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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 5/2019

Open Access 01-05-2019 | Original Article

Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer

Authors: Bernhard Grubmüller, Daniela Senn, Gero Kramer, Pascal Baltzer, David D’Andrea, Karl Hermann Grubmüller, Markus Mitterhauser, Harald Eidherr, Alexander R. Haug, Wolfgang Wadsak, Sarah Pfaff, Shahrokh F. Shariat, Marcus Hacker, Markus Hartenbach

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 5/2019

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Abstract

Purpose

The first aim of this study was to evaluate 68Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA PET) parameters for assessment of response to 177Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC). The second aim was to investigate factors associated with overall survival (OS).

Methods

We retrospectively assessed mean standardized uptake values (SUVmean) and total tumor volumes (TTV) on PSMA PET in 38 of 55 mCRPC patients before and after RLT. PSA testing and PSMA PET/CT(MRI) imaging were performed during the 8 weeks before and the 6 weeks after RLT. PSMA PET and CT(MRI) images were reviewed separately according to the modified PET Response Criteria in Solid Tumors (mPERCIST) and RECIST1.1. The results were compared with PSA responses. Associations between OS and the RECIST evaluation and changes in SUVmean, TTV, and PSA, CRP, LDH, hemoglobin and ALP levels were determined in a univariable survival analysis.

Results

The median PSA level at the time of pretherapy PSMA PET/CT(MRI) was 60.8 ng/ml (IQR 15.4, 264.2 ng/ml). After RLT the median PSA level decreased by 44%, TTV by 45.1%, SUVmean by 25.8% and RECIST by 11.3%. A PSA response was seen in 18 patients (47.4%), stable disease in 12 (31.6%) and progressive disease in 8 (21.1%). Contrary to the changes in SUVmean and the RECIST evaluation, the change in TTV was significantly associated with PSA response (p = 0.15, p = 0.58, and p < 0.001, respectively). After a median follow-up of 17 months (IQR 8.0, 24.2 months), 11 patients (28.9%) had died of their prostate cancer. The changes in both TTV and PSA levels were associated with OS (HR 1.001, 95% CI 1–1.003, p = 0.04, and HR 1.004, 95% CI 1.001–1.008, p = 0.01, respectively), while the changes in SUVmean and the RECIST evaluation were not. The pre-therapy CRP level was also associated with OS (HR 1.07, 95% CI 1.009–1.14, p = 0.02).

Conclusion

TTV on PSMA PET seems to be a reliable parameter for response assessment in mCRPC patients undergoing RLT and might overcome the limitations of RECIST in prostate cancer. Furthermore, the change in TTV was significantly associated with OS in our cohort.
Literature
1.
Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. New Engl J Med. 2004;351:1502–12.CrossRefPubMed
2.
Bahl A, Oudard S, Tombal B, Özgüroĝlu M, Hansen S, Kocak I, et al. Impact of cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial. Ann Oncol. 2013;24:2402–8.CrossRefPubMedPubMedCentral
3.
Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. New Engl J Med. 2013;368:138–48.CrossRefPubMed
4.
Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. New Engl J Med. 2014;371:424–33.CrossRefPubMed
5.
Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al. Alpha emitter Radium-223 and survival in metastatic prostate cancer. New Engl J Med. 2013;369:213–23.CrossRefPubMed
6.
Fendler WP, Rahbar K, Herrmann K, Kratochwil C, Eiber M. 177Lu-PSMA radioligand therapy for prostate cancer. J Nucl Med. 2017;58:1196–200.CrossRefPubMed
7.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed
8.
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;34:1402–18.CrossRefPubMedPubMedCentral
9.
Cook GJR, Azad G, Padhani AR. Bone imaging in prostate cancer: the evolving roles of nuclear medicine and radiology. Clin Transl Imaging. 2016;4:439–47.CrossRefPubMedPubMedCentral
10.
Hartenbach M, Hartenbach S, Bechtloff W, Danz B, Kraft K, Klemenz B, et al. Combined PET/MRI improves diagnostic accuracy in patients with prostate cancer: a prospective diagnostic trial. Clin Cancer Res. 2014;20:3244–53.CrossRefPubMed
11.
Lordick F, Ott K, Krause B-J, Weber WA, Becker K, Stein HJ, et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007;8:797–805.CrossRefPubMed
12.
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059–67.CrossRefPubMedPubMedCentral
13.
Grubmüller B, Baltzer P, D’Andrea D, Korn S, Haug AR, Hacker M, et al. 68Ga-PSMA 11 ligand PET imaging in patients with biochemical recurrence after radical prostatectomy – diagnostic performance and impact on therapeutic decision-making. Eur J Nucl Med Mol Imaging. 2017;49:1374–8.
14.
Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. Diagnostic efficacy of 68Gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol. 2016;195:1436–43.CrossRefPubMed
15.
Kaittanis C, Andreou C, Hieronymus H, Mao N, Foss CA, Eiber M, et al. Prostate-specific membrane antigen cleavage of vitamin B9 stimulates oncogenic signaling through metabotropic glutamate receptors. J Exp Med. 2018;215:159–75.CrossRefPubMedPubMedCentral
16.
Seitz AK, Rauscher I, Haller B, Krönke M, Luther S, Heck MM, et al. Preliminary results on response assessment using 68Ga-HBED-CC-PSMA PET/CT in patients with metastatic prostate cancer undergoing docetaxel chemotherapy. Eur J Nucl Med Mol Imaging. 2017;45:602–12.CrossRefPubMed
17.
Zhao J, Sun G, Liao B, Zhang X, Armstrong CM, Yin X, et al. Novel nomograms for castration-resistant prostate cancer and survival outcome in patients with de novo bone metastatic prostate cancer. BJU Int. 2018;120:818.
18.
Liao S-G, Cheng H-H, Lei Y. C-reactive protein is a prognostic marker for patients with castration-resistant prostate cancer. Oncol Res Treat. 2016;39:266–71.CrossRefPubMed
19.
Mori K, Kimura T, Onuma H, Kimura S, Yamamoto T, Sasaki H, et al. Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer. Prostate. 2017;77:1144–50.CrossRefPubMed
20.
Eiber M, Herrmann K, Calais J, Hadaschik B, Giesel FL, Hartenbach M, et al. Prostate cancer molecular imaging standardized evaluation (PROMISE): proposed miTNM classification for the interpretation of PSMA-ligand PET/CT. J Nucl Med. 2018;59:469–78.CrossRefPubMed
21.
Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50:122S–50S.CrossRefPubMed
22.
23.
Hillier SM, Kern AM, Maresca KP, Marquis JC, Eckelman WC, Joyal JL, et al. 123I-MIP-1072, a small-molecule inhibitor of prostate-specific membrane antigen, is effective at monitoring tumor response to taxane therapy. J Nucl Med. 2011;52:1087–93.CrossRefPubMed
24.
De Giorgi U, Caroli P, Burgio SL, Menna C, Conteduca V, Bianchi E, et al. Early outcome prediction on 18F-fluorocholine PET/CT in metastatic castration-resistant prostate cancer patients treated with abiraterone. Oncotarget Impact J. 2014;5:12448–58.
25.
Ceci F, Castellucci P, Graziani T, Schiavina R, Renzi R, Borghesi M, et al. 11C-choline PET/CT in castration-resistant prostate cancer patients treated with docetaxel. Eur J Nucl Med Mol Imaging. 2015;43:84–91.CrossRefPubMed
26.
Schmuck S, von Klot CA, Henkenberens C, Sohns JM, Christiansen H, Wester HJ, et al. Initial experience with volumetric 68Ga-PSMA I&T PET/CT for assessment of whole-body tumor burden as a quantitative imaging biomarker in patients with prostate cancer. J Nucl Med. 2017;58:1962–8.CrossRefPubMed
27.
Pyka T, Okamoto S, Dahlbender M, Tauber R, Retz M, Heck M, et al. Comparison of bone scintigraphy and 68Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:2114–21.CrossRefPubMed
28.
Rathke H, Giesel FL, Flechsig P, Kopka K, Mier W, Hohenfellner M, et al. Repeated 177Lu-labeled PSMA-617 radioligand therapy using treatment activities of up to 9.3 GBq. J Nucl Med. 2018;59:459–65.CrossRefPubMed
29.
Aide N, Lasnon C, Veit-Haibach P, Sera T, Sattler B, Boellaard R. EANM/EARL harmonization strategies in PET quantification: from daily practice to multicentre oncological studies. Eur J Nucl Med Mol Imaging. 2017;44:17–31.CrossRefPubMedPubMedCentral
Metadata
Title
Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer
Authors
Bernhard Grubmüller
Daniela Senn
Gero Kramer
Pascal Baltzer
David D’Andrea
Karl Hermann Grubmüller
Markus Mitterhauser
Harald Eidherr
Alexander R. Haug
Wolfgang Wadsak
Sarah Pfaff
Shahrokh F. Shariat
Marcus Hacker
Markus Hartenbach
Publication date
01-05-2019
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 5/2019
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-018-4236-4

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