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PubMed This is a summary of 19 peer-reviewed journal articles Updated
Pediatric Oncology

Mapping the Disease: Staging and Risk Groups

At a Glance

Neuroblastoma staging uses scans to categorize the tumor before treatment. A child's stage, age (with 18 months being a key threshold), and tumor biology are combined to determine their risk group—low, intermediate, or high—which directly guides their entire treatment plan.

In the world of neuroblastoma, doctors use a specific roadmap called staging to describe where the cancer is and how it behaves. Understanding your child’s stage helps the medical team determine the “risk group,” which is essentially a guide for how much treatment is needed [1][2].

The Modern Staging System: INRGSS

Historically, doctors staged neuroblastoma based on what they found after surgery. Today, we use the International Neuroblastoma Risk Group Staging System (INRGSS) [3]. This system is “pretreatment,” meaning it uses imaging to stage the disease before any surgery or intensive therapy begins [4][5].

The INRGSS uses four main categories:

  • L1: The tumor is in one place and does not involve any “danger zones” (vital structures like major blood vessels) [4].
  • L2: The tumor is localized but is touching or wrapping around nearby vital structures [4][1].
  • M: The cancer has spread (metastasized) to distant parts of the body [1].
  • MS: A unique stage found only in infants (see “The Mystery of Stage MS” below) [6].

Imaging Tools: CT, MRI, and MIBG Scans

To accurately stage the disease, doctors rely on multiple types of scans. While CT and MRI scans show the detailed anatomy of the tumor, the “gold standard” for neuroblastoma is the MIBG scan [1].

MIBG is a special radioactive tracer that is absorbed almost exclusively by neuroblastoma cells. When scanned, any neuroblastoma cells in the body “light up,” making it the most effective way to see if the cancer has spread to the bones or bone marrow [1]. Because young children need to remain perfectly still for these detailed scans, they routinely require sedation or general anesthesia—a very common and understandable source of anxiety for parents.

Imaging-Defined Risk Factors (IDRFs)

To decide between L1 and L2, radiologists look for Imaging-Defined Risk Factors (IDRFs) on the CT or MRI [4]. These are specific features—such as a tumor wrapping around a major artery or pushing on the airway—that might make surgery more difficult or risky [7][8].

If IDRFs are present, the tumor is L2. In many cases, doctors will use chemotherapy first to shrink the tumor and move it away from these vital structures, making future surgery safer [9][10].

Why Age Matters: The 18-Month Threshold

In neuroblastoma, a child’s age at diagnosis is one of the most powerful predictors of how the disease will behave [2]. Doctors use 18 months as a critical dividing line [1][11].

  • Infants (under 18 months): Often have tumors that are biologically less aggressive and more responsive to treatment [12][13].
  • Older Children (over 18 months): Often require more intensive therapy because their tumors tend to have more complex genetic changes [2][13].

The Mystery of Stage MS

Stage MS (formerly called Stage 4S) is a unique and often hopeful category found only in infants under 18 months old [6][14]. In this stage, the cancer may have spread to the liver, skin, or bone marrow, but it behaves very differently than “typical” metastatic cancer [6].

The most remarkable feature of Stage MS is its potential for spontaneous regression [15]. This means the tumor cells may naturally stop growing and disappear on their own, or “mature” into healthy, non-cancerous cells, without the need for intensive chemotherapy [16][17]. While monitored very closely for complications, many require only minimal treatment or even just “watchful waiting” [14][18].

Defining the Risk Group

Your doctor will combine the stage, your child’s age, and the tumor’s biology (like the MYCN gene status) to place your child into one of three risk groups [1]:

  1. Low Risk: Often requires only surgery or observation [14].
  2. Intermediate Risk: Usually requires surgery and a moderate course of chemotherapy [1].
  3. High Risk: Requires intensive, multi-step treatment to ensure the best possible outcome [19].

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Common questions in this guide

What is an MIBG scan used for in neuroblastoma?
An MIBG scan is the gold standard imaging test for neuroblastoma. It uses a safe radioactive tracer that is absorbed by neuroblastoma cells, making them 'light up' on the scan to show if the cancer has spread to bones or bone marrow.
Why is 18 months of age an important threshold for neuroblastoma?
In neuroblastoma, a child's age at diagnosis strongly predicts how the disease will behave. Infants under 18 months often have tumors that are biologically less aggressive, while older children typically require more intensive therapy.
What are Imaging-Defined Risk Factors (IDRFs)?
IDRFs are specific features seen on a CT or MRI, such as a tumor wrapping around a major artery. Their presence can make surgery more difficult and may mean chemotherapy is needed first to shrink the tumor away from vital structures.
What does Stage MS mean for an infant with neuroblastoma?
Stage MS is a unique category for infants under 18 months where the cancer has spread but behaves differently. Remarkably, these tumors can sometimes naturally stop growing or disappear on their own with minimal or no treatment.
How do doctors determine a neuroblastoma risk group?
Doctors combine the tumor's stage, the child's age, and the tumor's biology (like the MYCN gene status). This information places the child into a low, intermediate, or high-risk group, which determines how intensive their treatment needs to be.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on the imaging, which specific Imaging-Defined Risk Factors (IDRFs) were found?
  2. 2.Does my child's age at diagnosis place them in a more favorable risk category?
  3. 3.Will my child need sedation or general anesthesia for their upcoming MIBG or MRI scans?
  4. 4.For a Stage MS diagnosis, what signs of spontaneous regression will we be looking for, and how often will we scan?
  5. 5.If there are IDRFs present, will chemotherapy be used to shrink the tumor before surgery is attempted?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (19)
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    Tailoring Therapy for Children With Neuroblastoma on the Basis of Risk Group Classification: Past, Present, and Future.

    Liang WH, Federico SM, London WB, et al.

    JCO clinical cancer informatics 2020; (4()):895-905 doi:10.1200/CCI.20.00074.

    PMID: 33058692
  2. 2

    Revised Neuroblastoma Risk Classification System: A Report From the Children's Oncology Group.

    Irwin MS, Naranjo A, Zhang FF, et al.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2021; (39(29)):3229-3241 doi:10.1200/JCO.21.00278.

    PMID: 34319759
  3. 3

    Management of Neuroblastoma in Pediatric Patients.

    Croteau N, Nuchtern J, LaQuaglia MP

    Surgical oncology clinics of North America 2021; (30(2)):291-304 doi:10.1016/j.soc.2020.11.010.

    PMID: 33706901
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    Neuroblastoma image-defined risk factors in adrenal neuroblastoma: role of radiologist.

    Lanza C, Galeazzi V, Carboni N, et al.

    Gland surgery 2019; (8(Suppl 3)):S168-S177 doi:10.21037/gs.2019.06.01.

    PMID: 31559184
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    Neuroblastoma.

    Chung C, Boterberg T, Lucas J, et al.

    Pediatric blood & cancer 2021; (68 Suppl 2()):e28473 doi:10.1002/pbc.28473.

    PMID: 33818884
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    Neuroblastoma stage 4S: Tumor regression rate and risk factors of progressive disease.

    Tas ML, Nagtegaal M, Kraal KCJM, et al.

    Pediatric blood & cancer 2020; (67(4)):e28061 doi:10.1002/pbc.28061.

    PMID: 31736229
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    How well do image-defined risk factors (IDRFs) predict surgical outcomes and survival in patients with neuroblastoma? A systematic review and meta-analysis.

    Parhar D, Joharifard S, Lo AC, et al.

    Pediatric surgery international 2020; (36(8)):897-907 doi:10.1007/s00383-020-04696-y.

    PMID: 32533235
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    Perioperative complication incidence and risk factors for retroperitoneal neuroblastoma in children: analysis of 571 patients.

    He M, Cai JB, Wu X, et al.

    World journal of pediatrics : WJP 2024; (20(3)):250-258 doi:10.1007/s12519-023-00773-z.

    PMID: 38070095
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    Impact of Neoadjuvant Chemotherapy on Image-Defined Risk Factors in High-Risk Neuroblastoma.

    Mansfield SA, McCarville MB, Lucas JT, et al.

    Annals of surgical oncology 2022; (29(1)):661-670 doi:10.1245/s10434-021-10386-3.

    PMID: 34215956
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    Changes in image-defined risk factors with neoadjuvant chemotherapy in pediatric abdominal neuroblastoma.

    Wang H, Chen X, Zhu J, et al.

    Abdominal radiology (New York) 2022; (47(10)):3520-3530 doi:10.1007/s00261-022-03596-0.

    PMID: 35790567
  11. 11

    Impact of Genomic and Clinical Factors on Outcome of Children ≥18 Months of Age with Stage 3 Neuroblastoma with Unfavorable Histology and without MYCN Amplification: A Children's Oncology Group (COG) Report.

    Pinto N, Naranjo A, Ding X, et al.

    Clinical cancer research : an official journal of the American Association for Cancer Research 2023; (29(8)):1546-1556 doi:10.1158/1078-0432.CCR-22-3032.

    PMID: 36749880
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    Peripheral neuroblastic tumors: tumor biology and its implications for risk stratification.

    Anissi Eddaibouni A, Hachimi S, Bennani Guebessi N, et al.

    European journal of pediatrics 2025; (184(7)):447 doi:10.1007/s00431-025-06281-8.

    PMID: 40560457
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    Whole-exome sequencing reveals genetic variants in low-risk and high-risk neuroblastoma.

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    Gene 2023; (860()):147233 doi:10.1016/j.gene.2023.147233.

    PMID: 36736507
  14. 14

    Skeletal muscle metastases in neuroblastoma share common progenitors with primary tumor and biologically resemble stage MS disease.

    Fong C, Kushner BH, Di Giannatale A, et al.

    Frontiers in oncology 2022; (12()):1106597 doi:10.3389/fonc.2022.1106597.

    PMID: 36686814
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    Pirarubicin Combination Low-Dose Chemotherapy for Early Infantile Stage MS Neuroblastoma: Case Report.

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    Children (Basel, Switzerland) 2023; (10(5)) doi:10.3390/children10050871.

    PMID: 37238419
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    SLIT3-mediated intratumoral crosstalk induces neuroblastoma differentiation via a spontaneous regression-like program.

    Liu M, Lv D, Yan W, et al.

    Journal of translational medicine 2025; (23(1)):598 doi:10.1186/s12967-025-06621-0.

    PMID: 40448172
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    Study on differentially expressed genes between stage M and stage MS neuroblastoma.

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This page explains neuroblastoma staging and risk groups for educational purposes. Your pediatric oncologist is the best source for interpreting your child's specific imaging results and treatment plan.

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