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ABSTRACT Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is rapidly being established as arguably the leading contemporary imaging modality in the management of

prostate cancer. Outside of its conventional use in the de novo staging of localized disease and detection of biochemical recurrence, additional applications for the use of PSMA PET are

emerging. Uptake of PSMA tracers in other genitourinary malignancies, particularly renal cell carcinoma, has led to new fields of investigation. Therapeutic delivery of radiolabelled PSMA

small molecules has shown considerable promise in advanced prostate cancer. The ability to use the same molecule for imaging and therapy — theranostics — enables a highly personalized

approach. PSMA PET can also have a considerable influence in the selection and guidance of radiotherapy fields for high-risk and recurrent disease. Intriguingly, changes in intensity of PSMA

uptake during systemic therapy might provide early response assessment or novel insight into the biological responses of genitourinary malignancies to treatment. An evolving range of

radiolabelled PSMA radiopharmaceuticals is emerging in the multiple facets of modern clinical practice. KEY POINTS * Prostate-specific membrane antigen (PSMA) positron emission tomography

(PET) has most commonly been used for staging prostate cancer, with most studies in the setting of biochemical recurrence. However, PSMA is not expressed ubiquitously in prostate cancer and

PSMA can also be expressed in other solid organ malignancies and benign lesions. * The effect of PSMA PET has been demonstrated in both the definitive and salvage radiotherapy setting

through modification of treatment fields. * As PSMA PET has superior accuracy to choline PET–CT, metastasis-directed therapy (including stereotactic ablative body radiotherapy) can be

undertaken in the setting of oligometastatic disease. * PSMA theranostics (using radionuclides to target PSMA) has been evaluated in advanced disease with promising results in phase II

trials. * PSMA PET might have a role as an imaging biomarker in assessing response to systemic therapy. * The utility of PSMA PET in other genitourinary malignancies has been studied. It

might have a role in metastatic renal cell carcinoma, but there seems to be no role for PSMA PET in urothelial carcinoma. Access through your institution Buy or subscribe This is a preview

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* Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS RADIOTHERANOSTICS IN ADVANCED PROSTATE CANCER: CURRENT

AND FUTURE DIRECTIONS Article 14 April 2023 THE FUTURE OF PSMA PET AND WB MRI AS NEXT-GENERATION IMAGING TOOLS IN PROSTATE CANCER Article 04 July 2022 NEOADJUVANT LUTETIUM PSMA, THE TIME AND

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Google Scholar  Download references ACKNOWLEDGEMENTS S.S. is supported through a National Health and Medical Research Council Fellowship APP1122347 and Peter Mac Discovery Partner

Fellowship. AUTHOR INFORMATION Author notes * These authors contributed equally: Shankar Siva, Cristian Udovicich. AUTHORS AND AFFILIATIONS * Division of Radiation Oncology, Peter MacCallum

Cancer Centre, Melbourne, Australia Shankar Siva & Cristian Udovicich * Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia Shankar Siva, Ben Tran, 

Declan G. Murphy & Michael S. Hofman * Division of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia Ben Tran * Walter and Eliza Hall Institute of Medical Research,

Parkville, Australia Ben Tran * Department of Urology, Royal Melbourne Hospital, Melbourne, Victoria, Australia Homi Zargar * Department of Surgery, University of Melbourne, Melbourne,

Victoria, Australia Homi Zargar * Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia Declan G. Murphy * Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne,

Australia Michael S. Hofman Authors * Shankar Siva View author publications You can also search for this author inPubMed Google Scholar * Cristian Udovicich View author publications You can

also search for this author inPubMed Google Scholar * Ben Tran View author publications You can also search for this author inPubMed Google Scholar * Homi Zargar View author publications

You can also search for this author inPubMed Google Scholar * Declan G. Murphy View author publications You can also search for this author inPubMed Google Scholar * Michael S. Hofman View

author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS All authors researched data for the article, made substantial contributions to discussion of the

article content, wrote the manuscript, and reviewed and/or edited the manuscript before submission. CORRESPONDING AUTHOR Correspondence to Shankar Siva. ETHICS DECLARATIONS COMPETING

INTERESTS The authors declare no competing interests. ADDITIONAL INFORMATION PEER REVIEW INFORMATION _Nature Reviews Urology_ thanks T. Maurer and the other, anonymous, reviewer(s) for their

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SUPPLEMENTARY INFORMATION SUPPLEMENTARY VIDEO RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Siva, S., Udovicich, C., Tran, B. _et al._ Expanding the

role of small-molecule PSMA ligands beyond PET staging of prostate cancer. _Nat Rev Urol_ 17, 107–118 (2020). https://doi.org/10.1038/s41585-019-0272-5 Download citation * Accepted: 06

December 2019 * Published: 14 January 2020 * Issue Date: February 2020 * DOI: https://doi.org/10.1038/s41585-019-0272-5 SHARE THIS ARTICLE Anyone you share the following link with will be

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