Aim: We examined methylation changes in cell-free DNA (cfDNA) in metastatic castration resistant prostate cancer (mCRPC) during treatment. Materials and Methods: Genome-wide methylation analysis of sequentially collected cfDNA samples derived from mCRPC patients undergoing androgen-targeting therapy was performed. Results: Alterations in methylation states previously implicated in prostate cancer progression were observed and patients that maintained methylation changes throughout therapy tended to have a longer time to clinical progression (TTP). Importantly, we also report that markers associated with a highly aggressive form of the disease, Neuroendocrine-CRPC, were associated with a faster TTP. Conclusion: Our findings highlight the potential of monitoring cfDNA methylome during therapy in mCRPC, which may serve as predictive markers of response to androgen-targeting agents.### Competing Interest StatementThe authors have declared no competing interest.

Dynamics of the cell-free DNA methylome of metastatic prostate cancer during androgen-targeting treatment