Prostate specific membrane antigen (PSMA) as a biomarker in early and localized advanced prostate cancer: a narrative review

Jonathon Carll^1,2,3,*, Jacinta Bonaddio¹, Dixon Woon^1,4,5, Marlon Perera^1,4,5,6, Nathan Lawrentschuk^2,3,5,6, Thilakavathi Chengodu^1,3
1 Department of Surgery, University of Melbourne, Melbourne, VIC 3052, Australia
2 Department of Urology, The Royal Melbourne Hospital, Melbourne, VIC 3052, Australia
3 EJ Whitten Prostate Cancer Research Centre, Epworth Healthcare, Melbourne, VIC 3005, Australia
4 Department of Surgery, Austin Healthcare, Heidelberg, VIC 3084, Australia
5 Epworth Healthcare, Melbourne, VIC 3005, Australia
6 Department of Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC 3052, Australia
* Corresponding Author: Jonathon Carll. Email: email

Canadian Journal of Urology https://doi.org/10.32604/cju.2025.068908

Received 10 June 2025; Accepted 11 October 2025; Published online 03 December 2025

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Abstract

Prostate-specific membrane antigen (PSMA) is a surface membrane antigen that is highly overexpressed in prostate cancer, with heterogenous expression throughout the natural history of the disease. This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer. We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes. A search on PubMed, Medline, and Web of Science was performed using the following keywords: “PSMA”, “Prostate Specific Membrane Antigen”, “Prostate cancer”, “Biomarker”, “Diagnosis”. We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review. Key articles assessing the biology of PSMA, as well as its use as a potential diagnostic and therapeutic target in early prostate cancer, were assessed. The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed. The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed, along with any current evidence to support their use in early prostate cancer. PSMA is heavily expressed throughout the early stages of prostate cancer, and this has significant therapeutic implications. There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis, risk stratification, and prognostication of localised prostate cancer. PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer; however, this remains an area of ongoing research.