PSMA-PET Registry for Recurrent Prostate Cancer (PREP)

This study aims to institute a province-wide registry leveraging the availability of a new Positron Emission Tomography tracer, [18F]-DCFPyL and PET expertise across Ontario centers to improve our ability to characterize patterns of recurrence and personalize therapies in men with recurrent prostate cancer after primary treatment.

Study Overview

• Status: Completed
• Conditions: Recurrent Prostate Cancer
• Intervention / Treatment: Diagnostic test: [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET)

Detailed Description

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.

1. 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.
2. 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).
3. 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.
4. 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).

• Study Type: Interventional
• Enrollment (Actual): 9684
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital, General Campus
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Thunder Bay Regional Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre, University Health Network
    • Toronto, Ontario, Canada, M4N 3M5
      • Toronto Sunnybrook Cancer Centre
    • Windsor, Ontario, Canada
      • Windsor Regional Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Phase 2

Inclusion Criteria:

1. Written informed consent obtained
2. Male, Age ≥ 18 years
3. 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.

4. Suspected persistent or recurrent disease defined as one of the following (unless PET/CT requested as part of Cohort 7):

   1. 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
   2. 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

5. 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.
6. Karnofsky performance status 70 or better (ECOG 0, 1).
7. 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:

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

Phase 3

Inclusion Criteria:

1. Written informed consent obtained
2. Male, Age ≥ 18 years

3. 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.

4. 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.
5. Karnofsky performance status 70 or better (ECOG 0, 1)
6. 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.
7. 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:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Men who are node positive or who have persistently detectable PSA after initial radical prostatectomy will be restaged with [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET)	Diagnostic test: [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL or [18F]PSMA-1007 PET/CT Scan (PSMA PET).
Experimental: Cohort 2; Men with biochemical failure after initial prostatectomy will be restaged with [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET)	Diagnostic test: [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL or [18F]PSMA-1007 PET/CT Scan (PSMA PET).
Experimental: Cohort 3; Men with biochemical failure after initial radical prostatectomy and salvage radiotherapy will be restaged with [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET)	Diagnostic test: [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL or [18F]PSMA-1007 PET/CT Scan (PSMA PET).
Experimental: Cohort 4; Men with biochemical failure after initial radical prostatectomy with or without adjuvant/ salvage radiotherapy who are currently on salvage hormone therapy will be restaged with [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET)	Diagnostic test: [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL or [18F]PSMA-1007 PET/CT Scan (PSMA PET).
Experimental: Cohort 5; Men who have prior PSMA directed treatment for oligometastatic disease, such as lesion directed therapy (e.g. stereotactic radiosurgery) or systemic therapy (e.g. hormone therapy or chemotherapy) with subsequent biochemical failure will be restaged with [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET)	Diagnostic test: [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL or [18F]PSMA-1007 PET/CT Scan (PSMA PET).
Experimental: Cohort 6; Men with biochemical failure after primary radiation therapy (external beam, brachytherapy or combinations together with or without hormone therapy) will be restaged with [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET)	Diagnostic test: [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL or [18F]PSMA-1007 PET/CT Scan (PSMA PET).
Experimental: Cohort 7; [18F]-DCFPyL or [18F]PSMA-1007 as a problem-solving tool in patients with prostate cancer when confirmation of the site of disease and/or disease extent may impact clinical management. Patients in this cohort require approval from an independent adjudication by Cancer Care Ontario.	Diagnostic test: [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL or [18F]PSMA-1007 PET/CT Scan (PSMA PET).
Experimental: Cohort 0; Initial staging with [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET) for high risk men being evaluated for primary therapy with surgery or radiation. Men with adverse clinical staging features (cT3, PSA >20, Gleason Grade Group 4-5) have a higher risk of extra-prostatic spread and rates of clinical failure with prostate only directed treatment (surgery or radiation).	Diagnostic test: [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL or [18F]PSMA-1007 PET/CT Scan (PSMA PET).
Experimental: Cohort 8; Men with castrate resistant prostate cancer with progression after at least one line of second line hormone therapy or taxane therapy. PSMA targeting PET/CT will be used to assess if men accrued would meet the imaging biomarker eligibility criteria for RLT as published by Sartor (Sartor, 2021).	Diagnostic test: [18F]-DCFPyL or [18F]PSMA-1007 PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL or [18F]PSMA-1007 PET/CT Scan (PSMA PET).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of disease detection on PSMA PET	Phase 1: The number of men with detectable lesions on PSMA PET who have suspected recurrent or persistent disease post radical prostatectomy with or without adjuvant or salvage pelvic radiotherapy or hormone therapy as well as men treated with primary radiotherapy will be measured Phase 2: The number of men with detectable lesions on PSMA PET who have suspected recurrent or persistent disease post radical prostatectomy with or without adjuvant or salvage pelvic radiotherapy or hormone therapy as well as men treated with primary radiotherapy will be measured when PSMA PET/CT is used without routine pre-screening with conventional imaging.	5 years
To determine the proportion of men who have "actionable disease" identified on PSMA PET with [18F]-DCFPyL or [18F]PSMA-1007.	Phase 3: Actionable disease is defined as PET identified lesions where targeted therapy with radiation, surgery or other focal, PET lesion directed intervention (i.e. biopsy) is possible (men with oligometastatic and/or locoregional disease only).	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of men with oligometastatic recurrence (four or fewer sites including the prostate bed if positive) confirmed on PSMA PET/CT	Number of men with four or fewer sites of disease detected on PSMA PET	5 years
Number of men who have their management plan changed because of PSMA PET results	The number of men who have a change in management as indicated by responses from referring physicians on an impact questionnaire completed after PSMA PET scans are reported.	5 years
To determine the actual management delivered within 6 months of PSMA PET	Actual management within 6 months will be determined through linkage to existing health information registries and will include: Delivery of radiotherapy (anatomic site, dose and fractionation) - Cancer Care Ontario; Biopsy of suspected recurrences (anatomic site, histology) - Provincial pathology database; Use of salvage lymph node dissections - CIHI; Use of salvage hormonal therapy/androgen deprivation	5 years
Compare PSA response at 6 months against PSA at the time of PSMA PET	PSA response will be examined by comparing 6 month PSA against PSA at the time of PSMA PET through the Ontario Laboratory Information Services and correlated with actual management as determined in Outcome 5.	5 years
Compare the detection rates of PSMA PET/CT when conventional imaging is used as part of the eligibility criteria (PREP) versus when conventional imaging is omitted (PREP Phase 2)	Number of men with detectable lesions as determined in the primary objective for PREP will be compared to the number of men with detectable lesions as determined in primary objective for PREP Phase 2.	5 years
Determine correlations between PSA levels at time of study enrollment and presence of disease detected on PSMA PET	The likelihood of disease detected on PSMA PET will be correlated with absolute PSA level at the time of PSMA PET as supplied on the eligibility form.	5 years
To compare the detection rates of 18F-PSMA 1007 PET/CT versus detection rates achieved using 18F-DCFPyL PSMA	Phase 3	5 years
To compare the frequency and pattern of equivocal findings (Suspicion score 3) among men imaged with 18F-PSMA 1007 versus 18F-DCFPyL	Phase 3	5 years
To assess the compliance in utilizing a standardized reporting template for 18F-DCFPyL based on published guidelines. (Eiber et al. 2018)	Phase 3	5 years
To characterize semi-quantitative PSMA PET based parameters such as SUVmax within PET detected cancer lesions as well as normal structures (parotid, liver and spleen) as recommended as part of standardized reporting. (Eiber et al. 2018)	Phase 3	5 years
To determine the proportion of men imaged for progressive castrate resistant prostate cancer who meet the imaging biomarker eligibility for radioligand therapy as published by Sartor et al. (Sartor, 2021)	Phase 3	5 years
Determine which clinical pre-imaging variables in addition to PSA correlate with a positive scan	Phase 3 Clinical pre-imaging variables, i.e. PSA doubling time prior to imaging, Gleason Grade Group, clinical/pathologic stage, clinical scenario, time from primary treatment to imaging for men with recurrent disease	5 years
To characterize overall survival among men imaged on the Registry study through linkages to the provincial Ontario Registered Persons Database (RPDB).	Phase 3	5 years

Collaborators and Investigators

• Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
• Collaborators: Cancer Care Ontario; Centre for Probe Development and Commercialization
• Investigators: Principal Investigator: Ur Metser, MD, FRCPC, University Health Network, Toronto; Principal Investigator: Glenn Bauman, MD, FRCPC, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Publications and helpful links

General Publications

• Basso Dias A, Finelli A, Bauman G, Veit-Haibach P, Berlin A, Ortega C, Avery L, Metser U. Impact of 18F-DCFPyL PET on Staging and Treatment of Unfavorable Intermediate or High-Risk Prostate Cancer. Radiology. 2022 Sep;304(3):600-608. doi: 10.1148/radiol.211836. Epub 2022 May 24.
• Metser U, Zukotynski K, Mak V, Langer D, MacCrostie P, Finelli A, Kapoor A, Chin J, Lavallee L, Klotz LH, Hagerty M, Hildebrand C, Bauman G. Effect of 18F-DCFPyL PET/CT on the Management of Patients with Recurrent Prostate Cancer: Results of a Prospective Multicenter Registry Trial. Radiology. 2022 May;303(2):414-422. doi: 10.1148/radiol.211824. Epub 2022 Jan 25.
• Kohan A, Metser U, Luke W, Rashid M, Langer DL, MacCrostie P, Green B, Mak V, Kulkarni GS, Finelli A, Shayegan B, Pautler SE, Klotz L, Hagerty M, Lavallee LT, Hildebrand C, Bauman G. A Prospective Provincial Registry of 18F-PSMA PET/CT for Recurrent Prostate Cancer: Results for 4,135 Men. J Nucl Med. 2025 Aug 1;66(8):1223-1231. doi: 10.2967/jnumed.125.269653.

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2018
• Primary Completion (Actual): June 15, 2026
• Study Completion (Actual): June 15, 2026

Study Registration Dates

• First Submitted: October 17, 2018
• First Submitted That Met QC Criteria: October 22, 2018
• First Posted (Actual): October 24, 2018

Study Record Updates

• Last Update Posted (Actual): July 17, 2026
• Last Update Submitted That Met QC Criteria: July 15, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Prostate Cancer; Radiation Therapy; Radical Prostatectomy; PSMA-PET; Biochemical Failure; Node positive; [18F]DCFPyL and [18F]-PSMA 1007 PET/CT imaging
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Radiography; Image Interpretation, Computer-Assisted; Radiographic Image Enhancement; Image Enhancement; Photography; Tomography, X-Ray; Tomography, X-Ray Computed
• Other Study ID Numbers: 4826

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No