Recent research has focused on the role of immunotherapy and biomarkers in leiomyosarcoma (LMS), particularly in the context of advanced soft-tissue sarcomas. A phase II trial evaluated the efficacy of anti-PDL1 atezolizumab combined with stereotactic body radiation therapy (SBRT) in patients with advanced pretreated soft-tissue sarcoma. The study found that monocyte-lineage tumor infiltration could serve as a predictive biomarker for immunoradiotherapy response, highlighting the need for reliable biomarkers to identify patients who would benefit from such treatments (ref: Levy doi.org/10.1038/s41392-025-02173-3/). Furthermore, a large-scale multiomic analysis revealed that traditional immune checkpoint inhibitor (ICI) response biomarkers, such as PD-L1, did not vary significantly across different anatomic subtypes of LMS. Notably, uterine LMS (uLMS) was characterized as immune cold compared to non-uLMS, suggesting that the immunogenic potential varies by subtype and may influence treatment strategies (ref: Lagos doi.org/10.1158/1078-0432.CCR-24-2503/). Additionally, a prospective study on PSMA expression and PET/CT imaging in metastatic soft tissue sarcoma indicated that PSMA expression was heterogeneous, emphasizing the necessity for improved patient selection criteria for PSMA-targeted therapies (ref: Kleiburg doi.org/10.1007/s00259-025-07224-z/).

The efficacy of various chemotherapy regimens for advanced or metastatic leiomyosarcoma has been a significant focus of recent studies. A retrospective analysis at Stanford Medical Center compared first-line treatments, revealing that the doxorubicin combination therapy yielded the highest median progression-free survival (PFS) of 7.9 months, while doxorubicin alone provided the best median overall survival (OS) of 33.8 months (ref: Kim doi.org/10.3390/diseases13030079/). Additionally, the ISG-STS 1001 trial provided insights into the radiologic responses of high-risk soft-tissue sarcomas treated with neoadjuvant chemotherapy, comparing anthracycline plus ifosfamide to histology-tailored regimens. The findings indicated that the choice of chemotherapy could significantly impact radiologic responses, which are crucial for treatment planning (ref: Vanzulli doi.org/10.1016/j.esmoop.2025.104299/). Moreover, the potential of PARP inhibitors as targeted therapies for uterine LMS was explored, showing promising efficacy in patients with specific genetic profiles, thus opening avenues for personalized treatment approaches (ref: Rao doi.org/10.1200/PO-24-00765/).

Molecular and genomic profiling has emerged as a pivotal aspect of understanding leiomyosarcoma and other malignant mesenchymal tumors. A comprehensive genomic profiling study analyzed 94 malignant mesenchymal tumors, revealing insights into tumor mutational burden (TMB) and homologous recombination deficiency (HRD), which could guide therapeutic decisions (ref: Csepregi doi.org/10.3389/pore.2025.1612065/). The previously mentioned multiomic analysis of LMS subtypes further emphasized the importance of genomic characterization, as it demonstrated that traditional ICI response biomarkers did not differ significantly across anatomic subtypes, yet highlighted the immune cold nature of uLMS (ref: Lagos doi.org/10.1158/1078-0432.CCR-24-2503/). Additionally, an analysis of primary ovarian leiomyosarcoma indicated that surgical intervention remains the cornerstone of treatment, although the role of adjuvant therapies is still under investigation (ref: Ferraioli doi.org/10.1016/j.ijgc.2025.101692/).

Radiologic assessment plays a crucial role in evaluating treatment responses in sarcoma patients. The ISG-STS 1001 trial's secondary analysis provided valuable data on radiologic responses to neoadjuvant chemotherapy in high-risk soft-tissue sarcomas, indicating that the choice of chemotherapy significantly influences radiologic outcomes (ref: Vanzulli doi.org/10.1016/j.esmoop.2025.104299/). Furthermore, a study highlighted that low C-reactive protein (CRP) and high albumin levels were associated with poorer radiologic responses, suggesting that routine pre-treatment laboratory parameters could serve as prognostic indicators (ref: Berclaz doi.org/10.1186/s12885-025-13889-4/). Additionally, the phase II trial on immunoradiotherapy found that monocyte-lineage tumor infiltration could predict responses, underscoring the importance of integrating radiologic assessments with immunological markers to enhance treatment personalization (ref: Levy doi.org/10.1038/s41392-025-02173-3/).

Surgical management remains a cornerstone in the treatment of sarcomas, particularly in cases of primary ovarian leiomyosarcoma. A study by the French Sarcoma Group reported on 39 patients, emphasizing that surgery is essential for early-stage disease, although the role of adjuvant treatment remains uncertain (ref: Ferraioli doi.org/10.1016/j.ijgc.2025.101692/). Additionally, innovative approaches such as 3D reconstruction of resected tumor beds have been explored to enhance surgical planning and outcomes, demonstrating the potential for improved visualization in complex cases (ref: Mor doi.org/10.1111/ans.70089/). The differential diagnosis between benign and malignant neoplasms continues to challenge pathologists, indicating a need for ongoing research into molecular alterations that could aid in distinguishing between these entities (ref: de Almeida doi.org/10.3390/biomedicines13030560/).

Fertility-sparing management for uterine smooth muscle tumors of uncertain malignant potential (STUMP) has gained attention, with recent studies indicating that such approaches can be both feasible and safe for patients desiring future pregnancies. A multicenter retrospective study demonstrated positive reproductive and clinical outcomes, suggesting that fertility preservation strategies could be effectively implemented in this patient population (ref: Leone Roberti Maggiore doi.org/10.1093/hropen/). In parallel, the efficacy of PARP inhibitors in uterine LMS has been investigated, showing promising results for patients with specific genetic mutations, thus providing a dual approach to managing fertility and cancer treatment (ref: Rao doi.org/10.1200/PO-24-00765/). These findings highlight the importance of personalized treatment plans that consider both oncological and reproductive goals.

Diagnostic imaging plays a critical role in the management of sarcomas, with recent studies evaluating the effectiveness of various imaging modalities. A multi-institutional retrospective study assessed the diagnostic accuracy of contrast-enhanced computed tomography (CT) for distinguishing between benign and malignant colorectal mesenchymal tumors, finding that non-standardized contrast-enhanced CT was ineffective in making this distinction (ref: Bourgeois doi.org/10.1111/vco.13047/). Additionally, a prospective study on PSMA PET/CT imaging in metastatic soft tissue sarcoma patients revealed highly heterogeneous PSMA expression, suggesting that further exploration of PSMA-targeted therapies could be beneficial (ref: Kleiburg doi.org/10.1007/s00259-025-07224-z/). These studies underscore the need for continued advancements in imaging techniques to improve diagnostic accuracy and treatment planning in sarcoma patients.