Abstract
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. We analyzed a total of 203 CTC samples from 79 CRPC patients to investigate the proportion of positive mRNA expressions at different treatment phases. Among them, we elected to focus on specimens from 56 CRPC patients who progressed on therapy and were subsequently provided a new treatment (treatment-switch cohort). In this cohort, we investigated the association between PSMA expression in CTCs and treatment response. CTCs were detected in 55/79 patients and median serum PSA in CTC-positive patients was 67.0 ng/ml. In the treatment-switch cohort of 56 patients, 20 patients were positive for PSMA in CTCs. PSMA expression was inversely associated with percentage of change in prostate-specific antigen (PSA). The median PSA progression-free survival and overall survival were significantly shorter in the PSMA-positive cohort. Furthermore, PSMA expression was predictive of poorer treatment response, shorter PSA progression-free survival and overall survival. PSMA expression in circulating tumor cells may be a novel poor prognostic marker for CRPC.
Highlights
More than 90% of patients with metastatic treatment-naive prostate cancer initially respond to androgen deprivation therapy (ADT)
The proportion of mRNA expressions in these circulating tumor cells (CTCs)-positive 127 samples were as follows: 63% were positive for prostate-specific membrane antigen (PSMA), 71% positive for androgen receptor (AR), 25% positive for androgen receptor splice variant 7 (AR-V7), and 22% positive for Epidermal Growth Factor Receptor (EGFR)
To complement our small sample size, we further investigated the correlation between PSMA expression in primary prostate cancer tissue and overall survival in The Cancer Genome Atlas (TCGA) cohort, in which PSMA, AR, AR-V7 and EGFR mRNA expression data were available for 316 prostate cancer
Summary
More than 90% of patients with metastatic treatment-naive prostate cancer initially respond to androgen deprivation therapy (ADT). Most patients eventually progress to castration-resistant prostate cancer (CRPC), which is treated with sequential therapy [1]. Several drugs available for sequential therapy of CRPC, such as enzalutamide (ENZ), abiraterone (ABI), docetaxel (DOC), cabazitaxel (CBZ) and radium-223, have been shown to prolong the survival of CRPC patients [2]. Approximately 30% of CRPC patients show primary. PSMA expression in CTC is a poor prognostic marker for CRPC
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