Introduction: Primary thoracic synovial sarcoma (PTSS) is a rare malignancy presenting with varying clinical manifestations. There is a paucity of data with few studies dedicated to this unique subset of neoplasms. We present our findings from one of the largest real-world studies among patients with PTSS.

Methods: This is a single-centre, real-world study in patients with PTSS included between 2017 and 2023. Survival estimates were obtained by the Kaplan-Meier method and Cox regression analysis.

Results: 24 patients with a median age of 34.5 years (range 16–54) presented with chest pain (n = 11, 45.8%) and dyspnea (n = 10, 41.6%). Predominant primary sites of disease were the lung (n = 12, 50%) and mediastinum (n = 6, 25%). The stage at presentation was unresectable locally advanced (n = 10, 41.6%), localised (n = 8, 33.3%) and metastatic (n = 6, 25%) with pulmonary metastases (n = 10, 62.5%) and pleural effusion (n = 4, 25%). 16 (66.6%) patients underwent surgical resection including 7 (43.8%) who received neoadjuvant chemotherapy (NACT). NACT was given in ten patients producing stable disease in 5 (50%) and partial response in 3 (30%) patients, respectively, with surgery performed in 7 (70%). 11 (62.5%) operated patients had a microscopically complete resection and 10 (41.6%) received postoperative radiotherapy. Anthracyclines were given in 23 (95.8%) patients in the first line, while pazopanib was the most common therapy in the second and third lines, respectively. At a median follow-up of 32 months (range 16.7–47.2), the median overall survival (OS) was 41 months (95% CI: 23.7–58.2) and 8 months (95% CI: 1–25.6) overall and in metastatic disease, respectively. Presentation with metastases (p = 0.01) and treatment with surgical resection (p = 0.005) were significantly associated with OS on univariate analysis.

Interpretation: The locally advanced nature of the disease at presentation signifies the need for early diagnosis and technically superior definitive therapies. The survival outcomes for metastatic disease remain poor and the need for novel therapies for advanced disease remains unmet so far.

Clinical trial registration: Not applicable