Prediction of response and survival after standardized treatment with 7400&nbsp;MBq <sup>177</sup>Lu-PSMA-617 every 4&nbsp;weeks in patients with metastatic castration-resistant prostate cancer

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Abstract

Background and aims

[ ¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) is a new therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). However, identification of reliable prognostic factors is hampered by heterogeneous treatment regimens applied in previous studies. Hence, we sought clinical factors able to predict response and survival to PSMA-RLT in a homogenous group of patients, all receiving 7400 MBq every 4 weeks.

Patients and methods

Data of 61 patients (mean age 71.6 ± 6.9 years, median basal PSA 70.7 [range 1.0–4890 μg/L]), pretreated with abiraterone/enzalutamide (75.4%) and docetaxel/cabazitaxel (68.9%), received three cycles of PSMA-RLT (mean 7321 ± 592 MBq) at four weekly intervals and were analyzed retrospectively. General medical conditions and laboratory parameters of every patients were regularly assessed. Response to therapy was based on PSA levels 1 month after the 3rd cycle. Binary logistic regression test and Kaplan-Meier estimates were used to evaluate predictors and overall survival (OS).

Results

Forty-nine (80.3%) patients demonstrated a therapy response in terms of any PSA decline, while 21 (19.7%) patients showed increase or no changes in their PSA levels. Baseline hemoglobin (Hb) significantly predicted PSA reductions of ≥ 50% 4 weeks after receiving the 3rd PSMA-RLT ( P = 0.01, 95% CI: 1.09–2.09) with an AUC of 0.68 (95% CI: 0.54–0.81). The levels of basal Hb and basal PSA were able to predict survival of patients, both P < 0.05 (relative risk 1.51 and 0.79, 95% CI: 1.09–2.09 and 0.43–1.46), respectively. In comparison to patients with reduced basal Hb, patients with normal basal Hb levels lived significantly longer (median survival not reached vs. 89 weeks, P = 0.016). Also, patients with basal PSA levels ≤ 650 μg/L had a significantly longer survival than patients with basal PSA levels > 650 μg/L (median survival not reached vs. 97 weeks, P = 0.031). Neither pretreatments with abiraterone/enzalutamide or docetaxel/cabazitaxel nor distribution of metastasis affected survival and rate of response to PSMA-RLT.

Conclusion

Basal Hb level is an independent predictor for therapy response and survival in patients receiving PSMA-RLT every 4 weeks. Both baseline PSA ≤ 650 μg/L and normal Hb levels were associated with longer survival.

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(177)Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of (177)Lu-PSMA-617 in a large cohort of patients.

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Author and article information

Contributors

Alexander R. Haug:

ORCID: http://orcid.org/0000-0002-8308-6174

alexander.haug@meduniwien.ac.at

Journal

Journal ID (nlm-ta): Eur J Nucl Med Mol Imaging

Journal ID (iso-abbrev): Eur J Nucl Med Mol Imaging

Title: European Journal of Nuclear Medicine and Molecular Imaging

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 1619-7070

ISSN (Electronic): 1619-7089

Publication date (Electronic): 30 October 2020

Publication date PMC-release: 30 October 2020

Publication date (Print): 2021

Volume: 48

Issue: 5

Pages: 1650-1657

Affiliations

[1 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, , Medical University of Vienna, ; Vienna, Austria

[2 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Department of Urology, , Medical University of Vienna, ; Vienna, Austria

[3 ]GRID grid.5386.8, ISNI 000000041936877X, Department of Urology, , Weill Cornell Medical College, ; New York, NY USA

[4 ]GRID grid.4491.8, ISNI 0000 0004 1937 116X, Department of Urology, Second Faculty of Medicine, , Charles University, ; Prague, Czech Republic

[5 ]GRID grid.448878.f, ISNI 0000 0001 2288 8774, Institute for Urology and Reproductive Health, , I.M. Sechenov First Moscow State Medical University, ; Moscow, Russia

[6 ]GRID grid.267313.2, ISNI 0000 0000 9482 7121, Department of Urology, , University of Texas Southwestern Medical Center, ; Dallas, TX USA

[7 ]GRID grid.499898.d, Center for Biomarker Research in Medicine, , CBmed GmbH, ; Graz, Austria

[8 ]Ludwig Boltzmann Institute Applied Diagnostics, Vienna, Austria

[9 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Christian Doppler Laboratory for Applied Metabolomics (CDL AM), , Medical University of Vienna, ; Vienna, Austria

Author information

Alexander R. Haug http://orcid.org/0000-0002-8308-6174

Article

Publisher ID: 5082

DOI: 10.1007/s00259-020-05082-5

PMC ID: 8113146

PubMed ID: 33128131

SO-VID: edb22953-26bf-4d66-8098-c46c31064c5e

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 17 June 2020

Date accepted : 18 October 2020

Funding

Funded by: Medical University of Vienna

Open Access :

Open access funding provided by Medical University of Vienna.

Custom metadata

ScienceOpen disciplines: Radiology & Imaging

Keywords: psma-rlt,mcrpc,response prediction,survival prediction,psa

Data availability:

ScienceOpen disciplines: Radiology & Imaging

Keywords: psma-rlt, mcrpc, response prediction, survival prediction, psa

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