EMPIRE-1: Randomized Trial Comparing Conventional- vs Conventional Plus Fluciclovine (18F) PET/CT Imaging-Guided Post-Prostatectomy Radiotherapy for Prostate Cancer

Background: Molecular imaging is increasingly used to guide prostate cancer decisions and treatment planning. The specific aim was to evaluate the role of fluciclovine (18F) PET/CT [PET] in improving cancer control over conventional imaging for post-prostatectomy radiotherapy. Methods: Patients with prostate cancer with detectable PSA post-prostatectomy and negative conventional imaging were randomized to radiotherapy directed by conventional imaging (Arm 1) vs conventional imaging+PET (Arm 2). The treatment setting was an academic medical center with community affiliates. In Arm 2, radiotherapy decisions were rigidly determined by PET, which was also used for target delineation. Using a standard post-radiotherapy failure definition, failure rates at 3 years (primary study endpoint) were compared. Univariate and multivariable analyses were performed for demographic, disease, and treatment factors. Secondary endpoints included provider-reported gastrointestinal and genitourinary toxicities. Findings: From September 18, 2012 to March 4, 2019, 165 patients were randomized. PET findings resulted in a 35·4% rate of decision changes, including 4 patients having radiotherapy aborted. Median follow-up was 3·52 years. Three-year failure-free survival rate for Arm 1 vs Arm 2 was 63·0 vs 75·5% (difference,12·5; 95% CI:4·3-20·8; p=0·0028) and at 4-years was 51·2 vs 75·5% (difference,24·3; 95% CI:15·6-33·0; p<0·0001). On univariate analysis, Arm achieved a statistical trend(p=0·0540); Gleason sum, extracapsular extension, seminal vesicle invasion, pelvic field, and PSA reached significance. On multivariable analysis, Arm (HR=2·04[95%CI: 1·06-3·93], p=0·0327), extracapsular extension, pelvic field, and PSA reached significance. Toxicity was similar in both Arms. Interpretation: Inclusion of fluciclovine (18F) PET into post-prostatectomy radiotherapy decisions and planning resulted in a significant improvement in failure rate. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study. Trial Registration: Enrollment was done under ClinicalTrials.gov registration (NCT 01666808) which is closed to new participants. Funding: NIH R01 CA169188 [major source]; Blue Earth Diagnostics, Ltd. [cassette arrangement with Emory]. Declaration of Interests: ABJ reports personal fees from Blue Earth Diagnostics, Ltd. in the role of advisory board service outside the submitted work. ES - none. SG - none. RH - none. BH - none. PJR - none. JWS - none. PRP - none. KMX - none. MG discloses he is entitled to a royalty derived from sale of products related to the research described in this manuscript. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. For human research studies the consent forms it is stated that he is entitled to a share of sales royalty received by the University from Nihon under that agreement. The terms of this arrangement have been reviewed and approved by the University in accordance with its conflict of interest policies. VAM - none. SSJ - none. OK - none. BCC - none. MAB - none. OAA - none. AAA - none. VRD - none. DMS participates through the Emory Office of Sponsored Projects in sponsored grants including those funded or partially funded by Blue Earth Diagnostics, Ltd; Nihon MediPhysics Co, Ltd.; Telix Pharmaceuticals (US) Inc.; Advanced Accelerator Applications; FUJIFILM Pharmaceuticals U.S.A., Inc; Amgen Inc. Also reports consultant fees outside the submitted work from: Syncona; AIM Specialty Health; Global Medical Solutions Taiwan; Progenics Pharmaceuticals, Inc. Ethics Approval Statement: Signed informed consent was obtained from every trial participant. The treatment setting was at Winship Cancer Center of Emory University (academic medical center with community affiliates); institution review board approval was through Emory University.