What is the treatment approach for Rhabdomyosarcoma (RMS)?

Treatment Approach for Rhabdomyosarcoma

Rhabdomyosarcoma requires multimodality therapy combining surgery, chemotherapy, and radiotherapy in a coordinated treatment plan, with all patients managed by a specialized sarcoma multidisciplinary team at a reference center. 1, 2

Mandatory Multidisciplinary Team Requirement

• All patients with rhabdomyosarcoma must be managed by a specialized sarcoma multidisciplinary team including pathologists, radiologists, surgeons, radiation oncologists, and medical oncologists, preferably within reference centers treating high volumes of patients 1, 2
• This is non-negotiable given the complexity of treatment sequencing and the need for coordinated multimodality therapy 3, 4

Diagnostic Confirmation Requirements

• Establish histologic diagnosis through incisional surgical biopsy or complete tumor resection 1
• Perform immunohistochemistry and cytogenetics to identify specific subtypes (embryonal vs. alveolar rhabdomyosarcoma), as this determines prognosis and treatment intensity 1, 2
• Alveolar rhabdomyosarcoma carries significantly worse prognosis with median survival of only 17 months in some series 5
• Use dual classification: pretreatment TNM staging and postoperative clinical grouping for risk stratification 1

Staging Workup

• Chest CT scan is mandatory to exclude pulmonary metastases 2
• MRI with contrast is the preferred imaging modality for extremity and trunk wall tumors 2
• Consider abdominal/pelvic CT for specific histologic subtypes with high metastatic potential 2

Treatment Algorithm by Disease Stage

Localized Disease (Non-Metastatic)

Surgery:

• Perform wide excision whenever possible without causing major functional or cosmetic deficits, including the cutaneous scar and biopsy tract 1, 2, 4
• Complete resection with negative microscopic margins (Group I) is the goal, though often not feasible due to locally infiltrative growth patterns 1, 4
• Re-operation is mandatory in cases of previous marginal or intralesional resection 6, 2
• In radical surgery obtained by compartmental excision or amputation at large distance from primary tumor, adjuvant radiation therapy is not necessary 6

Chemotherapy:

• All patients with rhabdomyosarcoma require chemotherapy 4
• Adjuvant chemotherapy is standard of care for rhabdomyosarcoma (unlike other adult soft tissue sarcomas where it remains controversial) 6
• The backbone regimen is vincristine and dactinomycin with either cyclophosphamide (VAC) or ifosfamide (IVA) 4
• Dactinomycin is FDA-approved specifically for rhabdomyosarcoma as part of multi-phase combination chemotherapy 7

Radiotherapy:

• After wide excision of high-grade sarcomas, adjuvant radiation therapy is recommended 6, 2
• Standard postoperative radiation dose is 50-60 Gy in fractions of 1.8-2 Gy, with possible boosts up to 66 Gy depending on presentation and quality of surgery 2, 8
• For microscopically positive margins, add 16-18 Gy boost 8
• For macroscopic residual disease, add 20-26 Gy boost if normal tissue can be spared 8
• Preoperative radiotherapy typically uses 50 Gy, with surgery performed 4-8 weeks after completion 2, 8

Metastatic Disease

• Standard multiagent chemotherapy is the treatment of choice, typically using doxorubicin with or without ifosfamide 6, 1, 2
• Response evaluation should be performed after 2-3 cycles with the same radiological examinations that were positive before treatment 6, 2
• In cases of completely resectable lung metastases, surgery must be considered 6, 2
• High-dose chemotherapy with autologous stem cell transplant (HDT/ASCT) has no proven survival benefit in primary metastatic rhabdomyosarcoma and should not be performed outside clinical trials 1

Histologic Subtype-Specific Management

• Embryonal and alveolar rhabdomyosarcoma in adults must be managed using the same principles that apply to children 6, 1
• Pleomorphic rhabdomyosarcoma is viewed as a high-grade adult-type soft tissue sarcoma and managed accordingly with standard adult sarcoma protocols 6, 1

Expected Treatment Toxicities

• Severe hematologic toxicities are expected: 83% grade 3-4 neutropenia, 60% thrombocytopenia, and 45% anemia with intensive regimens 1
• Treatment-related death rates range from 0-4%, primarily from sepsis and anthracycline-related cardiotoxicity 1
• Long-term effects include myelosuppression, febrile neutropenia, hepatopathy, infertility, and second malignant neoplasms 4

Follow-Up Protocol

• Patients should be followed every 3 months with history and physical examination 6, 2
• MRI of the resection site twice yearly for the first 2-3 years, then once yearly 6, 2
• For high-grade tumors, chest X-ray every 3-4 months in the first 2-3 years, twice yearly up to the 5th year, and once yearly thereafter 6, 2

Critical Pitfalls to Avoid

• Do not treat rhabdomyosarcoma patients outside of specialized sarcoma centers - outcomes are significantly worse without multidisciplinary expertise 1, 2
• Do not omit chemotherapy - unlike other adult soft tissue sarcomas, chemotherapy is mandatory for rhabdomyosarcoma 6, 4
• Do not pursue HDT/ASCT outside clinical trials - there is no proven benefit and potential for significant harm 1
• Do not delay re-excision for inadequate initial margins - this is a critical determinant of local control 6, 2

Prognosis

• Five-year survival rate >70% has been achieved for patients with localized rhabdomyosarcoma 4
• Outcome for patients with metastatic disease remains poor, with 5-year overall survival of approximately 45% in adults 9
• Adult rhabdomyosarcoma has worse prognosis compared to childhood rhabdomyosarcoma and requires aggressive multidisciplinary treatment 9