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Review
. 2022 Mar 5:14:17588359221081922.
doi: 10.1177/17588359221081922. eCollection 2022.

Biomarkers to personalize treatment with 177Lu-PSMA-617 in men with metastatic castration-resistant prostate cancer - a state of the art review

Isabel Heidegger  1 , Claudia Kesch  2 , Alexander Kretschmer  3 , Igor Tsaur  4 , Francesco Ceci  5 , Massimo Valerio  6 , Derya Tilki  7 , Giancarlo Marra  8 , Felix Preisser  9 , Christian D Fankhauser  10 , Fabio Zattoni  11 , Peter Chiu  12 , Ignacio Puche-Sanz  13 , Jonathan Olivier  14 , Roderik C N van den Bergh  15 , Veeru Kasivisvanathan  16 , Andreas Pircher  17 , Irene Virgolini  18 , Giorgio Gandaglia  19
Affiliations
Review

Biomarkers to personalize treatment with 177Lu-PSMA-617 in men with metastatic castration-resistant prostate cancer - a state of the art review

Isabel Heidegger et al. Ther Adv Med Oncol. .

Abstract

Radioligand therapy with Lutetium-177 (177Lu)-Prostate-specific membrane antigen (PSMA) has shown to prolong survival in metastatic castration resistant prostate cancer (mCRPC). One of the major challenges for clinicians in the future is to select those patients who would benefit most from this therapy to position it in the treatment landscape of mCRPC. This, in turn, will lead to the delivery of personalized therapies. In this narrative review article we summarize recent studies investigating both predictive and prognostic clinical, imaging-based, and molecular biomarkers to predict treatment response to 177Lu-PSMA-617 radioligand therapy with the aim of identifying men who should be considered for this approach. Of note, the evidence on the role of biomarkers currently relies on small retrospective trials and their validation in larger prospective cohorts is necessary before these results can be translated in the clinical practice.

Keywords: 177Lu-PSMA-617 radioligand therapy; biomarkers; mCRPC.

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Conflict of interest statement

Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Mechanism of action of lutetium-177-labeled prostate-specific membrane antigen: PSMA-617 targeting ligand radiolabeled with [177Lu] binds to PSMA molecule on the prostate cancer cell membrane >177Lu-atom releases ß and γ particles > DNA damage > cell death. [177Lu], lutetium-177; PSMA, prostate-specific membrane antigen.
Figure 2.
Figure 2.
18 F-FDG PET-CT (a) and 68Ga-PSMA-11 PET-CT (b) images show an high uptake of FDG (SUV Max 9,25) in the liver metastasis with no relevant 68Ga-PSMA uptake.
Figure 3.
Figure 3.
Biomarkers associated with no/short response to 177Lu-PSMA-617 therapy. + indicates prognostic biomarker, 0 indicates predictive biomarker, + 0 indicates prognostic and predictive biomarker-; ARSI, androgen receptor signaling inhibitors.
See this image and copyright information in PMC

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