Systemic management of spinal metastases: current strategies and future directions.

Bones are a common dissemination site in prostate, breast, lung, and renal cancers. Bone metastases are associated with significant morbidity and reduced overall survival. The spine is the most frequently involved site, where metastases can lead to skeletal-related events (SREs) such as pain, pathological fractures, and spinal cord compression. Management of spinal metastases (SM) relies on a multidisciplinary approach combining local treatments (surgery, radiotherapy, interventional procedures) and systemic therapies. Bone-targeting agents, including bisphosphonates and denosumab, have demonstrated efficacy in reducing SRE incidence, although their use remains suboptimal in clinical practice. Conventional systemic therapies such as chemotherapy and endocrine therapy may negatively impact bone health and show limited efficacy in controlling SM. Immune checkpoint inhibitors have transformed the treatment landscape of several metastatic cancers, yet their activity in bone metastases appears reduced, likely due to the specific bone microenvironment. Targeted therapies represent the most promising systemic approach, with variable but sometimes significant activity in SM depending on tumor type and molecular profile. Optimal management of SM requires individualized, multidisciplinary strategies to optimize systemic disease control, local tumor management, and prevention of SREs.