Molecular and Genetic Biomarkers in Prostate Cancer Active Surveillance: Recent Developments and Future Perspectives

Smith, Stephanie F., Mills, Robert D., Cooper, Colin S. and Brewer, Daniel S. (2026) Molecular and Genetic Biomarkers in Prostate Cancer Active Surveillance: Recent Developments and Future Perspectives. Genes. ISSN 2073-4425

Microsoft Word (rba08-Smith_etal_Molecular_and_) - Published Version Available under License Creative Commons Attribution. Download (199kB)

Abstract

Background/Objectives: Active surveillance (AS) has become the standard of care for many men with localised prostate cancer, aiming to avoid the overtreatment of indolent disease while maintaining oncological safety. Despite improvements in diagnostic techniques, misclassification at diagnosis and the limited ability to predict disease progression remain major challenges in AS. Novel molecular and genetic biomarkers, assessed through liquid biopsy approaches, offer the potential to refine patient selection and support risk-adapted monitoring in AS. Methods: We conducted a narrative review of biomarkers in the context of AS for prostate cancer, framing the discussion in terms of the challenges in AS and how biomarkers may address these. PubMed and Embase were searched for English-language peer-reviewed studies published between 2000 and 2025. International guidelines (AUA, EAU, NCCN, NICE) and reference lists were reviewed manually. Priority was given to large prospective cohorts, meta-analyses, and high-impact publications. Results: Blood-based assays such as PHI and the 4K score, urinary tests including ExoDx and SelectMDx, and the Prostate Urine Risk (PUR) signatures have all shown associations with disease progression or decisions to undergo earlier treatment. However, studies are often small, use surrogate endpoints, and lack validation in MRI-integrated cohorts. Biomarkers appear most informative in men with Gleason Grade 1 (GG1) disease, while evidence in GG2 cohorts is limited. Cost-effectiveness, heterogeneity of endpoints, and uncertainty in managing discordant biomarker and MRI results remain barriers to clinical adoption. Conclusions: Molecular and genetic biomarkers show promise for improving AS by reducing diagnostic misclassification and enhancing prediction of progression. Future research should define clinically relevant cut-offs, clarify integration with MRI, and evaluate longitudinal use. Demonstrating utility in contemporary cohorts could enable the development of biomarker-guided, personalised AS that maintains safety while minimising harm.

Item Type:	Article
Additional Information:	Data Availability Statement: No new data were created or analysed in this study. Data sharing is not applicable to this article.
Uncontrolled Keywords:	active surveillance,biomarkers,prostate cancer,liquid biopsy,extracellular vesicles
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Depositing User:	LivePure Connector
Date Deposited:	07 Jan 2026 10:30
Last Modified:	07 Jan 2026 10:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101553
DOI:	10.3390/genes17010071

Downloads

Actions (login required)

View Item