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PSMA targeted radioligandtherapy in metastatic castration resistant prostate cancer after chemotherapy, abiraterone and/or enzalutamide. A retrospective analysis of overall survival

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

Abstract

Aim

Our aim was to evaluate overall survival and parameters prognosticating longer survival in a large and homogeneous group of patients treated with 177Lu-PSMA-617 radioligand therapy with heavily pretreated advanced metastatic castration resistant prostate cancer.

Methods

A total of 104 patients were treated with 351 cycles of 177Lu-PSMA-617. Prostate specific antigen (PSA) changes after the first cycle of therapy were documented prior to a second cycle. Patients were followed-up for overall survival (OS). Any PSA decline, PSA decline ≥50%, initial PSA, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), visceral metastases and cumulative injected activity were analyzed and evaluated according to OS. Multivariable analysis with parameters with a p-value ≤0.05 in univariate analysis was performed, additionally adjusting for age and presence of visceral metastases.

Results

A total of 51 patients (49%) died during the observation period. The majority of patients (97%) presented with bone metastases, 77% with lymph node metastases and 32% with visceral metastases. All patients were treated with at least one line of chemotherapy. Either abiraterone or enzalutamide had been given in 100% of the patients. Any PSA decline occurred in 70 (67%) and a PSA decline ≥50% in 34 (33%) of patients after the first cycle. The median OS was 56.0 weeks (95%CI: 50.5–61.5). Initial PSA decline ≥50%, initial LDH, visceral metastases, second line chemotherapy or prior radium-223 did not have an effect on survival, whereas any initial PSA decline, initial ALP <220 U/L and cumulative injected activity ≥18.8 GBq were associated with a longer survival. A step-by-step analysis revealed a PSA decline ≥20.87% as the most noticeable cut-off prognosticating longer survival, which remained an independent prognosticator of improved OS in the multivariate analysis.

Conclusion

177Lu-PSMA-617 RLT is a new effective therapeutic and seems to prolong survival in patients with advanced mCRPC pretreated with chemotherapy, abiraterone and/or enzalutamide.

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References

  1. Ahmadzadehfar H, Rahbar K, Kurpig S, et al. Early side effects and first results of radioligand therapy with (177)Lu-DKFZ-617 PSMA of castrate-resistant metastatic prostate cancer: a two-centre study. EJNMMI Res. 2015;5:114.

    PubMed  Google Scholar 

  2. Brauer A, Grubert LS, Roll W, et al. 177Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2017.

  3. Rahbar K, Ahmadzadehfar H, Kratochwil C, et al. German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. J Nucl Med. 2017;58:85–90.

    Article  CAS  PubMed  Google Scholar 

  4. Rahbar K, Bode A, Weckesser M, et al. Radioligand Therapy With 177Lu-PSMA-617 as A Novel Therapeutic Option in Patients With Metastatic Castration Resistant Prostate Cancer. Clin Nucl Med. 2016;41:522–8.

    Article  PubMed  Google Scholar 

  5. Rahbar K, Schmidt M, Heinzel A, et al. Response and Tolerability of a Single Dose of 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer: A Multicenter Retrospective Analysis. J Nucl Med. 2016;57:1334–8.

    Article  CAS  PubMed  Google Scholar 

  6. Ahmadzadehfar H, Wegen S, Yordanova A, et al. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [177Lu]Lu-PSMA-617. Eur J Nucl Med Mol Imaging. 2017;44(9):1448–54.

    Article  CAS  PubMed  Google Scholar 

  7. Ahmadzadehfar H, Zimbelmann S, Yordanova A, et al. Radioligand therapy of metastatic prostate cancer using 177Lu-PSMA-617 after radiation exposure to 223Ra-dichloride. Oncotarget. 2017;8:55567–74.

    PubMed  PubMed Central  Google Scholar 

  8. Fendler WP, Kratochwil C, Ahmadzadehfar H, et al. 177Lu-PSMA-617 therapy, dosimetry and follow-up in patients with metastatic castration-resistant prostate cancer. Nuklearmedizin. 2016;55:123–8.

    Article  PubMed  Google Scholar 

  9. Yordanova A, Becker A, Eppard E, et al. The impact of repeated cycles of radioligand therapy using [177Lu]Lu-PSMA-617 on renal function in patients with hormone refractory metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2017.

  10. Fendler WP, Reinhardt S, Ilhan H, et al. Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer. Oncotarget. 2017;8:3581–90.

    Article  PubMed  Google Scholar 

  11. Cornford P, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer. Eur Urol. 2017;71:630–42.

    Article  PubMed  Google Scholar 

  12. Scher HI, Morris MJ, Stadler WM, et al. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34:1402–18.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hothorn TaL B. On the Exact Distribution of Maximally Selected Rank Statistics. Computational Statistics & Data Analysis. 2003;43:121–37.

    Article  Google Scholar 

  14. Kulkarni HR, Singh A, Schuchardt C, et al. PSMA-Based Radioligand Therapy for Metastatic Castration-Resistant Prostate Cancer: The Bad Berka Experience since 2013. J Nucl Med. 2016;57:97S–104S.

    Article  CAS  PubMed  Google Scholar 

  15. Baum RP, Kulkarni HR, Schuchardt C, et al. Lutetium-177 PSMA radioligand therapy of metastatic castration-resistant prostate cancer: Safety and efficacy. J Nucl Med. 2016;57(7):1006–13.

    Article  CAS  PubMed  Google Scholar 

  16. Smith M, De Bono J, Sternberg C, et al. Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1. J Clin Oncol. 2016;34:3005–13.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank the Radiochemistry Group at both Departments of Nuclear Medicine for their highly reliable production of 177Lu-PSMA-617, and the nursing staff and the nuclear medicine technologists for their support.

Disclosures

The University of Münster received consulting fees from ABX Advanced Biochemical Compounds, Radeberg, Germany for K.R., M.B. and M.E.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, University Hospital Muenster, Muenster, Germany

    K. Rahbar & M. Schäfers

  2. Department of Urology, University Hospital Muenster, Muenster, Germany

    M. Boegemann

  3. Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany

    A. Yordanova, M. Essler & H. Ahmadzadehfar

  4. Institute of Biostatistics and Clinical Research, University Hospital Muenster, Muenster, Germany

    M. Eveslage

Authors
  1. K. Rahbar
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  2. M. Boegemann
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  4. M. Eveslage
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  5. M. Schäfers
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  6. M. Essler
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  7. H. Ahmadzadehfar
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Correspondence to K. Rahbar.

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The authors declare that they have no financial or non-financial competing interests.

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. This article does not contain any studies with animals performed by any of the authors. This study was approved by the local ethics committee (No. 2016–585-f-S, Ethikkommission der Ärztekammer Westfalen-Lippe und der Westfälischen Wilhelms-Universität Münster).

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Rahbar, K., Boegemann, M., Yordanova, A. et al. PSMA targeted radioligandtherapy in metastatic castration resistant prostate cancer after chemotherapy, abiraterone and/or enzalutamide. A retrospective analysis of overall survival. Eur J Nucl Med Mol Imaging 45, 12–19 (2018). https://doi.org/10.1007/s00259-017-3848-4

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  • DOI: https://doi.org/10.1007/s00259-017-3848-4

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