Clinical Applications of Liquid Biopsy in Prostate Cancer: From Screening to Predictive Biomarker

SIMPLE SUMMARY: Liquid biopsy (LB), encompassing the analysis of circulating tumor material in the blood or urine, has emerged as a powerful tool in the management of prostate cancer. In localized tumors, LB can distinguish between low- and high-grade cancers and can guide the decision to proceed with or defer tissue biopsy. In advanced disease states, LB has proven prognostic ability in addition to standard-of-care tests like the prostate-specific antigen and has been used in clinical trials to assess response. Certain LB analytes may predict resistance to androgen receptor signaling inhibitors, but how to incorporate their use into everyday clinical decision making remains unclear. Finally, for a minority of patients, LB can identify genomic alterations with significant therapeutic implications. Technological advances and creative uses of LB promise to greatly improve the management of prostate cancer patients in the near future. ABSTRACT: Prostate cancer (PC) remains the most common malignancy and the second most common cause of cancer death in men. As a result of highly variable biological behavior and development of resistance to available agents under therapeutic pressure, optimal management is often unclear. Traditional surgical biopsies, even when augmented by genomic studies, may fail to provide adequate guidance for clinical decisions as these can only provide a snapshot of a dynamic process. Additionally, surgical biopsies are cumbersome to perform repeatedly and often involve risk. Liquid biopsies (LB) are defined as the analysis of either corpuscular (circulating tumor cells, extracellular vesicles) or molecular (circulating DNA or RNA) tumor-derived material. LB could more precisely identify clinically relevant alterations that characterize the metastatic potential of tumors, predict response to specific treatments or actively monitor for the emergence of resistance. These tests can potentially be repeated as often as deemed necessary and can detect real-time response to treatment with minimal inconvenience to the patient. In the current review, we consider common clinical scenarios to describe available LB assays in PC as a platform to explore existing evidence for their use in guiding decision making and to discuss current limitations to their adoption in the clinic.