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68Ga-PSMA-11 PET/CT-derived metabolic parameters for determination of whole-body tumor burden and treatment response in prostate cancer

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Abstract

Purpose

We aimed at evaluating the role of 68Ga-PSMA-11 PET/CT-derived metabolic parameters for assessment of whole-body tumor burden and its capability to determine therapeutic response in patients with prostate cancer.

Methods

A total of 142 patients with biochemical recurrence of prostate cancer underwent PET/CT with [68Ga]Ga-PSMA-HBED-CC (68Ga-PSMA-11). Quantitative assessment of all 641 68Ga-PSMA-11-positive lesions in the field of view was performed to calculate PSMA-derived parameters, including whole-body PSMA tumor volume (PSMA-TV) and whole-body total lesion PSMA (TL-PSMA), as well as the established SUVmax and SUVmean values. All PET-derived parameters were tested for correlation with serum PSA levels and for association with Gleason scores.

In 23 patients who underwent 68Ga-PSMA-11 PET/CT before and after therapy with either external beam radiation, androgen deprivation, or docetaxel chemotherapy, SUVmax and TL-PSMA were compared to radiographic response assessment of CT images based on RECIST 1.1 criteria and to biochemical response determined by changes of serum PSA levels.

Results

PSMA-TV and TL-PSMA demonstrated a significant correlation with serum PSA levels (P < 0.0001) and TL-PSMA was significantly different for different Gleason scores. The agreement rate between TL-PSMA derived from PET and biochemical response was 87% (95% confidence interval, 0.66–0.97; Cohen’s κ = 0.78; P < 0.01) and, thus, higher than for SUVmax, which was 74% (95% CI, 0.52–0.90; κ = 0.55; P < 0.01). Furthermore, agreement with PSA was higher for TL-PSMA and SUVmax than for CT-based response evaluation. Discordant findings between PET and CT were most likely due to limitations of CT and RECIST in rating small lymph nodes as metastases, as well as bone involvement, which was sometimes not detectable in CT.

Conclusion

68Ga-PSMA-11 PET/CT-derived metabolic tumor parameters showed promising results for evaluation of treatment response. Especially, TL-PSMA demonstrated higher agreement rates with biochemical response compared to SUVmax. Larger, ideally prospective trials are needed to help to reveal the full potential of metabolic parameters derived from PET imaging with 68Ga-PSMA-11.

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References

  1. Freedland SJ, Presti JC, Amling CL, Kane CJ, Aronson WJ, Dorey F, et al. Time trends in biochemical recurrence after radical prostatectomy: results of the SEARCH database. Urology. 2003;61:736–41.

    Article  PubMed  Google Scholar 

  2. Khuntia D, Reddy CA, Mahadevan A, Klein EA, Kupelian PA. Recurrence-free survival rates after external-beam radiotherapy for patients with clinical T1–T3 prostate carcinoma in the prostate-specific antigen era. Cancer. 2004;100:1283–92.

    Article  PubMed  Google Scholar 

  3. Bubendorf L, Schöpfer A, Wagner U, Sauter G, Moch H, Willi N, et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 2000;31:578–83.

    Article  PubMed  CAS  Google Scholar 

  4. Afshar-Oromieh A, Babich JW, Kratochwil C, Giesel FL, Eisenhut M, Kopka K, et al. The rise of PSMA ligands for diagnosis and therapy of prostate cancer. J Nucl Med. 2016;57:79S–89S.

    Article  PubMed  CAS  Google Scholar 

  5. 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.

    Article  PubMed  Google Scholar 

  6. 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.

    Article  PubMed  Google Scholar 

  7. Maurer T, Eiber M, Schwaiger M, Gschwend JE. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol. 2016;13:226.

    Article  PubMed  CAS  Google Scholar 

  8. Ben-Haim S, Ell P. 18F-FDG PET and PET/CT in the evaluation of cancer treatment response. J Nucl Med. 2009;50:88–99.

    Article  PubMed  Google Scholar 

  9. Bäuerle T, Semmler W. Imaging response to systemic therapy for bone metastases. Eur Radiol. 2009;19:2495–507.

    Article  PubMed  Google Scholar 

  10. Sandblom G, Ladjevardi S, Garmo H, Varenhorst E. The impact of prostate-specific antigen level at diagnosis on the relative survival of 28,531 men with localized carcinoma of the prostate. Cancer. 2008;112:813–9.

    Article  PubMed  Google Scholar 

  11. van Rossum PS, Fried DV, Zhang L, Hofstetter WL, Ho L, Meijer GJ, et al. The value of 18F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma. Eur J Nucl Med Mol Imaging. 2017;44:71–80.

    Article  PubMed  CAS  Google Scholar 

  12. Mikhaeel NG, Smith D, Dunn JT, Phillips M, Møller H, Fields PA, et al. Combination of baseline metabolic tumour volume and early response on PET/CT improves progression-free survival prediction in DLBCL. Eur J Nucl Med Mol Imaging. 2016;43:1209–19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Schmuck S, von Klot CA, Henkenberens C, Sohns JM, Christiansen H, Wester H-J, 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.

    Article  PubMed  Google Scholar 

  14. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent—update 2013. Eur Urol. 2014;65:124–37.

    Article  PubMed  Google Scholar 

  15. Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, 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 

  16. Eder M, Neels O, Müller M, Bauder-Wüst U, Remde Y, Schäfer M, et al. Novel preclinical and radiopharmaceutical aspects of [68Ga] Ga-PSMA-HBED-CC: a new PET tracer for imaging of prostate cancer. Pharmaceuticals. 2014;7:779–96.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. 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. 2016;43:84–91.

    Article  PubMed  CAS  Google Scholar 

  18. Picchio M, Berardi G, Fodor A, Busnardo E, Crivellaro C, Giovacchini G, et al. 11C-choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients. Eur J Nucl Med Mol Imaging. 2014;41:1270–9.

    Article  PubMed  CAS  Google Scholar 

  19. Jereczek-Fossa BA, Beltramo G, Fariselli L, Fodor C, Santoro L, Vavassori A, et al. Robotic image-guided stereotactic radiotherapy, for isolated recurrent primary, lymph node or metastatic prostate cancer. Int J Radiat Oncol Biol Phys. 2012;82:889–97.

    Article  PubMed  Google Scholar 

  20. Joo Hyun O, Lodge MA, Wahl RL. Practical PERCIST: a simplified guide to PET response criteria in solid tumors 1.0. Radiology. 2016;280:576.

    Article  Google Scholar 

  21. Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, 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.

    Article  PubMed  CAS  Google Scholar 

  22. Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Meas. 1960;20:37–46.

    Article  Google Scholar 

  23. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–74.

    Article  PubMed  CAS  Google Scholar 

  24. Kasperzyk JL, Finn SP, Flavin RJ, Fiorentino M, Lis RT, Hendrickson WK, et al. Prostate-specific membrane antigen protein expression in tumor tissue and risk of lethal prostate cancer. Cancer Epidemiology and Prevention Biomarkers. 2013; https://doi.org/10.1158/1055-9965.EPI-13-0668.

  25. Marchal C, Redondo M, Padilla M, Caballero J, Rodrigo I, Garcia J, et al. Expression of prostate specific membrane antigen (PSMA) in prostatic adenocarcinoma and prostatic intraepithelial neoplasia. Histol Histopathol. 2004;19:715–8.

    PubMed  CAS  Google Scholar 

  26. Thalgott M, Rack B, Eiber M, Souvatzoglou M, Heck MM, Kronester C, et al. Categorical versus continuous circulating tumor cell enumeration as early surrogate marker for therapy response and prognosis during docetaxel therapy in metastatic prostate cancer patients. BMC Cancer. 2015;15:458.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  28. De Giorgi U, Caroli P, Scarpi E, Conteduca V, Burgio SL, Menna C, et al. 18F-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.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    Article  PubMed  CAS  Google Scholar 

  30. Seitz AK, Rauscher I, Haller B, Krönke M, Luther S, Heck MM, et al. Preliminary results on response assessment using 68 Ga-HBED-CC-PSMA PET/CT in patients with metastatic prostate cancer undergoing docetaxel chemotherapy. Eur J Nucl Med Mol Imaging. 2017:1–11.

  31. Min SJ, Jang HJ, Kim JH. Comparison of the RECIST and PERCIST criteria in solid tumors: a pooled analysis and review. Oncotarget. 2016;7:27848.

    PubMed  PubMed Central  Google Scholar 

  32. 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.

    Article  PubMed  Google Scholar 

  33. 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. 2017:1–11.

  34. 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.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Clinic of Nuclear Medicine, University Hospital Erlangen, Erlangen, Germany

    Christian Schmidkonz, Michael Cordes, Daniela Schmidt, Theresa Ida Goetz, Michael Beck, Olaf Prante, Torsten Kuwert & Philipp Ritt

  2. Institute of Radiology, University Hospital Erlangen, Erlangen, Germany

    Tobias Bäuerle, Alexander Cavallaro & Michael Uder

  3. Pattern Recognition Lab, University Erlangen-Nürnberg, Erlangen, Germany

    Theresa Ida Goetz

  4. Department of Urology and Pediatric Urology, University Hospital Erlangen, Erlangen, Germany

    Bernd Wullich & Peter Goebell

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  1. Christian Schmidkonz
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  2. Michael Cordes
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  3. Daniela Schmidt
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  4. Tobias Bäuerle
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Correspondence to Christian Schmidkonz.

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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.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflicts of interest

Schmidkonz C, Cordes M, Beck M, Goetz Th I, Schmidt D, Prante O, Kuwert T, Ritt P: The Clinic of Nuclear Medicine in Erlangen has research cooperation with Siemens in the field of SPECT/CT, but not related to the data contained in this manuscript.

Kuwert T: has received honoraria for lectures on behalf of Siemens Molecular Imaging.

Goebell P: has received honoraria for lectures and participation in expert meetings from Pfizer, Janssen-Cilag, Novartis, GSK, BMS, and Bayer.

Wullich B: has received honoraria for lectures and participation in expert meetings from Janssen-Cilag and Astellas.

Uder M: has received honoraria for lectures and grants from Siemens, Bayer, Bracco, and Medtronic.

Bäuerle T: has received Honoria for lectures and grants from Bayer, Bracco, and Boeringer Ingelheim.

Beck M: has received honoraria for lectures from Bayer.

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Schmidkonz, C., Cordes, M., Schmidt, D. et al. 68Ga-PSMA-11 PET/CT-derived metabolic parameters for determination of whole-body tumor burden and treatment response in prostate cancer. Eur J Nucl Med Mol Imaging 45, 1862–1872 (2018). https://doi.org/10.1007/s00259-018-4042-z

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  • DOI: https://doi.org/10.1007/s00259-018-4042-z

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