Subtype-Specific Prognosis, Recurrence Patterns, and Molecular Features in 148 Chinese Uterine Sarcomas: A Real-World Study

Background: Uterine sarcomas are rare, heterogeneous malignancies with distinct pathological behaviors. This study aimed to identify clinicopathological characteristics, prognostic risk factors, and potential therapeutic targets to enhance clinical management. Methods: A retrospective analysis was conducted on 148 patients with uterine sarcoma treated at Peking University People’s Hospital between 1996 and 2025. Clinical outcomes, pathological subtypes, and immunohistochemical profiles were assessed. Additionally, bioinformatics analyses from RNA bulk sequencing of GEO datasets (GSE87581, GSE85383, GSE222045 and GSE64763) were performed to elucidate molecular characteristics across subtypes. Results: The most prevalent subtypes were uterine leiomyosarcoma (uLMS; 38.5%) and low-grade endometrial stromal sarcoma (LG-ESS; 29.7%). The 5-year recurrence rate was 50.5%, with frequent metastases to the pelvis and lungs. LG-ESS demonstrated the most favorable 5-year survival rate (90.3%), significantly higher than that of uLMS (61.8%) and undifferentiated uterine sarcoma (50.0%). Multivariate analysis identified histological subtype, stage, and coagulative necrosis as independent prognostic factors for overall and progression-free survival. Transcriptomic profiling revealed immunosuppression (CSF1R/CSF3R expression) in high-grade ESS, while uLMS exhibited activation of cell cycle and homologous recombination pathways. Conclusions: Histological subtype, stage, and coagulative necrosis were critical prognostic factors in uterine sarcoma. The findings suggest that vigilant pulmonary surveillance and further investigation into tailored therapeutic strategies may be warranted-including endocrine therapy for hormone-receptor-positive tumors, immunotherapy for high-grade ESS, and PARP inhibitors for uLMS. However, these hypotheses require thorough preclinical and clinical validation. Additionally, caution should be exercised to avoid overtreatment of chemotherapy in early-stage uLMS.