PSMA-PET Registry for Recurrent Prostate Cancer

This registry study will provide Ontario centres access to a new Positron Emission Tomography (PET) tracer, [18F]-DCFPyL, to improve our ability to identify areas of prostate cancer recurrence in men who have undergone surgical removal of their prostate gland (radical prostatectomy) or radiation of their prostate (external beam radiation, brachytherapy or a combination of both) and there is a suspicion of recurrence of the cancer. Men with suspected persistent or recurrent disease can be identified on the basis of a rising Prostate Specific Antigen (PSA) blood test, or the presence of node positive disease at the time of their surgery, or a PSA blood test continues to be detectable within 3 months after their surgery. It is the aim of this study to determine if [18F]-DCFPyL PET/CT can potentially identify areas of prostate cancer recurrence not seen with usual imaging (bone scan/CT scans) and impact the management of the disease. A report of the results of the [18F]-DCFPyL PET/CT will be provided to the participating physicians to determine a treatment plan. As part of the patient eligibility for [18F]-DCFPyL PET/CT participating physicians will complete a questionnaire after the [18F]-DCFPyL PET/CT information is provided to report how the results impact patient management. Actual interventions following completion of the [18F]-DCFPyL PET/CT will be tracked by linkage to provincial registries. Six centres across Ontario will participate in the registry study which is expected to take 4 years to complete with an additional one year of follow-up to capture patient outcomes.

PREP Phase 2 was initiated to investigate the hypothesis that conventional imaging is not adding to the information provided by PSMA PET/CT alone. PREP Phase 2 will retain the same study design as Phase I but will remove bone scan and computed tomography as criteria for entry into the study except for those patients with higher PSA (>10 ng/ml).

Identical cohort sizes will be accrued in Phase 2 to permit comparison of detection rates with similar confidence intervals with and without conventional imaging. Transition to PREP Phase 2 occurred when overall accrual to PREP exceeded 80% of target.

PREP Phase 3 was initiated and includes major changes to the protocol based on our increased knowledge that have developed since the beginning of the registry study.

• 18F-PSMA 1007 will be utilized in addition to 18F-DCFPyL PSMA as the diagnostic radiopharmaceutical. The Centre for Probe Development and Commercialization has the capacity to supply 18F-PSMA 1007 under Health Canada approved (GMP) manufacturing and is supporting clinical trials of this agent across Ontario. The production efficiencies associated with 18F-PSMA 1007 will address identified bottlenecks in the provision of PSMA radiopharmaceuticals under the current model of centralized distribution and technology transfer collaborations are underway to bring additional sites of Health Canada GMP certified 18F-PSMA 1007 production across the province.
• The primary endpoint will shift from detection rate to proportion of men with "actionable disease" identified by 18F-PSMA PET/CT. Detection rates of 18F-PSMA PET/CT tracers have now been well characterized through prospective and retrospective studies, including the PREP Phase 1 and 2 studies. Likewise, overall management changes are in the range of 50-60% in response to PSMA PET/CT information. We hypothesize that the greatest impact of PSMA PET/CT from men with prostate cancer will be among those men with "actionable disease" where PSMA PET/CT information is used to inform a targeted treatment or diagnostic approach (for example inclusion of PET identified involved nodes as part of a salvage radiotherapy plan for post prostatectomy recurrence or addition of stereotactic radiotherapy for oligo-progressive disease identified in men with progression on systemic therapy).
• An additional Cohort will be added (Cohort 0) to allow the evaluation of high-risk men being imaged for staging prior to primary treatment with surgery or radiotherapy. The results of the proPSMA study is compelling evidence that use of PSMA PET/CT as initial staging for men with high risk disease is preferable to the use of conventional imaging. Additionally, staging of high-risk men with 18F-PSMA 1007 has shown impressive results with improved performance compared to computed tomography, bone scan and whole body MRI and a high degree of accuracy in identification of pathologically confirmed lymph nodes at the time of prostatectomy.
• An additional cohort (Cohort 8) was added to include men with metastatic castrate resistant prostate cancer (mCRPC) with progression following treatment with other agents. Within the context of the PREP Phase 3 Registry Study, Cohort 8 is proposed as an additional cohort to help estimate the prevalence of men who may be eligible for potential future PSMA targeting radioligand therapies RLT as a funded therapy in Ontario. Specifically, men imaged under Cohort 8 include clinical scenarios not covered by current HC approved indications for RLT (i.e. men with failure after first line therapy for metastatic CRPC).

Phase 2

Inclusion criteria

• Written informed consent obtained
• Male, Age ≥ 18 years
• Prior primary treatment for prostate cancer with curative intent such as radical prostatectomy or radiotherapy for localized prostate cancer. Unless PET/CT requested as part of Cohort 7.
• Suspected persistent or recurrent disease defined as one of the following (unless PET/CT requested as part of Cohort 7):

• High risk disease at the time of radical prostatectomy characterized by pathologically involved node(s) or persistently detectable PSA (>0.1ng/ml) within 3 months post-surgery
• Primary treatment for prostate cancer and biochemical failure (BF) with current management according to the following:

i. Following primary radical prostatectomy, BF is defined as rising PSA on at least 2 occasions measured at least 1 month apart and with the most recent PSA measured at >0.1 ng/ml

ii. Following primary radiotherapy for localized disease, BF is defined according to the Phoenix Definition, which is rising PSA on at least 2 occasions measured at least 1 month apart and with the most recent PSA measured greater than the nadir PSA + 2.0 ng/ml

• Patient scenario falls into one of the 7 pre-defined cohorts. When patient scenario falls outside cohorts 1-6 participation in the Registry must be approved through the established CCO adjudication process for Cohort 7.
• Karnofsky performance status 70 or better (ECOG 0, 1).
• If PSA >10 mg/mL, conventional imaging consisting of bone scan and abdo-pelvic CT scan within 3 months of registration that is either equivocal, negative (no lesions) or positive for oligometastatic disease (4 or fewer unequivocal lesions identified).

Exclusion criteria

• Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components.
• Prior PSMA PET scan within 6 months of enrollment.
• Patient cannot lie still for at least 60 minutes or comply with imaging.
• Patients falling outside of Cohorts 1-6 where independent adjudication by CCO does not support participation in the Registry.

Phase 3

Inclusion criteria

• Written informed consent obtained
• Male, Age ≥ 18 years
• Biopsy proven, clinically high risk (cT3, PSA ≥20, biopsy Gleason Grade Group 4-5) prostate cancer undergoing initial staging prior to primary treatment with surgery or radiotherapy

OR

Biochemical failure (BF) with current management defined as at least two consecutive rises in PSA measured at least 1 month apart with the most recent PSA level >0.1 ng/ml (post radical prostatectomy or post PSMA Directed therapy, Cohorts 1-5) or PSA level > nadir PSA + 2.0 ng/ml (Phoenix definition post radiotherapy failure, Cohorts 5, 6)

OR

Men with rising PSA and/or progression on conventional imaging despite prior second line hormone therapy or chemotherapy for castrate resistant prostate cancer (Cohort 8).

OR

PET/CT requested as part of Cohort 7.

• Patient scenario falls into one of the 8 pre-defined cohorts. When patient scenario falls outside cohorts 0-6 and 8, participation in the Registry must be approved through the established CCO adjudication process for Cohort 7.
• Karnofsky performance status 70 or better (ECOG 0, 1)
• If recurrent disease suspected and PSA prior to PSMA PET/CT is >10 ng/ml, conventional imaging consisting of bone scan and abdominal-pelvic CT scan performed within 3 months of registration that is either equivocal, negative (no lesions) or positive for oligometastatic disease (4 or fewer unequivocal lesions identified). Registration is defined as Form A: Eligibility is complete.
• If patient is enrolled in Cohort 8, conventional imaging consisting of at least bone scan and abdominal-pelvic CT scan completed within 3 months of registration. Registration is defined as Form A: Eligibility is complete.

Exclusion criteria

• Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
• Prior PSMA PET scan within 6 months of enrollment
• Institution of or change in systemic therapy within 6 weeks prior to PSMA PET/CT request
• Patient cannot lie still for at least 60 minutes or comply with imaging
• Patients falling outside of Cohorts 0-6 and 8 where independent adjudication by CCO does not support participation in the Registry