What is the best treatment for metastatic soft tissue sarcoma?

Treatment of Metastatic Soft Tissue Sarcoma

Anthracycline-based chemotherapy is the standard first-line treatment for metastatic soft tissue sarcoma, with doxorubicin monotherapy being the preferred option for most patients, while histology-specific approaches should be considered for certain subtypes. 1

First-Line Systemic Therapy

Standard Approach

• Single-agent doxorubicin is the standard first-line treatment for most metastatic soft tissue sarcomas [I, A] 1
• Combination therapy with doxorubicin plus ifosfamide offers higher response rates and progression-free survival but without proven overall survival benefit 1
  • Consider combination therapy when tumor response would improve symptoms or facilitate other treatment modalities 1
  • Higher toxicity profile must be weighed against potential benefits

Histology-Specific First-Line Approaches

• Leiomyosarcoma: Doxorubicin plus dacarbazine is preferred over ifosfamide-containing regimens [V, B] 1
• Angiosarcoma: Taxanes are highly effective and can be considered first-line [III, B] 1
• Liposarcoma: Anthracycline-based therapy with consideration of trabectedin in later lines 1
• Dermatofibrosarcoma protuberans: Imatinib is standard therapy for unresectable/metastatic disease [III, A] 1
• Alveolar soft part sarcoma: Consider targeted therapy first-line as this subtype is chemotherapy-resistant 1

Second-Line and Beyond

Sequential Treatment Options

1. Ifosfamide: If not used in first-line or consider high-dose (14 g/m²) even if standard dose was previously used [IV, C] 1

2. Trabectedin: Particularly effective in leiomyosarcoma and liposarcoma [I, B] 1, 2

   • FDA-approved for patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received prior anthracycline-containing regimen 2
   • Showed significant improvement in progression-free survival compared to dacarbazine 2

3. Gemcitabine ± docetaxel: Option for leiomyosarcoma and undifferentiated pleomorphic sarcoma [II, C] 1

4. Pazopanib: Option in non-adipogenic STS [I, B] 1

5. Eribulin: Superior to dacarbazine in liposarcomas with 7-month OS advantage in this subtype [II, A] 1

Management of Oligometastatic Disease

• Lung-only metastases:

  • For synchronous metastases: Start with chemotherapy, consider surgical resection if good response 1
  • For metachronous resectable metastases: Complete surgical excision is standard [IV, B] 1
  • Consider chemotherapy before surgery to assess tumor response 1

• Surgery for oligometastatic disease should be considered when feasible, especially for lung metastases 1

• Ablative therapies (RFA, SABR, cryotherapy) may be considered for oligometastatic disease, though data on survival benefit is limited 1

Prognostic Factors and Treatment Selection

Important factors affecting treatment decisions:

• Patient performance status
• Disease extent and pace of progression
• Histological subtype
• Previous treatments
• Potential sensitivity to available agents 1

Poor prognostic factors for overall survival include:

• Multiple involved organs
• Presence of bulky masses
• Elevated CRP levels 3

Common Pitfalls and Caveats

• Avoid histology-agnostic approaches: Treatment should be tailored to specific sarcoma subtypes whenever possible
• Don't overlook surgical options for oligometastatic disease, especially lung metastases
• Beware of increased toxicity with combination regimens, particularly in elderly or frail patients
• Don't delay second-line therapy after progression on first-line treatment
• Consider clinical trials for patients with advanced, previously treated disease

The management of metastatic soft tissue sarcoma remains challenging with limited survival benefit from current therapies. Median survival is typically 12-18 months despite treatment 1. Treatment decisions should balance potential benefits against toxicity, with consideration of patient preferences and quality of life.