Prostate-Specific Membrane Antigen in Circulating Tumor Cells is a New Predictive Marker for Castration-Resistant Prostate Cancer

Abstract

Purpose: The aim of this study is to elucidate the clinical significance of prostate-specific membrane antigen (PSMA) expression in circulating tumor cells (CTCs) from castration-resistant prostate cancer (CRPC) patients. Experimental Design: We analyzed total of 167 CTC samples from 68 CRPC patients to investigate the proportion of positive mRNA expressions at a different treatment phase. Among them, we next focused on 39 CRPC patients who had their CTC samples collected at the time of recurrence and thereafter were given new treatments (treatment-failure cohort). First, in this cohort, we assessed whether the presence of CTC per se affects treatment response. Then, we investigated the association between PSMA expression in CTCs and treatment response. Results: CTCs were detected in 105/167 samples (63%) and among 105 CTC-positive samples, 62% of them were positive for PSMA. PSMA was significantly more expressed in samples derived from heavily treated patients. In the treatment-failure cohort of 39 patients, 27 of them were positive for CTCs. Among them, 13 patients were positive for PSMA in CTCs. PSMA expression was inversely correlated with percentage of change in prostate-specific antigen (PSA) by treatment with a statistical significance. The median PSA progression-free survival was significantly shorter in the PSMA-positive cohort. Furthermore, PSMA expression in CTCs was predictive of poor treatment response. Conclusions: PSMA was significantly more expressed in CTCs derived from heavily treated patients. PSMA expression in CTCs was significantly associated with poor treatment response in CRPC. PSMA expression in CTCs can be a novel biomarker for CRPC. Funding: This work was supported by Astellas; and Sanofi Aventis. Declaration of Interests: Shigeo Horie has research grants from Astellas and Sanofi Aventis, honorarium from Astellas, Takeda, Astra Zeneca and Sanofi Aventis and Janssen. Other authors have declared no conflicts of interest. Ethical Approval Statement: This study was approved by the institutional review board of Juntendo hospital (admission number: 14-052), and all experiments were carried out in accordance with approved guidelines.