Synovial Cell Sarcoma Treatment & Management

Adjuvant chemotherapy and neoadjuvant chemotherapy have been proposed for patients with metastatic soft tissue sarcomas. Nevertheless, chemotherapy in the treatment of this sarcoma remains controversial. Ladenstein et al have reported improved survival rates with the use of adjuvant doxorubicin- and cyclophosphamide-based chemotherapy. Other authors have recommended combinations of doxorubicin (75 mg/m² via continuous infusion over 3 days) and bolus ifosfamide (2.5 g/m² daily for 4 days, or ifosfamide with liposomal daunorubicin). Granulocyte colony-stimulating factor may stimulate the bone marrow. Chemotherapy should be considered in patients with extremity tumors greater than 5 cm.^{[1, 2, 3, 7]}

Some studies have shown promising results in the treatment of synovial cell sarcoma xenografts with a murine monoclonal antibody.^[21] This monoclonal antibody attacks a frizzled homologue called FZD10 (a cell-surface receptor), which is present in the synovial sarcoma cells and absent in the normal organs. Clinical applications of these monoclonal antibodies are not still available. An additional innovative technique could be a SYT-SSX–derived peptide vaccine.^[12]

Another controversial aspect of treatment of synovial cell sarcoma is the efficacy of chemotherapy as adjuvant treatment after surgery. Chemotherapy has not proved to provide a significant benefit in survival rates in all series. A multicenter clinical trial for the treatment of patients with soft tissue sarcoma includes patients with soft tissue sarcoma stage IV and evaluates the clinical response of a treatment with topotecan and carboplatin. Information is available on the clinical trial web site.

Surgical excision is still the cornerstone of treatment for synovial cell sarcoma. A tumor-free margin of 1–3 cm is recommended.^[4] Maximal care must be taken to reduce the risk of local recurrence. As the tumor extends along fascial planes, careful preoperative planning with MRI is necessary before embarking on a wide excision. Because of the tumor's predilection for the popliteal fossa, limb salvage may not be possible because of the proximity of the neurovascular structures. Even with microscopically negative margins, patients could develop local recurrence. Rare local recurrence has been reported 15 years after the initial treatment.^[10] Surgical resection of isolated metastases may be possible if the tumor is well controlled. Palliative surgery may also be appropriate, particularly to alleviate pain or achieve hemorrhage control.^[22]

Staging prior to surgery is essential, as synovial cell sarcoma spreads along fascial planes. Radiologic evaluation before treatment is very important. Imaging techniques employed in preoperative evaluation include radiographs, MRI, and CT scans.

Synovial cell sarcoma has the ability to metastasize via the lymphatic system.^[23] Venous metastasis can occur as well. Synovial sarcoma is most likely to invade adjacent bone.

Preoperative radiation therapy is associated with an increased rate of wound problems. This neoadjuvant radiotherapy is sometimes proposed before surgery to reduce the size of the tumor.

The ideal surgical approach takes into account the location of the lesion and must always include the possibility of amputation in cases of unsuccessful total resection. Thus, a radical or wide resection is indicated, depending on the location of the tumor. The mass may be tagged so that the location of any close or contaminated margins can be identified. A primary amputation is proposed if the location and extension of the tumor do not provide adequate function of the extremity. Primary amputation is required in 20% of patients.^[1] Vascular resection and reconstruction are most often performed in the lower extremities.^[24]

Postoperative radiation therapy is usually required, particularly if the margins are close to vital neurovascular structures. The most common radiotherapy is external-beam radiation directed at the tumor site, including a margin of surrounding normal tissue. The decision about the timing of radiation therapy (ie, before or after surgery) is controversial.

Local radiation is usually 40-60 Gy. Vital neurologic structures, open physes, or an extreme peripheral location (hand or foot) can make external-beam radiation therapy potentially hazardous. Brachytherapy (radiation administered by a local implant) is an alternative consideration.^[25] Intensity-modulated radiation therapy (IMRT) has also been proposed.^[1]

Follow-up involves clinical examination, MRI of the surgical site, and CT scan of the chest. After surgical treatment, the authors recommend an MRI, a CT scan, and patient review every 3-6 months for the first 2 years and then every 6 months for the next 3 years. Most recurrent metastatic disease occurs within the first 2 years, but late recurrence has been documented.^[26]

The surgical complications are related to the site involved but include the general complications of wound infection, wound breakdown, neurologic or vascular injury, and hematoma or seroma formation.

Specific complications associated with this tumor are local recurrence and distant metastases. The risk of local recurrence is directly proportional to the adequacy of surgical clearance. Therefore, a wide excision is mandatory to reduce this risk. Essential neurologic structures may make a wide clearance impossible, especially in the popliteal fossa. Nerve grafting and/or later muscle transfers may need to be considered to allow the wide margin needed.

Synovial cell sarcoma has been reported to be a particularly metastasizing tumor.^[27] Many factors modify patient outcome,^{[11, 23, 28, 14]} such as tumor size, anatomic localization, and histologic grade. Nevertheless, histologic criteria such as nuclear grade, measures of mitotic count, and amount of necrosis are subjective and sometimes difficult to compare. Synovial cell sarcoma has survival rates of 50-60% at 5 years and 40-50% at 10 years. However, advances in oncologic therapy, particularly the development of monoclonal antibodies, may improve survival rates (see Future and Controversies).

A slight improvement in survival rate has been reported with the use of chemotherapy as adjuvant therapy.^{[7, 2, 3]} Recurrence has been reported up to 69 months after treatment and suggests a worse prognosis with low survival rates. Distant metastases at presentation suggests a bad prognosis (2-year survival rate of 25%)

Prognostic factors that correlate with a better prognosis have been described^[29] and include the following:

• Biphasic histologic pattern
• Patients with SYT/SSX2 fusion genes
• Location in the hand or foot
• Size < 5 cm
• Female sex
• Age < 50 years
• Negative resection margins

Some studies have shown promising results in the treatment of synovial cell sarcoma xenografts with a murine monoclonal antibody.^[21] This monoclonal antibody attacks a frizzled homologue called FZD10 (a cell-surface receptor), which is present in the synovial sarcoma cells and absent in the normal organs. Clinical applications of these monoclonal antibodies are not still available. An additional innovative technique could be a SYT-SSX – derived peptide vaccine.^[12]

Another controversial aspect of treatment of synovial cell sarcoma is the efficacy of chemotherapy as adjuvant treatment after surgery. Chemotherapy has not proved to provide a significant benefit in survival rates in all series. A multicenter clinical trial for the treatment of patients with soft tissue sarcoma includes patients with soft tissue sarcoma stage IV and evaluates the clinical response of a treatment with topotecan and carboplatin. Information is available on the clinical trial web site.