Abstract
Purpose
To evaluate 11C-choline PET/CT as a diagnostic tool for restaging prostate cancer (PCa), in a large, homogeneous and clinically relevant population of patients with biochemical recurrence (BCR) of PCa after primary therapy. The secondary aim was to assess the best timing for performing 11C-choline PET/CT during BCR.
Methods
We retrospectively analysed 9,632 11C-choline PET/CT scans performed in our institution for restaging PCa from January 2007 to June 2015. The inclusion criteria were: (1) proven PCa radically treated with radical prostatectomy (RP) or with primary external beam radiotherapy (EBRT); (2) PSA serum values available; (3) proven BCR (PSA >0.2 ng/mL after RP or PSA >2 ng/mL above the nadir after primary EBRT with rising PSA levels). Finally, 3,203 patients with recurrent PCa matching all the inclusion criteria were retrospectively enrolled and 4,426 scans were analysed.
Results
Overall, 52.8 % of the 11C-choline PET/CT scans (2,337/4,426) and 54.8 % of the patients (1,755/3,203) were positive. In 29.4 % of the scans, at least one distant finding was observed. The mean and median PSA values were, respectively, 4.9 and 2.1 ng/mL at the time of the scan (range 0.2 – 50 ng/mL). In our series, 995 scans were performed in patients with PSA levels between 1 and 2 ng/mL. In this subpopulation the positivity rate in the 995 scans was 44.7 %, with an incidence of distant findings of 19.2 % and an incidence of oligometastatic disease (one to three lesions) of 37.7 %. The absolute PSA value at the time of the scan and ongoing androgen deprivation therapy were associated with an increased probability of a positive 11C-choline PET/CT scan (p < 0.0001). In the ROC analysis, a PSA value of 1.16 ng/mL was the optimal cut-off value. In patients with a PSA value <1.16 ng/mL, 26.8 % of 1,426 11C-choline PET/CT scans were positive, with oligometastatic disease in 84.7 % of positive scans.
Conclusion
In a large cohort of patients, the feasibility of 11C-choline PET/CT for detecting the sites of metastatic disease in PCa patients with BCR was confirmed. The PSA level was the main predictor of a positive scan with 1.16 ng/mL as the optimal cut-off value. In the majority of positive scans oligometastatic disease, potentially treatable with salvage therapies, was observed.
Similar content being viewed by others
References
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30. doi:10.3322/caac.21332.
Mottet N, Bellmunt J, Briers E, van den Bergh RCN, Bolla M, van Casteren NJ, et al., Guidelines on prostate cancer. European Association of Urology; 2015.
Briganti A, Karnes RJ, Gandaglia G, Spahn M, Gontero P, Tosco L, et al. Natural history of surgically treated high-risk prostate cancer. Urol Oncol. 2015;33(4):163.e7–13.
Punnen S, Cooperberg MR, D’Amico AV, Karakiewicz PI, Moul JW, Scher HI, et al. Management of biochemical recurrence after primary treatment of prostate cancer: a systematic review of the literature. Eur Urol. 2013;64(6):905–15.
Freedland SJ, Presti Jr 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(4):736–41.
Boorjian SA, Eastham JA, Graefen M, Guillonneau B, Karnes RJ, Moul JW. A critical analysis of the long-term impact of radical prostatectomy on cancer control and function outcomes. Eur Urol. 2012;61(4):664–75.
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: what should we expect? Cancer. 2004;100(6):1283–92.
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(2):467–79.
Kattan MW, Wheeler TM, Scardino PT. Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer. J Clin Oncol. 1999;17(5):1499–507.
Choueiri TK, Dreicer R, Paciorek A, Carroll PR, Konety B. A model that predicts the probability of positive imaging in prostate cancer cases with biochemical failure after initial definitive local therapy. J Urol. 2008;179(3):906–10.
Suardi N, Gandaglia G, Gallina A, Di Trapani E, Scattoni V, Vizziello D. Long-term outcomes of salvage lymph node dissection for clinically recurrent prostate cancer: results of a single institution series with a minimum follow-up of 5 years. Eur Urol. 2015;67(2):299–309.
Ost P, Bossi A, Decaestecker K, De Meerleer G, Giannarini G, Karnes RJ. Metastasis-directed therapy of regional and distant recurrences after curative treatment of prostate cancer: a systematic review of the literature. Eur Urol. 2015;67(5):852–63.
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(1):55–63.
Picchio M, Mapelli P, Panebianco V, Castellucci P, Incerti E, Briganti A, et al. Imaging biomarkers in prostate cancer: role of PET/CT and MRI. Eur J Nucl Med Mol Imaging. 2015;42(4):644–55.
Mamede M, Ceci F, Castellucci P, Schiavina R, Fuccio C, Nanni C, et al. The role of 11C choline PET imaging in the early detection of recurrence in surgically treated prostate cancer patients with very low PSA level <0.5 ng/mL. Clin Nucl Med. 2013;38(9):e342–5.
Briganti A, Karnes RJ, Joniau S, Boorjian SA, Cozzarini C, Gandaglia G, et al. Prediction of outcome following early salvage radiotherapy among patients with biochemical recurrence after radical prostatectomy. Eur Urol. 2014;66(3):479–86.
Fossati N, Karnes RJ, Cozzarini C, Fiorino C, Gandaglia G, Joniau S, et al. Assessing the optimal timing for early salvage radiation therapy in patients with prostate-specific antigen rise after radical prostatectomy. Eur Urol. 2016;69(4):728–33.
Stephenson AJ, Scardino PT, Kattan MW, Pisansky TM, Slawin KM, Klein EA, et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol. 2007;25(15):2035–41. Erratum in: J Clin Oncol. 2007;25(26):4153.
Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart HG, Hadaschik BA, et al. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging. 2013;40(4):486–95.
Morigi JJ, Stricker PD, van Leeuwen PJ, Tang R, Ho B, Nguyen Q, et al. Prospective comparison of 18F-fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer patients who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med. 2015;56(8):1185–90.
Ceci F, Uprimny C, Nilica B, Geraldo L, Kendler D, Kroiss A, et al. (68)Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate? Eur J Nucl Med Mol Imaging. 2015;42(8):1284–94.
Pascali C, Bogni A, Iwata R, Cambie M, Bombardieri E. 11C-Methylation on C18 Sep-Pak cartridge: a convenient way to produce [N-methyl-11C]choline. J Labelled Comp Radiopharm. 2000;49:195–203.
Fanti S, Minozzi S, Castellucci P, Balduzzi S, Herrmann K, Krause BJ, et al. PET/CT with (11)C-choline for evaluation of prostate cancer patients with biochemical recurrence: meta-analysis and critical review of available data. Eur J Nucl Med Mol Imaging. 2016;43(1):55–69.
Castellucci P, Fanti S. Prostate cancer: identifying sites of recurrence with choline-PET-CT imaging. Nat Rev Urol. 2015;12(3):134–5.
Castellucci P, Ceci F, Graziani T, Schiavina R, Brunocilla E, Mazzarotto R, et al. Early biochemical relapse after radical prostatectomy: which prostate cancer patients may benefit from a restaging 11C-Choline PET/CT scan before salvage radiation therapy? J Nucl Med. 2014;55(9):1424–9.
Evangelista L, Briganti A, Fanti S, Joniau S, Reske S, Schiavina R, et al. New clinical indications for 18F/11C-choline, new tracers for positron emission tomography and a promising hybrid device for prostate cancer staging: a systematic review of the literature. Eur Urol. 2016. doi:10.1016/j.eururo.2016.01.029
Ceci F, Herrmann K, Castellucci P, Graziani T, Bluemel C, Schiavina R, et al. Impact of 11C-choline PET/CT on clinical decision making in recurrent prostate cancer: results from a retrospective two-centre trial. Eur J Nucl Med Mol Imaging. 2014;41(12):2222–31.
Soyka JD, Muster MA, Schmid DT, Seifert B, Schick U, Miralbell R, et al. Clinical impact of 18F-choline PET/CT in patients with recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2012;39(6):936–43.
Goldstein J, Even-Sapir E, Ben-Haim S, Saad A, Spieler B, Davidson T, et al. Does choline PET/CT change the management of prostate cancer patients with biochemical failure? Am J Clin Oncol. 2014. doi:10.1097/COC.0000000000000139
Ceci F, Castellucci P, Mamede M, Schiavina R, Rubello D, Fuccio C, et al. (11)C-Choline PET/CT in patients with hormone-resistant prostate cancer showing biochemical relapse after radical prostatectomy. Eur J Nucl Med Mol Imaging. 2013;40(2):149–55.
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(1):84–91.
Maines F, Caffo O, Donner D, Sperduti I, Bria E, Veccia A, et al. Serial (18)F-choline-PET imaging in patients receiving enzalutamide for metastatic castration-resistant prostate cancer: response assessment and imaging biomarkers. Future Oncol. 2016;12(3):333–42.
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(23):12448–58.
Meller B, Bremmer F, Sahlmann CO, Hijazi S, Bouter C, Trojan L, et al. Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy. EJNMMI Res. 2015;5(1):66.
Acknowledgments
The authors thank the whole Nuclear Medicine Team for their invaluable collaboration and their daily contribution over recent years. The authors thank Dr. Joshua James Morigi (Nuclear Medicine, University of Bologna) for language revision.
Author contributions
Tiziano Graziani and Francesco Ceci contributed equally.
Data collection: Tiziano Graziani, Giulia Polverari and Giacomo Maria Lima.
Data analysis: Francesco Ceci and Tiziano Graziani.
Statistical analysis: Francesco Ceci.
Manuscript writing and editing: Francesco Ceci and Paolo Castellucci.
Final manuscript revision: Alessio Giuseppe Morganti, Andrea Ardizzoni, Riccardo Schiavina and Stefano Fanti.
Project supervision: Paolo Castellucci and Stefano Fanti.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
None
Ethical approval
This study was performed according to the principles of the Declaration of Helsinki and its subsequent amendments.
Informed consent
Considering the retrospective design of the study, formal consent was not required.
Additional information
Tiziano Graziani and Francesco Ceci contributed equally to this work.
Rights and permissions
About this article
Cite this article
Graziani, T., Ceci, F., Castellucci, P. et al. 11C-Choline PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient series. Eur J Nucl Med Mol Imaging 43, 1971–1979 (2016). https://doi.org/10.1007/s00259-016-3428-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-016-3428-z