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

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.

Conflict of interest statement

Declaration of interests

JCa reports personal fees from Progenics Pharmaceuticals and RadioMedix and is a consultant for Blue Earth Diagnostics outside the submitted work. JCz is a founder, board member, and holds equity in Sofie Biosciences and Trethera Therapeutics, serves on the medical advisory board of Actinium, and is a member of the VISION trial steering committee, a clinical trial sponsored by Endocyte, outside the submitted work. WPF is a consultant for Endocyte and Ipsen and reports personal fees from Radiomedix Inc outside the submitted work. ME reports grants from ABX advanced biochemical compounds and Blue Earth Diagnostics, is a consultant for Progenics Pharmaceuticals and Janssen, and has a patent rhPSMA issued, outside the submitted work. TB-G reports grants and personal fees from Blue Earth Diagnostics outside the submitted work. BS-B reports grants and personal fees from Blue Earth Diagnostics and personal fees from Phillips outside the submitted work. CN reports grants and personal fees from Blue Earth Diagnostics outside the submitted work. TAH reports grants from Advanced Accelerator Applications and personal fees from GE Healthcare, Progenics Pharmaceuticals, Curium, and Ipsen outside the submitted work. MBR reports grants and non-financial support from Novartis, personal fees and non-financial support from Johnson & Johnson, non-financial support from Merck, Medivation, and Astellas, and has a patent “Inhibitors of the N-terminal Domain of the Androgen Receptor” pending, outside the submitted work. MSH reports grants and personal fees from Endocyte, Ipsen, and Sanofi Genzyme outside the submitted work. CR received speaker fees from GE Healthcare outside the submitted work. AUK reports personal fees from Varian Medical Systems, ViewRay, and Janssen Pharmaceuticals outside the submitted work. HJ is an investigator for ImaginAb and Subtle Medical outside the submitted work. All other authors declare no competing interests.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Figures

Figure 1:. Trial profile

The reference standard included histopathology, follow-up imaging, or PSA concentration decrease after PET-positive lesion-directed therapy without systemic therapy or without whole-pelvic lymph node radiotherapy. Patients without a reference standard were not excluded from primary and safety analyses; this was only used for the positive predictive value and sensitivity analyses.

Figure 2:. Detection rates per region and per patient (majority consensus reads)

PSMA=prostate-specific membrane antigen.