Local Recurrence and Metastasis Define Distinct Recurrence Phenotypes in Soft Tissue Sarcoma.

Background: Soft tissue sarcomas (STS) are clinically heterogeneous, yet local recurrence (LR) and metastasis are typically analyzed as separate endpoints. We aimed to determine whether recurrence in STS is better understood as distinct phenotypes defined by the interaction between local and metastatic disease. Methods: A total of 668 patients with histologically confirmed STS from two tertiary sarcoma centers were analyzed using prospective registry data (2018-2025). Patients were stratified into four predefined recurrence phenotypes: no event, metastasis only, LR only, and combined LR and metastasis. Tumor characteristics, treatment variables, surgical factors, recurrence timing, and event sequence were analyzed across groups. Results: Phenotypes were distributed as follows: no event (52.2%), metastasis only (23.8%), LR only (13.5%), and combined recurrence (10.5%). High-grade tumors (G3) were more frequent in metastasis-only (73.0%) and combined phenotypes (65.7%) than in LR only (38.9%) and no event (28.9%) (p < 0.001). Early LR (≤365 days) occurred substantially more often in the combined phenotype (51.4%) than in isolated LR (17.8%), whereas late LR predominated in isolated cases (82.2% vs. 48.6%) (p < 0.001). Among patients with LR, high grade (OR 2.79, 95% CI 1.42-5.49) and axial location (OR 2.28, 95% CI 1.17-4.47) were independently associated with combined recurrence. In the combined phenotype, metastasis preceded LR in 40.0%, LR preceded metastasis in 34.3%, and events were synchronous in 25.7%. Conclusions: Recurrence in STS comprises distinct phenotypes defined by the interaction of local and metastatic disease. In particular, the clinical significance of local recurrence depends on its metastatic context.