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Response and outcome of liver metastases in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing 177Lu-PSMA-617 radioligand therapy

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Little is known about the efficacy of prostate-specific membrane antigen (PSMA)–targeted radioligand therapy (RLT) against liver metastases of metastatic castration-resistant prostate cancer (mCRPC). We retrospectively analyzed efficacy-related outcomes of 177Lu-PSMA-617 RLT in this setting and potential predictors of those outcomes.

Methods

Twenty-eight consecutive mCRPC patients with liver metastases given 177Lu-PSMA-617 RLT were analyzed retrospectively. Their planned regimen was 4–6 cycles at 6 ± 2-week intervals; the mean activity/cycle was 6.5 ± 0.5 GBq. Hepatic response was determined by modified positron emission tomography response criteria in solid tumors; association of such response with overall survival (OS) was tested, as were relationships of the selected patient, disease, and treatment characteristics with hepatic progression-free survival (PFShep) and OS. Survival analyses used Kaplan–Meier curves, log-rank test at p < 0.05 significance, and Cox proportional-hazards modeling.

Results

Median (minimum–maximum) follow-up was 37.5 (2.3–50.6) months. In liver metastases, complete or partial response was observed in 6 patients (21%) each, and stable disease in 1 (4%), for hepatic disease control in 46%. Overall, median (95% confidence interval) PFShep was 5.7 (2.2–9.2) months, and OS, 11.7 (3.0–20.4) months. Patients with hepatic disease control did not reach the median OS, while those with hepatic progressive disease had median OS (95% confidence interval) of 6.4 (1.6–11.1) months. In multivariate analysis, hepatic disease control by 177Lu-PSMA-617 RLT was significantly independently associated with OS, as was a prostate-specific antigen decline of ≥ 50% after 2 RLT cycles, and good baseline performance status (Eastern Cooperative Oncology Group 0–1). Hepatic tumor burden (≤ 25% vs. > 25% of liver volume) had no apparent relationship with hepatic tumor response, PFShep, or OS.

Conclusion

177Lu-PSMA-617 RLT frequently controlled liver metastases, resulting in long PFShep and significantly improved OS. Hepatic tumor burden appeared to lack any relationship with treatment efficacy, supporting 177Lu-PSMA-617 RLT of late-stage/end-stage mCRPC with liver metastases.

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Acknowledgments

Robert J. Marlowe, Spencer-Fontayne Corporation, Jersey City, NJ, USA, edited this manuscript.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Saarland University, Homburg, Germany

    Fadi Khreish, Niklas Kochems, Florian Rosar, Martin Ries, Stephan Maus, Mark Bartholomä & Samer Ezziddin

  2. Department of Nuclear Medicine, Saarland University Hospital, Kirrberger Str. Geb. 50, 66421, Homburg, Germany

    Fadi Khreish

  3. Department of Nuclear Medicine, Frankfurt University, Frankfurt am Main, Germany

    Amir Sabet

  4. Department of Urology, Saarland University, Homburg, Germany

    Matthias Saar

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  1. Fadi Khreish
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Correspondence to Fadi Khreish.

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All procedures performed in the patients described herein were in accordance with the ethical standards of the Institutional and/or National Research Ethics Committees and with the 1964 Helsinki Declaration and its later amendments, or with comparable ethical standards. This report does not include any animal studies.

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Written informed consent for 177Lu-PSMA-617 RLT and the use of their de-identified data in scientific analyses and reports were obtained from all study participants.

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Khreish, F., Kochems, N., Rosar, F. et al. Response and outcome of liver metastases in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing 177Lu-PSMA-617 radioligand therapy. Eur J Nucl Med Mol Imaging 48, 103–112 (2021). https://doi.org/10.1007/s00259-020-04828-5

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