We previously reported that the activation of RANK and c‐Met signaling components in both experimental mouse models and human prostate cancer (PC) specimens predicts bone metastatic potential and PC patient survival. This study addresses whether a population of metastasis‐initiating cells (MICs) known to express a stronger RANKL, phosphorylated c‐Met (p‐c‐Met), and neuropilin‐1 (NRP1) signaling network than bystander or dormant cells (BDCs) can be detected in PC tissues from patients subjected to transurethral resection of the prostate (TURP) for urinary obstruction prior to the diagnosis of PC with or without prior hormonal manipulation, and whether the relative abundance of MICs over BDCs could predict castration‐resistant progression and PC patient survival.

We employed a multiplexed quantum‐dot labeling (mQDL) protocol to detect and quantify MICs and BDCs at the single cell level in TURP tissues obtained from 44 PC patients with documented overall survival and castration resistance status.

PC tissues with a higher number of MICs and an activated RANK signaling network, including increased expression of RANKL, p‐c‐Met, and NRP1 compared to BDCs, were found to correlate with the development of castration resistance and overall survival.

The assessment of PC cells with MIC and BDC phenotypes in primary PC tissues from hormone‐naïve patients can predict the progression to castration resistance and the overall survival of PC patients. Prostate 75:1312–1321, 2015. © 2015 Wiley Periodicals, Inc.