Circulating cell-free DNA and circulating tumor DNA as a prognostic biomarker in metastatic spine disease, is there a role?

Metastatic spine disease (MSD) impacts patient survival, yet existing prognostic scoring models lack robustness in predicting survival. Circulating cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) have emerged as promising non-invasive tumor-derived biomarkers reflecting disease burden and prognosis. However, its role in MSD remains underexplored. We aimed to review the utility of cfDNA and ctDNA in predicting treatment response, disease progression and survival in cancers commonly metastasizing to the spine, focusing on its potential application in MSD. A comprehensive literature search was conducted following PRISMA 2020 guidelines across five databases. Studies investigating six cancers were included. Sixteen studies evaluating 3,332 patients were included. Elevated baseline cfDNA and ctDNA levels correlated with higher tumor burden, shorter progression-free survival and overall-survival. Higher baseline cfDNA and ctDNA levels trended toward greater treatment resistance. Persistent cfDNA or ctDNA during or after treatment was linked to poorer response and higher recurrence risk. No studies evaluated cfDNA or ctDNA in MSD. cfDNA-derived chromosomal instability scores could stratify MSD patients by survival risk. No identified studies evaluated cfDNA or ctDNA in radiologically confirmed MSD. However, existing evidence suggests that cfDNA and ctDNA may hold promise as real-time biomarkers for MSD prognostication. Future research should evaluate whether cfDNA and ctDNA have prognostic value in MSD and whether they could eventually be integrated into existing MSD scoring systems to improve risk stratification.