18F-PSMA-1007 PET/CT Imaging in Patients with Biochemically Recurrent or High-risk Prostate Cancer

A single centre prospective cohort phase II study of 18F-PSMA-1007 PET/CT imaging in specific patient populations:

1. Adult patients (≥ 18 years old) with a history of radical prostatectomy for treatment of prostate cancer, and a serum prostate specific antigen (PSA) > 0.2 µg/L
2. Adult patients (≥ 18 years old) with a history of radiotherapy, cryotherapy, or brachytherapy for treatment of prostate cancer, and a serum PSA progressively rising to ≥ 2 µg/L (minimum two samples) OR a serum PSA doubling-time of < 9 months
3. Adult patients (≥ 18 years old) with a history of biopsy-proven prostate cancer and high-risk features for metastatic disease prior to treatment with radical prostatectomy, radiotherapy, cryotherapy, or brachytherapy. High-risk features include a Gleason score > 7, serum PSA > 20 µg/L, OR minimum clinical T-stage T2c.

All patients will have a comparison conventional imaging study performed within 10 days of the investigational PET/CT scan. The conventional imaging study will include a 99mTc -MDP bone scan including whole body planar imaging (top of skull to toes) as well as SPECT/CT imaging of the trunk (including clavicles to pelvis). In the absence of contraindications (renal failure with eGFR < 40 mL/min/1.73m2 or history of IV contrast allergy), all scans will include an IV-contrast enhanced CT scan of the chest, abdomen, and pelvis. In the presence of contraindications to IV contrast, a non-IV contrast enhanced CT scan of the chest, abdomen, and pelvis will be performed.

The biodistribution of 18F-PSMA-1007 produced by the Edmonton PET Centre will be evaluated in 2 ways:

• by comparing the biodistribution of tracer on the scans to an expected normal distribution.
• for any identified abnormal distribution, a lesion-by-lesion comparison to the conventional imaging study will be performed with lesions classified as follows:
• A - lesion identified on the investigational imaging study but not on the conventional imaging study
• B - matching lesions on both the investigational and conventional imaging studies
• C - lesion identified on the conventional imaging study but not on the investigational imaging study

The clinical efficacy of 18F-PSMA-1007 will be evaluated as follows:

• a follow-up questionnaire will be sent to referring clinicians 6 months after the scan to determine if the scans were of perceived clinical benefit.

The safety of 18F-PSMA-1007 produced by Edmonton PET Centre will be evaluated in 3 ways:

• the patients will be screened for adverse effects immediately post-injection as well as after the scan (approximately 2.5 hours after injection)
• the patients will be provided an information sheet and contact information for self-reporting of delayed adverse events (1-7 days post injection)
• a 6 month follow-up questionnaire will be sent to referring clinicians to determine if there were any perceived adverse events related to the injection

The diagnostic accuracy of 18F-PSMA-1007PET/CT produced by Edmonton PET Centre will be evaluated as follows:

• All lesions categorized as "A", "B", or "C" will be compared with a reference standard to determine sensitivity and specificity on both a per lesion and per patient level
• The reference standard will be defined a minimum of 1 year after completion of both scans based on available clinical data
• Lesional histopathology results will be used as the reference standard when available
• When pathology is unavailable, criteria for determining lesional positivity for metastatic disease will be based on recently published methodology (Lawhn-Heath et al., AJR 2019;213:1-8)
• If lesion the criteria for determining lesion positivity are not met, the lesion will be considered unevaluable and will be excluded from assessment of accuracy