Irene Casanova-Salas1, Alejandro Athie1, Paul C Boutros2, Marzia Del Re3, David T Miyamoto4, Kenneth J Pienta5, Edwin M Posadas6, Adam G Sowalsky7, Arnulf Stenzl8, Alexander W Wyatt9, Joaquin Mateo10. 1. Vall d'Hebron Institute of Oncology (VHIO) and Vall d'Hebron University Hospital, Barcelona, Spain. 2. Departments of Human Genetics and Urology, Institute for Precision Health and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA. 3. Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy. 4. Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. 5. The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 6. Translational Oncology Program & Urologic Oncology Program, Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 7. Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. 8. Department of Urology, University Hospital Tübingen, Tübingen, Germany. 9. Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. 10. Vall d'Hebron Institute of Oncology (VHIO) and Vall d'Hebron University Hospital, Barcelona, Spain. Electronic address: jmateo@vhio.net.
Abstract
CONTEXT: Genomic stratification can impact prostate cancer (PC) care through diagnostic, prognostic, and predictive biomarkers that aid in clinical decision-making. The temporal and spatial genomic heterogeneity of PC together with the challenges of acquiring metastatic tissue biopsies hinder implementation of tissue-based molecular profiling in routine clinical practice. Blood-based liquid biopsies are an attractive, minimally invasive alternative. OBJECTIVE: To review the clinical value of blood-based liquid biopsy assays in PC and identify potential applications to accelerate the development of precision medicine. EVIDENCE ACQUISITION: A systematic review of PubMed/MEDLINE was performed to identify relevant literature on blood-based circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs) in PC. EVIDENCE SYNTHESIS: Liquid biopsy has emerged as a practical tool to profile tumor dynamics over time, elucidating features that evolve (genome, epigenome, transcriptome, and proteome) with tumor progression. Liquid biopsy tests encompass analysis of DNA, RNA, and proteins that can be detected in CTCs, ctDNA, or EVs. Blood-based liquid biopsies have demonstrated promise in the context of localized tumors (diagnostic signatures, risk stratification, and disease monitoring) and advanced disease (response/resistance biomarkers and prognostic markers). CONCLUSIONS: Liquid biopsies have value as a source of prognostic, predictive, and response biomarkers in PC. Most clinical applications have been developed in the advanced metastatic setting, where CTC and ctDNA yields are significantly higher. However, standardization of assays and analytical/clinical validation is necessary prior to clinical implementation. PATIENT SUMMARY: Traces of tumors can be isolated from blood samples from patients with prostate cancer either as whole cells or as DNA fragments. These traces provide information on tumor features. These minimally invasive tests can guide diagnosis and treatment selection.
CONTEXT: Genomic stratification can impact prostate cancer (PC) care through diagnostic, prognostic, and predictive biomarkers that aid in clinical decision-making. The temporal and spatial genomic heterogeneity of PC together with the challenges of acquiring metastatic tissue biopsies hinder implementation of tissue-based molecular profiling in routine clinical practice. Blood-based liquid biopsies are an attractive, minimally invasive alternative. OBJECTIVE: To review the clinical value of blood-based liquid biopsy assays in PC and identify potential applications to accelerate the development of precision medicine. EVIDENCE ACQUISITION: A systematic review of PubMed/MEDLINE was performed to identify relevant literature on blood-based circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs) in PC. EVIDENCE SYNTHESIS: Liquid biopsy has emerged as a practical tool to profile tumor dynamics over time, elucidating features that evolve (genome, epigenome, transcriptome, and proteome) with tumor progression. Liquid biopsy tests encompass analysis of DNA, RNA, and proteins that can be detected in CTCs, ctDNA, or EVs. Blood-based liquid biopsies have demonstrated promise in the context of localized tumors (diagnostic signatures, risk stratification, and disease monitoring) and advanced disease (response/resistance biomarkers and prognostic markers). CONCLUSIONS: Liquid biopsies have value as a source of prognostic, predictive, and response biomarkers in PC. Most clinical applications have been developed in the advanced metastatic setting, where CTC and ctDNA yields are significantly higher. However, standardization of assays and analytical/clinical validation is necessary prior to clinical implementation. PATIENT SUMMARY: Traces of tumors can be isolated from blood samples from patients with prostate cancer either as whole cells or as DNA fragments. These traces provide information on tumor features. These minimally invasive tests can guide diagnosis and treatment selection.
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