Risk Factors for Local Recurrence and Metastasis in Soft Tissue Sarcomas of the Extremity

Objectives: We reviewed our institution's experience in treating soft tissue sarcomas of the extremity to identify factors associated with local recurrence, metastasis, and overall survival, to identify patients who may benefit from intensification of therapy. Methods: A retrospective analysis was performed for patients who underwent both limb-sparing surgery and external beam radiotherapy for extremity sarcoma. Those who had gross residual disease or who presented with recurrent or metastatic disease were excluded. The Kaplan-Meier product limit and multivariate Cox regression were used to estimate local failure-free probability, distant failure-free probability, and overall survival along with associations with patient, tumor, and treatment characteristics. Results: One hundred eighty-eight patients were included in the analysis. Twenty-five (13%) and 46 (24%) experienced local and distant recurrence, respectively. Patients with high/intermediate-grade tumors [hazard ratio (HR) = 5.63, 95% confidence interval (CI): 1.27-24.89, P = 0.023] or with multifocally positive margins (HR = 4.27, 95% CI: 1.20-15.24, P = 0.026) were more likely to fail locally. Those with a preceding local recurrence (HR = 8.58, 95% CI: 3.87-19.04, P < 0.0001), high/intermediate-grade tumors (HR = 5.68, 95% CI: 1.28-25.25, P = 0.023), or no secondary reexcision (HR = 2.5, 95% CI: 1.09-5.74, P = 0.031) were more likely to develop metastasis. Patients with local recurrence (HR = 3.6, 95% CI: 1.77-7.29, P < 0.001), metastasis (HR = 16.0, 95% CI: 7.93-32.31, P < 0.0001), or without secondary reexcision (HR = 3.2, 95% CI: 1.27-8.09, P = 0.014) had decreased overall survival. Conclusions: Patients whose tumor grade or margin status put them at high risk for local failure should be considered for intensification of therapy. Those with a local recurrence should be considered for increased surveillance or systemic therapy, as local failure is associated with subsequent metastasis and decreased survival.