Abstract
Background/Objectives: The prognostic associations of tumor genomics and metastatic patterns remain incompletely defined in leiomyosarcoma (LMS). We investigated the association between tumor mutations, sites of metastasis, and survival in patients with LMS. Methods: This single-center retrospective cohort study evaluated 110 patients with biopsy-proven LMS who underwent genomic testing between January 2009 and May 2023. Associations between tumor mutations, metastatic sites, and uterine vs. non-uterine LMS were assessed using χ2 or Fisher’s exact test. Progression-free survival/recurrence-free survival (PFS/RFS) and overall survival (OS) were estimated with the Kaplan–Meier method and compared using the log-rank test, and subsequent Cox proportional hazards regression examined associations of OS and PFS/RFS with tumor mutations and metastatic sites. Results: The study included 110 subjects (F/M: 81/29; median age, 57 years; 25/110 with metastatic disease). Overall, the most common mutations were in TP53 (74/110, 67%) and RB1 (24/110, 22%), and the most common metastatic sites were the lungs (79/99, 80%) and liver (37/99, 37%). In terms of metastatic patterns, peritoneal (24/50, 48%), pelvic (23/50, 46%), and pleural (9/50, 18%) metastases were more common in the uLMS group (p = 0.001, 0.01, and 0.04, respectively), whereas liver (27/60, 45%) and retroperitoneal (15/60, 25%) metastases were more common in the nuLMS group (p = 0.03 and 0.04, respectively). ATRX mutations (17/110, 15%) and pleural metastases (11/99, 11%) were independently associated with lower OS. Predictive survival models were generated, demonstrating variable interdependent associations between genomic alterations, metastatic sites, and outcomes (OS and PFS/RFS). Post hoc analysis of an independent cohort (N = 2606) demonstrated that ATRX mutations were similarly associated with lower OS (28.95 vs. 33.86 months; p = 0.006). Conclusions: Our study identifies differences in metastatic patterns between uterine and non-uterine LMS and highlights the adverse prognostic association of ATRX mutations and pleural metastases in a leiomyosarcoma-specific cohort.
