Phenotypes of Circulating Tumor Cells Predict Time to Castration Resistance in Metastatic Castration-Sensitive Prostate Cancer.

OBJECTIVES: To identify biomarkers that predict the response to standard androgen deprivation therapy (ADT) of patients newly diagnosed with metastatic castration-sensitive prostate cancer (CSPC) to improve therapeutic decision-making. We investigated whether the characterization of baseline circulating tumor cells (CTCs) predicted the effective period of standard ADT.

MATERIALS AND METHODS: The study included 108 patients newly diagnosed with high-volume metastatic CSPC. Enumeration and characterization of patients' baseline CTCs (CTC+ and CTC- indicate detectable and undetectable CTCs, respectively) were performed using the CanPatrol technique, which detects markers of the epithelial mesenchymal transition (EMT) in CTCs and classifies CTCs into epithelial, biophenotypic, and mesenchymal phenotypes.

RESULTS: After a median follow-up of 24 months, 90 (83.3%) patients progressed to castration-resistant prostate cancer (CRPC), 93 (86.1%) patients had detectable CTCs, and the median number of CTCs was 4. The rate of progression to CRPC was significantly higher for patients with mesenchymal CTC+ than for patients with CTC+/mesenchymal CTC- and CTC- (93.1% vs 71.4% and 73.3%, p=0.013). The median time to CRPC for patients with mesenchymal CTC+ was significantly shorter than for those with CTC+/mesenchymal CTC- and CTC- (10.5 months vs. 18.0 months and 14.0 months, 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.

CONCLUSIONS: 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 counseling patients and designing clinical trials. This article is protected by copyright. All rights reserved.