Neoadjuvant Chemotherapy Is Associated With Reduced Amputation Risk in Synovial Sarcoma of the Lower Extremity.

Background And Objectives: The combination of radiation and surgical resection represents the current standard of care for primary synovial sarcoma (SS). However, controversy remains regarding the role of chemotherapy. We sought to evaluate the impact of neoadjuvant chemotherapy on the likelihood of undergoing amputation for patients with lower extremity SS.

Methods: We identified all adults (≥ 18 years) diagnosed with nonmetastatic SS of the lower extremity who underwent definitive resection within the 2004-2021 National Cancer Database. Multivariable models were developed to assess the independent association of neoadjuvant chemotherapy with likelihood of amputation versus limb salvage. We secondarily considered the independent association of neoadjuvant treatment or amputation with overall survival at 5 years.

Results: Of 1207 patients, 376 (31%) received neoadjuvant chemotherapy. Patients who received neoadjuvant treatment were younger and more commonly presented with Stage III disease. Following comprehensive adjustment for patient, disease, and hospital factors, receipt of neoadjuvant chemotherapy was linked with significantly reduced likelihood of amputation (AOR 0.47, CI 0.27-0.84). Upon risk-adjusted survival analysis, receipt of neoadjuvant therapy was linked with similar outcomes, but amputation was associated with significantly greater mortality hazard over 5 years following resection (HR 1.75, CI 1.30-2.35).

Conclusions: In this national registry study, receipt of neoadjuvant chemotherapy was associated with significantly reduced odds of amputation. Amputation was linked with significantly greater mortality over 5 years while neoadjuvant chemotherapy did not improve 5-year overall survival.