The EMPIRE-1 (Emory Molecular Prostate Imaging for Radiotherapy Enhancement-1) trial reported a survival advantage in recurrent prostate cancer salvage radiotherapy (SRT) guided by 18F-fluciclovine PET/CT versus conventional imaging. We performed a post-hoc analysis of the EMPIRE-1 cohort stratified by protocol-specified criteria, comparing failure-free survival (FFS) between study arms. Methods: EMPIRE-1 randomized patients to either conventional imaging (Bone scan plus abdominopelvic CT or MRI) only SRT planning (arm A) or conventional imaging plus 18F-fluciclovine PET/CT (arm B). Randomization was stratified by PSA (<2.0 ng/mL versus ≥2.0 ng/mL), adverse pathology, and androgen-deprivation treatment (ADT) intent. We sub-divided patients in each arm using the randomization stratification criteria and compared FFS between patients' sub-groups across study arms. Results: Eighty-one and 76 patients received per-protocol SRT in study arms A and B, respectively. The median follow-up duration was 3.5 years (95% CI: 3.0 - 4.0). FFS was 63.0% and 51.2% at 36- and 48-months, respectively, in arm A and 75.5% at both 36- and 48-month follow-ups in arm B. Among patients with PSA <2ng/mL (mean = 0.42 ± 0.42), significantly higher FFS was seen in arm B than arm A at 36-months (83.2%, 95%CI: 70.0-91.0 versus 66.5%, 95%CI: 51.6-77.8, p<0.001) and 48-months (83.2%, 95%CI: 70.0-91.0 versus 56.2%, 95%CI: 40.5-69.2, p<0.001). No significant difference in FFS between study arms in patients with PSA ≥2ng/mL was observed. Among patients with adverse pathology, significantly higher FFS was seen in arm B than in arm A at 48-months (68.9%, 95%CI: 52.1-80.8 versus 42.8%, 95%CI: 26.2-58.3, p<0.001) though not at 36-months follow-up. FFS was higher in patients without adverse pathology in arm B vs arm A; 90.2%, 95%CI: 65.9-97.5 versus 73.1%, 95%CI: 42.9-89.0, P = 0.006, at both 36- and 48-months. 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-months (65.2%, 95%CI: 40.3-81.7 versus 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-months (80.7%, 95%CI: 64.9-90.0 versus 68.0%, 95%CI: 51.1-80.2) and 48-months (80.7%, 95%CI: 64.9-90.0 versus 58.6%, 95%CI: 41.0-72.6). Conclusion: The survival advantage due to the addition of 18F-fluciclovine PET/CT into SRT planning is maintained regardless of the presence of adverse pathology or ADT intent. Including 18F-fluciclovine PET/CT into SRT leads to survival benefits in patients with PSA <2 ng/mL, but not in patients with PSA≥ 2 ng/ml.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2022 Nov 03 [Epub ahead of print]
Ismaheel O Lawal, Omotayo A Adediran, Ashesh B Jani, Subir Goyal, Olayinka A Abiodun-Ojo, Vishal R Dhere, Charles V Marcus, Shreyas S Joshi, Viraj A Master, Pretesh R Patel, Mark Goodman, Joseph W Shelton, Omer Kucuk, Bruce Hershatter, Bridget Fielder, Raghuveer K Halkar, David M Schuster
Department of Radiology and Imaging Sciences, Emory University, United States., Department of Radiation Oncology, Winship Cancer Institute of Emory University, United States., Biostatics Shared Resource, Winship Cancer Institute of Emory University, United States., Department of Urology, Emory University, United States., Department of Medical Oncology, Winship Cancer Institute of Emory University, United States.