How should a suspected rhabdomyosarcoma be evaluated and managed?

Evaluation and Management of Suspected Rhabdomyosarcoma

All patients with suspected rhabdomyosarcoma must be immediately referred to a specialized sarcoma multidisciplinary team at a reference center before any definitive intervention, as this approach is mandatory for optimal outcomes and adherence to evidence-based protocols. 1

Initial Evaluation and Diagnostic Workup

Clinical Assessment

• Obtain detailed history focusing on tumor location, duration of symptoms, and any prior radiation exposure or genetic syndromes (Li-Fraumeni syndrome, neurofibromatosis) 1
• Perform physical examination documenting tumor size, depth (superficial vs. deep), and relationship to anatomical structures 1
• Refer any unexplained deep soft tissue mass or superficial lesion >5 cm in diameter to a sarcoma center before biopsy 1

Imaging Studies

• MRI is the primary imaging modality for extremity, pelvis, and trunk lesions to define local extent and relationship to neurovascular structures 1
• CT scan of the chest is mandatory to exclude lung metastases, as rhabdomyosarcoma commonly metastasizes to lungs 1
• CT is preferred for retroperitoneal/intra-abdominal tumors and calcified lesions 1
• Plain radiographs may help rule out bone tumors and detect bone erosion 1

Histologic Diagnosis

• Obtain tissue diagnosis through incisional surgical biopsy or core needle biopsy (image-guided CT or ultrasound-guided preferred) before initiating treatment 1
• Immunohistochemistry and cytogenetics are essential to distinguish embryonal from alveolar rhabdomyosarcoma subtypes, as this determines treatment approach 1, 2
• Molecular testing for PAX-FKHR fusion genes provides critical prognostic information in alveolar subtypes 2

Staging Evaluation

• Apply dual classification using pretreatment TNM staging and postoperative clinical grouping for risk stratification 3, 4
• For alveolar rhabdomyosarcoma with T2 tumors: perform bone marrow aspirate/biopsy and bone scan due to 23% bone marrow involvement rate and 13% lung metastasis rate 4
• For embryonal rhabdomyosarcoma with T1 tumors: omit bone marrow and bone scan evaluation as bone/bone marrow involvement rate is 0% in this subset 4

Management Approach

Multidisciplinary Team Requirement

• Management must occur at specialized sarcoma reference centers with weekly tumor boards including pathologists, radiologists, surgeons, radiation oncologists, medical oncologists, and pediatric oncologists 1
• The multidisciplinary team should review all cases before treatment initiation 1

Treatment Strategy by Disease Stage

Localized Disease

• Multimodality therapy combining surgery, chemotherapy, and radiotherapy is the standard approach, with sequencing determined by histologic subtype, stage, and risk stratification 3, 2
• Perform wide surgical excision whenever feasible without causing major functional or cosmetic deficits, including the cutaneous scar and biopsy tract 1, 3, 2
• The goal is complete resection with negative microscopic margins (Group I), though this is often not achievable due to locally infiltrative growth patterns 3, 2
• Adjuvant radiotherapy is recommended after wide excision based on surgical margins and clinical grouping 3, 2
• Multiagent chemotherapy is administered as part of the multimodality protocol 3, 2, 5

Metastatic Disease

• Standard multiagent chemotherapy is the treatment of choice, typically using doxorubicin-based regimens with or without ifosfamide 1, 3, 2
• High-dose chemotherapy with autologous stem cell transplant (HDT/ASCT) should NOT be used outside clinical trials, as multiple prospective studies show no survival benefit in primary metastatic disease and expose patients to treatment-related mortality of 0-4% 3, 2

Relapsed/Refractory Disease

• HDT/ASCT shows no proven survival benefit in relapsed rhabdomyosarcoma and should not be used outside clinical trials 3, 2
• Relapse rates are 30-40% in initially localized disease and 60-80% in metastatic disease 2

Histologic Subtype-Specific Considerations

• Embryonal and alveolar rhabdomyosarcoma in adults should be managed using the same principles that apply to children, often guided by international clinical trial protocols such as FaR-RMS 1
• Pleomorphic rhabdomyosarcoma is treated as a high-grade adult-type soft tissue sarcoma with standard adult protocols 1

Expected Toxicities and Monitoring

• Severe hematologic toxicities occur with standard chemotherapy: 83% grade 3-4 neutropenia, 60% thrombocytopenia, and 45% anemia with intensive regimens 3, 2
• Treatment-related mortality ranges from 0-4%, primarily from sepsis and anthracycline-related cardiotoxicity 3, 2
• Response evaluation should occur after 2-3 cycles of chemotherapy using the same radiological examinations that were positive before treatment 3

Critical Pitfalls to Avoid

• Never perform definitive surgery before multidisciplinary team review, as inappropriate resection can compromise subsequent treatment options 1
• Never use HDT/ASCT outside clinical trials despite theoretical rationale for dose intensification, as this consistently demonstrates no survival benefit with significantly higher toxicity 3, 2
• Never omit molecular testing and cytogenetics, as distinguishing embryonal from alveolar subtypes is essential for appropriate risk stratification and treatment planning 1, 2, 4
• Avoid managing these patients in non-specialized centers, as adherence to evidence-based guidelines at reference centers is associated with improved survival outcomes 1