PRISMA-PET - Primary Staging of Prostate Cancer: A Randomized Controlled Trial Comparing 18F-PSMA-1007 PET/CT to Conventional Imaging
Phase: NA
Conditions: Prostate Cancer
Sponsor: Odense University Hospital

 
6th july 2021   
 
 
Karen Middelbo Buch-Olsen, MD 
5th version  
 
 
 
Department of Nuclear Medicine 
EudraCT number 2021-000123-12  
 
Odense University Hospital 
NCT number not available  
 
 
kmbo@rsyd.dk 
 
 
 
 
 
PRISMA-PET – Primary Staging of Prostate Cancer: 
A Randomized Controlled Trial Comparing 
18F-PSMA-1007 PET/CT to Conventional Imaging 
 
 

 
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Sponsor and responsible for GCP-monitoring:  
Malene Grubbe Hildebrandt, MD, senior consultant, Head of Research, Department of Nuclear Medicine, J. 
B. Winsløwsvej 4, OUH Odense, 5000 Odense C, Denmark. No delegates. Telephone: +45 30 17 18 88.  
 
 
Date: ____________________ 
Signature:_________________________________________ 
 
Coordinating investigator and principal investigator, Odense:  
Karen Middelbo Buch-Olsen, MD, specialist, Department of Nuclear Medicine, OUH Odense, J. B. 
Winsløwsvej 4, OUH Odense, 5000 Odense C, Denmark. Telephone: +45 29 34 69 22 / +45 65 41 29 80. 
 
 
Date: ____________________ 
Signature:_________________________________________ 
 
Principal investigator, Vejle:  
Paw Christian Holdgaard, MD, senior consultant, Department of Nuclear Medicine, Hospital of Little Belt, 
Beridderbakken 9, 7100 Vejle. Telephone: +45 79 40 58 12 / +45 79 40 58 00. 
 
 
Date: ____________________ 
Signature:_________________________________________ 
 
Principal investigator, Esbjerg:  
Søren Hess, MD, senior consultant, Department of Radiology, Hospital of South West Jutland, Finsensgade 
35, 6700 Esbjerg. Telephone: +45 79 18 24 66 / +45 79 18 24 69. 
 
 
Date: ____________________ 
Signature:_________________________________________ 
 
 

 
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Involved departments:  
Department of Urology, OUH Odense, J. B. Winsløvsvej 4, 5000 Odense. 
Department of Urology, OUH Svendborg, Baagøes Àlle 15 5700 Svendborg 
Department of Urology, Hospital of Little Belt, Beridderbakken 4, 7100 Vejle.        
Department of Urology, Hospital of South West Jutland, Finsensgade 35, 6700 Esbjerg.        
Department of Urology, Hospital Sønderjylland, Kresten philipsens vej 15, 6200 Aabenraa.  
 
 
The project will be performed according to this protocol, relevant legislation and ICH-GCP 
guidelines.  
 
 
Time plan:  
We expect to start recruiting for the project in summer 2021. Recruiting and scanning procedures are 
expected to be finished in summer 2024, hence the medical part of the project will end by then. The 
patients will be followed for 20 years after inclusion in the patient record and with questionnaires. 

 
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Problem, aim, and hypothesis 
Molecular targeting treatments and diagnostics in Prostate cancer (PCa) have evolved in recent years, while 
mortality from PCa has remained unchanged in Denmark (1). One molecular target is the prostate specific 
membrane antigen (PSMA), which is overexpressed in prostate cancer cells and can therefore serve as 
target for diagnosis, staging, and treatment. Positron Emission Tomography (PET) / Computed Tomography 
(CT) with radiolabelled PSMA (PSMA-PET/CT) has recently been implemented in the Danish Prostate Cancer 
guidelines (DAPROCA) as a potential tool for detecting relapsing local and metastatic disease. This decision 
is based on convincing studies showing a superior diagnostic accuracy of PSMA-PET/CT compared to 
conventional imaging in this patient setting (1). 
When it comes to initial staging in primary PCa, however, there are only small diagnostic studies available 
performed retrospectively in heterogeneous study designs (2), and accordingly guidelines still recommend 
conventional imaging with contrast enhanced CT (CE-CT) and bone scintigraphy (BS) for staging in this 
setting(1). We believe that there is a need for larger prospective trials analyzing effects in terms of benefit 
for patients and society of implementing radiolabelled PSMA-PET/CT compared to conventional imaging for 
N-staging (lymph node metastases in the pelvic region) and M-staging (lymph node metastases outside the 
pelvic region, bone metastases and metastases in other organs). 
The overall aim of this project is in a randomized design to compare 18F-PSMA-PET/CT to conventional 
imaging for initial staging in intermediate and high risk PCa with regard to accuracy, impact on treatment 
strategy and progression free survival. In a subgroup analysis we aim to analyze the added value of 18F-
PSMA-PET/Magnetic Resonance (MR) for local staging. 
We hypothesize that 
 Staging intermediate and high risk PCa with 18F-PSMA PET/CT and PET/MRI is more 
accurate at local-, N- and M-staging compared to conventional staging and therefore 
will lead to a change in treatment strategy with improved progression free survival.  
 
Background 
PCa is the most frequent cancer form in men in developed countries (3) with approximately 4,500 new 
cases reported annually in Denmark, 980 of which are based in the Region of Southern Denmark (RSD). The 
relative 5-year survival is 87% (4). The course of disease ranges from well differentiated tumors localized to 
the prostate gland itself, being potentially curable, to aggressive, rapidly disseminating variants with poor 
prognosis despite intensive treatment. 
Choice of treatment regimen at primary diagnosis is based on risk stratification, staging of the disease, and 
general health condition of the patient (1, 5). In intermediate and high risk PCa, further staging procedures 
besides T-staging (6) is warranted. CE-CT or magnetic resonance (MR) is used for N-staging in cases when 
pelvic lymph node dissection is avoided during radical prostatectomy or when surgery is refrained from (7), 
although either modality has a reported sensitivity of approximately 40% (8). M-staging is traditionally 
obtained from BS, which reflects bone metabolism and has a reported sensitivity as well as specificity of 

 
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80% (9). An alternative modality reflecting bone metabolism is the 18F-sodium fluoride PET/CT (NaF-PET) 
which has a superior accuracy compared to BS (10, 11). BS has been substituted with NaF-PET in clinical 
routine at our department, and will as well in this study. Multiparametric MRI (mpMRI) of the pelvis may be 
performed in high-risk patients for accurate T-staging and thereby planning of resection level (R-staging) 
before radical prostatectomy. 
The treatment regimens for different stages of PCa ranges from observation, radiation therapy, radical 
prostatectomy and androgen deprivation to intensive chemotherapy and experimental therapeutic 
regimens (1, 5). The treatment regimens are associated with a specific risk of potential adverse effects, so 
correct staging is paramount in order to avoid unnecessary treatment complications. Curatively intended 
surgery or radiation treatment followed by a surveillance program is the initial intervention for patients 
with localized disease. 
The transmembrane protein, PSMA, is expressed in abundance on the surface of prostate cancer cells. 
Radiolabelled ligands targeting PSMA has been developed for use in PET/CT-scanners. The ligand PSMA-
1007 can be labelled with the positron emitting isotope 18F (12) and is only slowly excreted through the 
urine as opposed to the more widely used 68Ga-PSMA-11 (13). The slow urinary excretion of 18F-PSMA-1007 
poses the advantage of avoiding difficulties discriminating between excreted tracer in the urinary bladder 
from pathological uptake in adjacent lymph nodes. Another advantage of 18F labelled ligands is that they 
can be produced in large amounts on sites with a cyclotron whereas 68Ga is produced in a 68Ge/68Ga 
generator with limited capacity resulting in only a limited number of scans per generator per day.  Of 
further interest is that the molecular structure, biodistribution, and tumor uptake of 18F-PSMA-1007 is very 
similar to that of 177Lu-PSMA-617(12), which is a radiotherapeutic agent (14). This could provide invaluable 
information on dosimetry calculations as well as predictive information in a potential future theranostic 
approach. 
The 18F labeled PSMA-PET/CT has so far shown detection rates of up to 94% in patients with biochemical 
recurrence of PCa after radical prostatectomy with curative intend (15). Several studies of the feasibility of 
the 68Ga labelled PSMA-PET/CT in various settings of PCa patients and with various endpoints have been 
reported (2, 16-19). These all show promising results for 68Ga-PSMA PET/CT but also remark upon the 
heterogeneous nature of the somewhat sparse data available and call for randomized controlled trials. The 
literature regarding 18F-PSMA-PET/CT for staging of primary PCa comprises only two retrospective studies 
with 10 and 8 patients, respectively (20, 21), both of them also focusing on the added value of combining 
18F-PSMA-PET with mpMRI for a combined T- and N-staging. 
Indeed, randomized controlled studies in well powered designs addressing patient relevant outcomes of 
staging primary in PCa with 18F-PSMA-PET/CT compared to conventional imaging are considered highly 
relevant. This is also highlighted in a recent international consensus report on molecular imaging and 
theranostics in PCa (22). 
 
The research medicine 

 
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The research medicine, 18F-PSMA, is a PET-tracer produced and applied clinically every week in the 
Departments of Nuclear Medicine, RSD, for the detection of relapse of PCa after curative intended therapy, 
hence 18F-PSMA is medicine we know very well. We have the license to use 18F-PSMA intravenously for a 
PET/CT scan for all cancer types expressing PSMA on the surface, as prostate cancer does. The difference in 
this proposed protocolled use of the drug from the current clinical use is the time point for application in 
the disease course. Today it is used when the patients are suspected for relaps after curatively intended 
therapy. In the PCa patient setting, we will use 18F-PSMA when the patients are newly diagnosed with PCa 
and not yet treated. Research shows promising results for accuracy of 18F-PSMA-PET/CT in this patient 
setting (23), but the patient benefit from being staged with PSMA-PET/CT is not yet evaluated.  
The risks for the patients scanned with this drug are very discrete. We are not aware of any patients 
reacting allergically or with any other side effects, presumably because 18F-PSMA is administrated in 
extremely small doses, and it is not considered having any pharmacological or pharmaco-dynamic effect. 
We consider the risks of this medicine no larger than the medicine for conventional imaging.There will be 
no difference in the dose administered in our study compared with the use in clinical practice, 2 MBq pr kg. 
bodyweight, between 150 and 300 MBq; max. 1,8 mg PSMA and in many cases much less. The drug will be 
administered only once, 60 min before the scan, intravenously and in the coorporating departments by 
authorized personel as in the clinical setting. Paravenous injection can rarely happen with following local 
irritation shortly, but the medicine has a short half life in the body (< 2 hours).  
Labelling, storage, compliance and destruction of the medicine is not considered a problem, as the patients 
are injection in the involved departments as in clnical routine. As the patients are all men, anticonception 
for fertile women is not relevant. As the medicine is used in very small doses, excretion in seemen is in a 
level where anticonception is not considered relevant for this reason. 
The patients will be treated clinically following the national clinical guidelines for PCa at any time. 
The project will be monitored by the local GCP-unit at OUH, part of OPEN, J.B. Winsløws Vej 9, 3. sal, 5000 
Odense C. 
 
Safety 
We will register side effects from the 18F-PSMA during the 2 hours the patients are in our department after 
the injection. As the drug is non-detectable the next day, we expect potential side effects to show in this 
period – according to “the summary of product characteristics, 4.8” no adverse reactions to the medicine 
are reported. We will encourage the patients to contact the principal investigator if anything unusual 
happens during 24 hours after injection. Any suspected side effect will be registered in the REDCap 
database.  
In case of a Serious Adverse Event  they will be reported to the sponser within 24 hours from knowledge of 
it. The sponsor will report Suspected Unexpected Seriuos Adverse Reactions within 2 days to The Ethics 
Comite and the Danish Medicines Agency, as well as all principal investigators. Yearly reporting of safety 
and adverse events to The Ethics Comite and the Danish Medicines Agency  will be performed by the 
sponsor. 

 
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 As the medicine has the short half life in the body, the patients should be followed a maximum of 24 hours 
after injection. We will register the dose given in the electronic patient file as usually done in clinical 
practice, and it will be registered in the projects REDCap database along with the other project 
registrations. The medicine is well known to have no adverse effects and is only used for diagnoses. In case 
of reported “Serious Adverse Events” or “Suspected Unexpected Seriuos Adverse Reactions” related to the 
medicine, termination of the project will be considered.  
 
Research plan 
The study is planned in a prospective randomized controlled design as illustrated in appendix 1 and 2 and 
will be carried out in close collaboration with the Department of Urology. The patients will be included and 
randomized as a part of one of the initial doctors appointments in a consultation room, and they will be 
encouraged to bring a relative to this consultation. Patients are identified when they have an appointment 
at Department of Urology, and the researchers will be given information from the clinicians, which means 
that they will not access the patient journals before enrolling. The patients will be informed about the 
project from the PhD-student, a physician from the Nuclear Medicine Departments, an Urologist from the 
coorporating departments or a nurse involved in the project, all with expertise in prostate cancer. They will 
be offered time to consider enrolment in the trial. The patients will be offered further information and 
answering of upcoming questions over the telephone after the initial talk. At this time or one of the 
following days, when they have accepted to be enrolled in the project and signed the written consent, they 
will be randomized in REDCap, where the randomisation code is kept. The randomization will be stratified 
according to the patients clinical risk status and pathology of biopsies. The written consents will be 
collected at the Nuclear Medicine Department, when they meet for their scan and at the earliest the day 
after the information in Department of Urology. Our study population will comprise men with a newly 
diagnosed intermediate or high risk (including locally advanced) PCa (1) or with a clinical suspicion of 
metastases based on other findings. Included patients will be randomized into a control group (A) and an 
interventional group (B). Group A will be staged by conventional imaging, i.e. CE-CT for N-staging and NaF-
PET for M-staging. Group B will be staged by 18F-PSMA PET/CT for both N- and M-staging. A subset of 
patients with risk of extracapsular extension considered for radical prostatectomy in group B will also have 
an 18F-PSMA-PET/mpMRI-scan for T-staging (evaluation of the tumor). This scan will be performed in 
continuation of the 18F-PSMA-PET/CT, i.e. on the same administered dose of 18F-PSMA. Furthermore, a 
subgroup of patients in group B will have a blinded NaF-PET-scan for the purpose of performing 
comparative accuracy analyses. 
Biopsy of suspected metastatic lesions in N- and M-positive patients (suspicion of metastases) as well as 
lymph node specimen in N- and M-negative patients will be intended as reference standard in both groups 
as well as a nadir unmeasurably low post-surgery prostate specific antigen blood sample to indicate no 
residual disease where applicable. Reference standard in the accuracy analysis of 18F-PSMA PET/mpMRI 
with regard to T- staging is histopathology on surgical specimen. As the risk of distant metastases increases 
with increasing PSA-levels, analyses will be performed on both population level as a whole as well as in two 
PSA-strata with cut-off being PSA=100 ng/ml. 

 
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Treatment and subsequent follow-up will be planned on the basis of the results of the scans and according 
to current guidelines (1, 5). 
Follow-up data will be collected from patient journals by the researcher/principal investigator or a 
delegate, and will consist of clinical information, examination reports, blood test results, information about 
treatments and pathology reports, all performed in a clinical setup as determined by the clinician. No extra 
visists, scans or blood test are required except for questionnairesThe patients will be asked to fill in 
questionnaires (EQ-5D-5L, FACT-P and EPIC 26) concerning quality of life during at baseline and 3, 6, 12, 24, 
60, 120 og 236 months after recruitment. The questionnaires will be delivered to the patients e-boks from 
REDCap automatically at the specific time points. All collected information will be used in this project for 
analysis of treatment decision, relapse detection, overall survival and quality of life in the two patient 
groups. 
Primary endpoints (Group A vs. B) 
1. Treatment strategies and progression-free survival 
2. Quality of life measures 
Secondary endpoints 
1. Overall survival (Group A vs. B) 
2. 
18F-PSMA-PET/MR for evaluation of extension of tumor in the prostate gland and surrounding 
structures compared to histopathology on surgical specimen. 
3. Accuracy of 18F-PSMA-PET/CT compared to NaF-PET/CT for evaluation of bone metastases 
Four publications are planned, cf. section “Planned publications” below. Studies 1 and 4 will address the 
presumed patient benefit from staging with 18F-PSMA PET/CT in a randomized design, and outcome 
measures will consequently be impact on stage migration, treatment decision, progression free survival, 
and time to relapse in group A vs. group B. As studies 2 and 3 are comparative studies, outcome measures 
in this setting will be accuracy measures regarding N- and M-staging in study 2, and T- and R-staging as well 
as change in treatment intend in study 3. 
Beyond the scope of this PhD-project we plan a follow-up time period of up to 20 years for analysis of 
disease free period, overall survival and quality of life.  
Admittance to documents and data including patients journals are given to the relevant GCP-units and the 
Danish Medicines Agency for monitoring, audition and inspection of the project. 
 
Sample size and statistical analyses 
Assuming that staging intermediate and high risk PCa with 18F-PSMA PET/CT leads to upstaging in 20%, 398 
patients, i.e. 199 patients in each arm, will be necessary to estimate the proportion of upstaged patients 
with 18F-PSMA PET/CT with sufficient precision as the expected length of the Wilson-score 95% CI for this 
proportion will be 11% (simulation study with N=2000 trials). These numbers are sufficient to indicate that 
the proportion of upstaged patients with 18F-PSMA PET/CT is statistically significantly larger than 12.9% 

 
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under above assumptions (power: 80%; two-sided testing; Type I error: 5%). A total of 448 patients (224 in 
each arm) are sufficient to indicate a statistically significant difference in progression free survival with 
assumed hazard rates of 0.35 and 0.5 for 18F-PSMA PET/CT and conventional staging respectively, implying 
a hazard ratio of 0.7. Estimates are based on a study duration of 4 years, consisting of 3 years accrual time 
and minimum follow-up period of 1 year before the first data collection, and a loss-to-follow-up of 10% 
(two-sample comparison of survivor functions; Exponential test; Type I error: 5%). Therefore, 448 patients 
(224 in each arm) will be included in the study. For sample size calculation for the accuracy analyses 
planned in Group B only, we assumed a prevalence of metastases of 30%, sensitivity and specificity of 0.38 
and 0.91 for conventional imaging, and 0.85 and 0.98 for PSMA-PET/CT. Then, a sample size of 128 patients 
is sufficient to indicate a superior sensitivity for PSMA-PET/CT and a non-inferior specificity for PSMA-
PET/CT, with a non-inferiority margin of 0.052, at a significance level of 5% (two-sided) with a power of 
80%. We expect 224 patients from OUH, 80 patients from Hospital of Little Belt, 72 patients from Hospital 
of South West Jutland and 72 patients from Hospital Sønderjylland. Patients from Hospital Sønderjylland 
will have their scans performed in either Hospital of Little Belt or OUH Odense. 
Primary analyses will be done as indicated in the sample size rationale above. Cox proportional hazard 
regressions will be adjusted for available demographic and clinical baseline variables, and graphical displays 
will comprise Kaplan-Meier plots including risk tables (i.e. patients at risk in each group). 
Descriptive statistics will be done according to data type (mean±SD or median (range) for symmetrically 
and unsymmetrically distributed continuous variables, respectively, as judged visually with histograms 
including approximating Normal curves; frequencies and percentages for categorical variables). 
Exploratory, bivariate testing will be done with unpaired t-tests or, alternatively, Wilcoxon’s rank sum test 
on continuous and Chi-squared test, alternatively, Fisher’s exact test for categorical variables. Level of 
significance will be 5%. All analyses will be done with STATA/IC 15 (StataCorp, College Station, Texas 77845 
USA). If exceptions for this statistical plan is needed, it will be reported when published. 
Missing data will be reported in the publications. Illegitimate data will be excluded. Reason for un-used 
data will be reported. 
The primary analysis of QoL and morbidity will be based on the changes in the FACT-P questionnaire at the 
timepoints: inclusion and 12 months. An 8-point decline in the global FACT-P score will be considered 
clinically relevant. The secondary analyses include the group difference in a repeated measurement 
analysis, making use of data collected at the several time points of FACT-P. Secondary analyses will likewise 
be conducted using the EQ-5D-5 and EPIC-26. The time from baseline to decline of 8 points in global FACT-P 
score will be visualized by Kaplan-Meier plots and explored with a two-sided log-rank test. The level of 
significance will be 5%. All analyses will be done with STATA/IC 15 (StataCorp, College Station, Texas 77845 
USA). 
 
Organization and collaboration 
PRISMA-PET is intended to be a part time PhD-project spanning 4 years. It is planned to be one of several 
projects in a larger research program established in a collaborative research center, entitled: Personalized 

 
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Assessment of Prostate Cancer: A Research Centre in Clinical and Translational Molecular Medicine 
(PASSPORT). PASSPORT represents a multidisciplinary collaborative team. 
The overall purpose of PASSPORT is research, development and implementation of novel molecular imaging 
modalities and theranostic methods in PCa. The PRISMA-PET project focuses on the performance of 18F-
PSMA PET/CT and PET/mpMRI in primary staging of intermediate and high risk PCa. 
Other parallel PASSPORT projects in the clinical work package intend to investigate 18F-PSMA in recurrent 
and metastatic PCa, impact on clinical decision making and response monitoring, and treatment of 
progressive metastatic PCa with 177Lu-PSMA. Other work packages in PASSPORT aim at developing new 
therapeutic radiopharmaceuticals and at profiling PCa with biomarkers and genomic profiling. Several 
medical specialties and departments from OUH and intentionally from departments of other hospitals in 
RSD will be participating in PASSPORT center. Already participating specialties from OUH include nuclear 
medicine, urology, oncology, pathology, clinical biochemistry and clinical genetics, thus representing a truly 
multidisciplinary approach.  
 
Patient involvement 
We have included two patient representatives in our study group to: 
- 
Contribute in the development of information material for study participants. 
- 
Contribute with valuable input in relevant project meetings when discussing patient related issues 
as well as ethical considerations. 
- 
Aid in communicating study results to citizens, e.g. via the Danish prostate cancer patient 
organization “Prostatakræftforeningen” - PROPA. 
 
International collaboration 
Collaboration, including study visits, with the “Munich-group” and/or the “Heidelberg-group” with regards 
to PSMA-expertise is considered relevant, but not yet formalized. 
 
Feasibility 
Patient recruitment will be performed in collaboration with relevant departments of urology in RSD. One or 
more parallel PhD-projects on the same study population, but nested in the Department of Urology, OUH, 
is planned, thereby enabling patient recruitment on either of the two departments in close cooperation. It 
is considered achievable to include the required 448 patients in this setting. 
The Department of Nuclear Medicine, OUH, received approval to produce 18F-PSMA-1007 from the Danish 
Medicines Agency in 2019. 18F will routinely be produced on our two cyclotrons, and our well-equipped 
radiochemistry is trained in the production and labelling of a wide variety of PET-tracers complying with 
Good Manufacturing Practice (GMP). The tracers will be shipped to the cooperating departments. We 
currently have five state-of-the-art PET/CT-scanners and a PET/MRI-scanner, and will as such have all the 

 
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prerequisites for tracer production and performing the planned scans together with the cooperating 
Nuclear Medicine Departments. 
The PSMA-PET scans performed in OUH will be evaluated and documented as in clinical practice by the 
applicant and three supervisors as well as a PhD student from another PhD-project - all being Nuclear 
Medicine specialists along with specialists in radiology, and the same set-up is planned in the cooperating 
departments. Conventional scans will be evaluated as part of the daily routine at the Departments of 
Nuclear Medicine (NaF-PET) and Radiology (CE-CT, mpMRI). The SharePoint and RedCap systems will be 
used for data collection and management in line with the European data protection regulation (GDPR) 
implemented by May 25 2018. Sharepoint will be used for safe storage of permissions and registrations, 
and REDCap for patient data. 
 
Ethical aspects 
All study procedures will be performed after having obtained informed consent from each patient. The 
project will be performed according to this protocol, comply with the Declaration of Helsinki and ICH-Good 
Clinical Practice guideline and relevant legislation (GDPR, the Health Act and the Data Protection Act)  and 
as well as follow procedures for control of quality. If the protocol is not strictly followed, the sponsor will be 
informed by the principal investigators by mail or telephone. Approval is obtained by the local Ethical 
Committee (S-20190161 11-12-2019 and 31-03-2020)  and the study protocol has been registered at the 
Danish Data Protection Agency (20/20086, 01-05-2020) . The study will be registered at the international 
clinical trial-registries (clinicaltrials.gov) before it is initiated. The patients are insured as a part of the 
clinical set up. No extra insurance is taken. 
The critical data of the project will be the time point for progression, determined by the second of two 
following PSA blood tests with rising values. Time of death will be registered, possibly from our personal 
register. QoL questionairres will be evaluated statistically.  
Radiation dose for each element of the different scan types are estimated to: 
- 
NaF-PET: 4.8 mSv from NaF and 3-6 mSv from low-dose CT, i.e. 7.8-10.8 mSv. 
- 
18F-PSMA PET/CT: 3.1-4.6 mSv from PSMA and 10 mSv from CE-CT, i.e. 13.1-14.6 mSv 
- 
mpMRI gives no radiation dose 
Radiation dose from staging by conventional imaging in group A will add up to 17.8-20.8 mSv. Patients in 
group B will receive a total of 20.9-25.4 mSv from 18F-PSMA PET/CT and the blinded NaF-PET, i.e. an 
additional radiation dose of up to 7.6 mSv. As annual background radiation dose in Denmark amounts to 3-
5 mSv and the patient population consists of primarily middle-aged to elderly patients, the added radiation 
dose in group B is considered well within limits of reason. 
 
Planned publications  
1. Clinical impact on stage migration and treatment strategy when using 18F-PSMA PET/CT compared 
to conventional imaging in primary staging of PCa (Group A vs B). 

 
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2. A prospective comparative accuracy study of 18F-PSMA PET/CT for N- and M-staging compared to 
conventional imaging in primary PCa (Group B). 
3. The added value of PSMA-PET/mpMRI compared to PSMA-PET/CT on T, N, and R-staging (R = 
resection level) (Subgroup of B). 
4. The impact on progression free survival and biochemical relapse when using 18F-PSMA PET/CT 
compared to conventional imaging in primary staging of PCa (Group A vs. B - planned as a joint 
publication with PhD student from the Department of Urology). 
It is the intention to publish the results no matter if they are positive, negative or inconclusive. The results 
will be published inwww.clinicaltrialsregister.eu. 
Authorship order will be depending on work effort and involvement according to the Vancouver 
Declaration (IMJCE). No clauses agreed.  
 
Initiators of the project:  
Malene Grubbe Hildebrandt, Nuclear Medicine Department, OUH Odense  
Mie Holm Vilstrup, Nuclear Medicine Department, OUH Odense 
Mads Hvid Poulsen, Department of Urology, OUH Odense  
Steinbjørn Hansen, Department of Oncology, OUH Odense 
 
Funding 
Funding for one year salary for Principal Investigator (578.000 kr) and scans (600.000 kr) has been 
received from The Region of Southern Denmark. The researchers are all employed in The Region of 
Southern Denmark for clinical work. 
No industrial financing. 
Still applying for further financing,  
Funding will be spent at salary for PhD-student (75 % salary in 4 years), nurse for recruitment, scans 
that are not clinical/standard, GCP-monitoring and OPEN/REDCap. 
Funding will be deposited in a bank account for research in Nuclear Medicine Department OUH 
Odense (Jyske Bank, 7562 0001090051; SE: 30 04 91 79, CVR: 29 19 09 09).  
 
 
 
 
 

 
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Appendix 1, inclusion and exclusion criteria 
 
Inclusion critera, all must be fulfilled 
Exclusion criteria, any criterion fulfilled 
warrants exclusion 
Has given informed consent to participate 
Consent not given 
Can 
read 
and 
understand 
provided 
patient 
information material in Danish 
Inability to read and/or understand provided 
patient information material in Danish 
Biopsy verified, newly diagnosed and untreated PCa 
Previously given consent to this study 
withdrawn for any reason 
Any, some, or all of the following features: 
 
PSA ≥ 20 ng/ml OR 
 
Gleason Score ≥ 4+3 OR 
 
Tumor stage cT2c or above as determined by 
digital rectal exploration and/or transrectal 
ultrasonography 
 
Suspicion of metastases as judged clinically, e.g. 
bone pain 
Staging by imaging not warranted as judged 
clinically 
Staging by imaging is warranted 
Allergy towards NaF, PSMA or other 
contents in the solutions 
 
 

 
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Appendix 2, patient flow 
 
 
Patient with newly 
diagnosed PCa 
Low risk AND no 
suspicion of 
metastases - 
EXCLUDED 
Intermediate OR high 
risk OR suspicion of 
metastases 
Staging by imaging 
indicated 
No - EXCLUDED 
Yes - randomization 
Group A: Conventional 
imaging (CE-CT+NaF-
PET) 
Multidisciplinary team 
conference (MDT) 
Biopsies, further 
imaging, treatment 
and follow-up 
according to MDT 
Group B: Intervention 
(18F-PSMA-
PET/CT)+blinded NaF-
PET 
Multidisciplinary team 
conference (MDT) 
Biopsies, further 
imaging, treatment 
and follow-up 
according to MDT 

 
14 
6th july 2021  
5th version  
EudraCT number 2021-000123-12 
References 
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