¹⁸F-Fluciclovine or ⁶⁸Ga-PSMA-11 PET/CT-guided Salvage Radiotherapy Changes in Postprostatectomy Biochemical Recurrence: Secondary Analysis of the EMPIRE-2 Trial.

Abstract

Background PET with gallium 68 (⁶⁸Ga) prostate-specific membrane antigen (PSMA)-11 and fluorine 18 (¹⁸F) fluciclovine has influenced salvage radiation therapy (sRT) planning in postprostatectomy biochemical recurrence. Purpose To assess the comparative impact of ¹⁸F-fluciclovine and ⁶⁸Ga-PSMA-11 PET/CT on sRT changes in postprostatectomy biochemical recurrence. Materials and Methods In this secondary analysis of a prospective randomized controlled trial, men with detectable prostate-specific antigen (PSA) levels after prostatectomy were randomly assigned to undergo ¹⁸F-fluciclovine PET/CT (arm A) or ⁶⁸Ga-PSMA-11 PET/CT (arm B) between May 2019 and May 2023. The Clopper-Pearson binomial method was used to evaluate decision changes on whether to offer radiation therapy (RT) and to which field (with or without boost) between the pre- and post-PET time points in each arm, and to compare decision changes between the arms. Results A total of 140 eligible participants (age range, 47-83 years) were randomly assigned 1:1 to arm A (mean age, 63 years ± 8 [SD]; median pre-RT PSA level, 0.27 ng/mL) or to arm B (mean age, 65 years ± 8; median pre-RT PSA, 0.35 ng/mL). Six participants (five in the ¹⁸F-fluciclovine group and one in the ⁶⁸Ga-PSMA-11 group) withdrew from the trial before undergoing PET/CT. Overall sRT decision changes occurred in 19 of 65 participants (29%) in arm A (<i>P</i> < .001) and 29 of 69 participants (42%) in arm B (<i>P</i> < .001), but there was no evidence of a difference between arms (<i>P</i> = .12). Among participants for whom the final decision was to offer them sRT, treatment field (and/or boost) changes occurred in 43 of 60 participants (72%) in arm A (<i>P</i> < .001) and 33 of 61 participants (54%) in arm B (<i>P</i> < .001) and were more likely with ¹⁸F-fluciclovine PET/CT than with ⁶⁸Ga-PSMA-11 PET/CT (<i>P</i> = .046). Conclusion In postprostatectomy biochemical recurrence, the use of ¹⁸F-fluciclovine and ⁶⁸Ga-PSMA-11 for PET/CT-guided sRT planning resulted in substantial treatment decision changes, but there was no difference in the likelihood of a decision change between the two radiotracers. Treatment field (and/or boost) changes were more likely with ¹⁸F-fluciclovine PET/CT than with ⁶⁸Ga-PSMA-11 PET/CT. Clinical trial registration no. NCT03762759 © RSNA, 2026 <i>Supplemental material is available for this article.</i> See also the editorial by Iravani in this issue.