Determination of the Diagnostic Detection Rate of Axumin (Fluciclovine) Digital PET/CT, Post-prostatectomy
Determination of the Diagnostic Detection Rate of Axumin (Fluciclovine) Digital PET/CT, Post-prostatectomy
Fluciclovine F18 (Axumin) has been demonstrated to provide good delineation of recurrence of
 prostate cancer after definitive therapies. Fluciclovine in conjunction with the
 high-resolution digital Vereos (Phillips) PET-CT scanner may detect low volume recurrence in
 the prostatectomy bed or metastatic site (s).

 20-40 % of men will suffer a biochemical recurrence of their prostate cancer after radical
 prostatectomy, depending on their final pathological staging, defined as a rising PSA > 0.2
 ng/ml.

 The ability to more accurately diagnose local recurrence (i.e. pelvis) or oligometastasis may
 lead to the opportunity of precise therapy of these sites with more durable cancer responses,
 less morbidity and potential cure in selective men after Radical Prostatectomy.

 The ability to diagnose widespread metastatic Prostate Cancer after Radical Prostatectomy, or
 disease that is inaccessible to local selective therapies would spare these men the cost and
 morbidity of inappropriate therapy.

 The diagnosis of true stage D0 Prostate Cancer (No objective evidence of metastases) in men
 after Radical Prostatectomy would yield improved overall and disease specific survival if
 Androgen Deprivation Therapy was initiated at its earliest stage. This would also obviate the
 need for inappropriate local therapies (i.e. pelvic radiotherapy).

 The aim is to compare the detection rate of standard of care (CT Pelvis/Abdomen, MR Pelvis,
 Bone Scan) with Fluciclovine PET/CT performed on the Vereos Philips Scanner. The study aims
 to compare the performance of Digital (high resolution) PET to CT/MRI/Bone scan rather than
 analog (lower resolution) PET. Prior studies have tested analog PET compared to other
 modalities. One could make an inference that if our study's Digital PET performs better than
 the performance of Analog PET in those studies, then Digital PET should have a better
 detection rate than Analog PET. However, investigators are not making a direct comparison
 between digital and Analog in our comparison.
Aim:

 Compare the detection rate of standard of care (CT Pelvis/Abdomen, MR Pelvis, Bone Scan) with
 Fluciclovine PET/CT performed on the Vereos Philips Scanner. The study aims to compare the
 performance of Digital (high resolution) PET to CT/MRI/Bone scan rather than analog (lower
 resolution) PET. This was reported in Michopoulou S, O'Shaughnessy E, Thomson K, Guy MJ.
 Discovery Molecular Imaging Digital Ready PET/CT performance evaluation according to the NEMA
 NU2-2012 standard. Nucl Med Commun. 2018 Nov 27; doi:10.1097/MNM.0000000000000962. Prior
 studies have tested analog PET compared to other modalities. One could make an inference that
 if our study's Digital PET performs better than the performance of Analog PET in those
 studies, then Digital PET should have a better detection rate than Analog PET. However,
 investigators are not making a direct comparison between digital and Analog in our
 comparison.

 Background:

 Fluciclovine F18 (Fluciclovine) has been demonstrated to provide good delineation of
 recurrence of prostate cancer after definitive therapies (Odewole OA et al 2016).
 Fluciclovine in conjunction with the high-resolution digital Vereos (Phillips) PET-CT scanner
 may detect low volume recurrence in the prostatectomy bed or metastatic site (s).

 20-40 % of men will suffer a biochemical recurrence of their prostate cancer after radical
 prostatectomy, depending on their final pathological staging, defined as a rising PSA > 0.2
 ng/ml.

 The ability to more accurately diagnose local recurrence (i.e. pelvis) or oligometastasis may
 lead to the opportunity of precise therapy of these sites with more durable cancer responses,
 less morbidity and potential cure in selective men after Radical Prostatectomy.

 The ability to diagnose widespread metastatic Prostate Cancer after Radical Prostatectomy, or
 disease that is inaccessible to local selective therapies would spare these men the cost and
 morbidity of inappropriate therapy.

 The diagnosis of true stage D0 Prostate Cancer (No objective evidence of metastases) in men
 after Radical Prostatectomy would yield improved overall and disease specific survival if
 Androgen Deprivation Therapy was initiated at its earliest stage. This would also obviate the
 need for inappropriate local therapies (i.e. pelvic radiotherapy).

 Preliminary Studies:

 The safety, efficacy, reproducibility, and reliability of Fluciclovine was initially
 evaluated by the Emory group in men with suspected recurrence of prostate cancer based on
 rising PSA levels following radical prostatectomy and/or radiotherapy. Fluciclovine's safety,
 detection rate, and diagnostic performance was further validated in a multi-site data
 aggregation study using data from Emory, Noway, and Italy.

 The performance of Fluciclovine seems to be affected by degree of PSA elevation.
 Statistically significant difference in performance compared to CT was found at PSA levels >1
 ng/ml. However, at a PSA level of <1 ng/ml, no statistically significant difference was found
 by Odewole et al. These findings were independent of PSA doubling time and Gleason Score.

 The Bologna study evaluated the concordance between Fluciclovine and C11 Choline scans in
 patients with median PSA value of 1.44 ng/ml (interquartile range = 0.78 to 2.8 ng/ml).5 The
 accuracy of Fluciclovine was 38% vs 32% for C11 Choline. In a subsequent Emory study which
 studied Fluciclovine without a correlative imaging test, Fluciclovine scan detected
 recurrence in 72% (18/25) of patients with PSA of <1 ng/ml. However, there was no
 reconciliation of false positive examinations, as all abnormal radiotracer uptake were deemed
 a true positive. Performance of Fluciclovine was again noted to improve with increasing PSA
 levels, at 83% (5/6) for PSA of 1-<2 ng/ml and 100% (11/11) for PSA>= 2 ng/ml.

 Rationale:

 A Fluciclovine scan can detect and localize recurrent prostate cancer. Fluciclovine is an
 FDA-approved diagnostic imaging agent, also known as a "tracer," which may help determine if
 and where the prostate cancer has recurred.

 Procedures:

 Fluciclovine is used as a tracer for a PET/CT scan. Patients will need to prepare for the
 Fluciclovine (fluciclovine F 18) injection and scan. They will need avoid any significant
 exercise for at least a full 24 hours prior to Fluciclovine PET/CT scan and not eat or drink
 for at least 4 hours prior to PET/CT scan (other than small amounts of water for taking
 medications).

 With respect to determining if a finding is true positive, investigators will follow the
 following process. The research PET scan of each patient and SOC imaging will be read by
 radiologists blinded to the results of the other test. The results of both will then be
 reviewed by PI for concordance. If the research PET scan finds sites of disease that were not
 identified on SOC imaging, the case will be brought to Interdisciplinary UVMMC Genitourinary
 tumor board. Depending on the site of disease and presence of other concordant sites of
 metastatic disease between scans, it may have no impact on the SOC treatment. If it is deemed
 by the UVMMC Genitourinary Tumor Board that it will have a meaningful impact on treatment
 decisions and the detected lesion is accessible to be safely sampled, the patient will be
 approached by their treating physician to discuss the discordant findings, their
 significance, and the rationale behind a biopsy and its impact on their care.

 The sampling will then be performed a part of standard-of-care work-up, given that these
 patients would have been eligible for Fluciclovine PET imaging in this setting, per FDA
 label. Given the low PSA range of our target population in this study, the likelihood that
 these lesions would be amenable to sampling using conventional image guidance is low.
 Therefore, in cases where the research scan finds additional disease that would alter
 therapy, the decision of whether to act on it will be based on the overall clinical scenario
 of each patient, and will be decided by the treating team with the support of the UVMMC
 Genitourinary Tumor Board.
Inclusion Criteria:

 1. Prostatectomy patients with previously undetectable PSA and subsequent biochemical
 recurrence defined by PSA between 0.2 ng/ml and 1.0 ng/ml within 4 weeks prior to
 Fluciclovine scan

 2. Age >40

 3. Ability to provide informed consent

 Exclusion Criteria:

 1. History of allergic reaction to Fluciclovine

 2. Anti Androgen treatment in the 6 months prior to enrollment

 3. Any patient whose body habitus, as determined by radiology personnel, will effectively
 inhibit the ability to obtain PET/CT imaging or will interfere with the images so as
 to make them clinically uninterpretable.