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Review
. 2025 Jun 16:9:100305.
doi: 10.1016/j.jlb.2025.100305. eCollection 2025 Sep.

Blood and urine-based biomarkers in prostate cancer: Current advances, clinical applications, and future directions

Felice Crocetto  1 , Michele Musone  1 , Stefano Chianese  1 , Paolo Conforti  1 , Gaetano Digitale Selvaggio  1 , Vincenzo Francesco Caputo  2 , Roberto Falabella  2 , Francesco Del Giudice  3 , Carlo Giulioni  4 , Angelo Cafarelli  4 , Giuseppe Lucarelli  5 , Gian Maria Busetto  6 , Matteo Ferro  7 , Biagio Barone  8 , Fabio Zattoni  9   10 , Daniela Terracciano  11
Affiliations
Review

Blood and urine-based biomarkers in prostate cancer: Current advances, clinical applications, and future directions

Felice Crocetto et al. J Liq Biopsy. .

Abstract

Prostate cancer (PCa) is one of the most prevalent malignancies in men, characterized by high clinical and molecular heterogeneity. Despite the widespread use of prostate-specific antigen (PSA) for diagnosis and monitoring, its limited specificity and sensitivity necessitate the development of more accurate biomarkers. This review provides a comprehensive overview of current and emerging diagnostic, prognostic, and predictive biomarkers in PCa, highlighting their clinical applications and future perspectives. PSA, though historically central in PCa screening, lacks tumor specificity, often leading to unnecessary biopsies or missed aggressive cancers. Recent blood-based biomarkers, such as the Prostate Health Index (PHI) and 4Kscore, improve specificity by integrating PSA isoforms or kallikrein protein levels with clinical parameters. Urine-based biomarkers like PCA3 and SelectMDx further enhance diagnostic precision, particularly in distinguishing high-grade tumors, and show potential in active surveillance settings. Prognostic markers such as Bcl-2, Ki-67, and EZH2, alongside genetic alterations like MCM7 and 8q gain, help stratify patients by tumor aggressiveness and risk of recurrence. Liquid biopsies, including circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), offer non-invasive alternatives for molecular profiling, especially in metastatic castration-resistant PCa (mCRPC), and can identify actionable alterations such as BRCA1/2 or ATM mutations. Emerging technologies such as machine learning and single-cell omics are reshaping biomarker discovery. Artificial intelligence-driven models, like the replication stress signature (RSS), show promise in predicting relapse and therapeutic response. Single-cell RNA sequencing and spatial transcriptomics have deepened our understanding of PCa heterogeneity, tumour microenvironment, and resistance mechanisms. Furthermore, novel biomarkers, including exosome RNAs and immune-related markers (PD-L1, SOX2, TcellinfGEP), offer insights into tumour progression and immunotherapeutic potential. The urinary and gut microbiomes are also being explored for their diagnostic and prognostic roles in PCa. In conclusion, integrating advanced molecular tools and biomarker-guided platforms into clinical practice can significantly enhance early detection, personalized treatment, and monitoring in prostate cancer, paving the way for precision oncology.

Keywords: Artificial intelligence; Biomarkers; Liquid biopsy; Precision medicine; Prostate cancer.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Key stages and markers in prostate cancer.
See this image and copyright information in PMC

References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: a cancer journal for clinicians. 2021;71(3):209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Siegel R.L., Miller K.D., Wagle N.S., Jemal A. Cancer statistics, 2023. CA: a cancer journal for clinicians. 2023;73(1):17–48. doi: 10.3322/caac.21763. - DOI - PubMed
    1. Mottet N., van den Bergh, Briers E., Van den Broeck T., Cumberbatch M.G., De Santis M., Fanti S., Fossati N., Gandaglia G., Gillessen S., Grivas N., Grummet J., Henry A.M., van der Kwast, Lam T.B., Lardas M., Liew M., Mason M.D., Moris L., Oprea-Lager D.E.…Cornford P. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. European urology. 2021;79(2):243–262. doi: 10.1016/j.eururo.2020.09.042. - DOI - PubMed
    1. Mohler J.L., Antonarakis E.S., Armstrong A.J., D’Amico A.V., Davis B.J., Dorff T., Eastham J.A., Enke C.A., Farrington T.A., Higano C.S., Horwitz E.M., Hurwitz M., Ippolito J.E., Kane C.J., Kuettel M.R., Lang J.M., McKenney J., Netto G., Penson D.F., Plimack E.R.…Freedman-Cass D.A. Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN. 2019;17(5):479–505. doi: 10.6004/jnccn.2019.0023. - DOI - PubMed
    1. Schröder F.H., Hugosson J., Roobol M.J., Tammela T.L., Ciatto S., Nelen V., Kwiatkowski M., Lujan M., Lilja H., Zappa M., Denis L.J., Recker F., Berenguer A., Määttänen L., Bangma C.H., Aus G., Villers A., Rebillard X., van der Kwast T.…Blijenberg B.G., ERSPC Investigators Screening and prostate-cancer mortality in a randomized European study. The New England journal of medicine. 2009;360(13):1320–1328. doi: 10.1056/NEJMoa0810084. - DOI - PubMed

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