Jeremie Calais1, Francesco Ceci2, Matthias Eiber3, Thomas A Hope4, Michael S Hofman5, Christoph Rischpler6, Tore Bach-Gansmo7, Cristina Nanni8, Bital Savir-Baruch9, David Elashoff10, Tristan Grogan11, Magnus Dahlbom12, Roger Slavik13, Jeannine Gartmann12, Kathleen Nguyen12, Vincent Lok12, Hossein Jadvar14, Amar U Kishan15, Matthew B Rettig16, Robert E Reiter16, Wolfgang P Fendler17, Johannes Czernin18. 1. Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Institute of Urologic Oncology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: jcalais@mednet.ucla.edu. 2. Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Nuclear Medicine, Department of Medical Sciences, University of Turin, Turin, Italy. 3. Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Munich, Germany. 4. Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA. 5. Molecular Imaging and Nuclear Medicine Therapeutics, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia. 6. Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. 7. Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway. 8. Metropolitan Nuclear Medicine, S Orsola-Malpighi University Hospital, Bologna, Italy. 9. Division of Nuclear Medicine, Department of Radiology, Loyola University Medical Center, Maywood, IL, USA. 10. Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA; Department of Medicine Statistics Core, University of California Los Angeles, Los Angeles, CA, USA. 11. Department of Medicine Statistics Core, University of California Los Angeles, Los Angeles, CA, USA. 12. Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA. 13. Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA. 14. Division of Nuclear Medicine, Department of Radiology, University of Southern California, Los Angeles, CA, USA. 15. Institute of Urologic Oncology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA; Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA. 16. Institute of Urologic Oncology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA; Department of Urology, University of California Los Angeles, Los Angeles, CA, USA. 17. Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. 18. Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Institute of Urologic Oncology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.
Abstract
BACKGROUND: National Comprehensive Cancer Network guidelines consider 18F-fluciclovine PET-CT for prostate cancer biochemical recurrence localisation after radical prostatectomy, whereas European Association of Urology guidelines recommend prostate-specific membrane antigen (PSMA) PET-CT. To the best of our knowledge, no prospective head-to-head comparison between these tests has been done so far. The aim of this study was to compare prospectively paired 18F-fluciclovine and PSMA PET-CT scans for localising biochemical recurrence of prostate cancer after radical prostatectomy in patients with low prostate-specific antigen (PSA) concentrations (<2·0 ng/mL). METHODS: This was a prospective, single-centre, open-label, single-arm comparative study done at University of California Los Angeles (Los Angeles, CA, USA). Patients older than 18 years of age with prostate cancer biochemical recurrence after radical prostatectomy and PSA levels ranging from 0·2 to 2·0 ng/mL without any prior salvage therapy and with a Karnofsky performance status of at least 50 were eligible. Patients underwent 18F-fluciclovine (reference test) and PSMA (index test) PET-CT scans within 15 days. Detection rate of biochemical recurrence at the patient level and by anatomical region was the primary endpoint. A statistical power analysis demonstrated that a sample size of 50 patients was needed to show a 22% difference in detection rates in favour of PSMA (test for superiority). Each PET scan was interpreted by three independent masked readers and a consensus majority interpretation was generated (two vs one) to determine positive findings. This study is registered with ClinicalTrials.gov, number NCT02940262, and is complete. FINDINGS: Between Feb 26, 2018, and Sept 20, 2018, 143 patients were screened for eligibility, of whom 50 patients were enrolled into the study. Median follow-up was 8 months (IQR 7-9). The primary endpoint was met; detection rates were significantly lower with 18F-fluciclovine PET-CT (13 [26%; 95% CI 15-40] of 50) than with PSMA PET-CT (28 [56%; 41-70] of 50), with an odds ratio (OR) of 4·8 (95% CI 1·6-19·2; p=0·0026) at the patient level; in the subanalysis of the pelvic nodes region (four [8%; 2-19] with 18F-fluciclovine vs 15 [30%; 18-45] with PSMA PET-CT; OR 12·0 [1·8-513·0], p=0·0034); and in the subanalysis of any extrapelvic lesions (none [0%; 0-6] vs eight [16%; 7-29]; OR non-estimable [95% CI non-estimable], p=0·0078). INTERPRETATION: With higher detection rates, PSMA should be the PET tracer of choice when PET-CT imaging is considered for subsequent treatment management decisions in patients with prostate cancer and biochemical recurrence after radical prostatectomy and low PSA concentrations (≤2·0 ng/mL). Further research is needed to investigate whether higher detection rates translate into improved oncological outcomes. FUNDING: None.
BACKGROUND: National Comprehensive Cancer Network guidelines consider 18F-fluciclovine PET-CT for prostate cancer biochemical recurrence localisation after radical prostatectomy, whereas European Association of Urology guidelines recommend prostate-specific membrane antigen (PSMA) PET-CT. To the best of our knowledge, no prospective head-to-head comparison between these tests has been done so far. The aim of this study was to compare prospectively paired 18F-fluciclovine and PSMA PET-CT scans for localising biochemical recurrence of prostate cancer after radical prostatectomy in patients with low prostate-specific antigen (PSA) concentrations (<2·0 ng/mL). METHODS: This was a prospective, single-centre, open-label, single-arm comparative study done at University of California Los Angeles (Los Angeles, CA, USA). Patients older than 18 years of age with prostate cancer biochemical recurrence after radical prostatectomy and PSA levels ranging from 0·2 to 2·0 ng/mL without any prior salvage therapy and with a Karnofsky performance status of at least 50 were eligible. Patients underwent 18F-fluciclovine (reference test) and PSMA (index test) PET-CT scans within 15 days. Detection rate of biochemical recurrence at the patient level and by anatomical region was the primary endpoint. A statistical power analysis demonstrated that a sample size of 50 patients was needed to show a 22% difference in detection rates in favour of PSMA (test for superiority). Each PET scan was interpreted by three independent masked readers and a consensus majority interpretation was generated (two vs one) to determine positive findings. This study is registered with ClinicalTrials.gov, number NCT02940262, and is complete. FINDINGS: Between Feb 26, 2018, and Sept 20, 2018, 143 patients were screened for eligibility, of whom 50 patients were enrolled into the study. Median follow-up was 8 months (IQR 7-9). The primary endpoint was met; detection rates were significantly lower with 18F-fluciclovine PET-CT (13 [26%; 95% CI 15-40] of 50) than with PSMA PET-CT (28 [56%; 41-70] of 50), with an odds ratio (OR) of 4·8 (95% CI 1·6-19·2; p=0·0026) at the patient level; in the subanalysis of the pelvic nodes region (four [8%; 2-19] with 18F-fluciclovine vs 15 [30%; 18-45] with PSMA PET-CT; OR 12·0 [1·8-513·0], p=0·0034); and in the subanalysis of any extrapelvic lesions (none [0%; 0-6] vs eight [16%; 7-29]; OR non-estimable [95% CI non-estimable], p=0·0078). INTERPRETATION: With higher detection rates, PSMA should be the PET tracer of choice when PET-CT imaging is considered for subsequent treatment management decisions in patients with prostate cancer and biochemical recurrence after radical prostatectomy and low PSA concentrations (≤2·0 ng/mL). Further research is needed to investigate whether higher detection rates translate into improved oncological outcomes. FUNDING: None.
Authors: Wolfgang P Fendler; Matthias Eiber; Mohsen Beheshti; Jamshed Bomanji; Francesco Ceci; Steven Cho; Frederik Giesel; Uwe Haberkorn; Thomas A Hope; Klaus Kopka; Bernd J Krause; Felix M Mottaghy; Heiko Schöder; John Sunderland; Simon Wan; Hans-Jürgen Wester; Stefano Fanti; Ken Herrmann Journal: Eur J Nucl Med Mol Imaging Date: 2017-06 Impact factor: 9.236
Authors: Matthias Eiber; Ken Herrmann; Jeremie Calais; Boris Hadaschik; Frederik L Giesel; Markus Hartenbach; Thomas Hope; Robert Reiter; Tobias Maurer; Wolfgang A Weber; Wolfgang P Fendler Journal: J Nucl Med Date: 2017-11-09 Impact factor: 10.057
Authors: Bital Savir-Baruch; Kevin P Banks; Jonathan E McConathy; Olga P Molchanova-Cook; Ephraim E Parent; Amol Takalkar; Mark Tulchinsky; Jian Q Yu; Rathan M Subramaniam; David M Schuster Journal: Clin Nucl Med Date: 2018-12 Impact factor: 7.794
Authors: Gerald L Andriole; Lale Kostakoglu; Albert Chau; Fenghai Duan; Umar Mahmood; David A Mankoff; David M Schuster; Barry A Siegel Journal: J Urol Date: 2019-02 Impact factor: 7.450
Authors: Matthias Eiber; Tobias Maurer; Michael Souvatzoglou; Ambros J Beer; Alexander Ruffani; Bernhard Haller; Frank-Philipp Graner; Hubert Kübler; Uwe Haberkorn; Michael Eisenhut; Hans-Jürgen Wester; Jürgen E Gschwend; Markus Schwaiger Journal: J Nucl Med Date: 2015-03-19 Impact factor: 10.057
Authors: Christoph Rischpler; Teresa I Beck; Shozo Okamoto; Anna M Schlitter; Karina Knorr; Markus Schwaiger; Jürgen Gschwend; Tobias Maurer; Philipp T Meyer; Matthias Eiber Journal: J Nucl Med Date: 2018-01-25 Impact factor: 10.057
Authors: Oluwaseun A Odewole; Funmilayo I Tade; Peter T Nieh; Bital Savir-Baruch; Ashesh B Jani; Viraj A Master; Peter J Rossi; Raghuveer K Halkar; Adeboye O Osunkoya; Oladunni Akin-Akintayo; Chao Zhang; Zhengjia Chen; Mark M Goodman; David M Schuster Journal: Eur J Nucl Med Mol Imaging Date: 2016-04-18 Impact factor: 9.236
Authors: Clemens Kratochwil; Wolfgang Peter Fendler; Matthias Eiber; Richard Baum; Murat Fani Bozkurt; Johannes Czernin; Roberto C Delgado Bolton; Samer Ezziddin; Flavio Forrer; Rodney J Hicks; Thomas A Hope; Levant Kabasakal; Mark Konijnenberg; Klaus Kopka; Michael Lassmann; Felix M Mottaghy; Wim Oyen; Kambiz Rahbar; Heiko Schöder; Irene Virgolini; Hans-Jürgen Wester; Lisa Bodei; Stefano Fanti; Uwe Haberkorn; Ken Herrmann Journal: Eur J Nucl Med Mol Imaging Date: 2019-08-22 Impact factor: 9.236
Authors: Frédéric Bois; Camille Noirot; Sébastien Dietemann; Ismini C Mainta; Thomas Zilli; Valentina Garibotto; Martin A Walter Journal: Am J Nucl Med Mol Imaging Date: 2020-12-15
Authors: Francesco Paparo; Alice Peirano; João Matos; Lorenzo Bacigalupo; Umberto Rossi; Ilaria Mussetto; Gianluca Bottoni; Martina Ugolini; Carlo Introini; Filippo Grillo Ruggieri; Gian Andrea Rollandi; Arnoldo Piccardo Journal: Abdom Radiol (NY) Date: 2020-11
Authors: Francesco Ceci; Lorenzo Bianchi; Marco Borghesi; Giulia Polverari; Andrea Farolfi; Alberto Briganti; Riccardo Schiavina; Eugenio Brunocilla; Paolo Castellucci; Stefano Fanti Journal: Eur J Nucl Med Mol Imaging Date: 2019-09-06 Impact factor: 9.236