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18F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide

European Journal of Nuclear Medicine and Molecular Imaging volume 42, pages 1276–1283 (2015)Cite this article

An Erratum to this article was published on 22 April 2015

Abstract

Purpose

We investigated the role of 18F-methylcholine (FCH) PET/CT in the early evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide.

Methods

The study group comprised 36 patients with a median age of 72 years (range 48–90 years) who were treated with enzalutamide 160 mg once daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate-specific antigen (PSA) response. FCH PET/CT was performed at baseline and repeated after 3–6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS).

Results

At a median follow-up of 24.2 months (range 1.8–27.3 months), 34 patients were evaluable for early FCH PET/CT evaluation of response, and of these 17 showed progressive disease (PD) and 17 had stable disease or a partial response. A decrease in PSA level of more than 50 % was observed in 21 patients. Early FCH PET/CT PD predicted radiological PD 3 months in advance of CT in 12 of 18 patients (66 %) and was discordant with the decrease in PSA level in 13 patients. In 6 of these, biochemical PD was confirmed in 2 months. In multivariate analysis, only decrease in PSA level and FCH PET/CT were significant predictors of PFS (p = 0.0005 and p = 0.029, respectively), whereas decrease in PSA level alone was predictive of OS (p = 0.007).

Conclusion

This is one of the first studies to evaluate the role of FCH PET/CT as an early predictor of outcome in mCRPC patients treated with enzalutamide. Our preliminary results suggest that the combination of FCH PET/CT and decrease in PSA level could be a valid tool to predict PFS in mCRPC patients. PSA remains the single most important prognostic factor, while FCH PET/CT does not add more information on OS beyond that obtained from PSA. Further studies in larger populations are needed to confirm these data and to clarify the role of FCH PET/CT in predicting response to enzalutamide in mCRPC patients.

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References

  1. Logothetis CJ, Gallick GE, Maity SN, Kim J, Aparicio A, Efstathiou E, et al. Molecular classification of prostate cancer progression: foundation for marker-driven treatment of prostate cancer. Cancer Discov. 2013;3:849–61.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  2. Attard G, Richards J, de Bono JS. New strategies in metastatic prostate cancer: targeting the androgen receptor signaling pathway. Clin Cancer Res. 2011;17:1649–57.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  3. Karantanos T, Corn PG, Thompson TC. Prostate cancer progression after androgen deprivation therapy: mechanisms of castrate resistance and novel therapeutic approaches. Oncogene. 2013;2:5501–11.

    Article  Google Scholar 

  4. Yuan X, Cai C, Chen S, Chen S, Yu Z, Balk SP. Androgen receptor functions in castration-resistant prostate cancer and mechanisms of resistance to new agents targeting the androgen axis. Oncogene. 2014;33:2815–25.

    CAS  PubMed  Article  Google Scholar 

  5. Pignatta S, Arienti C, Zoli W, Di Donato M, Castoria G, Gabucci E, et al. Prolonged exposure to (R)-bicalutamide generates a LNCaP subclone with alteration of mitochondrial genome. Mol Cell Endocrinol. 2014;382:314–24.

    CAS  PubMed  Article  Google Scholar 

  6. Mostaghel EA, Plymate SR, Montgomery B. Molecular pathways: targeting resistance in the androgen receptor for therapeutic benefit. Clin Cancer Res. 2014;20:791–8.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  7. Scher HI, Beer TM, Higano CS, Anand A, Taplin ME, Efstathiou E, et al. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet. 2010;375:1437–46.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  8. 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.

    CAS  PubMed  Article  Google Scholar 

  9. 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.

    PubMed Central  PubMed  Article  Google Scholar 

  10. Picchio M, Messa C, Landoni C, Gianolli L, Sironi S, Brioschi M, et al. Value of [11C]choline-positron emission tomography for re-staging prostate cancer: a comparison with [18F]fluorodeoxyglucose-positron emission tomography. J Urol. 2003;169:1337–40.

    CAS  PubMed  Article  Google Scholar 

  11. Price DT, Coleman RE, Liao RP, Robertson CN, Polascik TJ, DeGrado TR. Comparison of [18F]fluorocholine and [18F]fluorodeoxyglucose for positron emission tomography of androgen dependent and androgen independent prostate cancer. J Urol. 2002;168:273–80.

    PubMed  Article  Google Scholar 

  12. Richter JA, Rodriguez M, Rioja J, Peñuelas I, Martí-Climent J, Garrastachu P, et al. Dual tracer 11C-choline and FDG-PET in the diagnosis of biochemical prostate cancer relapse after radical treatment. Mol Imaging Biol. 2010;12:210–7.

    PubMed  Article  Google Scholar 

  13. Krause BJ, Souvatzoglou M, Tuncel M, Herrmann K, Buck AK, Praus C, et al. The detection rate of [11C]choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer. Eur J Nucl Med Mol Imaging. 2008;35:18–23.

    CAS  PubMed  Article  Google Scholar 

  14. Castellucci P, Fuccio C, Nanni C, Santi I, Rizzello A, Lodi F, et al. Influence of trigger PSA and PSA kinetics on 11C-choline PET/CT detection rate in patients with biochemical relapse after radical prostatectomy. J Nucl Med. 2009;50:1394–400.

    PubMed  Article  Google Scholar 

  15. Giovacchini G, Picchio M, Coradeschi E, Bettinardi V, Gianolli L, Scattoni V, et al. Predictive factors of [11C]choline PET/CT in patients with biochemical failure after radical prostatectomy. Eur J Nucl Med Mol Imaging. 2010;37:301–9.

    PubMed  Article  Google Scholar 

  16. McCarthy M, Siew T, Campbell A, Lenzo N, Spry N, Vivian J, et al. 18F-Fluoromethylcholine (FCH) PET imaging in patients with castration-resistant prostate cancer: prospective comparison with standard imaging. Eur J Nucl Med Mol Imaging. 2011;38:14–22.

    PubMed  Article  Google Scholar 

  17. Beheshti M, Vali R, Waldenberger P, Fitz F, Nader M, Hammer J, et al. The use of F-18 choline PET in the assessment of bone metastases in prostate cancer: correlation with morphological changes on CT. Mol Imaging Biol. 2010;12:98–107.

    PubMed  Article  Google Scholar 

  18. Castellucci P, Fuccio C, Rubello D, Schiavina R, Santi I, Nanni C, et al. Is there a role for 11C-choline PET/CT in the early detection of metastatic disease in surgically treated prostate cancer patients with a mild PSA increase <1.5 ng/ml? Eur J Nucl Med Mol Imaging. 2011;38:55–63.

    PubMed  Article  Google Scholar 

  19. Bauman G, Belhocine T, Kovacs M, Ward A, Beheshti M, Rachinsky I. 18F-fluorocholine for prostate cancer imaging: a systematic review of the literature. Prostate Cancer Prostatic Dis. 2012;15:45–55.

    CAS  PubMed  Article  Google Scholar 

  20. Langsteger W, Balogova S, Huchet V, Beheshti M, Paycha F, Egrot C, et al. Fluorocholine (18F) and sodium fluoride (18F) PET/CT in the detection of prostate cancer: prospective comparison of diagnostic performance determined by masked reading. Q J Nucl Med Mol Imaging. 2011;55:448–57.

    CAS  PubMed  Google Scholar 

  21. Kwee SA, Coel MN, Ly BH, Lim J. 18F-Choline PET/CT imaging of RECIST measurable lesions in hormone refractory prostate cancer. Ann Nucl Med. 2009;23:541–8.

    CAS  PubMed  Article  Google Scholar 

  22. Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26:1148–59.

    PubMed Central  PubMed  Article  Google Scholar 

  23. 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.

  24. Mawlawi O, Podoloff DA, Kohlmyer S, Williams JJ, Stearns CW, Culp RF, et al. Performance characteristics of a newly developed PET/CT scanner using NEMA standards in 2D and 3D modes. J Nucl Med. 2004;45:1734–42.

    PubMed  Google Scholar 

  25. 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.

    PubMed Central  PubMed  Google Scholar 

  26. 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.

    PubMed  Article  Google Scholar 

  27. Giovacchini G, Picchio M, Garcia-Parra R, Briganti A, Abdollah F, Gianolli L, et al. 11C-choline PET/CT predicts prostate cancer-specific survival in patients with biochemical failure during androgen-deprivation therapy. J Nucl Med. 2014;55:233–41.

    CAS  PubMed  Article  Google Scholar 

  28. Jadvar H. Molecular imaging of prostate cancer with [F-18]-fluorodeoxyglucose PET. Nat Rev Urol. 2009;6:317–23.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  29. Jadvar H, Desai B, Ji L, Conti PS, Dorff TB, Groshen SG, et al. Baseline 18F-FDG PET/CT parameters as imaging biomarkers of overall survival in castrate-resistant metastatic prostate cancer. J Nucl Med. 2013;54:1195–201.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  30. Beheshti M, Langsteger W. Choline PET/CT compared with bone scintigraphy in the detection of bone metastases in prostate cancer patients. Eur J Nucl Med Mol Imaging. 2012;39:910–1.

    PubMed  Article  Google Scholar 

  31. Picchio M, Spinapolice EG, Fallanca F, Crivellaro C, Giovacchini G, Gianolli L, et al. [11C]Choline PET/CT detection of bone metastases in patients with PSA progression after primary treatment for prostate cancer: comparison with bone scintigraphy. Eur J Nucl Med Mol Imaging. 2012;39:13–26.

    CAS  PubMed  Article  Google Scholar 

  32. Ryan CJ, Shah S, Efstathiou E, Smith MR, Taplin ME, Bubley GJ, et al. Phase II study of abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer displaying bone flare discordant with serologic response. Clin Cancer Res. 2011;17:4854–61.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  33. De Giorgi U, Valero V, Rohren E, Mego M, Doyle GV, Miller MC, et al. Circulating tumor cells and bone metastases as detected by FDG-PET/CT in patients with metastatic breast cancer. Ann Oncol. 2010;21:33–9.

    PubMed  Article  Google Scholar 

  34. De Giorgi U, Mego M, Rohren EM, Liu P, Handy BC, Reuben JM, et al. 18F-FDG PET/CT findings and circulating tumor cell counts in the monitoring of systemic therapies for bone metastases from breast cancer. J Nucl Med. 2010;51:1213–8.

    PubMed  Article  Google Scholar 

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Acknowledgments

We thank Ursula Elbling for editorial assistance.

Conflicts of interest

None.

Author information

Affiliations

  1. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via Maroncelli 40, 47014, Meldola, Italy

    Ugo De Giorgi, Vincenza Conteduca, Salvatore Luca Burgio, Cecilia Menna, Lorena Rossi & Dino Amadori

  2. Diagnostic Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Paola Caroli, Giovanni Paganelli & Federica Matteucci

  3. Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Emanuela Scarpi

  4. Nuclear Medicine Unit, Morgagni-Pierantoni Hospital, Forlì, Italy

    Andrea Moretti & Riccardo Galassi

Authors
  1. Ugo De Giorgi
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  2. Paola Caroli
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Correspondence to Ugo De Giorgi.

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De Giorgi, U., Caroli, P., Scarpi, E. 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 42, 1276–1283 (2015). https://doi.org/10.1007/s00259-015-3042-5

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  • DOI: https://doi.org/10.1007/s00259-015-3042-5

Keywords

  • FCH PET/CT
  • Choline PET/CT
  • Enzalutamide
  • Therapeutic monitoring
  • Prostate cancer
  • CRPC