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In prostate cancer, marked by high heterogeneity and frequent bone metastases, tissue biopsy is often challenging, highlighting the clinical value of circulating biomarkers. Circulating tumor DNA (ctDNA) is the most clinically advanced analyte, supporting detection of actionable alterations such as BRCA1\/2 and ATM mutations, guiding targeted therapies, and enabling real-time monitoring of treatment response and resistance. Circulating tumor cells (CTCs) and extracellular vesicles (EVs) provide complementary insights into tumor biology and disease progression. However, challenges remain, including limited sensitivity in low tumor burden and biological confounders such as clonal hematopoiesis (CH), which can lead to false-positive findings. Emerging approaches, including fragmentomics and methylation profiling, offer improved tumor specificity and may help overcome these limitations. Together, these advances support the integration of liquid biopsy into clinical practice for personalized management and longitudinal monitoring in prostate cancer.<\/jats:p>","DOI":"10.3390\/cancers18091366","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T11:40:12Z","timestamp":1777981212000},"page":"1366","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Liquid Biopsy in Advanced Prostate Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9076-4415","authenticated-orcid":false,"given":"Pilar","family":"Mediavilla-Medel","sequence":"first","affiliation":[{"name":"Liquid Biopsy Laboratory, Department of Medical Oncology, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Garc\u00eda-Sim\u00f3n","sequence":"additional","affiliation":[{"name":"Liquid Biopsy Laboratory, Department of Medical Oncology, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6570-009X","authenticated-orcid":false,"given":"Ar\u00e1nzazu","family":"Gonz\u00e1lez-del-Alba","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1634-7397","authenticated-orcid":false,"given":"Atocha","family":"Romero","sequence":"additional","affiliation":[{"name":"Liquid Biopsy Laboratory, Department of Medical Oncology, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Majadahonda, Spain"},{"name":"Department of Medical Oncology, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/s41571-020-00457-x","article-title":"Liquid biopsy enters the clinic\u2014Implementation issues and future challenges","volume":"18","author":"Ignatiadis","year":"2021","journal-title":"Nat. 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