Cell-free DNA in prostate cancer and treatment selection

Metastatic prostate cancer is a leading cause of global cancer-related mortality. Contemporary treatment strategies are increasingly guided by genomic analyses, which are typically performed on archival or newly obtained biopsies. Nevertheless, tissue biopsies in this context face significant technical and clinical challenges. Circulating tumor DNA (ctDNA) testing from peripheral blood is a promising approach that addresses many of these limitations and enables sequential testing.

This review examines the evidence for ctDNA in prostate cancer management and considers where it may be most effectively integrated into clinical practice. We discuss the strengths and limitations of ctDNA-based diagnostics, the key principles guiding clinical interpretation, and future directions, including novel applications under development in clinical trials.

In the metastatic castration-resistant prostate cancer (mCRPC) setting, ctDNA genomic profiling is an established method to identify patients eligible for PARP inhibitor therapy, and an emerging biomarker for prognostication, treatment selection, and response assessment. The results of ongoing clinical trials will inform on the future role of ctDNA for prostate cancer.