Approach Considerations
There are no contraindications for surgical treatment of synovial sarcoma (also referred to as synovial cell sarcoma), which is potentially life-saving. There is a relative contraindication for treating these patients in primary centers. Early referral to tertiary centers for definitive treatment must be preferred. Ideally, treatment should be performed by a multidisciplinary team with personnel experienced in the management of soft-tissue sarcomas.
Chemotherapy
Adjuvant chemotherapy and neoadjuvant chemotherapy have been proposed for patients with metastatic soft-tissue sarcomas. Although chemotherapy in the treatment of synovial sarcoma has been controversial, some studies have shown overall survival benefits in selected patients. [30]
Ladenstein et al reported improved survival rates with the use of adjuvant doxorubicin- and cyclophosphamide-based chemotherapy. [13] 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 (G-CSF) may stimulate the bone marrow. Chemotherapy should be considered in patients with extremity tumors larger than 5 cm. [1, 2, 3]
In a study that included 32 patients with advanced synovial sarcoma who had already been treated with first-line chemotherapy (ie, doxorubicin ± ifosfamide) and subsequently received second-line chemotherapy, Kojima et al compared several second-line regimens: doxorubicin ± ifosfamide, ifosfamide + etoposide, docetaxel + gemcitabine, pazopanib, trabectedin, and eribulin. [31] The rate of response to second-line therapy was poor, at 9.4%.
Some studies showed promising results in the treatment of synovial sarcoma xenografts with a murine monoclonal antibody. [32] This monoclonal antibody attacks a frizzled homologue called FZD10 (a cell-surface receptor), which is present in synovial sarcoma cells and absent in normal organs. Clinical applications of these monoclonal antibodies are not yet available. An additional innovative technique could be an SYT-SSX–derived peptide vaccine. [9]
The efficacy of chemotherapy as adjuvant treatment after surgery has been a controversial aspect of treatment of synovial sarcoma. Chemotherapy has not proved to provide a significant benefit in survival rates in all series. [33] However, a retrospective analysis of 271 patients with synovial sarcoma, of whom 41% received adjuvant chemotherapy, found that the 5-year metastasis-free survival (MFS) rate was 60% for those who were treated with chemotherapy and 48% for those who were not. [34] The authors recommended that patients with high-risk synovial sarcoma (tumors >5 cm) be the first to be considered for this type of treatment.
A multicenter clinical trial for the treatment of patients with soft-tissue sarcoma included patients with stage IV sarcomas and evaluated the clinical response to treatment with topotecan and carboplatin. Information is available on the clinical trial web site. [35]
Surgical Therapy
Surgical excision is still the cornerstone of treatment for synovial sarcoma. A tumor-free margin of 1-3 cm is recommended. [4] Maximal care must be taken to reduce the risk of local recurrence. Careful preoperative planning is essential. 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. [7] 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. [36]
Preparation for surgery
Because synovial sarcoma spreads along fascial planes, careful preoperative staging is crucial. Radiologic evaluation before treatment is very important. Imaging techniques employed in preoperative evaluation include radiography, magnetic resonance imaging (MRI), and computed tomography (CT).
Synovial sarcoma has the ability to metastasize via the lymphatic system. [15] Venous metastasis can occur as well. Synovial sarcoma is most likely to invade adjacent bone.
Preoperative radiation therapy (RT) is associated with an increased rate of wound problems. This neoadjuvant RT is sometimes proposed before surgery to reduce the size of the tumor.
Operative details
The ideal surgical approach to synovial sarcoma 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. [37]
Radiation Therapy
RT is usually required in addition to surgery, particularly if the margins are close to vital neurovascular structures. The most common form of RT in this setting is external-beam RT (EBRT) that is directed at the tumor site and that includes a margin of surrounding normal tissue. The timing of RT (ie, before or after surgery) has been debated. A study by Scheer et al found that preoperative RT was associated with greater local relapse-free survival in patients with advanced synovial sarcoma. [38]
The local radiation dose is usually 40-60 Gy. Proximity of vital neurologic structures, open physes, or an extreme peripheral location (hand or foot) can make EBRT potentially hazardous. Brachytherapy (radiation administered by a local implant) is an alternative consideration. [39] Intensity-modulated radiation therapy (IMRT) has also been proposed. [1]
Complications
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. Accordingly, it may be necessary to consider nerve grafting, later muscle transfers, or both in order to allow the wide margin required.
Long-Term Monitoring
Follow-up involves clinical examination, MRI of the surgical site, and CT of the chest. After surgical treatment, the authors recommend MRI, CT, and a 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 develops within the first 2 years, but late recurrence has been documented. [40]
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Lateral radiograph depicts a synovial sarcoma of the dorsum of the hand. A small nodule, present for 5 years, rapidly enlarged to the present size over 2 months.
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T1-weighted MRI depicts a synovial sarcoma of the dorsum of the hand. The tumor has low signal on T1 weighting.
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T2-weighted MRI depicts a synovial sarcoma of the dorsum of the hand. The tumor has a heterogeneous signal on T2 weighting, indicative of a variable growth pattern.
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Although synovial sarcoma typically has a biphasic histology, this disease is often monophasic (lacking glandular differentiation), which produces the picture of a small, round blue cell tumor.
