Higher Negative Margin Rates with Intraoperative Ultrasound-Guided Excision for Myxofibrosarcoma: A Single-Center Cohort Study with External Comparisons.

Background/Objectives: Myxofibrosarcoma (MFS) shows infiltrative fascial extensions that complicate margin achievement and drive local recurrence. We evaluated whether intraoperative ultrasound guidance improves negative margin achievement and oncological outcomes compared with conventional excision. Methods: In this retrospective cohort study at a single tertiary referral center, patients with MFS underwent conventional excision (2008-2013; n = 15) or ultrasound-guided excision (2014-2024; n = 50; primary comparative analysis n = 47 after excluding three patients). The primary outcome was negative margin achievement; secondary outcomes were overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). Exploratory matching-adjusted indirect comparisons (MAICs) were performed against seven published international MFS cohorts. Results: Overall R0 (negative) margin rates did not differ between cohorts (97.9% vs. 93.3%; p = 0.428). Among R0 margins, however, a wide clearance (R0-wide, ≥1 mm) was more frequent in the US-guided cohort, whereas R0-close (<1 mm) margins predominated after conventional excision (R0-wide 83.0% vs. 46.7%; odds ratio 5.38, 95% CI 1.30-23.73; p = 0.014). Median follow-up was 49 months; five-year OS, LRFS, and DMFS were 97.5%, 94.3%, and 83.7%. In the internal historical comparison, LRFS was directionally higher with ultrasound guidance (94.3% vs. 68.2%; HR 0.26; p = 0.059). In MAICs, LRFS favored the US-guided cohort in all five comparisons and OS in two of four. Conclusions: Intraoperative ultrasound guidance was associated with a higher rate of wide (R0-wide, ≥1 mm) negative margins and favorable local disease control in MFS; whether wider microscopic clearance itself improves local control requires prospective multicenter evaluation.