Current status and future directions of systemic therapy in high-grade bone sarcomas

Chemotherapy combined with radical surgery is the gold standard treatment for high-grade bone sarcomas. The number of cured patients has remained unchanged over the past decades. Approximately 30% of patients with stage IIB tumors, 70% with stage IIIB tumors, and more than 80% of recurrent bone sarcomas are resistant to currently used chemotherapy regimens and ultimately die from the disease. Currently available targeted therapies, mainly multiple tyrosine kinase inhibitors, are not curative, but a significant proportion of patients with advanced sarcomas achieve disease stabilization. This opens up the possibility of combining local and systemic treatments to consolidate clinical response, reduce tumor burden, and prolong progression-free interval. The optimal combination of systemic and local treatment methods (surgery, radiation therapy, radiosurgery) makes it possible to impact metastatic lesions, transforming an advanced tumor process into a chronic disease in responding patients. Early detection of relapse may improve the effectiveness of systemic treatment due to low tumor burden and lack of established resistance mechanisms. Future directions in the field of advanced sarcoma include the development of personalized treatment approaches and further studies of tumor biology based on “omics” technologies.