Uterine Sarcomas: Clinical Management and a Review of Systemic Therapy

IMPORTANCE: Uterine sarcomas are rare but aggressive tumors with high rates of recurrence and limited effective treatment options; a deeper understanding of their molecular and histologic diversity is critical to improving outcomes. OBJECTIVE: To provide a comprehensive overview of clinical management and current systemic treatment strategies for uterine sarcomas. Specific histologic subtypes and molecular features are also reviewed. EVIDENCE ACQUISITION: A thorough review of the literature was conducted using PubMed and clinical trial databases, with a focus on recent studies evaluating histology-specific management, molecular diagnostics, and novel systemic therapies across uterine sarcoma subtypes. RESULTS: Uterine sarcomas comprise 3% to 5% of uterine malignancies and include multiple distinct subtypes such as leiomyosarcoma, low and high-grade endometrial stromal sarcoma, undifferentiated uterine sarcoma, and adenosarcoma. Each displays unique clinical behavior and molecular alterations that guide treatment. While surgery remains the foundation of management for early-stage disease, the role of adjuvant therapy is unclear and best guided by individual risk. In advanced disease, combination regimens such as doxorubicin and trabectedin have shown improved outcomes in the treatment of leiomyosarcomas. Targeted therapies, hormonal agents, and immunotherapy have variable activity across subtypes. Molecular diagnostics, including next-generation sequencing, are increasingly essential in diagnosis, prognostication, and treatment planning. CONCLUSIONS AND RELEVANCE: The landscape of uterine sarcoma treatment is rapidly evolving due to advances in molecular biology and emerging systemic therapies. Personalized management based on histology and molecular profiling, along with the development of subtype-specific clinical trials, will be essential in improving survival. Centralized, multidisciplinary care remains a cornerstone for patients with these rare tumors.