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Prognostic value of 18F–choline PET/CT metabolic parameters in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide

  • Paola Caroli
  • Ugo De Giorgi
  • Emanuela Scarpi
  • Lorenzo Fantini
  • Andrea Moretti
  • Riccardo Galassi
  • Monica Celli
  • Vincenza Conteduca
  • Lorena Rossi
  • Emanuela Bianchi
  • Giovanni Paganelli
  • Federica Matteucci
Original Article

Abstract

Purpose

The role of 18F–choline positron emission tomography/computed tomography (FCH-PET/CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been firmly established in recent years. We analyzed the prognostic value of functional parameters such as mean standardized uptake volume (SUVmean), maximum standardized uptake volume (SUVmax), metabolic total volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax), and total lesion activity (TLA: the product of MTV and mean standardized uptake value) estimated with FCH-PET/CT in mCRPC patients in progression after docetaxel and treated with new antiandrogen receptor therapies, abiraterone or enzalutamide.

Methods

We retrospectively studied 94 mCRPC patients, mean age 74 years (range 42–90), previously treated with docetaxel who were treated with either abiraterone (n = 52) or enzalutamide (n = 42). An FCH-PET/CT was performed at baseline, and patients were evaluated on a monthly basis for serological PSA response and every 3 months for radiological response. We measured MTV, SUVmean, SUVmax and TLA for each lesion and analyzed the sum of MTV (SMTV), SUVmean (SSUVmean), SUVmax (SSUVmax) and TLA (STLA) values for a maximum of 20 lesions. Univariate analysis was used to correlate these data with PFS and OS.

Results

We observed a median SMTV of 130 cm3, median SSUVmax of 106.5 and a median STLA of 495,070. All of these parameters were significant for PFS and OS in univariate analysis, while only STLA was significant for PFS and OS in multivariate analysis after adjusting for lesion and age (p < 0.0001 and p = 0.001, respectively). Baseline PSA values maintained a certain reliability for OS (p = 0.034).

Conclusions

Semiquantitative parameters of FCH-PET/CT play a prognostic role in mCRCP patients treated with abiraterone or enzalutamide.

Keywords

TLA FCH-PET/CT Abiraterone Enzalutamide CRPC Castration-resistant prostate cancer 

Notes

Acknowledgements

The authors would like to thank Grainne Eileen Tierney for editorial assistance.

Author contributions

Study concepts and design: PC, UDG and FM.

Provision of study materials or patients: UDG, VC, EB and LR.

Collection and assembly of data: PC, FM, UDG and MS.

Diagnostic imaging: RG, AM, PC, MC, LF and FM.

Analysis and interpretation of data: PC, UDG, FM, PG and MS.

Drafting of manuscript: PC.

Critical revision of the manuscript for important intellectual content: FM and PG.

All authors read and approved the final manuscript.

Compliance with ethical standards

Ethical approval

The protocol was approved by the Ethics Committee of Area Vasta Romagna and by the competent Italian regulatory authorities. The study was performed in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.

Informed consent

All patients gave their written informed consent.

Conflicts of interest

The authors declare that they have no competing interests.

References

  1. 1.
    Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, et al. International variation in prostate cancer incidence and mortality rates. Eur Urol. 2012;61:1079–92.CrossRefPubMedGoogle Scholar
  2. 2.
    Pfitzenmaier J, Pahernik S, Tremmel T, Haferkamp A, Buse S, Hohenfellner M. Positive surgical margins after radical prostatectomy: do they have an impact on biochemical or clinical progression. BJU Int. 2008;102:1413–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Attard G, Parker C, Eeles RA, Schröder F, Tomlins SA, Tannock I, et al. Prostate cancer. Lancet. 2016;387:70–82.CrossRefPubMedGoogle Scholar
  4. 4.
    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.CrossRefPubMedGoogle Scholar
  5. 5.
    De Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97.CrossRefPubMedGoogle Scholar
  7. 7.
    Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368:138–48.CrossRefPubMedGoogle Scholar
  8. 8.
    Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424–33.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376:1147–5.CrossRefPubMedGoogle Scholar
  10. 10.
    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. N Engl J Med. 2013;369:213–23.CrossRefPubMedGoogle Scholar
  11. 11.
    Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22.CrossRefPubMedGoogle Scholar
  12. 12.
    Scher HI, Lu D, Schreiber NA, Louw J, Graf RP, Vargas HA, et al. Association of AR-V7 on circulating tumor cells as a treatment-specific biomarker with outcomes and survival in castration-resistant prostate cancer. JAMA Oncol. 2016;2:1441–9.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Salvi S, Casadio V, Conteduca V, Burgio SL, Menna C, Bianchi E, et al. Circulating cell-free AR and CYP17A1 copy number variations may associate with outcome of metastatic castration-resistant prostate cancer patients treated with abiraterone. Br J Cancer. 2015;112:1717–24.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Salvi S, Casadio V, Conteduca V, Lolli C, Gurioli G, Martignano F, et al. Circulating AR copy number and outcome to enzalutamide in docetaxel-treated metastatic castration-resistant prostate cancer. Oncotarget. 2016;7:37839–45.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Challapalli A, Barwick T, Tomasi G, O’ Doherty M, Contractor K, Stewart S, et al. Exploring the potential of [11C]choline-PET/CT as a novel imaging biomarker for predicting early treatment response in prostate cancer. Nucl Med Commun. 2014;35:20–9.CrossRefPubMedGoogle Scholar
  16. 16.
    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.CrossRefPubMedGoogle Scholar
  17. 17.
    Conteduca V, Wetterskog D, Sharabiani MTA, et al. Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study. Ann Oncol. 2017;28:1508–16.CrossRefPubMedGoogle Scholar
  18. 18.
    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.CrossRefPubMedGoogle Scholar
  19. 19.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Kwee SA, Lim J, Watanabe A, Kromer-Baker K, Coel MN. Prognosis related to metastatic burden measured by 18F-Fluorocholine PET/CT in castration resistant prostate cancer. J Nucl Med. 2014;55:905–10.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Ho KC, Fang YD, Chung HW, Liu YC, Chang JW, Hou MM, et al. TLG-S criteria are superior to both EORTC and PERCIST for predicting outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib. Eur J Nucl Med Mol Imaging. 2016;43:2155–65.CrossRefPubMedGoogle Scholar
  22. 22.
    Marinelli B, Espinet-Col C, Ulaner GA, McArthur HL, Gonen M, Jochelson M, et al. Prognostic value of FDG PET/CT-based metabolic tumor volumes in metastatic triple negative breast cancer patients. Am J Nucl Med Mol Imaging. 2026;6:120–7.Google Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Paola Caroli
    • 1
  • Ugo De Giorgi
    • 2
  • Emanuela Scarpi
    • 3
  • Lorenzo Fantini
    • 1
  • Andrea Moretti
    • 4
  • Riccardo Galassi
    • 4
  • Monica Celli
    • 1
  • Vincenza Conteduca
    • 2
  • Lorena Rossi
    • 2
  • Emanuela Bianchi
    • 5
  • Giovanni Paganelli
    • 1
  • Federica Matteucci
    • 1
  1. 1.Nuclear Medicine UnitIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCSMeldolaItaly
  2. 2.Department of Medical OncologyIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCSMeldolaItaly
  3. 3.Unit of Biostatistics and Clinical Trials UnitIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCSMeldolaItaly
  4. 4.Nuclear Medicine UnitMorgagni Pierantoni HospitalForlìItaly
  5. 5.Department of Medical OncologyInfermi HospitalRiminiItaly

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