The FALCON trial evaluated 85 men with first biochemical recurrence after local definitive therapy who were being considered for curative intent salvage therapy at 6 centers in the United Kingdom.4 In this prospective trial, the initial management plan was recorded prior to 18F-fluciclovine PET/CT imaging, then the new management plan was documented based on PET/CT results. The overall detection rate was 52% in this trial and 61% of men had a change in the treatment plan in response to results of 18F-fluciclovine PET/CT imaging. A major change, where there was an alteration in treatment modality, occurred in 36% of patients imaged. An additional 25% had a change marked as “other,” consistent with a treatment change within modality, for instance, alteration of a previously planned salvage radiation field.
A similarly designed, multicenter trial in the United States enrolled 213 men with biochemically-recurrent prostate cancer to the LOCATE study.5 The overall detection rate was 57% in this trial, and this rate of detection was 50% in men with a PSA level between 0.5-1.0 ng/mL. In the LOCATE trial, treatment plans were revised for 59% of patients, with 46% of patients undergoing a major change and 13% of patients undergoing a minor change. Although encouraging, the necessary next steps in the field will be to determine if changes made in response to 18F-fluciclovine PET/CT imaging findings are intelligently leading to better long-term outcomes for patients.
One can envision many ways to use a novel next-generation imaging technology like 18F-fluciclovine PET/CT. Most current studies focus on detecting prostate cancer in the biochemically-recurrent disease state, where findings on 18F-fluciclovine PET/CT could guide salvage radiation therapy or even direct oligometastatic pelvic lymph node dissection or radiation. Besides imaging to detect a lesion in the recurrent prostate cancer disease state, where 18F-fluciclovine PET/CT holds United States Food and Drug Administration approval, additional studies could be performed in both earlier and more advanced disease states. Initial staging of high-risk prostate cancer, to better define surgical, radiation and/or systemic therapy approaches could be explored. Additionally, known metastases could be followed for treatment response or pharmacodynamic measurement in response to systemic therapy.
Below, we have outlined multiple ongoing trials with 18F-fluciclovine PET occurring in various disease states with different primary endpoints. We have provided a snippet of information for each trial to summarize the key patient population and the goal of the study. As the field continues to evolve, there will be more trials that evaluate the long-term outcomes of patients who are treated differently in response to findings on 18F-fluciclovine PET/CT. Those trials will eventually be able to show the benefits of more sensitive imaging, but we must accept that it will be years before we have outcomes from those trials. In a future article, I will highlight those trials, many of which will be led by United States National Clinical Trials Network organizations. Additionally, this field of next generation imaging will continue to evolve as prostate-specific membrane antigen (PSMA)-targeted PET imaging and theranostic trials mature. We will keep a close watch on these topics and highlight them in future articles as well.
Clinical Trials with 18F-fluciclovine PET/CT Imaging for Biochemical Recurrence
- 18F-fluciclovine PET/CT vs. 68Ga-PSMA PET imaging to detect and guide salvage radiation therapy (NCT03762759)
- 18F-fluciclovine PET/CT vs. CT/MRI + bone scan for detection (NCT03527199)
- 18F-fluciclovine PET/MRI to identify potential previously false negative MRI findings (NCT03635866)
- 18F-fluciclovine PET to improve staging for those with negative standard imaging (NCT03081884)
- 18F-fluciclovine PET/CT to evaluate patients with oligometastatic hormone-sensitive metastatic prostate cancer on a companion protocol of radium-223 with radiation (NCT03707184)
- 18F-fluciclovine PET/CT to determine true positive and false positive rates in men with bone metastatic prostate cancer planning to undergo biopsy (NCT03496844)
- 18F-fluciclovine PET/CT to measure response to docetaxel therapy for men with metastatic castration-resistant prostate cancer (NCT02830880)
Written by: Evan Yu, MD
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- Nanni C et al. Eur J Nucl Med Mol Imaging 2016; 43:1601-10.
- Teoh E et al. ASTRO 2017; LBA-8.
- Andriole GL et al. AUA 2018; Abstract 18-6136.