What is the recommended management approach for a patient with epithelioid sarcoma?

Management of Epithelioid Sarcoma

Epithelioid sarcoma requires wide surgical excision with negative margins as the primary treatment, followed by adjuvant radiotherapy for most cases, with consideration of abdominal/pelvic CT staging due to its unique propensity for nodal and peritoneal metastases, and tazemetostat as a targeted therapy option for advanced disease. 1

Initial Staging and Workup

Epithelioid sarcoma demands specific staging beyond standard soft tissue sarcoma protocols:

• Obtain abdominal/pelvic CT scan in addition to chest CT, as epithelioid sarcoma has an unusually high rate of peritoneal and hepatic metastases compared to other soft tissue sarcomas 1
• Perform regional lymph node clinical assessment and imaging, as epithelioid sarcoma demonstrates nodal involvement in 50-62% of cases—substantially higher than other sarcoma subtypes 1, 2, 3
• MRI of the primary tumor site is essential for surgical planning 1
• Core needle biopsy should be performed by the specialist sarcoma team, placed along the planned resection axis 1

Surgical Management

Surgery must achieve wide excision with negative margins (R0 resection), ideally ≥1 cm or to an intact fascial plane. 1

• All surgery should be performed by a sarcoma-trained surgeon within a specialist multidisciplinary team 1
• For inadvertent excisions with positive margins, re-excision of the surgical bed is strongly recommended if achievable with acceptable morbidity 1
• Seven of 11 patients in one series underwent nodal evaluation given the high nodal metastasis rate 2
• Amputation may be required in select cases, though limb-sparing surgery with adjuvant radiotherapy is preferred when oncologically sound 4

Adjuvant Radiotherapy

Adjuvant radiotherapy should be administered in the majority of epithelioid sarcoma cases given the high local recurrence rate (50-56%). 2, 4, 5

• Postoperative radiotherapy dose: 50-60 Gy in 1.8-2 Gy fractions, with boosts up to 66 Gy for close or positive margins 1
• One series using median dose of 68 Gy (range 50-84 Gy) achieved local control in 4 of 5 patients treated with surgery plus radiotherapy, with functional extremity preservation 4
• Radiotherapy combined with surgery achieves superior local control compared to surgery alone, though local recurrence rates remain elevated at 50-56% even with combined modality treatment 2, 4, 5
• Preoperative radiotherapy (50 Gy) is an alternative approach that may facilitate limb-sparing surgery 4

Systemic Therapy Considerations

For localized disease, the role of adjuvant chemotherapy remains unproven, as chemotherapy has not demonstrated impact on disease-free survival in epithelioid sarcoma. 2, 3

• Standard first-line chemotherapy for metastatic disease includes doxorubicin-based regimens or doxorubicin plus ifosfamide 1
• Tazemetostat (EZH2 inhibitor) represents a histology-specific targeted therapy option for advanced epithelioid sarcoma 1
• Eribulin may provide benefit in chemotherapy-refractory cases, with one case report demonstrating 13-month stable disease in cystic lung metastases 6
• Pazopanib and other multi-kinase inhibitors have activity in soft tissue sarcomas but lack epithelioid sarcoma-specific data 1

Follow-Up Protocol

Intensive surveillance is mandatory given the 50% local recurrence rate and 62.5% rate of pulmonary metastases. 2, 3

• History and physical examination every 3-6 months for the first 2-3 years, then annually 1
• Chest CT imaging every 3-4 months for 2-3 years (not just chest X-ray, given high pulmonary metastasis rate) 3
• MRI of the primary site every 6 months for 2-3 years, then annually 1
• Abdominal/pelvic imaging should be considered periodically given the propensity for peritoneal and hepatic metastases 1
• Continue surveillance beyond 5 years, as late recurrences occur 3

Critical Prognostic Factors and Pitfalls

The prognosis of epithelioid sarcoma is notably worse than other soft tissue sarcomas, with 5-year survival of only 25-65% and median survival of 31 months. 2, 3

• Pulmonary metastases correlate with significantly decreased survival 3
• Nodal involvement occurs in 50-62% of cases—far exceeding other sarcoma subtypes—and mandates regional nodal assessment 1, 2, 3
• Local recurrence develops in 50-56% of patients despite aggressive combined modality treatment 2, 5
• Delay in diagnosis is common and adversely affects outcomes—maintain high clinical suspicion for slow-growing masses in distal extremities of young adults 3
• The proximal/axial variant has worse prognosis than the classic distal extremity presentation 3

Multidisciplinary Team Approach

All treatment decisions must be made by a specialist sarcoma multidisciplinary team including surgical oncology, radiation oncology, medical oncology, pathology, and radiology expertise. 1