Delayed response after repeated 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer
Radioligand therapy (RLT) using Lutetium-177 labeled PSMA-617 (Lu-PSMA) ligand is a new therapeutic option for salvage therapy in heavily pretreated patients with metastatic castration resistant prostate cancer. The aim of this retrospective study was to analyze response in patients receiving 3 cycles of Lu-PSMA.
Seventy-one patients (median age: 72 years; range 44–87) received 3 cycles of RLT with Lu-PSMA (mean administered activity: 6.016 ± 0.543 GBq) every 8 weeks. Response was evaluated using serum PSA levels and a PSA decline ≥50% was considered as biochemical response. Additionally, any PSA decline after the first cycle was evaluated for further therapy effects after the second and third cycle.
A total of 213 cycles were performed in 71 patients. Data for response and adverse events were available for all patients. A PSA decline ≥50% and some PSA decline occurred in 56% and 66% of the patients. Of 30 patients with a PSA response after the first cycle, 28 remained responders and 12/41 of non-responders responded to further therapy cycles.
RLT with Lu-177-PSMA-617 shows respectable response rates. In this retrospective analysis, a relevant number of patients showed a delayed response, even if they did not respond to the first cycle of the therapy.
KeywordsProstate-specific membrane antigen PSMA mCRPC Prostate cancer
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.
Compliance with ethical standards
The University of Muenster received consulting fees from ABX Advanced Biochemical Compounds, Radeberg, Germany for K.R., M.B. and M.E. The authors declare they have no conflict of interest according to the subject and matter of the presented article.
Conflict of interest
The authors declare that they have no financial or non-financial competing interests.
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).
- 1.Ahmadzadehfar H, Rahbar K, Kurpig S, Bogemann M, Claesener M, Eppard E, 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(1):114. https://doi.org/10.1186/s13550-015-0114-2.PubMedGoogle Scholar
- 2.Brauer A, Grubert LS, Roll W, Schrader AJ, Schafers M, Bogemann M, et al. 177Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2017; https://doi.org/10.1007/s00259-017-3751-z.
- 4.Fendler WP, Rahbar K, Herrmann K, Kratochwil C, Eiber M. 177Lu-PSMA radioligand therapy for prostate cancer. J Nucl Med. 2017; https://doi.org/10.2967/jnumed.117.191023.
- 6.Rahbar K, Bode A, Weckesser M, Avramovic N, Claesener M, Stegger L, 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(7):522–8. https://doi.org/10.1097/RLU.0000000000001240.CrossRefPubMedGoogle Scholar
- 7.Rahbar K, Schmidt M, Heinzel A, Eppard E, Bode A, Yordanova 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(9):1334–8. https://doi.org/10.2967/jnumed.116.173757.CrossRefPubMedGoogle Scholar
- 8.Ahmadzadehfar H, Eppard E, Kurpig S, Fimmers R, Yordanova A, Schlenkhoff CD, et al. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Oncotarget. 2016;7(11):12477–88. 10.18632/oncotarget.7245.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, 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(12):1402–18. https://doi.org/10.1200/JCO.2015.64.2702.CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Ahmadzadehfar H, Wegen S, Yordanova A, Fimmers R, Kurpig S, Eppard E, 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; https://doi.org/10.1007/s00259-017-3716-2.