Advances in uterine sarcoma management: A mini-review of clinical practice and molecular insights

Uterine sarcomas are rare, biologically heterogeneous mesenchymal malignancies with the poorest survival among uterine cancers. Management has historically been extrapolated from soft tissue sarcomas, but these tumors are increasingly recognized as histologically and molecularly distinct diseases. This review summarizes current understanding of the diagnosis, classification, and management of uterine leiomyosarcoma, low- and high-grade endometrial stromal sarcoma, undifferentiated uterine sarcoma, and adenosarcoma, and discusses emerging molecular and therapeutic advances. Preoperative diagnosis remains challenging, and diffusion-weighted magnetic resonance imaging, immunohistochemistry, and next-generation sequencing have improved diagnostic accuracy and identification of actionable molecular alterations. Complete surgical resection remains the standard for localized disease, with the extent of surgical staging guided by histologic subtype and hormone receptor status. Adjuvant radiation and chemotherapy show limited survival benefit overall, though select high-grade tumors may benefit from doxorubicin-based regimens. For advanced or recurrent leiomyosarcoma, combination doxorubicin plus trabectedin has become a new first-line standard, and targeted agents such as pazopanib, cabozantinib with temozolomide, and PARP inhibitors in BRCA-altered tumors have expanded treatment options. Endocrine therapy remains central to management of low-grade endometrial stromal sarcoma, while immune checkpoint inhibitors have shown limited efficacy outside of rare microsatellite instability-high tumors. Emerging tools such as circulating tumor DNA are being explored to improve surveillance and early detection of recurrence. Continued progress in histology-specific and molecularly stratified clinical trials will be essential to further refine risk-adapted, biomarker-driven treatment strategies and improve outcomes for patients with uterine sarcoma.