Beyond the AJR: Integrating 18F-Fluciclovine PET/CT Into Salvage Radiotherapy Planning for Recurrent Prostate Cancer Reduces Rates of Biochemical Failure (EMPIRE-1 Trial)

Abstract Background A systematic literature review of the performance of 18Fluorine-fluciclovine PET/CT for imaging of men with recurrent prostate cancer was performed. Methods Scientific literature databases (MEDLINE, ScienceDirect and Cochrane Libraries) were searched systematically during Oct 2020 using PRISMA criteria. No limit was put on the date of publication. Prospective studies reporting a patient-level 18F-fluciclovine detection rate (DR) from ≥25 patients with recurrent prostate cancer were sought. Proceedings of relevant meetings held from 2018 through Oct 2020 were searched for abstracts meeting criteria. Results Searches identified 321 unique articles. In total, nine articles (six papers and three conference abstracts), comprising a total of 850 patients met inclusion criteria. Most studies (n = 6) relied on ASTRO-Phoenix Criteria, EAU-ESTRO-SIOG, and/or ASTRO-AUA guidelines to identify patients with biochemical recurrence. Patients’ PSA levels ranged from 0.02–301.7 ng/mL (median level per study, 0.34–4.10 ng/mL [n = 8]). Approximately 64% of patients had undergone prostatectomy, but three studies focused solely on post-prostatectomy patients. Adherence to imaging protocol guidelines was heterogeneous, with variance seen in administered activity, uptake and scan times. Overall patient-level DR varied between studies from 26% to 83%, with 78% of studies reporting a DR > 50%. DR was proportional to PSA, but even at PSA < 0.5 ng/mL DR of up to 53% were reported. Prostate/bed DR (n = 7) ranged from 18% to 78% and extra-prostatic rates (n = 6) from 8% to 72%. Pelvic node and bone lesion DR ranged from 8% to 47% and 0% to 26%, respectively (n = 5). 18F-Fluciclovine PET/CT was shown to impact patient management and outcomes. Two studies reported 59–63% of patients to have a management change post-scan. A further study showed significant increase in failure-free survival following 18F-fluciclovine-guided compared with conventional imaging-guided radiotherapy planning. Conclusions 18F-Fluciclovine PET/CT shows good performance in patients with recurrent prostate cancer leading to measurable clinical benefits. Careful adherence to recommended imaging protocols may help optimize DR.

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Randomized phase III trial of 68Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT].

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.tps136 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. TPS136-TPS136

Author(s):

Jeremie Calais ◽

Johannes Czernin ◽

Wolfgang P Fendler ◽

David Elashoff ◽

Nicholas George Nickols

Keyword(s):

Prostate Cancer ◽

Clinical Trial ◽

Success Rate ◽

Primary Endpoint ◽

Salvage Radiotherapy ◽

Phase Iii ◽

Radiotherapy Planning ◽

Phase 3 ◽

Pet Ct ◽

Biochemical Progression

TPS136 Background: Salvage radiotherapy (SRT) for prostate cancer (PCa) biochemical recurrence (BCR) after radical prostatectomy (RP) is commonly initiated in patients with PSA < 1 ng/mL, a threshold at which standard-of-care imaging is insensitive for detecting recurrence. The purpose of this randomized phase 3 trial is to evaluate the success rate of SRT for PCa BCR after RP with and without planning based on 68Ga-PSMA-11 PET/CT (PSMA). Here we present the study protocol. Methods: This is an interventional phase 3 randomized prospective open label clinical trial with parallel assignment designed for superiority. Patients who are planned to undergo SRT for PCa BCR with PSA > 0.1 ng/ml are eligible. The choice of treating the prostate bed with/without pelvic lymph nodes, with/without androgen deprivation therapy, is left to the discretion of the treating radiation oncologist (RO). RO may or may not change the RT plan depending on the PSMA findings. Any other imaging is allowed for SRT planning if done per routine care. The primary endpoint is the success rate of SRT measured as biochemical progression-free survival (PFS) after initiation of SRT. Biochemical progression is defined by PSA≥0.2 ng/mL and rising. Based on literature data we hypothesized that 1) the incorporation of PSMA to SRT planning will improve 5-year PFS by 20%, 2) the 5-year PFS will be 60% in standard Arm 1 and 80% in interventional Arm 2, and 3) 13% of subjects randomized to Arm 2 will have extra-pelvic metastasis detected by PSMA and will not be included in analysis of the primary endpoint. We will randomize 193 patients (1:1.13 ratio) to proceed with standard SRT (n = 90) or undergo PSMA scan (free of charge for patients) prior SRT planning (n = 103). Patients will be followed for 5 years after the date of initiation of SRT. Discussion: Main pitfalls in study design include 1) drop-out of patients randomized to the control arm and 2) potential FDA approval of PSMA PET imaging probes in the near future (no randomization to standard arm would be then acceptable). This is the first prospective randomized phase 3 trial designed to determine whether PET/CT can improve outcome of SRT in patients with BCR. Clinical trial information: NCT03582774.

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