Chen PJ, et al. - Researchers assessed the role of very-small nuclear circulating tumor cells (vsnCTCs) as an aggressive biomarker in metastatic castration-resistant prostate cancer (mCRPC). vsnCTCs represent a subgroup of prostate cancer (PC) circulating tumor cells (CTCs) with especially small nuclei ( < 8.54 μm) that correlate with poor prognosis and the appearance of visceral metastases (VM). A biological pathway that possibly drives this morphologic phenomenon was also investigated, with the presumption that emerin mislocalization is related to vsnCTC formation and may be a vital part of metastasis. The CTCs from patients' blood were analyzed and this data was associated with clinical outcomes. Samples were obtained from 35 mCRPC patients who initiated abiraterone, enzalutamide, or taxane-based chemotherapy after failing first-line androgen deprivation therapy. Findings revealed worse overall survival, progression free survival, and faster time to VM were associated with the presence of one or more vsnCTCs. Thus, vsnCTCs is a possible biomarker for predicting worse outcome. In vsnCTCs vs WBC, lower emerin content was found. In vsnCTCs vs CTCs with larger nuclei, emerin mislocalization was more prominent.