Lancet 2021 May 07
F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-1): a single centre, open-label, phase 2/3 randomised controlled trial.
Abstract
Background
Molecular imaging is increasingly used to guide treatment decisions and planning in prostate cancer. We aimed to evaluate the role of 18F-fluciclovine-PET/CT in improving cancer control compared with conventional imaging (bone scan and either CT or MRI) alone for salvage postprostatectomy radiotherapy.
Methods
In EMPIRE-1, a single-centre, open-label, phase 2/3 randomised controlled trial, patients with prostate cancer with detectable PSA after prostatectomy and negative conventional imaging (no extrapelvic or bone findings) were randomly assigned in a 1:1 ratio to radiotherapy directed by conventional imaging alone or to conventional imaging plus 18F-fluciclovine-PET/CT. Computer-generated randomisation was stratified by PSA concentration, adverse pathology indicators, and androgen deprivation therapy intent. In the 18F-fluciclovine-PET/CT group, radiotherapy decisions were rigidly determined by PET findings, which were also used for target delineation. The primary endpoint was 3 year event-free survival, with events defined as biochemical or clinical recurrence or progression, or initiation of systemic therapy, using univariate and multivariable analyses in patients who received radiotherapy. This trial is registered with ClinicalTrials.gov, NCT01666808 and is closed to new participants.
Findings
From Sept 18, 2012, to March 4, 2019, 165 patients were randomly assigned, with median follow-up of 3·52 years (95% CI 2·98-3·95). PET findings resulted in four patients in the 18F-fluciclovine-PET/CT group having radiotherapy aborted; these patients were excluded from survival analyses. Median survival was not reached (95% CI 35·2-not reached; 33% of 81 patients had events) in the conventional imaging group compared with not reached (95% CI not reached-not reached; 20% of 76 patients) in the 18F-fluciclovine-PET/CT group, and 3 year event-free survival was 63·0% (95% CI 49·2-74·0) in the conventional imaging group versus 75·5% (95% CI 62·5-84·6) for 18F-fluciclovine-PET/CT (difference 12·5; 95% CI 4·3-20·8; p=0·0028). In adjusted analyses, study group (hazard ratio 2·04 [95% CI 1·06-3·93], p=0·0327) was significantly associated with event-free survival. Toxicity was similar in both study groups, with the most common adverse events being late urinary frequency or urgency (37 [46%] of 81 patients in the conventional imaging group and 31 [41%] of 76 in the PET group), and acute diarrhoea (11 [14%] in the conventional imaging group and 16 [21%] in the PET group).
Interpretation
Inclusion of 18F-fluciclovine-PET into postprostatectomy radiotherapy decision making and planning significantly improved survival free from biochemical recurrence or persistence. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study.
Funding
National Institutes of Health/National Cancer Institute, Blue Earth Diagnostics, and Winship Cancer Institute of Emory University.
Related Questions
Would you offer salvage radiation for prostate bed recurrence on PSMA PET in a patient with limited bone mets?
I don’t currently offer salvage post-op RT (PORT) to patients with osseous metastatic disease on PSMA-based PET/CT, which is consistent with the per-protocol treatment strategy on EMPIRE-1 (Jani et al., PMID 33971152). I would, however, be open to offering such a treatment on a clinical trial. An ex...
Do you always obtain PSMA PET as initial staging for high risk and very high risk localized prostate cancer patients?
I do obtain a PSMA PET/CT or PET/MRI in all patients with high risk localized prostate cancer. However, when this is not available due to insurance coverage issues or lack of access to PSMA PET, it is still acceptable to stage with bone scan and CT or MRI. I prefer PSMA PET because it has better per...
Given results of SAKK 09/10 in which dose escalation for salvage prostate radiotherapy to 70 Gy was not superior to 64 Gy, would you ever consider a higher dose?
For years, the dogma was that you needed at least 66 Gy to control disease in the prostate bed in patients with a biochemical failure. The SAKK 09/10 trial seemed to challenge that notion. Even in this population of patients who were relatively favorable in the sense that they were node negative, an...
Would you consider radical prostatectomy for a young male with unfavorable intermediate risk cT3a prostate cancer and PSMA PET concerning for regional lymph nodes involvement but negative conventional imaging?
I would approach this scenario by considering two main issues. The first issue is what the probability of the patient truly having pN+ disease based on cN+ findings on advanced imaging. There have recently been two trials published from the Netherlands, PEPPER (using 68¸Ga-PSMA-11) and SALT (using 1...