Circulating tumor DNA for disease monitoring in bone sarcomas: clinical applications, challenges, and future perspectives

Bone sarcomas (BSs) are rare, biologically heterogeneous malignancies for which disease recurrence and metastatic progression remain major determinants of poor patient outcomes. Therefore, reliable tools to aid the assessment of response to treatment, the detection of molecular residual disease (MRD) and the timely identification of disease recurrence are essential but still limited to conventional imaging and tissue-based approaches. Circulating tumor DNA (ctDNA), a tumor-derived fraction of cell-free DNA detectable through liquid biopsy (LB), has emerged as a promising non-invasive biomarker capable of capturing dynamic molecular changes throughout the course of the disease. Increasing evidence supports its potential for postoperative surveillance, early relapse detection, response assessment and longitudinal monitoring. Nevertheless, several biological and technical barriers, including low ctDNA abundance, genomic heterogeneity among BS subtypes, and the lack of standardized analytical workflows continue to hinder widespread clinical implementation. This mini review provides an overview of the current landscape of ctDNA applications for MRD detection and disease monitoring in BSs, examines the key challenges to its clinical adoption, explores technological advances and outlines ongoing clinical studies that are expected to shape its future role in patient management.