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Prognostic biomarkers in men with metastatic castration-resistant prostate cancer receiving [177Lu]-PSMA-617

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Abstract

Purpose

We analysed quantitative biomarkers derived from both baseline whole-body imaging and blood serum to identify prognostic markers in patients treated within the lutetium-177 prostate-specific membrane antigen (LuPSMA) phase 2 trial.

Methods

PET image analysis was carried out using whole-body segmentation quantifying molecular tumour volume (SUV > 3 threshold for PSMA, SUV > liver+2sd for fluorodeoxyglucose (FDG) including SUVmax and SUVmean. For baseline bone scans, EXINI bone scan index (BSI) was used to calculate the percentage of involved bone. Baseline alkaline phosphatase (ALP), lactate dehydrogenase (LDH), prostate specific antigen (PSA) and PSA doubling time were also used in this analysis. We used univariate cox regression analysis and log-rank comparison with optimised cut-offs to find suitable biomarkers prognostic of overall survival from time of enrolment.

Results

This analysis identified FDG-positive tumour volume (FDGvol; HR 2.6; 95% CI, 1.4–4.8), mean intensity of PSMA-avid tumour uptake (PSMAmean; HR 0.89; 95% CI, 0.8–0.98), bone scan index (BSI; HR 2.3; 95% CI, 1.2–4.4), ALP (HR 1.1; 95% CI, 1–1.2) and LDH (HR 1.2; 95% CI, 1–1.5) as biomarkers prognostic of overall survival.

Conclusions

In addition to established biomarkers, both FDG and PSMA PET/CT parameters have prognostic significance for survival in men undergoing LuPSMA therapy.

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References

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Acknowledgements

EXINI quantitative bone analysis was kindly performed by Dr. Lars Edenbrandt. MH is supported by a Clinical Fellowship from the Peter MacCallum Foundation. For the clinical study, Lutetium-177 was kindly supplied by the Australian Nuclear Science and Technology Organisation ANSTO, Sydney, Australia) and PSMA-617 from Advanced Biochemical Compounds (ABX, Radeberg, Germany) and Endocyte (a Novartis company). MH additionally acknowledges grant support from Movember Australia, Prostate Cancer Foundation (PCF), the Prostate Cancer Foundation of Australia (PCFA), US Department of Defence and the Victorian Cancer Agency (VCA).

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Correspondence to Michael S. Hofman.

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Conflict of interest

MH is the chair of the ANZUP TheraP Study which receives research support from Prostate Cancer Foundation of Australia (PCFA) and Endocyte (a Novartis company). Unrelated to this work, he has received honorarium and travel support from Janssen, Ipsen and Sanofi Genzyme. RJH is supported by a National Health and Medical Research Foundation Practitioner Fellowship and receives research support from the Neuroendocrine Tumor Research Foundation (NETRF), Clarity Pharmaceuticals and Ipsen. He holds stock in Telix Pharmaceuticals. SS reports a consulting or advisory role for Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Astra Zeneca, Janssen and Roche; and research funding from research support from the Movember Australia, Prostate Cancer Foundation (PCF), the Victoria Cancer Agency (VCA), Endocyte, Astra Zeneca, Amgen, Bristol-Myers Squibb and Merck Sharp & Dohme.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Peter Mac ethics committee (approval date: 26 August 2015) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This trial is registered with the Australian New Zealand Clinical Trials Registry, number 12615000912583. This article does not contain any studies with animals performed by any of the authors. The study was investigator-initiated and sponsored by the Peter MacCallum Cancer Centre, Melbourne, Australia. All patients signed written informed consent prior to participation in the study. The authors are responsible for the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review and approval of the manuscript. MSH had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Data sharing

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Ferdinandus, J., Violet, J., Sandhu, S. et al. Prognostic biomarkers in men with metastatic castration-resistant prostate cancer receiving [177Lu]-PSMA-617. Eur J Nucl Med Mol Imaging 47, 2322–2327 (2020). https://doi.org/10.1007/s00259-020-04723-z

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