Clinical Heterogeneity and Survival Disparities in Leiomyosarcoma: An Exploratory Single-Center Retrospective Observational Study

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Background: Leiomyosarcoma (LMS) is a rare aggressive sarcoma with substantial heterogeneity in anatomical presentation, stage, treatment, and survival. We evaluated clinical characteristics, treatment patterns, and survival, with particular emphasis on whether anatomical site independently predicted overall survival (OS). Methods: We retrospectively reviewed 240 adults with histologically confirmed LMS diagnosed between January 2015 and May 2026. OS was calculated from diagnosis to death or last contact, with administrative censoring on 1 July 2026. Kaplan–Meier and Cox proportional-hazards methods were used to evaluate age, sex, anatomical site, histologic grade, and disease stage. Multivariable models adjusted for age, sex, grade, and stage assessed the independent association of anatomical site with OS. Results: Median age was 56 years, and 152 patients (63.3%) were female. Disease was localized in 120 (50.0%), de novo metastatic in 53 (22.1%), recurrent metastatic in 35 (14.6%), and recurrent localized in 12 (5.0%). Median OS was 37.0 months. Localized disease was associated with substantially longer OS than metastatic disease (61.0 vs. 13.0 months; p < 0.001). Grade 3 disease was associated with shorter OS than grade 1/2 disease (25.6 vs. 61.1 months; p < 0.001). In multivariable analyses, metastatic disease remained strongly associated with inferior OS (HR, 5.59–5.94; p < 0.001), as did age ≥ 50 years (HR, 1.86–1.92; p = 0.006–0.004) and grade 3 histology (HR, 1.74–1.92; p = 0.018–0.007). Anatomical site was not independently associated with OS (extremity/trunk vs. non-extremity: HR, 1.60; p = 0.063; non-uterine vs. uterine: HR, 1.23; p = 0.41). Conclusions: Disease stage was the strongest prognostic factor, while older age and grade 3 histology were independently associated with poorer OS. Although extremity/trunk LMS showed better univariable survival, anatomical site was not independently associated with OS after adjustment.