18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial

Jeremie Calais; Francesco Ceci; Matthias Eiber; Thomas A Hope; Michael S Hofman; Christoph Rischpler; Tore Bach-Gansmo; Cristina Nanni; Bital Savir-Baruch; David Elashoff; Tristan Grogan; Magnus Dahlbom; Roger Slavik; Jeannine Gartmann; Kathleen Nguyen; Vincent Lok; Hossein Jadvar; Amar U Kishan; Matthew B Rettig; Robert E Reiter; Wolfgang P Fendler; Johannes Czernin

doi:10.1016/S1470-2045(19)30415-2

¹⁸F-fluciclovine PET-CT and ⁶⁸Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial

Lancet Oncol. 2019 Sep;20(9):1286-1294. doi: 10.1016/S1470-2045(19)30415-2. Epub 2019 Jul 30.

Authors

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

Affiliations

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.

Publication types

Clinical Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Carboxylic Acids / administration & dosage*
Contrast Media / administration & dosage
Cyclobutanes / administration & dosage*
Edetic Acid / administration & dosage
Edetic Acid / analogs & derivatives*
Gallium Isotopes
Gallium Radioisotopes
Humans
Male
Middle Aged
Neoplasm Recurrence, Local / blood
Neoplasm Recurrence, Local / diagnostic imaging*
Neoplasm Recurrence, Local / pathology
Neoplasm Recurrence, Local / surgery
Oligopeptides / administration & dosage*
Positron Emission Tomography Computed Tomography / methods*
Prospective Studies
Prostate-Specific Antigen / blood
Prostatectomy / methods
Prostatic Neoplasms / blood
Prostatic Neoplasms / diagnostic imaging*
Prostatic Neoplasms / pathology
Prostatic Neoplasms / surgery

Substances

Carboxylic Acids
Contrast Media
Cyclobutanes
Gallium Isotopes
Gallium Radioisotopes
Oligopeptides
gallium 68 PSMA-11
fluciclovine F-18
Edetic Acid
Prostate-Specific Antigen

Associated data

ClinicalTrials.gov/NCT02940262

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding