ON THIS PAGE: You will learn about how doctors describe the extent of disease in the patient's body. This is called the stage. Use the menu to see other pages.
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The International Neuroblastoma Risk Group Staging System (INRGSS)
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International Neuroblastoma Staging System Committee (INSS) system
What is staging?
Staging is a way of describing a tumor, such as whether it is only located in one area of the body or if the tumor has spread and is affecting other parts of the body.
Doctors use diagnostic tests to find out the tumor's stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor to recommend the best kind of treatment and can help predict a patient's prognosis, which is the chance of recovery. There are different stage descriptions for different types of cancer. Once a diagnosis of neuroblastoma is confirmed, how much the tumor has grown and spread is evaluated or staged.
The International Neuroblastoma Staging System Committee (INSS), a surgical/pathological staging system developed in 1988, was the first internationally accepted staging system for neuroblastoma. In 2009, the International Neuroblastoma Risk Group (INRG) Task Force proposed a new staging system (INRGSS) that was based on imaging.
The International Neuroblastoma Risk Group Staging System (INRGSS)
The INRGSS was designed specifically for the International Neuroblastoma Risk Group (INRG) pre-treatment classification system (see "Risk groups," below). Unlike the INSS explained below, the INRGSS uses only the results of imaging tests taken before surgery. It does not include surgical results or spread to lymph nodes to determine the stage. Knowledge regarding the presence or absence of image-defined risk factors (IDRF) is required for this staging system.
Stage L1: The tumor is located only in the area where it started; no IDRFs are found on imaging scans, such as a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan.
Stage L2: The tumor has not spread beyond the area where it started and the nearby tissue; IDRFs are found on imaging scans, such as a CT or MRI scan.
Stage M: The tumor has spread to other parts of the body (except stage MS; see below).
Stage MS: The tumor has spread to only the skin, liver, and/or bone marrow (with less than 10% bone marrow involvement) in a patient younger than 18 months.
International Neuroblastoma Staging System Committee (INSS) system
This is the staging system previously used for neuroblastoma. The following is a brief summary of each INSS stage.
Stage 1: The tumor can be removed completely during surgery. Lymph nodes attached to the tumor removed during surgery may or may not contain cancer, but other lymph nodes near the tumor do not.
Stage 2A: The tumor is located only in the area it started and cannot be completely removed during surgery. Nearby lymph nodes do not contain cancer.
Stage 2B: The tumor is located only in the area where it started and may or may not be completely removed during surgery, but nearby lymph nodes do contain cancer.
Stage 3: The tumor cannot be removed with surgery. It has spread to regional lymph nodes (lymph nodes near the tumor) or other areas near the tumor, but not to other parts of the body.
Stage 4: The original tumor has spread to distant lymph nodes (lymph nodes in other parts of the body), bones, bone marrow, liver, skin, and/or other organs, except for those listed in stage 4S, below.
Stage 4S: The original tumor is located only where it started (as in stage 1, 2A, or 2B) and has spread only to the skin, liver, and/or bone marrow in infants younger than 1. The spread to the bone marrow is minimal (usually less than 10% of cells examined show cancer).
Risk groups for neuroblastoma
Neuroblastoma grows and reacts differently to treatment in different people. This is called the disease’s clinical behavior. Some children are cured with surgery alone or surgery with chemotherapy (see Types of Treatment). Others have a very aggressive disease that is resistant to treatment and difficult to cure. By using a combination of factors, doctors can usually predict how clinically aggressive the tumor will be and tailor treatments accordingly.
In the INRG classification system, a combination of clinical, pathologic, and genetic markers are used to predict the clinical behavior of the tumor and how it will respond to treatment. These markers are used to define risk. Each neuroblastoma is classified into 1 of 4 categories (very low-risk, low-risk, intermediate-risk, or high-risk) using the following factors:
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The stage of the disease according to the INRGSS (see above)
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The child's age at the time of diagnosis
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Histologic category, such as maturing ganglioneuroma versus ganglioneuroblastoma, intermixed versus ganglioneuroblastoma, or nodular versus neuroblastoma
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Grade, or how cells of the tumor are differentiated
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MYCN gene status
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Chromosome 11q status
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Tumor cell ploidy, which is the DNA content of tumor cells
The Children’s Oncology Group currently uses the following factors to determine risk:
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The stage of the disease according to the INRG system (see above)
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The child's age at the time of diagnosis
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MYCN gene status
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Tumor ploidy (this is only important for children younger than 18 months)
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Tumor histopathology according to the International Neuroblastoma Pathologic Classification (INPC) system
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Segmental chromosomal aberration (SCA) status, or changes in the chromosome number or structure
Descriptions of low-risk, intermediate-risk, and high-risk neuroblastoma according to the current Children’s Oncology Group definitions are listed below. There are some differences in risk classification definitions between the Children's Oncology Group and INRG.
Low-risk neuroblastoma
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Stage L1 in infants younger than 1 year of age with a tumor smaller than 5 centimeters (cm) who have not undergone surgery and are observed, also called a "wait and watch" approach (see Types of Treatment). This type of neuroblastoma is also called "provisional low risk."
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Stage L1 in infants and children with tumors that were completely removed with surgery (see Types of Treatment)
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Stage L1 in infants and children with tumors with no MYCN amplification that have not been completely removed with surgery
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Stage MS in infants younger than 1 year with no tumor-related symptoms, no MYCN amplification, and all favorable biology
Intermediate-risk neuroblastoma
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Stage L2 with no MYCN amplification in children younger than 18 months with or without all favorable biology, children 18 months to 5 years old with favorable histology, and children 5 years or older with differentiating histology
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Stage M in infants younger than 1 year with no MYCN amplification and children 1 year to 18 months with no MYCN amplification and all favorable biology
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Stage MS in infants younger than 1 year with tumor-related symptoms, or with no tumor-related symptoms and no MYCN amplification but any unfavorable biology
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Stage MS in children 1 year to 18 months with no MYCN amplification and all favorable biology
High-risk neuroblastoma
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Stage L1 in infants younger than 1 year that has not been completely removed with surgery and has MYCN amplification
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Stage L1 in children 1 year or older that has not been completely removed with surgery and has MYCN amplification
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Stage L2 with MYCN amplification
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Stage L2 with no MYCN amplification in children 18 months to 5 years old with unfavorable histology or in children 5 years or older with undifferentiated or poorly differentiated histology
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Stage M in children 18 months or older, or in children younger than 18 months with MYCN amplification
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Stage M in children 1 year to 18 months with no MYCN amplification but any unfavorable biology
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Stage MS in children younger than 1 year with MYCN amplification
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Stage MS in children 1 year to 18 months either with MYCN amplification or with no MYCN amplification but any unfavorable biology
Used with permission from Wolters Kluwer Health, Inc.
Descriptions of very low-risk, low-risk, intermediate-risk, and high-risk neuroblastoma according to INRG definitions are listed below.
Very low-risk neuroblastoma
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Stage L1/L2 with ganglioneuroma maturing or ganglioneuroblastoma intermixed histology
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Stage L1 with non-amplified MYCN
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Stage MS in children younger than 18 months of age with no 11q aberration
Low-risk neuroblastoma
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Stage L2 in children younger than 18 months of age with no 11q aberration
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Stage L2 in children older than 18 months of age with ganglioneuroblastoma nodular or neuroblastoma with differentiating histology and no 11q aberration
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Stage M in children younger than 18 months without MYCN amplification and hyperdiploidy
Intermediate-risk neuroblastoma
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Stage L2 in children younger than 18 months without MYCN amplification with 11q aberration
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Stage L2 in children older than 18 months with ganglioneuroblastoma nodular or neuroblastoma with differentiating histology with 11q aberration
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Stage L2 in children older than 18 months with ganglioneuroblastoma nodular or neuroblastoma with poorly differentiated or undifferentiated histology
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Stage M in children younger than 12 months with diploidy
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Stage M in children 12 months to 18 months with diploidy
High-risk neuroblastoma
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Stage L1 with MYCN amplification
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Stage L2 with MYCN amplification
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Stage M in children younger than 18 months of age with MYCN amplification
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Stage M in children older than 18 months
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Stage MS in children younger than 18 months with 11q aberration
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Stage MS in children younger than 18 months of age with MYCN amplification
Treatment is tailored according to the risk assignment. Most patients with very low-risk and low-risk disease commonly receive surgery alone. Sometimes, infants with a small localized tumor have been successfully watched closely without any surgery, an approach called "observation" or "wait and watch."
Patients with intermediate-risk disease receive surgery and chemotherapy. In the most recently completed Children’s Oncology Group clinical trial for patients with intermediate-risk neuroblastoma, the initial number of cycles of chemotherapy was determined by the presence or absence of tumor genetic changes in chromosomes 1p and 11q, tumor histology, tumor ploidy, stage, and the child's age.
A very intensive approach, often using several types of treatments, is used for patients with high-risk neuroblastoma. More information about specific treatment options can be found in the Types of Treatment section.
Recurrent and refractory neuroblastoma
Recurrent: Recurrent neuroblastoma is cancer that has come back after treatment. This is also called relapsed neuroblastoma. If cancer does return, there will be another round of tests to learn about the extent of the recurrence. These tests and scans are often similar to those done at the time of the original diagnosis.
Refractory: If the cancer does not decrease in size or respond completely to treatment, it is called refractory neuroblastoma.
Information about the cancer’s stage and risk group will help the doctor recommend a specific treatment plan. The next section in this guide is Types of Treatment. Use the menu to choose a different section to read in this guide.