Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 4/2018

01-04-2018 | Original Article

Preliminary results on response assessment using 68Ga-HBED-CC-PSMA PET/CT in patients with metastatic prostate cancer undergoing docetaxel chemotherapy

Authors: Anna Katharina Seitz, Isabel Rauscher, Bernhard Haller, Markus Krönke, Sophia Luther, Matthias M. Heck, Thomas Horn, Jürgen E. Gschwend, Markus Schwaiger, Matthias Eiber, Tobias Maurer

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 4/2018

Login to get access

Abstract

Purpose

To investigate the value of 68Ga-HBED-CC PSMA (68Ga-PSMA) PET/CT for response assessment in metastatic castration-sensitive and castration-resistant prostate cancer (mCSPC and mCRPC) during docetaxel chemotherapy.

Methods

68Ga-PSMA PET/CT was performed in seven mCSPC patients before and after six cycles of upfront docetaxel chemotherapy and in 16 mCRPC patients before and after three cycles of palliative docetaxel chemotherapy. Radiographic treatment response was evaluated separately on the 68Ga-PSMA PET and CT datasets. Changes in 68Ga-PSMA uptake (SUVmean) were assessed on a per-patient and a per-lesion basis using the PERCIST scoring system with slight modification. Treatment response was defined as absence of any PSMA uptake in all target lesions on posttreatment PET (complete response, CR) or a decrease in summed SUVmean of ≥30% (partial response, PR). The appearance of a new PET-positive lesion or an increase in summed SUVmean of ≥30% (progressive disease, PD) indicated nonresponse. A moderate change in summed SUVmean (between −30% and +30%) without a change in the number of target lesions was defined as stable disease (SD). For treatment response assessment on CT, RECIST1.1 criteria were used. Radiographic responses on 68Ga-PSMA PET [RR(PET)] and on CT [RR(CT)] were compared and correlated with biochemical response (BR). A decrease in serum PSA level of ≥50% was defined as biochemical PR.

Results

Biochemical PR was found in six of seven patients with mCSPC (86%, 95% confidence interval 42% to 99.6%). The concordance rate was higher between BR and RR(PET) than between BR and RR(CT) (6/7 vs. 3/6 patients. 68Ga-PSMA PET and CT were concordant in only three patients (50%, 12% to 88%). In mCRPC patients, biochemical PR was found in six of 16 patients (38%, 15% to 65%). Outcome prediction was concordant between BR and RR(PET) in nine of 16 patients (56%), and between BR and RR(CT) in only four of 12 patients (33%) with target lesions on CT. 68Ga-PSMA PET and CT results corresponded in seven of 12 patients (58%, 28% to 85%).

Conclusion

Our preliminary results suggest that 68Ga-PSMA PET might be a promising method for treatment response assessment in mCSPC and mCRPC. The data indicate that for different metastatic sites, the performance of 68Ga-PSMA PET in response assessment might be superior to that of the conventional CT approach and could help differentiate between progressive disease and treatment response. Because of the limited number of patients, the differences revealed in our study were not statistically significant. Thus larger and prospective studies are clearly needed and warranted to confirm the value of 68Ga-PSMA PET as an imaging biomarker for response assessment.
Appendix
Available only for authorised users
Literature
1.
go back to reference Siegel RL, Sahar L, Portier KM, Ward EM, Jemal A. Cancer death rates in US congressional districts. CA Cancer J Clin. 2015;65:339–44.CrossRefPubMed Siegel RL, Sahar L, Portier KM, Ward EM, Jemal A. Cancer death rates in US congressional districts. CA Cancer J Clin. 2015;65:339–44.CrossRefPubMed
2.
go back to reference Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. J Urol. 2002;168:9–12.CrossRefPubMed Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. J Urol. 2002;168:9–12.CrossRefPubMed
3.
go back to reference Sridhar SS, Freedland SJ, Gleave ME, Higano C, Mulders P, Parker C, et al. Castration-resistant prostate cancer: from new pathophysiology to new treatment. Eur Urol. 2014;65:289–99.CrossRefPubMed Sridhar SS, Freedland SJ, Gleave ME, Higano C, Mulders P, Parker C, et al. Castration-resistant prostate cancer: from new pathophysiology to new treatment. Eur Urol. 2014;65:289–99.CrossRefPubMed
4.
go back to reference 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. N Engl J Med. 2004;351:1502–12.CrossRefPubMed 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. N Engl J Med. 2004;351:1502–12.CrossRefPubMed
5.
go back to reference James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163–77.CrossRefPubMedPubMedCentral James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163–77.CrossRefPubMedPubMedCentral
6.
go back to reference Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737–46.CrossRefPubMedPubMedCentral Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737–46.CrossRefPubMedPubMedCentral
7.
go back to reference 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 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
8.
go back to reference Cook GJ, 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 Cook GJ, 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
9.
go back to reference Lordick F, Ott K, Krause BJ, 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 Lordick F, Ott K, Krause BJ, 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
11.
go back to reference 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;32:3059–68.CrossRefPubMedPubMedCentral 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;32:3059–68.CrossRefPubMedPubMedCentral
12.
go back to reference Caffo O, Maines F, Donner D, Veccia A, Chierichetti F, Galligioni E. Impact of enzalutamide administration on primary prostate cancer volume: a metabolic evaluation by choline positron emission tomography in castration-resistant prostate cancer patients. Clin Genitourin Cancer. 2014;12:312–6.CrossRefPubMed Caffo O, Maines F, Donner D, Veccia A, Chierichetti F, Galligioni E. Impact of enzalutamide administration on primary prostate cancer volume: a metabolic evaluation by choline positron emission tomography in castration-resistant prostate cancer patients. Clin Genitourin Cancer. 2014;12:312–6.CrossRefPubMed
13.
go back to reference Ceci F, Castellucci P, Graziani T, Schiavina R, Renzi R, Borghesi M, et al. (11)C-choline PET/CT in castration-resistant prostate cancer patients treated with docetaxel. Eur J Nucl Med Mol Imaging. 2016;43:84–91.CrossRefPubMed Ceci F, Castellucci P, Graziani T, Schiavina R, Renzi R, Borghesi M, et al. (11)C-choline PET/CT in castration-resistant prostate cancer patients treated with docetaxel. Eur J Nucl Med Mol Imaging. 2016;43:84–91.CrossRefPubMed
14.
go back to reference 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. 2014;5:12448–58.CrossRefPubMedPubMedCentral 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. 2014;5:12448–58.CrossRefPubMedPubMedCentral
15.
go back to reference Schwarzenböck SM, Eiber M, Kundt G, Retz M, Sakretz M, Kurth J, et al. Prospective evaluation of [11C]choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:2105–13.CrossRefPubMed Schwarzenböck SM, Eiber M, Kundt G, Retz M, Sakretz M, Kurth J, et al. Prospective evaluation of [11C]choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:2105–13.CrossRefPubMed
16.
go back to reference De Giorgi U, Caroli P, Scarpi E, Conteduca V, Burgio SL, Menna C, et al. (18)F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide. Eur J Nucl Med Mol Imaging. 2015;42:1276–83.CrossRefPubMed De Giorgi U, Caroli P, Scarpi E, Conteduca V, Burgio SL, Menna C, et al. (18)F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide. Eur J Nucl Med Mol Imaging. 2015;42:1276–83.CrossRefPubMed
17.
go back to reference Maurer T, Eiber M, Schwaiger M, Gschwend JE. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol. 2016;13:226–35.CrossRefPubMed Maurer T, Eiber M, Schwaiger M, Gschwend JE. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol. 2016;13:226–35.CrossRefPubMed
18.
go back to reference Afshar-Oromieh A, Haberkorn U, Hadaschik B, Habl G, Eder M, Eisenhut M, et al. PET/MRI with a 68Ga-PSMA ligand for the detection of prostate cancer. Eur J Nucl Med Mol Imaging. 2013;40:1629–30.CrossRefPubMed Afshar-Oromieh A, Haberkorn U, Hadaschik B, Habl G, Eder M, Eisenhut M, et al. PET/MRI with a 68Ga-PSMA ligand for the detection of prostate cancer. Eur J Nucl Med Mol Imaging. 2013;40:1629–30.CrossRefPubMed
19.
go back to reference Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:197–209.CrossRefPubMed Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:197–209.CrossRefPubMed
20.
go back to reference Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56:668–74.CrossRefPubMed Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56:668–74.CrossRefPubMed
21.
go back to reference Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. Diagnostic efficacy of (68)gallium-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 Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. Diagnostic efficacy of (68)gallium-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
22.
go back to reference Pyka T, Okamoto S, Dahlbender M, Tauber R, Retz M, Heck M, et al. Comparison of bone scintigraphy and Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:2114–21.CrossRefPubMed Pyka T, Okamoto S, Dahlbender M, Tauber R, Retz M, Heck M, et al. Comparison of bone scintigraphy and Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:2114–21.CrossRefPubMed
23.
go back to reference Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014;65:467–79.CrossRefPubMed Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014;65:467–79.CrossRefPubMed
24.
go back to reference Eder M, Schafer M, Bauder-Wust U, Hull WE, Wangler C, Mier W, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem. 2012;23:688–97.CrossRefPubMed Eder M, Schafer M, Bauder-Wust U, Hull WE, Wangler C, Mier W, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem. 2012;23:688–97.CrossRefPubMed
25.
go back to reference Martin R, Juttler S, Muller M, Wester HJ. Cationic eluate pretreatment for automated synthesis of [68Ga]CPCR4.2. Nucl Med Biol. 2014;41:84–9.CrossRefPubMed Martin R, Juttler S, Muller M, Wester HJ. Cationic eluate pretreatment for automated synthesis of [68Ga]CPCR4.2. Nucl Med Biol. 2014;41:84–9.CrossRefPubMed
26.
go back to reference 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(Suppl 1):122S–50S.CrossRefPubMedPubMedCentral 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(Suppl 1):122S–50S.CrossRefPubMedPubMedCentral
27.
go back to reference 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 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
28.
go back to reference Eiber M, Weirich G, Holzapfel K, Souvatzoglou M, Haller B, Rauscher I, et al. Simultaneous Ga-PSMA HBED-CC PET/MRI improves the localization of primary prostate cancer. Eur Urol. 2016;70:829–36.CrossRefPubMed Eiber M, Weirich G, Holzapfel K, Souvatzoglou M, Haller B, Rauscher I, et al. Simultaneous Ga-PSMA HBED-CC PET/MRI improves the localization of primary prostate cancer. Eur Urol. 2016;70:829–36.CrossRefPubMed
29.
go back to reference Budaus L, Leyh-Bannurah SR, Salomon G, Michl U, Heinzer H, Huland H, et al. Initial experience of (68)Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol. 2016;69:393–6.CrossRefPubMed Budaus L, Leyh-Bannurah SR, Salomon G, Michl U, Heinzer H, Huland H, et al. Initial experience of (68)Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol. 2016;69:393–6.CrossRefPubMed
30.
go back to reference 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 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
31.
go back to reference Halabi S, Kelly WK, Ma H, Zhou H, Solomon NC, Fizazi K, et al. Meta-analysis evaluating the impact of site of metastasis on overall survival in men with castration-resistant prostate cancer. J Clin Oncol. 2016;34:1652–9.CrossRefPubMedPubMedCentral Halabi S, Kelly WK, Ma H, Zhou H, Solomon NC, Fizazi K, et al. Meta-analysis evaluating the impact of site of metastasis on overall survival in men with castration-resistant prostate cancer. J Clin Oncol. 2016;34:1652–9.CrossRefPubMedPubMedCentral
Metadata
Title
Preliminary results on response assessment using 68Ga-HBED-CC-PSMA PET/CT in patients with metastatic prostate cancer undergoing docetaxel chemotherapy
Authors
Anna Katharina Seitz
Isabel Rauscher
Bernhard Haller
Markus Krönke
Sophia Luther
Matthias M. Heck
Thomas Horn
Jürgen E. Gschwend
Markus Schwaiger
Matthias Eiber
Tobias Maurer
Publication date
01-04-2018
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 4/2018
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-017-3887-x

Other articles of this Issue 4/2018

European Journal of Nuclear Medicine and Molecular Imaging 4/2018 Go to the issue