{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:25:18Z","timestamp":1787869518637,"version":"build-2784847793"},"reference-count":215,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>A circulating tumor DNA (ctDNA) assay is an emerging non-invasive diagnostic approach providing real-time insights into the heterogeneous tumor molecular landscape of advanced prostate cancer, overcoming the limitations of traditional tissue biopsies and PSA. Detection methods include droplet digital PCR, next-generation sequencing, and new epigenomic and fragmentomic strategies (investigational) designed to improve sensitivity in cases of low ctDNA shedding. While ctDNA\u2019s role in localized prostate cancer is limited, it offers significant prognostic value in metastatic cases, where high ctDNA levels correlate with shorter survival. Additionally, longitudinal ctDNA monitoring can predict treatment response and identify emerging resistance mechanisms, including androgen receptor alterations associated with androgen receptor pathway inhibitor therapy and BRCA reversion mutations linked to PARP inhibitors. Importantly, liquid biopsy enables genomic characterization to inform treatment decision-making, particularly in clinical scenarios where tissue biopsy is challenging, such as bone-only disease. However, the widespread clinical implementation of ctDNA analysis is hindered by several analytical challenges, including low sensitivity in localized disease and low disease burden, and the risk of false positives due to clonal hematopoiesis. Furthermore, greater efforts are required to standardize pre-analytical workflows and post-analytical data interpretation and reporting across institutions. This review aims to summarize the evolving role of cfDNA technologies in localized and advanced prostate cancer, highlighting their prognostic and predictive value and their role in uncovering mechanisms of treatment resistance.<\/jats:p>","DOI":"10.3390\/cancers18111702","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:30:33Z","timestamp":1779669033000},"page":"1702","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Circulating Tumor DNA as Emerging Predictive and Prognostic Biomarker in Prostate Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Bicky","family":"Thapa","sequence":"first","affiliation":[{"name":"Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Venturini","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute (SCRI), London W1G 6AD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atish D.","family":"Choudhury","sequence":"additional","affiliation":[{"name":"Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4270-7023","authenticated-orcid":false,"given":"Edoardo","family":"Francini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s12957-025-03733-1","article-title":"Global Burden of Prostate Cancer: Age-Period-Cohort Analysis from 1990 to 2021 and Projections until 2040","volume":"23","author":"Chu","year":"2025","journal-title":"World J. 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