What is the treatment for synovial sarcoma?

Treatment of Synovial Sarcoma

Wide surgical excision with negative margins is the cornerstone of treatment for localized synovial sarcoma, followed by adjuvant radiation therapy for high-grade, deep tumors >5 cm, with consideration of doxorubicin plus ifosfamide chemotherapy for high-risk patients. 1

Diagnosis and Staging Requirements

Before initiating treatment, specific diagnostic and staging steps are mandatory:

• Core needle biopsy is required for histopathological confirmation, with molecular testing to identify the characteristic SS18 gene rearrangement 1, 2
• Chest CT scan is mandatory to exclude pulmonary metastases 3, 1
• Regional lymph node assessment must be performed specifically for synovial sarcoma, as it has a higher propensity for nodal involvement compared to other soft tissue sarcomas 3, 1
• MRI is the preferred imaging modality for extremity and trunk tumors to guide surgical planning 1

All cases must be reviewed by a specialist Sarcoma Multidisciplinary Team before treatment decisions are finalized 1.

Surgical Management

Surgery is the primary curative modality and must be performed by a surgeon with specific sarcoma expertise 3, 1:

• Wide excision with R0 (negative) margins is the standard procedure, removing the tumor with a rim of normal tissue 3, 1
• Margins can be minimal (<1 cm) when resistant anatomical barriers such as muscular fasciae, periosteum, or perineurium are present 3, 1
• Re-operation should be performed if initial margins are positive or if the tumor was inadequately resected at an outside facility 1

Critical pitfall: Inadequate primary surgery performed outside referral centers is an independent risk factor for local recurrence, which increases the risk of tumor-related death by 3.66-fold 4. Referral to a sarcoma center should occur before any surgical intervention 3.

Radiation Therapy

Adjuvant radiation therapy is standard for specific tumor characteristics 3, 1:

• Indicated for: High-grade, deep tumors >5 cm 3, 1
• Dosing: 50-60 Gy in fractions of 1.8-2 Gy, with possible boosts up to 66 Gy depending on surgical quality 3, 1
• Timing options: Postoperative (standard) or preoperative at 50 Gy 3, 1

Radiation therapy may be considered for smaller or superficial tumors on an individualized basis, particularly if margins are close or positive 3.

Chemotherapy

The role of chemotherapy varies by disease stage and risk stratification:

High-Risk Localized Disease

• Doxorubicin plus ifosfamide should be considered for high-risk patients (age ≥25 years, tumor size ≥5 cm, poorly differentiated histology) 1, 5, 4
• This combination can be administered neoadjuvantly (which may facilitate surgery) or adjuvantly 3, 5
• Synovial sarcoma is relatively chemosensitive compared to other soft tissue sarcomas, making chemotherapy more likely to provide benefit 5, 2

Risk stratification is critical: Low-risk patients (age <25 years, tumor size <5 cm, well-differentiated histology) have 88% disease-free survival, while high-risk patients have only 18% disease-free survival 4. This dramatic difference justifies more aggressive systemic therapy in the high-risk group.

Metastatic Disease

• First-line: Doxorubicin plus ifosfamide combination for fit patients 1, 5
• Sequential therapy: Doxorubicin followed by ifosfamide for patients who cannot tolerate combination therapy 5
• Second-line options: Pazopanib and trabectedin have demonstrated activity 5

Special Considerations for Retroperitoneal Synovial Sarcoma

• Neoadjuvant chemotherapy should be strongly considered for retroperitoneal synovial sarcoma given its chemosensitive nature 3
• Regional hyperthermia plus systemic chemotherapy showed PFS, DFS, and OS advantages in retroperitoneal sarcomas 3

Follow-Up Protocol

Surveillance intensity should be risk-stratified 1:

High-risk patients (who typically relapse within 2-3 years):

• Clinical examination every 3-4 months for the first 2-3 years 1
• MRI of primary site twice yearly for 2-3 years, then annually 1
• Chest imaging (X-ray or CT) every 3-4 months for 2-3 years, twice yearly up to 5 years, then annually 1

Low-risk patients may relapse later and require extended surveillance beyond the typical 2-3 year window 1.

Critical Pitfalls to Avoid

• Biopsy before referral: The biopsy should ideally be performed by the surgeon who will perform definitive resection, as improper biopsy technique can contaminate tissue planes and compromise subsequent surgery 6
• Inadequate staging: Failure to assess regional lymph nodes is a specific error for synovial sarcoma, as nodal involvement is more common than in other soft tissue sarcomas 3
• Treating as low-grade: Synovial sarcoma is generally high-grade despite occasional well-differentiated histology; treatment intensity should not be reduced based on histologic appearance alone 4, 6
• Cardiotoxicity monitoring: Cumulative doxorubicin dose must be monitored to minimize cardiac effects 1
• Neutropenia management: Prophylactic G-CSF should be considered in older patients (>65 years) or those with comorbidities receiving chemotherapy 1