Uterine leiomyosarcoma (uLMS) is a rare tumor with a high risk of recurrence and poor prognosis. Despite this, some patients experience no disease recurrence and longer overall survival compared to other patients with the same diagnosis. There have been few studies evaluating the association of patient and tumor characteristics with clinical outcomes and overall survival. Additionally, studies are scarce that evaluate the molecular composition of uterine leiomyosarcomas and potential associations between somatic mutations and clinical outcomes. The objective of this study is to determine the relationship between patient and tumor characteristics, including somatic mutations, clinical courses, and survival in patients diagnosed with uLMS.

An IRB-approved retrospective chart review of patients diagnosed with uLMS at any stage from January 2006 to September 2024 at a single institution was performed. Patient demographics, tumor characteristics, clinical characteristics, and treatments received were analyzed. Overall survival (OS) was evaluated using the Kaplan Meier method. Log-rank tests were used to determine the presence of statistically significant differences between the survival of groups. Descriptive statistics of the demographics, oncologic characteristics, and treatments were used to summarize data. Next generation sequencing (NGS) data was obtained from two databases, Foundation Medicine and Caris Life Sciences.

56 patients met inclusion criteria for this study. The median age of the patient population at diagnosis was 54 years (48-61 yrs). Of these patients, 66.1% were Caucasian. 12.5% were African American. 3.6% were Hispanic. 17.9% were of another race. 24 patients (42.9%) were Stage I at diagnosis. 20 patients (35.7%) were Stage IV at diagnosis. Median OS of the patient population was 68 months (35.1-124). Patients were divided into cohorts of short-term survivors and long-term survivors. Short-term survival was defined as survival < 1 year. Long-term survival was defined as survival > 1 year. 16 patients (28.6%) were short-term survivors. 40 patients (71.4%) were long-term survivors. Median overall survival (OS) in the short-term survivor population was 8.51 months, while median overall survival in the long-term survivor population was 86 months.

19 patients (33.9%) of the total patient population had foundation testing performed on tumor specimens. TP53 was the most common mutation present, followed by ATRX and RB1. None of the mutations identified were associated with short- or long-term survival.

Short-term survivors and long-term survivors were analyzed to determine factors associated with survival. Stage at diagnosis was significantly associated with survival with 62.5% of short-term survivors being stage IV at diagnosis compared to just 25% of long-term survivors (p-value <0.001). Having undergone more than 1 line of therapy was associated with improved survival (p-value 0.019) as was having surgery at time of diagnosis (p-value 0.020). Residual disease after surgery, defined as > 1 cm, was associated with worse survival (p-value 0.007). ER/PR receptor status, patient race, and tobacco use did not correlate with overall survival.

Uterine leiomyosarcoma is a devastating cancer that has not seen an overall improved survival rate despite years of study. One possible barrier to this is the overall rarity of this malignancy. However, the overall poor prognosis of uterine leiomyosarcoma highlights the importance of studying patient and tumor characteristics to determine if any associations exist between these and overall survival. The prognostic factors associated with improved survival in our study suggest that upfront surgery with no residual disease left improves overall survival. Additionally, gynecologic cancer treatment has evolved to include many targeted therapies based on tumor genetics. However, treatment of uterine leiomyosarcomas has not followed this trend. The somatic mutations found in our study are similar to what has been previously reported about uterine leiomyosarcomas. While our study did not find an association of any of these mutations with disease progression or disease recurrence, future studies are needed with larger sample sizes to further assess if there is a relationship of certain tumor characteristics with overall survival and if certain therapies could target tumor mutations to decrease disease progression.