Phenotypes of circulating tumour cells predict time to castration resistance in metastatic castration-sensitive prostate cancer.

Abstract

To identify biomarkers that predict the response to standard androgen deprivation therapy (ADT) of patients newly diagnosed with metastatic castration-sensitive prostate cancer (CSPC) in order to improve therapeutic decision-making, and to investigate whether the characterization of baseline circulating tumour cells (CTCs) would predict the effective period of standard ADT. The study included 108 patients newly diagnosed with high-volume metastatic CSPC. Enumeration and characterization of patients' baseline CTCs (CTCs+ and CTCs-, indicating detectable and undetectable CTCs, respectively) were performed using the CanPatrol technique, which detects markers of the epithelial to mesenchymal transition (EMT) in CTCs, and classifies CTCs into epithelial, biophenotypic and mesenchymal phenotypes. After a median follow-up of 24months, 90 patients (83.3%) progressed to castration-resistant prostate cancer (CRPC), 93 patients (86.1%) had detectable CTCs, and the median number of CTCs was 4. The rate of progression to CRPC was significantly higher for patients with mesenchymal CTCs+ than for patients with CTCs+/mesenchymal CTCs- and CTCs- (93.1% vs 71.4% and 73.3%; P = 0.013). The median time to CRPC for patients with mesenchymal CTCs+ was significantly shorter than for those with CTCs+/mesenchymal CTCs- and CTCs- (10.5months vs 18.0 and 14.0months; P = 0.003). Multivariate Cox regression analysis suggested that the CTC phenotype was the only independent prognostic factor influencing the progression of disease from CSPC to CRPC. Characterization of baseline CTCs according to the EMT phenotype predicted the effective period of standard ADT for patients newly diagnosed with metastatic CSPC. These findings are important for counselling patients and designing clinical trials.