[¹⁸F]-Fluciclovine or [⁶⁸Ga]-PSMA-11 Molecular Imaging To Guide Dose Escalation of Salvage Radiotherapy After Radical Prostatectomy for Prostate Cancer: The EMPIRE-2 Trial.

Abstract

In EMPIRE-1, [¹⁸F]-fluciclovine positron emission tomography (PET) imaging to guide salvage radiotherapy (RT) for prostate cancer recurrence after prostatectomy resulted in an improvement in event-free survival (EFS) over conventional imaging alone. The aim of EMPIRE-2 was to explore the impact of RT dose escalation to sites of uptake on PET in comparison to EMPIRE-1. EMPIRE-2 was a randomized trial of [¹⁸F]-fluciclovine versus [⁶⁸Ga]-PSMA-11 in a cohort of men with biochemical progression after prostatectomy and negative conventional imaging findings. After stratification, patients were randomized to RT guided by [¹⁸F]-fluciclovine PET (arm 1) or [⁶⁸Ga]-PSMA-11 PET (arm 2). PET findings were used for treatment decisions and for RT dose escalation (≤76.0 Gy to the prostate bed and ≤56.0 Gy to the pelvis). The primary endpoint was 2-yr EFS in comparison to the [¹⁸F]-fluciclovine RT arm in EMPIRE-1. The secondary endpoint was a planned EFS comparison for [¹⁸F]-fluciclovine versus [⁶⁸Ga]-PSMA-11 in EMPIRE-2. In the cohort of 140 patients, 59 randomized to arm 1 patients and 60 randomized to arm 2 completed RT. Median follow-up was 2.6 yr (interquartile range 1.8-4.0). The 2-yr EFS rates were 87% for the overall EMPIRE-2 cohort versus 80% for the EMPIRE-1 comparison cohort (difference 7.7%, 95% confidence interval [CI] 4.7-12%; p = 0.01). After propensity score weighting, the corresponding 2-yr EFS rates were 84% versus 73% (difference 11%, 95% CI 3.6-24%; p = 0.01). The 2-yr EFS rates in the EMPIRE-2 study arms were 87% for [¹⁸F]-fluciclovine versus 88% for [⁶⁸Ga]-PSMA-11 (difference 0.7%, 95% CI 0.3-1.3%; p > 0.9). Use of either [¹⁸F]-fluciclovine or [⁶⁸Ga]-PSMA-11 imaging to guide RT dose escalation to sites of PET uptake in the prostate bed and/or pelvis was associated with an improvement in EFS in comparison to a prior trial without dose escalation.