Evolving insights in blood-based liquid biopsies for prostate cancer interrogation

During the last decade, blood sampling of cancer patients aimed at analyzing the presence of cells, membrane-bound vesicles, or molecules released by primary tumors or metastatic growths emerged as an alternative to traditional tissue biopsies. The advent of this minimally invasive approach, known as blood-based liquid biopsy, began to play a pivotal role in the management of diverse cancers, establishing itself as a vital component of precision medicine. Here, we discuss three blood-based liquid biopsies, namely circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and tumor-derived exosomes, as they relate to prostate cancer (PCa) management. The advances achieved in the molecular characterization of these types of liquid biopsies and their potential to predict recurrence, improve responses to certain treatments, and evaluate prognosis, in PCa patients, are highlighted herein. While there is currently full clinical validation for only one CTC-based and one ctDNA-based liquid biopsy for patients with metastatic castration-resistant PCa, the adoption of additional methods is anticipated as they undergo standardization and achieve analytical and clinical validation. Advantages and disadvantages of different blood-based liquid biopsy approaches in the context of PCa are outlined herein, while also considering potential synergies through combinatory strategies.