Differences in Failure-Free Survival After Salvage Radiotherapy Guided by Conventional Imaging Versus 18F-Fluciclovine PET/CT in Postprostatectomy Patients: A Post Hoc Substratification Analysis of the EMPIRE-1 Trial

The EMPIRE-1 (Emory Molecular Prostate Imaging for Radiotherapy Enhancement 1) trial reported a survival advantage in recurrent pros-tate cancer salvage radiotherapy (SRT) guided by 18F-fluciclovine PET/CT versus conventional imaging. We performed a post hoc analy-sis of the EMPIRE-1 cohort stratified by protocol-specified criteria, comparing failure-free survival (FFS) between study arms. Methods: EMPIRE-1 randomized patients to SRT planning via either conven-tional imaging only (bone scanning plus abdominopelvic CT or MRI) (arm A) or conventional imaging plus 18F-fluciclovine PET/CT (arm B). Randomization was stratified by prostate-specific antigen (PSA) level (<2.0 vs. >= 2.0 ng/mL), adverse pathology, and androgen-deprivation therapy (ADT) intent. We subdivided patients in each arm using the randomization stratification criteria and compared FFS between patient subgroups across study arms. Results: Eighty-one and 76 patients received per-protocol SRT in study arms A and B, respectively. The median follow-up was 3.5 y (95% CI, 3.0-4.0). FFS was 63.0% and 51.2% at 36 and 48 mo, respectively, in arm A and 75.5% at both 36 and 48 mo in arm B. Among patients with a PSA of less than 2 ng/mL (mean, 0.42 +/- 0.42 ng/mL), significantly higher FFS was seen in arm B than arm A at 36 mo (83.2% [95% CI, 70.0-91.0] vs. 66.5% [95% CI, 51.6-77.8], P < 0.001) and 48 mo (83.2% [95% CI, 70.0-91.0] vs. 56.2% [95% CI, 40.5-69.2], P < 0.001). No significant difference in FFS between study arms in patients with a PSA of at least 2 ng/mL was observed. Among patients with adverse pathology, significantly higher FFS was seen in arm B than arm A at 48 mo (68.9% [95% CI, 52.1-80.8] vs. 42.8% [95% CI, 26.2-58.3], P < 0.001) though not at the 36-mo follow-up. FFS was higher in patients without adverse pathology in arm B versus arm A (90.2% [95% CI, 65.9-97.5] vs. 73.1% [95% CI, 42.9-89.0], P = 0.006) at both 36 and 48 mo. Patients in whom ADT was intended in arm B had higher FFS than those in arm A, with the difference reaching statistical significance at 48 mo (65.2% [95% CI, 40.3-81.7] vs. 29.1 [95% CI, 6.5-57.2], P < 0.001). Patients without ADT intent in arm B had significantly higher FFS than patients in arm A at 36 mo (80.7% [95% CI, 64.9-90.0] vs. 68.0% [95% CI, 51.1-80.2]) and 48 mo (80.7% [95% CI, 64.9-90.0] vs. 58.6% [95% CI, 41.0-72.6]). Conclusion: The survival advantage due to the addition of 18F-fluciclovine PET/CT to SRT planning is maintained regardless of the presence of adverse pathology or ADT intent. Including 18F-fluciclovine PET/CT to SRT leads to survival ben-efits in patients with a PSA of less than 2 ng/mL but not in patients with a PSA of 2 ng/mL or higher.