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  • Review Article
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Expanding the role of small-molecule PSMA ligands beyond PET staging of prostate cancer

Nature Reviews Urology volume 17, pages 107–118 (2020)Cite this article

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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.

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Fig. 1: The potential utility of PSMA PET in non-standard urological settings.
Fig. 2: A patient with a left-sided renal cell carcinoma solitary pulmonary oligometastasis, subsequently treated with SABR.
Fig. 3: A patient with a solitary L5 spinal metastasis.
Fig. 4: A patient with Gleason 10 metastatic castration-resistant prostate cancer with progressive disease after docetaxel and enzalutamide.
Fig. 5: A patient with high-risk prostate cancer and spinous process osseous metastasis.

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Acknowledgements

S.S. is supported through a National Health and Medical Research Council Fellowship APP1122347 and Peter Mac Discovery Partner Fellowship.

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Author notes

  1. These authors contributed equally: Shankar Siva, Cristian Udovicich.

Authors and Affiliations

  1. Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia

    Shankar Siva & Cristian Udovicich

  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia

    Shankar Siva, Ben Tran, Declan G. Murphy & Michael S. Hofman

  3. Division of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia

    Ben Tran

  4. Walter and Eliza Hall Institute of Medical Research, Parkville, Australia

    Ben Tran

  5. Department of Urology, Royal Melbourne Hospital, Melbourne, Victoria, Australia

    Homi Zargar

  6. Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia

    Homi Zargar

  7. Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia

    Declan G. Murphy

  8. Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia

    Michael S. Hofman

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  1. Shankar Siva
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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.

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Correspondence to Shankar Siva.

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Nature Reviews Urology thanks T. Maurer and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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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

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