Rhabdomyosarcoma Staging and Risk Stratification: IRSG System
The Intergroup Rhabdomyosarcoma Study Group (IRSG) staging system classifies patients into four stages based on tumor size, nodal status, metastatic disease, and primary site location, with risk stratification determining treatment intensity and prognosis.
IRSG Staging System
The IRSG staging system uses a TNM-based pretreatment classification that incorporates:
- Tumor (T): Size (<5 cm or ≥5 cm) rather than invasiveness 1
- Nodes (N): Clinical status of regional lymph nodes
- Metastasis (M): Presence or absence of distant metastasis
- Site: Favorable vs. unfavorable anatomic location
IRSG Stage Classification
| Stage | Characteristics |
|---|---|
| Stage 1 | Favorable site, any size, N0, M0 |
| Stage 2 | Unfavorable site, ≤5 cm, N0, M0 |
| Stage 3 | Unfavorable site, >5 cm or N1, M0 |
| Stage 4 | Any site, any size, any N, M1 |
Favorable sites include: orbit, head and neck (excluding parameningeal), genitourinary (non-bladder/prostate), biliary tract
Clinical Grouping System
In addition to pretreatment staging, the IRSG uses a post-surgical clinical grouping system:
| Group | Definition |
|---|---|
| Group I | Localized disease, completely resected |
| Group II | Microscopic residual or regional nodes involved, completely resected |
| Group III | Incomplete resection with gross residual disease |
| Group IV | Distant metastatic disease present at diagnosis |
Risk Stratification
The current risk-based approach combines histology, stage, and group:
Low Risk
- Embryonal histology + Stage 1 (any group) or Stage 2/3 (Group I/II)
- 3-year failure-free survival: ~85-90% 2
Intermediate Risk
- Embryonal histology + Stage 2/3, Group III
- Alveolar histology, Stage 1-3, Group I-III
- 3-year failure-free survival: ~65-70% 3, 2
High Risk
- Any histology, Stage 4 (metastatic disease)
- 3-year survival rate: <30% 4
Prognostic Factors
Several factors influence prognosis in rhabdomyosarcoma:
- Histology: Embryonal has better prognosis than alveolar
- Molecular features: PAX7-FOXO1 fusion has more favorable prognosis than PAX3-FOXO1 in alveolar RMS 5
- Age: Patients >10 years with paratesticular primaries have worse outcomes (3-year FFS: 63% vs 90%) 2
- Primary site: Orbital and GU (non-bladder/prostate) sites have better outcomes
- Tumor size: Tumors <5 cm have better prognosis
- Metastatic status: Presence of metastasis significantly worsens prognosis
Treatment Implications
The risk stratification directly determines treatment intensity:
- Low risk: May be treated with VA (vincristine, actinomycin D) chemotherapy alone, with radiation for Group II 2
- Intermediate risk: Requires more intensive three-drug chemotherapy regimens 3, 2
- High risk: Requires intensive multimodal therapy, though high-dose chemotherapy with autologous stem cell transplantation has not shown significant survival improvement 5, 4
Important Clinical Considerations
- Molecular testing is increasingly important for diagnosis and prognosis, particularly for alveolar RMS to identify PAX-FOXO1 fusion status 5
- The IRSG staging system has evolved over time, with ongoing refinement based on treatment outcomes 1, 6
- Adolescent and young adult patients have superior outcomes when treated with pediatric protocols 4
- The IRSG staging system should be periodically reevaluated as treatment approaches evolve 1
The IRSG staging system remains the foundation for risk stratification in RMS, though it continues to be refined with each successive study to better predict outcomes and guide treatment decisions.