European Registry of Next Generation Imaging in Advanced Prostate Cancer
Conditions: Prostate Cancer, Advanced Prostate Cancer, Metastatic Prostate Cancer (mPC)
Sponsor: Fundacio Puigvert

Institut de Recerca Sant Pau 
 
RING project 
Fundació Puigvert 
 
13 JUN 24 
Protocol RG01-01 
 
Confidential 
 
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European Registry of Next Generation Imaging in Advanced 
Prostate Cancer 
Version 5.3 
 13th June 2024 
 
Sponsor 
Fundació Institut de Recerca de l’Hospital de la Santa 
Creu i Sant Pau (Barcelona, Spain)  
Supporters 
J&J Innovative Medicine (ex Janssen) – funder 
EAU Research Foundation – scientific support and 
endorsement 
Coordinator site  
Fundació Puigvert 
Version Number  
5.3 
Protocol number 
RG01-01 
Date 
13th June 2024 
 
Confidentiality statement 
This document contains confidential information. This information can only be disclosed to 
the target study staff and the Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) that reviews this protocol. This information may not be used for purposes other 
than the evaluation or performance of this study without the prior written consent of the 
Sponsor. 
 
This study will be conducted by the protocol, Good Clinical Practice (GCP), and any other 
applicable regulatory requirements, including the archiving of essential documents. 
 
 

Institut de Recerca Sant Pau 
 
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INVESTIGATOR AGREEMENT 
RING study 
RG01-01: European Registry of Next Generation Imaging in Advanced Prostate Cancer 
 
 
I have read and understand this protocol and agree that it contains all the details for the study 
as described. I will conduct this protocol as outlined therein and will make all reasonable 
efforts to complete the study within the designated time.  
 
I agree to conduct this trial according to the Declaration of Helsinki, the International 
Conference on Harmonization (ICH), the Guideline for Good Clinical Practice (GCP), and all 
applicable regulatory requirements. 
 
I understand that the study may be terminated, or enrolment suspended at any time by the 
Sponsor, with or without cause, or by me, if it becomes necessary to do so in the best interests 
of the study subjects.  
 
 
 
 
 
_________________________________ 
Investigator’s Name (print) 
 
_________________________________  
__________________ 
Investigator’s Signature  
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Invited investigators and clinical site 
Name 
Specialty 
Institution 
Prof. Francesco 
Sanguedolce - Principal 
Investigator 
Uro-oncology Unit 
Fundació Puigvert, Institut 
Reserca Sant Pau, Barcelona, 
Spain 
Prof. Anders Bjartell 
Urological cancer 
Department
Skane University Hospital, 
Malmö, Sweden
Prof. Stefano Fanti  
 
 
Prof. Riccardo Schiavina 
Nuclear Medicine 
Division  
IRCCS  Sant´Orsola Hospital, 
Alma Mater University of 
Bologna, Italy 
 
Dept. of Urology 
Prof. Christian Thomas 
 
Department of Adult 
and Pediatric Urology 
University Hospital, TU Dresden 
Dresden, Germany 
Prof. Jozefina Casuscelli 
 
Prof. Alexander Buchner 
Department of Urology 
München LMU  
LMU-University Clinic, 
München, Germany 
Prof. Igor Tsaur 
 
 
Apl.Prof. Dr. Steffen 
Rausch  
 
Department of Urology 
Universitätsklinik Tübingen,  
Tübingen, Germany 
Urogenital Tumour 
Center 
Universitätsklinik Tübingen, 
Dept. of Urology, 
Tübingen, Germany 
Prof. Alain Ruffion  
 
 
Prof. Olivier Rouvière 
 
Oncology Research 
Center, Department of 
Urology
Hospices Civils de Lyon, Dept. of 
Urology, Lyon, 
France 
 
Department of Urinary 
and Vascular Imaging 
Prof. Morgan Rouprêt 
 
Department of Urology 
University Hospital La Pitié-
Salpêtrière, Paris, France 
Prof. George Thalmann 
Oncourology 
department with 
Prostate Center 
University Hospital of Bern, Dept. 
of Urology, Bern, Switzerland 
Prof. Rodrick van der Bergh 
 
 
Robert van Soest 
Department of Urology 
and oncology 
 
Anser Prostate Cancer 
network 
ERASMUS MC, Rotterdam 
The Netherlands 
Franciscus Hospital  
Prof. Steven Joniau 
 
Urogenital, Abdominal 
and Plastic Surgery 
Unit 
UZ Leuven, Dept. of Urology, 
Leuven, Belgium 
 

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Prof. Andrea Minervini 
 
 
Dr Fabrizio di Maida 
Department of Urology 
and Surgical Andrology 
 
AOUC Azienda Ospedaliero-
Universitaria Careggi, Firenze, 
Italy 
 
Prof. Alberto Briganti 
 
Dr Armando Stabile 
Division of 
Experimental 
Oncology/Unit of 
Urology
IRCCS Ospedale San Raffaele, 
Dept. of Urology, Milan, Italy 
 
Prof. Piotr Chlosta 
 
Department of Urology 
Jagiellonian University Medical 
College, Kracow, Poland 
Prof. Alberto Breda 
 
Uro-oncology Unit 
Fundació Puigvert, Dept. of 
urology, Barcelona, Spain 
 
 
 
 
 
 
 
 
PROTOCOL AMENDMENT HISTORY 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details of Changes 
made 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
Abbreviations ........................................................................................................................... 6 
Summary ................................................................................................................................... 7 
Section 1: Introduction .......................................................................................................... 10 
Section 2: The RING Registry .............................................................................................. 11 
2.1 Study Objectives .......................................................................................................... 111 
2.2 Study Endpoints ............................................................................................................. 11 
2.3 Design of study to establish RING patient database ...................................................... 12 
2.4 Study Setting .................................................................................................................. 12 
2.5 Study plan and procedures ............................................................................................. 12 
2.6 Screening participants and informed consent................................................................. 13 
2.7 Withdrawal Procedures .................................................................................................. 13 
2.8 Inclusion and exclusion criteria...................................................................................... 13 
2.9 Data Collection ............................................................................................................... 14 
2.10 Data monitoring, quality control, and assurance ........................................................ 166 
2.11 Adverse event monitoring and reporting .................................................................... 166 
2.12 Final report, publication, and data-sharing policy...................................................... 177 
2.13 Data Security Arrangements ...................................................................................... 177 
2.14 Compliance with the Data Protection Act .................................................................. 177 
2.15 Ethical approval and good clinical practice ............................................................... 177 
2.16 Sponsorship and Funding Arrangements ................................................................... 188 
2.17 Study Management:...................................................................................................... 18 
2.18 Study Duration/end of study ........................................................................................ 19 
2.19 Statistical Analysis ....................................................................................................... 20 
Section 3: References ......................................................................................................... 2121 
 
 
 

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Clinical study  
“European Registry of Next Generation Imaging in 
Advanced Prostate Cancer” 
 
Abbreviations 
 
AE 
 
Adverse Event 
APC 
 
Advanced Prostate Cancer 
CRO  
Contract Research Organization 
CT 
 
Computed Tomography 
DSS 
 
Disease-Specific Survival 
EAU  
European Association of Urology 
EAU RF 
EAU Research Foundation 
eCRF  
electronic Case Report Form 
EPCCE 
European Association of Urology Prostate Cancer Centres of Excellence 
EU 
 
European Union  
GCP 
 
Good Clinical Practice 
GDPR  
General Data Protection Regulation 
HA 
 
Health Authorities 
ICF 
 
Informed Consent Form  
ICH 
 
International Conference on Harmonization 
IEC 
 
Independent Ethics Committee 
IRB 
 
Institutional Review Board 
ISF 
 
Investigator Site File 
IT 
 
Information Technology 
mHSPC 
metastatic Hormone-Sensitive Prostate Cancer 
MRI 
 
Magnetic Resonance Imaging 
NGI 
 
Next-Generation Imaging 
OS 
 
Overall Survival 
PCWG  
Prostate Cancer Working Group 
PET 
 
Positron Emission Tomography 
PFS 
 
Progression-Free Survival 
PI 
 
Principal Investigator 
PSA 
 
Prostatic Specific Antigen 
PSA-DT 
PSA Doubling Time 
PSMA  
Prostate-Specific Membrane Antigen 
RECIST 
Response Evaluation Criteria in Solid Tumor 
RedCap 
Research electronic data Capture 
RING  
Registry of Next Generation Imaging  
SD 
 
Standard Deviation 
SSE 
 
Symptomatic Skeletal-related events 
SUV  
Standardized Uptake Value 
WB-MRI 
Whole-Body MRI 
 

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Summary  
 
Study title 
“European Registry of Next Generation Imaging in Advanced Prostate 
Cancer” 
Acronym 
RING 
Protocol 
number and 
protocol 
version 
RG01-01; V_5.2 
Sponsor name 
Fundació Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau 
(Barcelona, Spain) 
Study Design 
No-profit, 
non-interventional, 
multicentre, 
international, 
prospective, 
investigator-initiated registry enrolling patients with histologically proven 
prostate cancer at high risk of harbouring metastasis (either as treatment naïve 
patients or recurrent disease in patients with former local treatment) who require 
imaging staging.  
The registry is planned to be run in two stages:  
1) Stage 1: cross-sectional observation of patients recruited according to 
selection criteria.  
2) Stage 2: longitudinal observation of patients recruited and in follow-up.
Study 
treatments or 
interventions 
Standard of care. Drugs, treatments, and/or interventions are routinely 
administered to patients per local standards. Treatment decisions will be made 
at the treating physician’s discretion, per routine clinical practice. 
Eligibility 
Criteria 
Inclusion criteria: 
1. Adult male patients (≥18 years with no upper age limit). 
2. Histologically proven prostate cancer.  
3. Patients who require imaging exploration (conventional, Next-Generation 
Imaging (NGI), or their combination) at high risk for harbouring metastatic 
deposits at the hormone-sensitive stage, either at the diagnostic workout of 
a “naïve” patient or at biochemical relapse/progression after local treatment.
4. Patients who authorize their participation in the study by signing a written 
informed consent form (ICF). 
Exclusion criteria: 
1. Patients participating in other interventional or non-interventional study 
which requires NGI as a triage test for metastatic assessment. 

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2. Patients with evidence of any other clinically significant disease or condition 
which in the opinion of the investigator discourages their participation in the 
study.  
3. Patients who will not be able to complete the study.
Sample Size 
An average of 35 patients/year per centre (for a minimum of 12 centres 
involved) was estimated, with an overall number of 600 patients recruited in the 
1.5 years of the study’s recruitment period (whichever comes first). Patients will 
be consecutively selected in the outpatient clinics, and those who sign the 
informed consent will be included in the registry. 
Study 
Procedures 
Patients will provide the ICF before the enrolment in the study and at the start 
of data collection. Patients must meet all the inclusion criteria and do not meet 
any of the exclusion criteria. 
Patients will be managed according to the local usual clinical practice. 
The study will consist of two stages: 1) landscape analysis, and 2) follow-up 
analysis. 
The data will be extracted from patient’s medical records and recorded in the 
RedCap (Research Electronic Data Capture) Registry DataBase. 
 
The registry is going to be developed according to the recommendations on the 
design, implementation, governance, and long-term sustainability of disease 
registries in the European Union (EU).  
The responsible investigators will ensure that the data collection process strictly 
complies with the guiding principles of the applicable laws and regulations in 
the country where this prospective non-interventional registry is being carried 
out. 
A Contract Research Organization (CRO) will be responsible for data 
management: review, cleaning up, queries, etc. Timely updated reports will be 
sent to the participating centres. 
Study 
Objectives 
Stage 1: cross-sectional observation 
1. To identify the proportion of patients for whom, an imaging work-up with 
NGI at baseline may result beneficial, according to physician criteria. 
2. Assess management prompted by NGI vs. conventional imaging in usual 
clinical practice. 
3. To identify the proportion of patients for whom conventional imaging is 
considered informative enough for making a clinical decision, according to 
physician criteria. 
4. Stratification of metastatic prostate cancer patients by the number, volume, 
and location of deposits, according to the different imaging tools employed.
5. Reclassification of HSPC (M0 vs low vs. high volume) based on NGI respect 
to CI when both imaging modalities are used. 

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Stage 2: longitudinal observation 
1. Evaluation of survival outcomes and their relationship with the imaging 
pathway undertaken. 
2. Identification of prognostic factors related to treatment response and disease 
progression. 
Study 
Endpoints 
Stage 1: landscape analysis 
1. Proportion of patients requiring NGI, conventional imaging, or a 
combination of both imaging tools. 
2. Clinical variables associated to each imaging pathway. 
3. Proportion of patients with a change of treatment determined by the 
imaging test result. 
 
Stage 2: follow-up analysis 
1. Progression-free survival (PFS) (biochemical, clinical and radiologic) or 
need for change of treatment (overall and per imaging subgroups) 
2. Disease-specific survival (DSS) (overall and per imaging subgroups). 
3. Symptomatic skeletal-related events (SSE) and SSE-free survival (overall 
and per imaging subgroups). 
4. Imaging biomarkers related to treatment response and disease progression 
[SUV, type of tracer, scoring system used and relevant scores, etc.]. 
Recruitment 
period 
18 months.  
Follow up 
For the purpose of Stage 2 of the project, a minimal mean follow-up time of 24 
months is needed to satisfy the main survival outcome (progression-free 
survival/need for change of treatment). 
Central 
IEC/IRB  
Fundació Puigvert, Barcelona, Spain. 
Statistical 
analysis 
Different analyses have been planned by using the information collected at 
baseline and during follow-up. A description of the collected data will be 
performed. Qualitative variables will be described with absolute frequencies and 
percentages.  
The description of quantitative variables will be performed using the mean, 
standard deviation (SD), median, and inter-quartile ranges.  
The Kolmogorov-Smirnov test will be used to assess the normality of 
distributions. 
Financing 
resources 
Stage 1 of the registry is supported by the contribution of Janssen.  
Additional fund raising will be undertaken to carry out phase 2 of the study 

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Section 1: Introduction 
 
Next-generation imaging (NGI) is going to revolutionize the management of prostate cancer 
patients at all stages of the disease process. 
The advent of magnetic resonance imaging (MRI) and positron emission tomography / 
computed tomography (PET/CT) technologies in advanced prostate cancer (APC) is already 
impacting both the disease diagnosis pathways as well as the treatment follow-up. In particular, 
whole-body MRI (WB-MRI) and PET/CT with new tracers (F/Ga-PSMA, 18F-fluciclovine, 
etc.) have been adopted in multiple centres because of their increased accuracy in the 
assessment of the metastatic dissemination of prostate cancer and/or of response to systemic 
treatments (new antiandrogen agents, chemotherapy, theranostic, etc) than traditional CT and 
bone scans, commonly referred to as conventional imaging (1).  
The Prostate Cancer Working Group 3 (PCWG3) and the response evaluation criteria in solid 
tumour (RECIST)-v1.1 criteria only define the progression of metastases based on 
conventional imaging findings; nevertheless, they do not define a positive benefit of treatment, 
instead relying on prostatic specific antigen (PSA) changes which are known to be inaccurate 
in response assessment settings for hormone sensitivity and castration-resistant disease state 
(2,3).  
In the proPSMA trial, the PET-CT PSMA for high-risk prostate cancer patients has been shown 
to prompt management change more frequently than conventional imaging before curative 
treatment in 28% vs. 15% of the cases, respectively (4). 
In patients with biochemical recurrence after primary treatment, MRI and PET/CT-PSMA are 
the tools of preference according to the latest version of the EAU Guidelines on prostate cancer, 
with MRI especially useful to guide biopsy of the prostate for salvage treatment after primary 
radiotherapy, and PET/CT-PSMA to differentiate local vs distant recurrent disease after local 
treatment(5). 
Accordingly, more precise detection of metastatic disease as well as of the detection of non-
responsiveness of known disease to systemic therapy may help promote patient health by 
allowing timely adjustments of treatments. On the other hand, it is not yet clear whether earlier 
shifts of systemic therapies are beneficial, although accumulating data strongly suggests that 
lower volume/risk patients have improved prognoses(6). These are unmet clinical needs, as 
previously highlighted by the European Association of Urology (EAU) Guidelines on Prostate 
Cancer for the lack of evidence in this regard(5). 
Few clinical trials are investigating the impact of NGI in the setting of advanced prostate cancer 
(7,8). Those reporting such studies are usually undertaken in highly specialized centres, with 
small sample sizes of very highly selected patients. 
International registries may have the advantage of providing complementary evidence by 
capturing real-life data to better define the clinical utility of NGI technologies in centres that 
have already adopted them for routine patient care. 
We aim to understand when, which, and why NGI investigations are undertaken in the 
assessment of real-life APC populations, to:  
• 
Better identify patients who potentially benefit from an earlier/finer assessment of 
metastatic prostate cancer at baseline with NGI. 
• 
Better identify patients for whom conventional imaging is informative enough for 
making a clinical decision. 
• 
Assess change of management prompted by NGI vs. conventional imaging in usual 
clinical practice. 

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Section 2: The RING Registry 
2.1 Study Objectives  
This registry is intended to collect real-world data on patient demographics, medical history, 
clinical endpoints, histological tumour characteristics and imaging explorations of the patients 
with prostate cancer at high risk for harbouring metastatic deposits at the hormone-sensitive 
stage, who require imaging exploration (conventional, NGI, or their combination) either at the 
diagnostic workup of a “naïve” patient or at biochemical relapse/progression after local 
treatment.   
Stage 1: cross-sectional observation 
1. To identify the proportion of patients for whom an imaging work-up with NGI at baseline 
may result beneficial, according to physician criteria. 
2. Assess management prompted by NGI vs. conventional imaging in usual clinical practice. 
3. To identify the proportion of patients for whom conventional imaging is considered 
informative enough for making a clinical decision, according to physician criteria. 
4. Stratification of metastatic prostate cancer patients by the number, volume, and location of 
deposits, according to the different imaging tools employed. 
5. Reclassification of HSPC (M0 vs low vs. high volume) based on NGI respect to CI when 
both imaging modalities are used. 
 
Stage 2: longitudinal observation 
1. Evaluation of survival outcomes and their relationship with the imaging pathway 
undertaken (overall and per subgroup of imaging modality). 
2. Identification of prognostic factors related to treatment response and disease progression. 
2.2 Study Endpoints 
Stage 1: landscape analysis 
1. Proportion of patients requiring NGI, conventional imaging, or a combination of both 
imaging tools. 
2. Clinical variables associated to each imaging pathway. 
3. Proportion of patients with a change of treatment determined by the imaging test result, 
when multiple imaging tests have been realized. 
 
Stage 2: Follow-up analysis 
1. Progression-free survival (PFS) (biochemical, clinical and radiologic) or need for change 
of treatment (overall and per imaging subgroups) 
2. Disease-specific survival (DSS) (overall and per imaging subgroups). 
3. Symptomatic skeletal-related events (SSE) and SSE-free survival (overall and per imaging 
subgroups). 
4. Imaging biomarkers related to treatment response and disease progression [SUV, type of 
tracer, scoring system used and relevant scores, etc.]. 
 

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2.3 Design of study to establish RING patient database. 
This is a no-profit, non-interventional, multicentre, international, prospective, investigator-
initiated registry designed to establish a database of demographics, medical history, 
clinical endpoints, and tumour characteristics at histology and imaging explorations 
from patients with histologically proven prostate cancer at high risk of harbouring 
metastasis (either as treatment naïve patients or recurrent disease in patients with former 
local treatment) who require imaging staging.  
The registry is planned to be run in two stages:  
1) 
Stage 1: cross-sectional observation of patients recruited according to selection criteria.  
2) 
Stage 2: longitudinal observation of patients recruited and in follow-up. 
 
2.4 Study Setting  
This is a multicentre study conducted in specialist prostate cancer centres in tertiary/university 
hospital settings fulfilling EPCCE criteria.  
The planned sites are (pending confirmation upon contract negotiation): 
Fundació Puigvert, Barcelona, Spain
Skane University Hospital, Malmö, Sweden
IRCCS AOU Bologna  - Policlinico Sant´Orsola, Alma Mater Studiorum University of 
Bologna, Italy
University Hospital, Dresden, Germany
München LMU, LMU-University Clinic, München, Germany
UniversitätsklinikTübingen, Germany
Hospices Civils de Lyon, Lyon, France
University Hospital La Pitié-Salpêtrière, Paris, France
University Hospital of Bern, Bern, Switzerland
ERASMUS MC /Franciscus Hospital, Rotterdam, the Netherlands /
UZ Leuven, Leuven, Belgium
AOUC Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy
IRCCS Ospedale San Raffaele, Milan, Italy
Jagiellonian University Medical College, Kracow, Poland
 
Each site should submit the protocol and ICF to the relevant IEC/IRB. The CRO will support 
sites Investigators on this regard, and the IRB of the Coordinator site will be provided to 
facilitate the process.   
 
2.5 Study plan and procedures  
As a non-interventional study, patients will be managed according to their local procedures and 
policies. The registry will be developed in collaboration with those prostate cancer centres with 
high quality standards in clinical practice, research, investigation, and training in prostate 
cancer, as identified by the European Prostate Cancer Centres of Excellence. 
 

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2.6 Screening participants and informed consent 
Participants will be selected in outpatient clinical attendance and will be screened for eligibility 
according to the inclusion and exclusion criteria as already defined in this protocol. A screening 
log will be kept tracking details of subjects invited to participate in the study. The log will also 
ensure that potential participants are approached only once. 
If patients are eligible for inclusion, they will be provided with a copy of the ICF containing 
details of the registry aims the type of clinical information collected, and the way these latter 
will be managed. As soon as the patient has got sufficient time for them to process the 
information and to make a decision and eventual questions will be appropriately addressed and 
discussed by/with the involved site staff (as per the delegation log, including medical staff and 
research nurses), the patients will be invited to provide written informed consent by signing 
and dating the study consent form. Written informed consent will always be obtained before 
study-specific procedures/investigations. Patients who decline their participation should be 
reported in the screening log and reported as screening failure. 
The original signed consent form will be retained in the Investigator Site File (ISF), and the 
participant will receive a copy of the ICF. Alternatively, where electronic medical records are 
in use then the investigator will comply with local consent policy at their site. The right to 
refuse to participate without giving reasons will be respected. Participants will be informed and 
will be required to agree to their medical records being inspected by the Sponsor or their 
delegate, if required, but understand that their confidential details will not be disclosed outside 
the research team.   
 
2.7 Withdrawal Procedures 
Patients will be considered as included in the study once they have signed the ICF. 
Participants have the right to withdraw from the study at any time for any reason, and without 
giving a reason. Should a participant decide to withdraw from the study, all efforts will be made 
to report the reason for withdrawal as thoroughly as possible in the Registry DataBase 
(RedCap). 
 
2.8 Inclusion and exclusion criteria  
The inclusion criteria are broad, and the exclusion criteria are deliberately sparse to allow the 
inclusion of a large and varied population representative of real-life prostate cancer 
management across Europe. 
 
Inclusion Criteria 
Consecutive patients referred with prostate cancer meeting the following inclusion criteria will 
be recruited: 
1. Adult male patients (≥18 years with no upper age limit). 
2. Histologically proven prostate cancer.  
3. Patients who require imaging exploration (conventional, NGI, or their combination) are at 
high risk for harbouring metastatic deposits at the hormone-sensitive stage, either at the 
diagnostic workout of a “naïve” patient or at biochemical relapse/progression after local 
treatment. 
4. Patients who authorize their participation in the study by signing a written ICF. 
 

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Exclusion criteria  
A subject will not be eligible for inclusion in this study if any of the following criteria apply: 
1. Patients participating in other interventional or non-interventional study which requires 
NGI as a triage test for metastatic assessment. 
2. Patients with evidence of any other clinically significant disease or condition which in the 
opinion of the investigator discourages their participation in the study.  
3. Patients who will not be able to complete the study. 
 
2.9 Data Collection  
The recruited centres will form a local team of investigators, which will include one urologist 
and one imaging expert (radiologist or nuclear medicine physician) and led by a Principal 
Investigator (PI) of their choice.  
The informed consent form should be signed at the baseline visit before data will be recorded 
in the database. All the relevant patients’ information will be collected according to the 
electronic Case Report Form (eCRF) and fed into the information technology (IT) platform of 
the registry; for the stage 2 phase, the number of visits and modality of follow-up will be 
according to the usual clinical practice. Clinical data will be included in the eCRF by using a 
pseudonymised process, by de-identifying patients name(s) and surname(s) with a local site 
code followed by a progressive number, according to screening sequence. 
Recruitment will be open for 18 months. 
Stage 1: “Landscape” visit will take place 4 to 6 weeks after the baseline visit, or as soon as 
the diagnostic work up is completed, and a decision is made for the type of treatment the patient 
will undertake.  
Stage 2: Follow-up monitoring will take place according to local protocol schedule, and data 
will be collected every 3 months concerning the closest visit to each time-point. A minimum 
follow-up time of 24 will be required to get a sufficient number of expected events to satisfy 
the main survival outcome (progression-free survival/need for a change of treatment), even 
though the ideal follow-up time to collect the >50% of most the survival events should be 3 to 
5 years, and 5 to 10 years for the overall survival.  
The following domains are covered: demographics, clinical variables, tumour characteristics 
at histology, and imaging explorations.  
The relevant data will be recorded in the Registry DataBase (RedCap).  
It is important to note that the imaging explorations to be performed are those planned by usual 
clinical practice. The participation in this study does not imply a modification in the pattern of 
imaging explorations use. 
It is the site investigator’s responsibility to ensure adequate source documentation for all 
collected data. Designated investigator staff will enter the data required by the protocol into 
the eCRFs. The investigator must certify that the data are complete and accurate by entering a 
password. After being reviewed for completeness, plausibility, and correctness by the monitor, 
the data are locked. At 1 year an interim analysis will be conducted to verify conditions to 
extend recruitment and/or follow-up to satisfy the primary endpoints. 
A CRO will be responsible for data management (review, cleaning up, query, etc.); timely 
updated reports will be sent to the participating centres. 
 
 
 
 

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Study calendar:   
All patients included should be evaluated according to the evaluation calendar presented below: 
 
 
 
 
 
 
Evaluation 
Baseline  
visit 
Interval 
time for 
baseline 
imaging 
diagnostic 
work up 
Landscape 
visit 
(4-6 weeks from 
baseline, or as soon 
as a treatment 
decision is made) 
Interim analysis (1 year) 
Follow-up visits 
(every 3 months, 
covering a minimum 
of 24 months from 
baseline) 
Informed Consent Form  
√ 
 
 
 
Selection criteria  
√ 
 
 
 
Socio-demographic data 
(age, family history of 
prostate, breast, or ovarian 
cancer)
√ 
 
 
 
Past medical history (other 
than prostate cancer)  
√ 
 
 
 
Tumour characteristics 
(prostate cancer), including 
diagnosis date  
√ 
 
 
 
Imaging explorations (NGI, 
conventional or 
combination)  
 
√ 
 
 
√ 
 
Relevant information from 
imaging explorations
 
 
√ 
 
√ 
 
Patients with treatment 
decision (determined by the 
of imaging test)
 
 
√ 
 
PSA / PSA DT  
√ 
 
 
√ 
Events 
(biochemical/radiological/cl
inical progression) 
 
 
 
√ 
Relevant concomitant 
treatments 
 
 
√ 
√ 

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2.10 Data monitoring, quality control, and assurance 
In this study, monitoring will be done remotely, by videoconference and/or email 
correspondence. The Investigator and institutions involved in this study will agree to allow 
study monitors from the Sponsor or its designee direct access (through the computer) to all 
source data, and documents, including a subject’s complete medical record if necessary. eCRFs 
will be checked by the monitor remotely and queries will be created if there is any inconsistency 
with the patient source documents. The number of monitoring visits will depend on the course 
of the study/patient recruitment. Direct access must also be granted to authorized auditors, 
IRB/IEC reviewers, and all applicable regulatory bodies as necessary.  
Monitoring of the study will be arranged by the Sponsor or its designee (e.g., CRO). The study 
site may also be subject to quality assurance audits by the Sponsor or its designee (e.g., CRO), 
as well as inspection by the appropriate regulatory agencies. The site investigator and their 
relevant personnel must be available during the monitoring visits and any scheduled audits, 
and study-related records must be made available, and sufficient time must be devoted to the 
monitoring process. 
The completion of the study involves the collection and processing of personal data. All 
processing of personal data at the clinic and by the Sponsor must be carried out by national 
legislation concerning the protection of personal data. The site Investigator is responsible for 
the subject’s privacy, as well as for the quality of data collected. On the eCRF or other 
documents submitted to the Sponsor, subjects will be identified by a subject identification code 
only. Documents that are not submitted to the Sponsor (e.g., signed ICF) should be kept in a 
strictly confidential file by the Investigator (ISF). As part of the required content of the ICF, 
subjects will be informed that their records may be reviewed by the Sponsor or its designee 
and by regulatory agencies. Should access to medical records require a separate waiver or 
authorization, it is the investigator’s responsibility to obtain such permission from the subject 
in writing before the subject is entered into the study. 
All monitoring findings will be reported and followed up with the appropriate persons 
promptly. 
 
2.11 Adverse event monitoring and documenting 
This is a low-risk study and there are no unexpected adverse reactions from the study 
procedures as they are part of standard care. Any intervention is expected to be aligned to 
standard care. Any adverse event related to the ongoing treatment, and/or to the imaging 
exploration, and/or to any intervention should be reported by the site Investigator to the local 
authorities according to the relevant regulations in place, as by usual clinical practice. 
Definitions 
Adverse event (AE) 
Any untoward medical occurrence in a subject to whom a study intervention or procedure has 
been administered, including occurrences that are not necessarily caused by or related to that 
intervention. An AE, therefore, does not necessarily have a causal relationship with a new 
initiated treatment 
Product Quality Complaint (PQC): 
Any complaint for a medical product that indicates a potential quality issue during 
manufacturing, packaging, release testing, stability monitoring, dose preparation, storage or 
distribution of the product or delivery system is considered a PQC. Not all PQCs involve a 
patient.   

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RING project 
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Protocol RG01-01 
 
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The notification of undesirable effects related to the use of medical devices will be carried out 
in accordance with the provisions of European law. 
 
2.12 Final report, publication, and data-sharing policy 
All study information is considered confidential and the property of the Sponsor until 
publication. The results or conclusions of this study may be sent to scientific conferences and 
medical journals. The investigator agrees to keep this information strictly confidential and will 
not use it for any other purpose without written permission from the Sponsor.  
Once the study has been completed and the statistical analysis performed, the Sponsor will 
prepare the final report of the study. This report will contain a description of the objectives and 
methodology of the study as well as the results and conclusions. It will be sent to the IEC/IRB 
and Health Authorities (HA) if requested.  
 
2.13 Data Security Arrangements  
The database will be held and administered by the Sponsor. The database administrators have 
considerable experience in managing large databases for oncology diseases. Database 
management will require regular review of cases with feedback to site investigators to clarify 
data inconsistencies and to address missing or incomplete data. An audit of the informed 
consent process and source data verification will be conducted on a sampling basis.  
 
2.14 Compliance with the Data Protection Act 
All data entered will be anonymized and will be processed according to the General Data 
Protection Regulation (GDPR) - Regulation (EU) 2016/679. This will be the responsibility of 
the Host institution. Each participating centre will need to ensure they are in line with GDPR 
guidance and that they are satisfied with processes before data entry. The information included 
in the RING database will be only accessible to the data manager and the members of the 
Steering Committee, for both monitoring and statistical analysis. The site investigator and the 
sponsor are jointly responsible for the treatment of patients’ personal data. 
 
 
 
2.15 Ethical approval and good clinical practice  
The investigator will ensure that the study is conducted in compliance with the study protocol, 
the ethical principles contained in the latest version of the Declaration of Helsinki developed 
by the World Medical Association, the principles of GCP, and the long-term sustainability of 
disease registries in the EU.  Each partner site will obtain the IEC/IRB approval. Additionally, 
any other necessary approvals required by partner sites will be obtained before the 
commencement of the study at the site. All patients must provide written informed consent to 
participate. It is the responsibility of the investigator at individual sites to obtain the appropriate 
approvals and to ensure that informed consent is in place. The site investigator and the sponsor 
are jointly responsible for the treatment of patients’ personal data. 
 

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RING project 
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2.16 Sponsorship, Stakeholders, and Funding Arrangements  
The Sponsor is defined as the organization responsible for the administration and management 
of the study. In this case, the sponsoring organization will be the Fundació Institut de Recerca 
de l’Hospital de la Santa Creu i Sant Pau (Barcelona, Spain). 
The project has received the endorsement and scientific support from the EAU-Research 
Foundation.  
The study and network activities may be funded by educational and research grants from the 
pharmaceutical industry, academic funders, professional societies, or charities as appropriate.  
In the Stage 1 part of the study, will be supported by the contribution of Janssen. Further fund 
raising will apply to undertake the Stage 2 e part of the project. In each case, the investigators 
will discuss and agree on a research contract with individual funding bodies to cover:  
- The work to be undertaken  
- The financial contribution and payment terms  
- The share of technical, commercial, and economic risks for each part  
- The right to publication of results  
- Ownership of work and access rights to data  
- Agreed liabilities and indemnities  
 
2.17 Study Management:   
Principal investigator responsibilities: 
• 
Ensuring that no participant is recruited into the study until all relevant regulatory 
permissions and approvals have been obtained. 
• 
Obtaining written informed consent from participants before any study-specific procedures. 
• 
Familiarity with the study procedures. 
• 
Compliance with the protocol, documentation of AE of Grade 3 and 4. 
• 
Study conducts and the welfare of study subjects. 
• 
Screening and recruitment of subjects. 
• 
Provision of adequate medical care in the event of an adverse event. 
• 
Compliance with the Declaration of Helsinki developed by the World Medical Association, 
the principles of GCP, the long-term sustainability of disease registries in the EU, and any 
other relevant legislation and regulatory guidance. 
• 
The PI shall be qualified by education, training, and experience to assume responsibility 
for the proper conduct of the trial.  S/he shall provide a current signed & dated curriculum 
vitae as evidence for the Trial Master File. 
• 
Ensuring Study Site team members are appropriately qualified by education, training, and 
experience to undertake the conduct of the study. 
• 
Availability for Investigator meetings, monitoring visits, and in the case of an audit. 
• 
Maintaining study documentation and compliance with reporting requests. 
• 
Maintaining a site file, including copies of study approval, list of subjects, and their signed 
informed consent forms. 
• 
Documenting appropriate delegation of tasks to other study personnel e.g., research nurse, 
co-investigator (s), trial coordinators, and data managers. 
• 
Ensuring data collected is accurate, timely & complete. 
• 
Providing updates on the progress of the trial. 
• 
Ensuring subject confidentiality is maintained during the project and archival period. 
• 
Ensuring archival of study documentation for a minimum of 15 years following the end of 
the study unless local arrangements require a longer period. 

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Protocol amendments, deviations, and breaches  
Amendments to the current registry study protocol should be made only after consultation 
between an authorized representative of the Sponsor and the investigator. Amendments to the 
protocol must be prepared by a representative of the Sponsor and reviewed and approved 
initially by the Sponsor's medical team and a biostatistician. 
All substantial amendments to the protocol should be sent to the same IEC/IRB for approval 
by local requirements. Approval must be expected before any changes are made, except those 
necessary to eliminate immediate risks to trial patients. A record of non-substantial 
amendments (when the change/s involves only logistical or administrative aspects in the study, 
e.g., change of telephone number, change of monitor, must be kept. 
Study documentation  
The investigator is responsible for maintaining an ISF during and after the study. A 
representative of the Sponsor is responsible for establishing the file. The study monitor will 
deliver it to the investigator and instruct the investigator on the appropriate use of the file. The 
relevant contents and completeness of the file will be monitored. The Investigator’s file 
includes the correspondence, copy of the final signed protocol including appendices and 
amendments, ethics committee approval and other correspondence with the ethics committee, 
agreements, copy of the notification to the regulatory authority, signed copies of ICFs, 
information to study team members, patient identification list, final study report, source data 
other than those archived in the hospital records, investigator's copies of completed eCRFs and 
study termination form. 
The investigator is responsible for retaining the ISF for at least 5 years to allow for audit or 
inspection after terminating the study. The investigator should ensure that the patient’s files 
(patient’s medical history) can be archived for at least 15 years in the hospital.  
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (e.g., retirement, relocation), the Sponsor should be prospectively notified. The 
study records must be transferred to a designee acceptable to the Sponsor. The investigator 
must obtain the Sponsor's written permission before disposing of any records, even if retention 
requirements have been met. 
 
2.18 Study Duration/end of study  
The planned start date will be in 2024. The study recruitment period will be 18 months. 
During the study, the investigator will collect data from the patient´s medical records, necessary 
to complete the eCRF. 
 
The end of the study is defined as data entry for the last patient visit. The Sponsor or Steering 
Committee has the right at any time to terminate the study for clinical or administrative reasons. 
The end of the study will be reported to the Sponsor and the appropriate IEC/IRB within 
appropriate local and/or national timelines by individual Sites. Individual Sites will be 
responsible for ensuring appropriate follow-up and information to participants in the event of 
premature termination of the study. 
 
 
 
 
 

Institut de Recerca Sant Pau 
 
RING project 
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Protocol RG01-01 
 
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2.19 Statistical Analysis 
Data collection and data analysis 
The investigator must include the required data in an eCRF according to standard procedures. 
At the end of the study, a statistical report will be performed with all tables, lists, and figures 
as per the statistical analysis plan. 
 
Statistical Analysis Plan and Statistical Methods 
This collection of cases has the main objective to analyse the clinical management of the APC 
population in a real-life context. Different analyses have been planned by using the information 
collected at baseline and during follow-up.  
A description of the collected cases will be performed. Qualitative variables will be described 
with absolute frequencies and percentages. The description of quantitative variables will be 
performed using the mean, SD, median, and quartiles. The Kolmogorov-Smirnov test will be 
used to assess the normality of distributions. 
Sample size calculation 
In the context of a registry, there is no sample size required to be calculated. However, given 
the prevalence of the targeted stage disease and the mean volume of the centres involved, an 
average of 35 consecutive patients/year per centre was estimated, with an overall number of 
600 patients recruited in the 1.5 years of the study’s recruitment period (whichever comes first).  
Baseline visits will be done coinciding with any of the routine follow-up visits of the patient, 
without any alteration of the standard clinical practice of the site. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol RG01-01 
 
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Eiber M, Herrmann K, Fendler WP, Maurer T. 68Ga-labeled Prostate-specific 
Membrane Antigen Positron Emission Tomography for Prostate Cancer Imaging: The 
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Ma TM, Gafita A, Shabsovich D, Juarez J, Grogan TR, Thin P, et al. Identifying the 
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