{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:34:17Z","timestamp":1760060057103,"version":"build-2065373602"},"reference-count":169,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,27]],"date-time":"2025-07-27T00:00:00Z","timestamp":1753574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Oradea"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Second-generation androgen receptor signaling inhibitors are one of the main treatment options in metastatic castration-resistant prostate cancer (mCRPC). Nonetheless, a considerable proportion show limited response to treatment, which indicates the need for convenient, easily accessible predictor biomarkers, a role suited for liquid biopsy. Methods: We conducted a PRISMA-compliant systematic review of four databases (Embase, Medline, Scopus, Web of Science) to identify all studies (observational studies and clinical trials) investigating cell-free DNA, circulating tumor cells, exosomes, and circulating RNAs as prognostic markers in metastatic castration-resistant patients starting androgen receptor signaling inhibitors. We excluded studies that evaluated combination therapies, rare histological subtypes or included nonmetastatic or castrate-sensitive disease. We also evaluated whether published papers followed reporting guidelines (REMARK, STROBE, or CONSORT for abstracts). Results: We identified a total of 123 reports, from which we identified only a few well-studied and consistent biomarkers: androgen receptor overexpression\/copy number gain and splice variant 7, as well as disease burden markers (circulating tumor DNA fraction and circulating tumor cell concentration). Alterations or copy number loss in tumor suppressors PTEN, RB1, and TP53 were second in terms of quantity and consistency of evidence. However, a large majority of identified biomarkers were relatively understudied or inconsistent. We identified two potential vulnerabilities: inconsistent adherence to reporting guidelines and the under-inclusion of patients of non-Western European ancestry. Conclusions: A large number of biomarkers were linked to worse outcomes in prostate cancer; nonetheless, in most cases, the evidence is limited or inconsistent, or even contradictory. The main exceptions pertain to androgen receptor signaling and disease burden, and, to a smaller extent, to certain tumor suppressor genes. Further studies are needed to confirm their clinical utility, using clear and consistent methodologies and including patients from currently understudied populations.<\/jats:p>","DOI":"10.3390\/cancers17152482","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T08:51:33Z","timestamp":1753692693000},"page":"2482","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liquid Biopsy Biomarkers in Metastatic Castration-Resistant Prostate Cancer Treated with Second-Generation Antiandrogens: Ready for Clinical Practice? A Systematic Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2035-8339","authenticated-orcid":false,"given":"Andrei-Vlad","family":"Badulescu","sequence":"first","affiliation":[{"name":"Doctoral School of Biomedical Sciences, University of Oradea, 410087 Oradea, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2875-2936","authenticated-orcid":false,"given":"Razvan","family":"Rahota","sequence":"additional","affiliation":[{"name":"Department of Morphological Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2923-6813","authenticated-orcid":false,"given":"Alon","family":"Vigdorovits","sequence":"additional","affiliation":[{"name":"Doctoral School of Biomedical Sciences, University of Oradea, 410087 Oradea, Romania"},{"name":"Department of Morphological Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania"},{"name":"Department of Pathology, Bihor County Clinical Emergency Hospital, 410169 Oradea, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7474-4561","authenticated-orcid":false,"given":"Ovidiu Laurean","family":"Pop","sequence":"additional","affiliation":[{"name":"Department of Morphological Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania"},{"name":"Department of Pathology, Bihor County Clinical Emergency Hospital, 410169 Oradea, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,27]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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