In a single-institution phase II/III trial (EMPIRE-1) reported in The Lancet, Ashesh B. Jani, MD, and colleagues found that use of fluciclovine F-18 positron-emission tomography/computed tomography (PET/CT) in addition to conventional imaging to guide postprostatectomy salvage radiotherapy was associated with better event-free survival vs conventional imaging alone in patients with prostate cancer.

Ashesh B. Jani, MD

Study Details

In the open-label trial, 165 patients at Winship Cancer Institute of Emory University were randomly assigned between September 2012 and March 2019 to undergo conventional imaging (bone scan and either CT or magnetic resonance imaging) plus fluciclovine F-18 PET/CT (PET group, n = 83) or conventional imaging alone (n = 82) to guide salvage radiotherapy. The primary endpoint was 3-year event-free survival (with events defined as biochemical or clinical recurrence or progression) or initiation of systemic therapy.

Event-Free Survival

PET findings in four patients in the PET group resulted in abortion of radiotherapy, with the patients being excluded from survival analyses. An additional 3 patients in the PET group and 2 patients in the conventional imaging group were excluded from analyses, leaving 76 evaluable patients in the PET group and 81 in the conventional imaging group.

Median follow-up was 3.52 years (95% confidence interval [CI] = 2.98–3.95 years). Event-free survival at 3 years was 75.5% (95% CI = 62.5%–84.6%) in the PET group vs 63.0% (95% CI = 49.2%–74.0%) in the conventional imaging group (difference = 12.5%, 95% CI = 4.3%–20.8%, P = .0028). On multivariate analysis, the hazard ratio for event-free survival for the conventional imaging group vs the PET group was 2.04 (95% CI = 1.06–3.93, P = .0327).  

Among the 15 patients in the PET group with event-free survival events, all had biochemical events (biochemical evidence of disease progression or inadequate treatment response on the basis of prostate-specific antigen concentrations) and 10 also had imaging events; all with imaging events received salvage therapy (androgen-deprivation therapy, salvage radiotherapy, salvage lymph node dissection, or a combination), with 1 additional patient receiving salvage therapy after a biochemical event.

Among 27 patients in the conventional imaging group with events, all had biochemical events, with 13 also having imaging events; all with imaging events received salvage therapy, with 2 additional patients receiving salvage therapy after biochemical events.

Failure-free survival at 4 years was 75.5% vs 51.2% (difference = 24.3%, 95% CI = 15.6%–33.0%, P < .0001). Median overall survival was not reached (95% CI = not reached–not reached; events in 20% of 76 patients) in the PET group vs not reached (95% CI = 35.2 months–not reached; events in 33% of 81 patients) in the conventional imaging group.

Toxicity

Toxicity was similar in the two study groups, with the most common adverse events being late urinary frequency or urgency (41% in PET group vs 46% in conventional imaging group) and acute diarrhea (21% vs 14%). Grade 3 toxicity was infrequent in both groups, and no grade 4 or 5 toxicity was reported in either group.

The investigators concluded, “Inclusion of fluciclovine F-18 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.”

Dr. Jani, of the Department of Radiation Oncology, Winship Cancer Institute of Emory University, is the corresponding author for The Lancet article.

Disclosure: The study was funded by the National Cancer Institute, Winship Cancer Institute of Emory University, and Blue Earth Diagnostics. For full disclosures of the study authors, visit thelancet.com.