Background: Undifferentiated pleomorphic sarcomas are a frequent subtype within the heterogeneous group of soft tissue sarcomas. As the attainment of negative margins can be complicated at the extremities, we determined the prognostic significance of surgical margins in our patient population. Methods: We retrospectively determined the relationship between local recurrence-free survival (LRFS), overall survival (OS), and potential prognostic factors in 192 patients with UPS of the extremities who were suitable for surgical treatment in curative intent. The median follow-up time was 5.1 years. Results: The rates of LRFS and OS after 2 years were 75.7% and 87.2% in patients with R0-resected primary tumors and 49.1% and 81.8% in patients with R1/R2-status (LRFS: p = 0.013; OS: p = 0.001). Adjuvant radiotherapy significantly improved LRFS (5-year: 67.6% vs. 48.4%; p < 0.001) and OS (5-year: 82.8 vs. 61.8; p = 0.016). Both, negative margins and adjuvant radiotherapy were found to be independent prognostic factors in multivariate analysis. Conclusions: The data from this study could underscore the beneficial prognostic impact of negative margins on LRFS and OS. However, the width of negative margins seemed to be not relevant. Notably, adjuvant radiotherapy was not only able to decrease the risk of local failure but also improved OS in a significant manner.

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