Vascular Invasion and Survival in Extremity Leiomyosarcoma: An Exploratory Single-Center Cohort Study from the Oxford Sarcoma Service.

Abstract

Background/objectives: Extremity leiomyosarcoma is an uncommon soft tissue sarcoma with a more favorable prognosis than other anatomical subtypes. Risk stratification currently rests on tumor grade, size, and metastatic status. Vascular invasion is an established predictor of metastasis in mixed soft tissue sarcoma cohorts but has seldom been formally examined in extremity leiomyosarcoma. We assessed its prognostic value in a single-center cohort.

Methods: We retrospectively studied 62 adults who underwent resection of primary localized extremity leiomyosarcoma at a tertiary sarcoma center between January 2015 and February 2025. Vascular invasion was reported contemporaneously at original diagnostic reporting by specialist sarcoma histopathologists. Overall (OS), disease-specific (DSS), local recurrence-free (LRFS), and metastasis-free (MFS) survival were estimated by the Kaplan-Meier method and compared using log-rank tests. Death from another cause was treated as a competing event for disease-specific death and distant metastasis in a sensitivity analysis. Multivariable Cox models were refitted using Firth's penalized likelihood, with discrimination corrected for optimism by bootstrapping.

Results: Median follow-up was 59.5 months. Five-year OS, DSS, and MFS were 71.0%, 80.2%, and 74.6%. Vascular invasion was reported in 11 of 62 patients (17.7%) and was associated with inferior OS (p = 0.002), DSS (p < 0.001), and MFS (p < 0.001), but not LRFS (p = 0.631). Adjusted for grade, it was associated with inferior OS (HR 3.89, 95% CI 1.35-11.26), DSS (HR 5.48, 95% CI 1.46-20.58), and MFS (HR 5.63, 95% CI 1.69-18.80). The association persisted on separate adjustment for tumor size, depth, and neoadjuvant radiotherapy.

Conclusions: Vascular invasion was associated with inferior survival in localized extremity leiomyosarcoma. With 17 deaths and 14 metastatic events, these are exploratory estimates, but they support documenting vascular invasion explicitly, as present or absent, in routine histopathological reporting so that its role can be evaluated at scale.