Clinical Utility of Circulating Tumor Cells in Advanced Prostate Cancer

Men with metastatic castration-resistant prostate cancer (mCRPC) frequently have circulating tumor cells (CTCs) that are detectable in their peripheral blood. The CellSearch (R) method of enumerating CTCs is presently the only FDA-cleared CTC test available clinically for men with mCRPC and has been shown to have prognostic significance in this setting, both before and during systemic therapy. Clinical utility, reflecting the ability of this test to favorably change outcomes, is a more controversial and higher bar. The CellSearch (R) CTC assay can provide updated prognostic and potentially surrogate information in specific clinical scenarios and in clinical trials, but formal randomized trials of clinical utility remain an unmet clinical need. Recent data suggest that CTCs may harbor genetic information (such as the androgen receptor splice variant 7, AR-V7) relevant to changing clinical management and predicting treatment sensitivity or resistance to cancer therapies such as enzalutamide, abiraterone, and taxane chemotherapies. Further molecular characterization of CTCs, cell-free DNA, or RNA can also provide additional information that may have clinical utility. Thus, CTC research is moving toward predictive medicine, based on the biologic characterization and improvements in clinical outcomes associated with heterogeneous cell types both within and between patients.