (appearance under the microscope)

• any child who is Stage 3, older than age 1, whose cancer has extra copies of the MYCN gene

• any child who is Stage 4, younger than 18 months, whose cancer has extra copies of the MYCN gene

• any child who is Stage 4 and older than 18 months

• any child who is Stage 4S (younger than age 1), whose cancer has extra copies of the MYCN gene

5-year survival rates based on risk groups

Survival rates are often used by cancer doctors to produce a standard way of discussing a person's prognosis (outlook). The 5-year survival rate refers to the percentage of patients who live at least 5 years after their cancer is diagnosed. Of course, many children live much longer than 5 years. These numbers are based on children treated several years ago; improvements in treatment since then may result in a more favorable outlook for children now being diagnosed with the neuroblastoma.

Survival statistics can sometimes be useful as a general guide, but they may not accurately represent any one child's prognosis. Other factors may also affect outlook. Your child's doctor is likely to be a good source as to whether these numbers may apply to your child's case, as he or she is familiar with the aspects of the particular situation.

Survival by risk group

Low-risk group: Low-risk children have a 5-year survival rate of around 90% to 95%.

Intermediate-risk group: In intermediate-risk children, the 5-year survival rate is around 85% to 90%.

High-risk group: The 5-year survival rate in high-risk children is around 30%.

Last Medical Review: 10/22/2008
Last Revised: 10/22/2008