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Review Open Access

Evolving role of biomarkers beyond prostate‑specific antigen in refining prostate cancer screening: From blood‑based tests to urinary and genetic markers (Review)

  • Authors:
    • Luxi Li
    • Linyue Zhang
    • Zehong Li
    • Keqiang Chai
    • Weidong Ren
  • View Affiliations / Copyright

    Affiliations: The Urology Center, First People's Hospital of Baiyin City (The Third Affiliated Hospital of Gansu University of Chinese Medicine), Baiyin, Gansu 730900, P.R. China, Health Management Center, First People's Hospital of Baiyin City (The Third Affiliated Hospital of Gansu University of Chinese Medicine), Baiyin, Gansu 730900, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 244
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    Published online on: July 2, 2026
       https://doi.org/10.3892/mmr.2026.13954
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Abstract

Prostate‑specific antigen (PSA) screening reduces prostate cancer (PCa) mortality but is limited by overdiagnosis and poor specificity for clinically significant disease. These limitations drive the need for more accurate biomarkers to distinguish aggressive cancers from indolent lesions. The present review examined advanced blood‑based markers, including PSA isoforms, liquid biopsy components and the Prostate Health Index; urinary biomarkers, such as PCa antigen 3, transmembrane protease serine 2‑v‑ets erythroblastosis virus E26 oncogene homolog fusion and the MyProstateScore 2.0 panel; and genetic markers ranging from high‑penetrance germline mutations to polygenic risk scores. It further explored the integration of these biomarkers with multiparametric MRI, risk‑calculator models and health‑economic evaluations to optimize screening pathways. Future directions involve multi‑omic profiling, artificial intelligence and novel biosensing technologies. The present review aimed to provide a comprehensive and balanced perspective on emerging biomarkers that are reshaping personalized PCa screening.
View Figures

Figure 1

Evolving landscape of blood-based
biomarkers in PCa screening: From PSA derivatives to liquid biopsy.
This figure illustrates the progression and integration of advanced
blood-based biomarkers into a potential screening-diagnostic
pathway for PCa. It compares established biomarkers such as the PHI
and 4Kscore, which refine risk using PSA isoforms, against emerging
liquid biopsy components (circulating tumor cells, cell-free DNA
and methylation markers). The pathway highlights how these tools
can triage patients, reduce unnecessary procedures, and guide
personalized clinical decisions. This evolving landscape signifies
a shift from volume-based PSA testing towards molecularly-informed,
precision screening strategies. Thus, blood-based biomarkers (PHI,
4Kscore and liquid biopsy) improve risk stratification, reduce
unnecessary biopsies, and support personalized screening decisions.
This figure was created using the online graphic design website
Figdraw (www.figdraw.com). PCa, prostate
cancer; PSA, prostate-specific antigen; tPSA, total PSA; fPSA, free
PSA; PHI, Prostate Health Index; GSTP1, glutathione S-transferase
Pi 1; AR, androgen receptor; RASSF1, Ras association
domain-containing protein 1.

Figure 2

Multimodal, integrated framework for
personalized prostate cancer screening and clinical
decision-making. This figure outlines a dynamic, biomarker-informed
pathway for refining prostate cancer screening. It integrates
clinical parameters, novel biomarkers (blood, urine, genetic), and
multiparametric MRI within sequential decision nodes to optimize
the detection of clinically significant disease while minimizing
unnecessary procedures. The framework emphasizes risk-adapted
triage, multimodal data synthesis and cost-effective resource
allocation, moving toward a personalized screening strategy.
Consequently, integrating clinical, biomarker, and MRI data in a
sequential, risk-adapted manner enhances detection of clinically
significant prostate cancer while reducing overdiagnosis and
healthcare costs. This figure was created using the online graphic
design website Figdraw (www.figdraw.com). PCA3, prostate cancer antigen 3;
PI-RADS, prostate imaging-reporting and data system; PSA,
prostate-specific antigen.
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Copy and paste a formatted citation
Spandidos Publications style
Li L, Zhang L, Li Z, Chai K and Ren W: Evolving role of biomarkers beyond prostate‑specific antigen in refining prostate cancer screening: From blood‑based tests to urinary and genetic markers (Review). Mol Med Rep 34: 244, 2026.
APA
Li, L., Zhang, L., Li, Z., Chai, K., & Ren, W. (2026). Evolving role of biomarkers beyond prostate‑specific antigen in refining prostate cancer screening: From blood‑based tests to urinary and genetic markers (Review). Molecular Medicine Reports, 34, 244. https://doi.org/10.3892/mmr.2026.13954
MLA
Li, L., Zhang, L., Li, Z., Chai, K., Ren, W."Evolving role of biomarkers beyond prostate‑specific antigen in refining prostate cancer screening: From blood‑based tests to urinary and genetic markers (Review)". Molecular Medicine Reports 34.3 (2026): 244.
Chicago
Li, L., Zhang, L., Li, Z., Chai, K., Ren, W."Evolving role of biomarkers beyond prostate‑specific antigen in refining prostate cancer screening: From blood‑based tests to urinary and genetic markers (Review)". Molecular Medicine Reports 34, no. 3 (2026): 244. https://doi.org/10.3892/mmr.2026.13954
Copy and paste a formatted citation
x
Spandidos Publications style
Li L, Zhang L, Li Z, Chai K and Ren W: Evolving role of biomarkers beyond prostate‑specific antigen in refining prostate cancer screening: From blood‑based tests to urinary and genetic markers (Review). Mol Med Rep 34: 244, 2026.
APA
Li, L., Zhang, L., Li, Z., Chai, K., & Ren, W. (2026). Evolving role of biomarkers beyond prostate‑specific antigen in refining prostate cancer screening: From blood‑based tests to urinary and genetic markers (Review). Molecular Medicine Reports, 34, 244. https://doi.org/10.3892/mmr.2026.13954
MLA
Li, L., Zhang, L., Li, Z., Chai, K., Ren, W."Evolving role of biomarkers beyond prostate‑specific antigen in refining prostate cancer screening: From blood‑based tests to urinary and genetic markers (Review)". Molecular Medicine Reports 34.3 (2026): 244.
Chicago
Li, L., Zhang, L., Li, Z., Chai, K., Ren, W."Evolving role of biomarkers beyond prostate‑specific antigen in refining prostate cancer screening: From blood‑based tests to urinary and genetic markers (Review)". Molecular Medicine Reports 34, no. 3 (2026): 244. https://doi.org/10.3892/mmr.2026.13954
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