Early changes of PSMA PET expression after initiation of androgen receptor signaling inhibitors in CRPC: an international multicenter retrospective study - PubMed (original) (raw)

Multicenter Study

. 2025 Aug;52(10):3700-3708.

doi: 10.1007/s00259-025-07178-2. Epub 2025 Mar 26.

Lena M Unterrainer 1 2 3, Tristan Grogan 6, Masatoshi Hotta 4 7, Loïc Djaileb 4 8, Andrei Gafita 4 9, Ida Sonni 4 10 11, Matthew B Rettig 12 13, Florian Rosar 14, Samer Ezziddin 14, Chloé S Denis 15, Ivan de Kouchkovsky 16 17, Rahul Aggarwal 16 17, Louise Emmett 18, Thomas A Hope 19, Johannes Czernin 4, Jeremie Calais 4

Affiliations

Multicenter Study

Early changes of PSMA PET expression after initiation of androgen receptor signaling inhibitors in CRPC: an international multicenter retrospective study

Lena M Unterrainer et al. Eur J Nucl Med Mol Imaging. 2025 Aug.

Abstract

Background: An increase of PSMA expression under androgen receptor signaling inhibitors (ARSi) measured on PSMA PET was reported: However, results were inconsistently reproduced clinically and the frequency and timing of the PSMA expression modulation by ARSi remains unknown.

Methods: In this multicenter retrospective study, we aimed at assessing in patients with CRPC the influence of ARSi early after initiation (≤ 30 days) on PSMA expression at the whole-body (WB) level by using WB PSMA PET quantitative parameters. (m)CRPC patients from 5 international sites who underwent a PSMA PET prior to (PET1) and early (< 30 days) after (PET2) ARSi initiation were included. WB-PSMA PET quantitative parameters (PSMA-positive WB-tumor volume (TV), WB-SUVmax, WB-SUVmean) and PSA changes between PET1 and PET2 (PSA1/PSA2) were evaluated. Changes of WB-TV / WB-SUVmax/mean between PET1 and PET2 were considered significant if ≥ 30% of increase or decrease.

Results: Fifty-six patients who initiated ARSi treatment were included. 30/56 (53.6%) were treated with an ARSi for the first time, 26/56 (41.1%) were previously treated with another ARSi agent and 29/56 (51.9%) received prior chemotherapy. 10/56 (17.9%) had a significantly increasing PSA of ≥ 25% between PET1 and PET2. 15/56 (27%), 14/56 (25%) and 1/56 (1.8%) patients had a significantly increasing WB-TV, WB-SUVmax or WB SUVmean of ≥ 30% between PET1 and PET2, respectively. The patients with significant WB-TV increase (n = 15) and with significant WB SUVmax increase (n = 14) did not differ significantly from the ones with stable or decreased WB-TV (n = 41) or WB-SUVmax (n = 42) in their clinical characteristics or their PSA responses.

Conclusions: In this analysis of patients with early PSMA PET follow-up after ARSi initiation, we observed a PSMA-upregulation by WB-PET imaging in 25% of the patients. Further studies are needed to better understand the potential synergistic and / or additive effects of AR- and PSMA-targeted approaches.

Clinical trial number: Not applicable.

Keywords: (m)CRPC; ARSi; PET; PSMA.

© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

PubMed Disclaimer

Conflict of interest statement

Declarations. Human ethics and consent to participate: This study was approved by sites’ institutional review board. Conflicts of interest: Lena M. Unterrainer reports funding from Bavarian Cancer Research Center (BZKF) and from the Munich Clinician Scientist Program (MCSP). She reports fees from Novartis (speaker), Telix (consultant) and Astellas Pharma Inc. (speaker) outside of the submitted work. Jeremie Calais acknowledged grant support from the Prostate Cancer Foundation (PCF). Jeremie Calais reports grants from support to his institution from Lantheus, Novartis, and POINT biopharma. He also reports Consulting activities (advisory boards, speaker, blinded reader) for Advanced Accelerator Applications, Amgen, Astellas, Bayer, Blue Earth Diagnostics Inc., Curium Pharma, Coretag, DS Pharma, Fibrogen, GE Healthcare, Isoray, IBA RadioPharma, Janssen Pharmaceuticals, Monrol, Lightpoint medical, Lantheus, Novartis, Nucleus Radiopharma, Pfizer, POINT biopharma, Progenics, Radiomedix, Radiopharm Theranostics, Sanofi, Siemens-Varian, SOFIE, Telix Pharmaceuticals, outside of the submitted work. Johannes Czernin reports the following disclosures: Sofie Biosciences (Founder) Trethera Corporation (Founder), Atkis Oncology (Medical Advisory Board). Thomas Hope has grant funding to the institution from Bayer, Clovis Oncology, GE Healthcare, Lantheus, Janssen, Novartis, Telix Pharmaceuticals, the Prostate CancerFoundation, and the National Cancer Institute (R01CA235741 and R01CA212148). He received personal fees from Bayer, Cardinal Health, BlueEarth Diagnostics, Lantheus, RayzeBio, Sanofi and received fees from and has an equity interest in Curium and AdvanCell. Louise Emmett reports the following disclosures: Advisory board: Novartis, Astellas, Clarity, Advancell and Trial support from: PCF challenge, Movember, Clarity, Novartis, St Vincent's Clinic foundation. The authors have no disclosures or conflicts of interest to declare relevant to this work.

References

    1. Lückerath K, Wei L, Fendler WP, Evans-Axelsson S, Stuparu AD, Slavik R, et al. Preclinical evaluation of PSMA expression in response to androgen receptor Blockade for theranostics in prostate cancer. EJNMMI Res. 2018;8:1–9.
    1. Staniszewska M, Fragoso Costa P, Eiber M, Klose JM, Wosniack J, Reis H, et al. Enzalutamide enhances PSMA expression of PSMA-low prostate cancer. Int J Mol Sci. 2021;22(14):7431.
    1. Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF, et al. Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2020;382(23):2197–206.
    1. Schoen MW, Carson KR, Eisen SA, Bennett CL, Luo S, Reimers MA, et al. Survival of veterans treated with enzalutamide and abiraterone for metastatic castrate resistant prostate cancer based on comorbid diseases. Prostate Cancer Prostatic Dis. 2023;26(4):743–50.
    1. Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. Diagnostic efficacy of 68gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol. 2016;195(5):1436–43.

Publication types

MeSH terms

Substances

LinkOut - more resources