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Measuring response in metastatic castration-resistant prostate cancer using PSMA PET/CT: comparison of RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP 1.0 criteria

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Abstract

Purpose

To compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the adapted Prostate Cancer Working Group Criteria 3 (aPCWG3), the adapted Positron Emission Tomography Response Criteria in Solid Tumors (aPERCIST), the PSMA PET Progression (PPP), and the Response Evaluation Criteria In PSMA-Imaging (RECIP) 1.0 for response evaluation using prostate-specific membrane antigen (PSMA)-PET/CT in men with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA radioligand therapy.

Methods

A total of 124 patients were included in this multicenter retrospective study. All patients received 177Lu-PSMA and underwent PSMA-PET/CT scans at baseline (bPET) and at 12 weeks (iPET). Imaging responses according to RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP 1.0 were interpreted by consensus among three blinded readers. Changes in total tumor burden were obtained using the semi-automatic qPSMA software. The response according to each criterion was classified to progressive disease (PD) vs no-PD. Primary outcome measure was the prognostic value (by Cox regression analysis) for overall survival (OS). Secondary outcome measure was the inter-reader reliability (by Cohen’s κ coefficient).

Results

A total of 43 (35%) of patients had non-measurable disease according to RECIST 1.1. Sixteen (13%), 66 (52%), 72 (58%), 69 (56%), and 39 (32%) of 124 patients had PD according to RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP, respectively. PD vs no-PD had significantly higher risk of death according to aPCWG3 (HR = 2.37; 95%CI, 1.62–3.48; p < 0.001), aPERCIST (HR = 2.48; 95%CI, 1.68–3.66; p < 0.001), PPP (HR = 2.72; 95%CI, 1.85–4.01; p < 0.001), RECIP 1.0 (HR = 4.33; 95%CI, 2.80–6.70; p < 0.001), but not according to RECIST 1.1 (HR = 1.29; 95%CI, 0.73–2.27; p = 0.38). The κ index of RECIST 1.1, aPCWG3, aPERCIST 1.0, PPP, and RECIP 1.0 for identifying PD vs no-PD were 0.50 (95%CI, 0.32–0.76), 0.72 (95%CI, 0.63–0.82), 0.68 (95%CI, 0.63–0.73), 0.73 (95%CI, 0.63–0.83), and 0.83 (95%CI, 0.77–0.88), respectively.

Conclusion

PSMA-PET-specific criteria for early response evaluation in men with mCRPC treated with 177Lu-PSMA achieved higher prognostic values and inter-reader reliabilities in comparison to conventional CT assessment or to criteria adapted to PSMA-PET from other imaging modalities. RECIP 1.0 identified the fewest patients with PD and achieved the highest risk of death for PD vs. no-PD, suggesting that other classification methods tend to overcall progression. Prospective validation of our findings on an independent patient cohort is warranted.

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Funding

The research leading to these results received funding from the Prostate Cancer Foundation (grant 21YOUN18).

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Authors and Affiliations

  1. Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, 200 Medical Plaza, Suite B114-61, Los Angeles, CA, 90095, USA

    Andrei Gafita, Vishnu Murthy, Wesley R. Armstrong, Jeremie Calais & Matthias R. Benz

  2. Department of Nuclear Medicine, Technical University Munich, Klinikum Rechts Der Isar, Munich, Germany

    Andrei Gafita, Isabel Rauscher, Wang Hui, Wolfgang A. Weber & Matthias Eiber

  3. Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany

    Wolfgang P. Fendler, Ken Herrmann & Manuel Weber

  4. Department of Radiological Sciences, University of California Los Angeles, Los Angeles, CA, USA

    Matthias R. Benz

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  1. Andrei Gafita
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Correspondence to Andrei Gafita.

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Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The retrospective analysis was approved by the Ethics Committee of each participating site (TUM 115/18S, UCLA IRB #20–000954, UKE 19–8570-BO) which waived the necessity for study specific consent.

Conflict of interest

ME reports fees from Blue Earth Diagnostics Ltd. (consultant, research funding), Novartis/AAA (consultant), Telix (consultant), Bayer (consultant, research funding), RayzeBio (consultant), Point Biopharma (consultant) and Janssen Pharmaceuticals (consultant, speakers bureau), Parexel (image review) and Bioclinica (image review) outside the submitted work and a patent application for rhPSMA. JCa reports prior consulting activities outside of the submitted work for Advanced Accelerator Applications, Blue Earth Diagnostics, Curium Pharma, GE Healthcare, IBA Radiopharma, Janssen Pharmaceuticals, POINT biopharma, Progenics Pharmaceuticals, Radiomedix, and Telix Pharmaceuticals. KH reports personal fees from Bayer, personal fees and other from Sofie Biosciences, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from BTG, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, personal fees from Bain Capital, and personal fees from MPM Capital outside the submitted work. WPF reports fees from SOFIE Bioscience (research funding), Janssen (consultant, speakers bureau), Calyx (consultant), Bayer (consultant, speakers bureau, research funding), Parexel (image review), and AAA (speakers bureau) outside of the submitted work. WAW was on advisory boards and received compensation from Bayer, Blue Earth Diagnostics, Endocyte, ITM, RayzeBio, and Pentixapharm. He has received research support from BMS, Imaginab, Ipsen, and Piramal. No other potential conflict of interest relevant to this article was reported.

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This article is part of the Topical Collection on Oncology - Genitourinary.

Andrei Gafita and Isabel Rauscher are joint first authorship.

Manuel Weber and Matthias R. Benz are joint senior authorship.

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Gafita, A., Rauscher, I., Fendler, W.P. et al. Measuring response in metastatic castration-resistant prostate cancer using PSMA PET/CT: comparison of RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP 1.0 criteria. Eur J Nucl Med Mol Imaging 49, 4271–4281 (2022). https://doi.org/10.1007/s00259-022-05882-x

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