Pancreatic Circulating Tumor Cells: An Update

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by late diagnosis, early metastasis, and poor response to therapy. Liquid biopsy approaches, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes, offer a minimally invasive method to monitor tumor burden, progression, and treatment response in real time. This review aims to synthesize recent findings on CTCs in PDAC, evaluate detection technologies, and explore their clinical and translational potential. Methods: We conducted a comprehensive literature search using PubMed and Google Scholar, focusing on original studies and reviews published within the past 15 years. Articles were selected based on relevance to CTC biology, detection methods, clinical correlations, and integration with other biomarkers. Attention was paid to studies published since 2018 and landmark earlier works. Results: CTCs are detectable in PDAC patients and are consistently associated with worse survival and higher recurrence rates. However, detection sensitivity varies widely by method. EpCAM-based platforms like CellSearch® detect CTCs in ~7–48% of cases, while newer size-based and microfluidic approaches report rates above 75%. CTCs exhibit epithelial–mesenchymal and stem-like phenotypes and can form clusters with high metastatic potential. Recent studies demonstrate molecular heterogeneity and show that CTC-derived organoids are feasible for functional studies. Nonetheless, technical variability and the lack of standardization remain major obstacles. Conclusions: CTCs represent a promising biomarker for prognosis and treatment monitoring in PDAC. Further refinement of enrichment techniques, molecular profiling strategies, and prospective clinical validation are needed to integrate CTC assays into routine PDAC management.