The use of 18F-fluciclovine-PET/CT in guiding salvage treatment with radiotherapy after prostatectomy reduced the likelihood of biochemical recurrence or suboptimal response to treatment in patients with prostate cancer without evidence of extrapelvic disease with conventional imaging.
The use of 18F-fluciclovine-PET/CT in guiding salvage treatment with radiotherapy after prostatectomy reduced the likelihood of biochemical recurrence or suboptimal response to treatment in patients with prostate cancer without evidence of extrapelvic disease with conventional imaging, according to findings from the phase 2/3 randomized, controlled EMPIRE-1 trial (NCT01666808) that were published in The Lancet.
Data showed that the median survival was not reached in the conventional imaging group [(n = 82; 95% CI, 35.2–not reached); 33% of 81 patients had events] or the 18F-fluciclovine-PET/CT group [(n = 83; 95% CI, not reached–not reached); 20% of 76 patients]. The 3-year event-free survival (EFS) was 63.0% (95% CI, 49.2%-74.0%) in the conventional imaging group vs 75.5% (95% CI, 62.5%-84.6%) in the 18F-fluciclovine-PET/CT group (difference 12.5%; 95% CI, 4.3%-20.8%; P =.0028).
In adjusted analyses, there was a significant correlation between the study group and EFS (HR, 2.04; 95% CI, 1.06-3.93; P = .0327).
“To the best of our knowledge, our report is the first such prospective randomised trial of molecular imaging with cancer control as the primary end point in prostate cancer. Our study findings suggest that incorporation of 18F-fluciclovine PET/CT in radiotherapy planning resulted in significant improvement in [3-year] event-free survival in adjusted analyses, which persisted for up to 4 years of available follow-up data,” Ashesh B. Jani, MD, lead study author, and professor in the Department of Radiation Oncology at Winship Cancer Institute of Emory University, and co-authors wrote in the study publication.
In the trial, patients with prostate cancer with detectable prostate-specific antigen (PSA) after prostatectomy and negative conventional imaging––no extrapelvic or bone findings––were randomized to radiotherapy directed by conventional imaging alone or conventional imaging plus 18F-fluciclovine-PET/CT.
The primary end point of the study was 3-year EFS rate, defined as biochemical or clinical recurrence or progression, or initiation of systemic therapy, using univariate and multivariable analyses in patients who received radiotherapy. Events included a PSA of 0.2 ng/mL higher than the postradiotherapy nadir, followed by another rise; persistent PSA, imaging or digital rectal examination failure; or initiation of systemic therapy.
Secondary end points included comparison of pre-PET and post-PET treatment decisions, and acute and late provider-reported gastrointestinal and genitourinary adverse effects (AEs) with the Common Terminology Criteria for Adverse Events version 5.0.
Computer-generated randomization was stratified by PSA concentration, adverse pathology indicators, and androgen deprivation therapy (ADT) intent.
In the conventional imaging group, radiotherapy decisions were based on presurgical disease features, prostatectomy pathological findings, and PSA trajectory. Radiotherapy to the prostate bed only or to the pelvis was delivered at the discretion of the treating physician.
In the 18F-fluciclovine-PET/CT group, radiotherapy decisions were based on PET findings, which were also used for target delineation.
Patients were followed up at 1, 6, 12, 18, 24, 30, and 36 months after radiotherapy treatment with PSA and physical evaluation. Longer-follow-up beyond 36 months was permitted. ADT, if given, was typically 6 months in duration and started concurrently with radiotherapy after PET was performed.
From September 18, 2012 to March 4, 2019, 165 patients were randomized, with a median follow-up of 3.52 years (95% CI, 2.98-3.95). Four patients in the 18F-fluciclovine-PET/CT group forwent radiotherapy because of the results of their PET findings; these patients were excluded from survival analyses.
Additional results reflected a difference in 4-year failure-free survival between both groups, of 51.2% vs 75.5% (difference 24.3%; 95% CI, 15.6%-33.0%; P < .0001).
Of the 27 patients who had events in the conventional imaging group, all were biochemical events; 13 of these patients also had imaging events and received salvage therapy, including ADT, salvage radiotherapy, salvage lymph node dissection, or a combination of these treatments. Similarly, of the 15 patients who had events in the 18F-fluciclovine-PET/CT group, all had biochemical events; 10 patients also had imaging events. All patients who had imaging events received salvage therapy.
Two patients in the conventional imaging group and 1 patient in the 18F-fluciclovine-PET/CT group started ADT at the time of biochemical evidence of disease progression or inadequate treatment response, in the absence of imaging events.
18F-fluciclovine-PET/CT imaging led to a change of radiotherapy choice for 28 (35%) patients. Androgen deprivation therapy was offered for 6 months in 3 patients for whom no ADT had been planned and was extended to 18 months in 2 patients for whom only 6 months of therapy had been planned based on PET imaging results.
Regarding safety, toxicity was similar in both study groups. The most frequent AEs were late urinary frequency or urgency (n = 37, 46% of 81 patients in the conventional imaging group; n = 31, 41% of 76 in the PET group), and acute diarrhea (n = 11, 14% in the conventional imaging group; n = 16, 21% in the PET group).
“The current study shows that, complementary to efforts in these other areas, integration of novel PET radiotracers into radiotherapy decisions and planning can make a clinical impact and warrants further study,” concluded the study authors.
Jani AB, Schreibmann E, Goyal S, et al. 18F-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. Lancet. Published online May 7, 2021. Accessed May 12, 2021. doi:10.1016/S0140-6736(21)00581-X