In this cohort of advanced prostate cancer patients, we evaluated the feasibility of a multi-parametric, non-invasive profiling approach that integrates liquid biopsy readouts for CTC enumeration, CTC Arv7 and synaptophysin (SYP) staining, genomic analysis of individual CTCs and matched plasma cfDNA, and CTC clustering analysis together with comprehensive radiomic analysis of companion bone metastasis CT scans. Here, SYP is linked to prostate cancer.