A narrative review of the current state of circulating tumor cells in prostate cancer diagnostic.

Abstract

Circulating tumor cells (CTCs) in prostate cancer (PCa) have been an area of interest over the past 35 years. The aim of this narrative review is to summarize data on CTC application in PCa diagnosis. Several CTC detection tools have been developed; however, most of them only assess subpopulations expressing matching biomarkers. Thus, a combined detection system might be useful, and priority should be given to creating a universal panel that covers a broad spectrum of PCa subtypes. Expression of CD82 and several other markers carries prognostic value and correlates with stage and relapse risk. In metastatic PCa, CTC detection correlates with both survival and response to therapy. AR-V7 expression by CTCs is associated with resistance to androgen receptor signaling inhibitors (ARSis), while the response to taxanes remains unaffected. OCT4 expression in CTCs is associated with higher serum LDH levels, worse radiographic progression-free survival, and overall survival. Ezrin overexpression in CTCs is associated with bone metastasis in PCa patients. HER2-positive CTC detection correlates with worse overall and progression-free survival among patients treated with ARSis. Prostate-specific membrane antigen (PSMA) expression in CTCs was associated with metastases, lower overall survival and progression-free survival, as well as poor response to chemotherapy in mCRPCa. Overall, CTC detection for PCa screening, early diagnosis, and prognosis in localized disease offers limited added value. Conversely, in metastatic PCa it shows promising results as a prognostic marker. AR-V7 expression by CTCs is a predictor of response to ARS inhibitors, while PSMA expression in CTCs is associated with metastases, poor prognosis, and suboptimal treatment response. OCT4, HER2, and ezrin in CTCs were also predictors of poor prognosis and treatment response, but the data is limited. If explored further, microRNAs could serve as a potential alternative to circulating tumor cells, as they are - in theory - able to perform the same functions.