What is the treatment for undifferentiated pleomorphic sarcoma?

Treatment for Undifferentiated Pleomorphic Sarcoma

Wide surgical excision is the primary treatment for undifferentiated pleomorphic sarcoma (UPS), with adjuvant radiotherapy and chemotherapy considered for high-risk cases. 1, 2

Surgical Management

• Complete surgical resection with negative margins is the cornerstone of treatment and the most important factor for improved survival 2
• For primary tumors, wide excision should be performed with the goal of achieving negative histopathological margins 1, 2
• Limb-sparing surgery is preferred when possible, but amputation may be necessary in cases where adequate margins cannot be achieved otherwise 2
• Preoperative core/punch biopsy is recommended to secure diagnosis before definitive surgery, especially for tumors in anatomically challenging locations 1

Adjuvant Therapy

Radiotherapy

• Adjuvant radiotherapy should be considered in the following scenarios:
  • When surgical margins are positive or close 1
  • For tumors in locations where wide excision is not possible (e.g., scalp) 1
  • For high-grade tumors with adverse features (deep subcutis invasion, tumor necrosis, lymphovascular invasion, or perineural invasion) 1
• Reconstructive procedures should be planned to be robust enough to tolerate postoperative radiotherapy 1

Chemotherapy

• Adjuvant chemotherapy should be considered for:
  • High-risk localized UPS (tumors ≥5 cm, particularly those 10-15 cm) 3
  • High-grade tumors with risk factors for recurrence 4
• Conventional chemotherapy regimens for UPS typically include doxorubicin-based combinations 4
• The 5-year overall survival rate improves with adjuvant chemotherapy (82.3% vs 78.6% without chemotherapy) 3

Management of Advanced/Metastatic Disease

• For metastatic disease, systemic therapy is required but conventional chemotherapy has limited efficacy (response rates of only 27-33%) 4
• Treatment options for advanced disease include:
  • Systemic chemotherapy with doxorubicin-based regimens 4
  • Consideration of immune checkpoint inhibitors, which have shown promising results in recent clinical trials 4, 5
  • Combined approaches with radiation therapy and immunotherapy for selected cases 5
• For oligometastatic disease, local treatments such as surgery, radiofrequency ablation, cryotherapy, or stereotactic radiotherapy should be considered 1

Prognostic Factors

• Negative surgical margins are the most significant factor for improved survival 2, 6
• Other important prognostic factors include:
  • Primary vs. recurrent disease (5-year survival: 84% vs. 62%) 2
  • Tumor size (larger tumors have worse prognosis) 6, 3
  • Tumor grade (higher grade correlates with worse outcomes) 2
  • Patient age (older age is associated with decreased overall survival) 6
  • Presence of metastatic disease at diagnosis 6

Follow-up

• Regular follow-up is essential for early detection of recurrence
• For intermediate to high-grade UPS, follow-up every 3-4 months in the first 2-3 years, then twice a year up to the fifth year, and once a year thereafter 1
• Imaging should include assessment of the primary site and chest imaging to detect potential metastases 1

Special Considerations

• UPS management should be discussed in a specialized sarcoma multidisciplinary team 1
• For tumors in challenging anatomical locations, preoperative treatment may be considered to reduce tumor size and facilitate surgical resection 1
• The combination of radiation therapy with immunotherapy has shown promising results in case reports of metastatic UPS and warrants further investigation 5