A Randomized Controlled Trial Comparing Bp-MRI and Mp-MRI on the Screening Accuracy for Clinically Significant Prostate Cancer Before MRI-fusion Targeted Biopsy
Phase: NA
Conditions: Randomized Controlled Trial, Prostate Cancer, Magnetic Resonance Imaging
Sponsor: Chang Gung Memorial Hospital

Protocol: BMPFB Trial                                                                                                                        
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CLINICAL STUDY PROTOCOL 
 
A randomized controlled trial comparing bp-MRI and mp-MRI on the 
screening accuracy for clinically significant prostate cancer before 
MRI-fusion targeted biopsy 
 
 
VERSION NO.3 
 DATES (20240429) 
 
 
 
INVESTIGATORS 
See-Tong Pang 
 
 
 
 
 
SITES 
Chang Gung Memorial Hospital at Linkou 
 
 

Protocol: BMPFB Trial                                                                                                                        
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Table of Contents 
 
Section 
Page 
1. Synopsis ...................................................................................................................................1 
2. Introduction and Rationale ........................................................................................................... 7 
3. Objectives and Endpoints ........................................................................................................9 
3.1. Study Objectives ................................................................................................................ 9 
3.2. Study endpoints ................................................................................................................. 9 
4. Study Design..........................................................................................................................10 
4.1. Overall Design (Flow Chart) ........................................................................................... 11 
4.2. Number of Patients ........................................................................................................... 11 
4.3. Schedule of Activities (Time-Event scheme) .................................................................. 12 
5. Study Population ....................................................................................................................13 
5.1. Inclusion Criteria .............................................................................................................. 13 
5.2. Exclusion Criteria ............................................................................................................ 13 
5.3. Withdrawal criteria ..................................................................................................................... 13 
6. Treatments .............................................................................................................................13 
6.1. Treatments Administration .............................................................................................. 13 
6.2. Concomitant Therapy ...................................................................................................... 13 
7. Efficacy Assessments ............................................................................................................13 
8. Safety Assessments 
9. Adverse Event reporting 
9.1. Definition and reports of Adverse Events ........................................................................ 14 
9.2. Adverse event follow-up .................................................................................................. 14 
10. Criteria for the termination of the trials 
11. Statistical Considerations 
11.1. Sample Size Determination ............................................................................................15 
11.2. Planned Statistical methods of analysis ..........................................................................16 
11.2.1. Efficacy analyses ......................................................................................................16 
11.2.2. Safety analyses .........................................................................................................16 
11.2.3. Additional analyses ..................................................................................................16 
11.2.4. The level of significance ..........................................................................................16 
11.2.5. Analysis Population ..................................................................................................16 
12. Direct access to source data/documents 
13. Ethical considerations 
14. Data handling and keeping 
15. Financing and Insurance 
16. References..............................................................................................................................17 

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1. Synopsis 
 
 
Protocol Title：A randomized controlled trial comparing bp-MRI and mp-MRI on the 
screening accuracy for clinically significant prostate cancer before MRI-fusion targeted 
biopsy.      
Study Objectives：We aim to address these questions for Taiwan males suspicious of 
csPCA, with PSA range of 4-20 ng/ml by conducting a RCT trial. 
     
Investigational product(s)：Magnetic Resonance Imaging (MRI) 
 
Development Phase：⃞ I   ⃞II    ■III     ⃞IV    ⃞其它______   ⃞不適用 
 
    Study Design： 
1. ■ Experimental Group 
□ Control Group ：  □  Placebo  
□ Study Drug  (Name、Dose、Usage)  __________________ 
□ Other _____________ 
2. Blinding：■ Open  □ Evaluator-blind  □ Single-blind(patient)  □ Double-blind(patient+PI)   
□ Double Dummy   □ Other ______________ 
3.  Randomization:  ■ Yes   □ No 
4. □ Parallel design   □ Crossover design   □ Other ____________   ■ Not applicable 
5.  Treatment Period：____________(days/weeks/months/years)  ■ Not applicable 
  6.  Study Period: _____2_____years   (or From 01/02/2024 to 31/01/2026) 
6. Dose adjustment：□ Mandatory     □ Selectively       □ No        ■ Not applicable 
7. Study location：■ Single □ Multi-center  □  Global  
Endpoints (Outcome measure)： 
1. Primary endpoint: 
The proportion of men with clinically significant Prostate cancer(csPCa), defined as a 
diagnosis of ISUP (International Society of Urogenital Pathology) Grade group ≥2 prostate 
cancer, in at least one biopsy core. 
     
2. Secondary endpoints: 
1. The proportion of men with a diagnosis of any PCa 
2. The proportion of men with a diagnosis of clinically insignificant PCa, defined as ISUP 
grade group 1 PCa (ISUP 1 PCa) 
3. The proportion of men with a diagnosis of csPCa 
Only in targeted biopsy 
Only in systematic biopsy 
4. The proportion of csPCa of all suspicious lesions from bp-MRI and mp-MRI. 
 
3. Exploratory endpoints (if any):  
nil 

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Inclusion/Exclusion Criteria： 
Inclusion criteria (All of the followings) 
1. 
Men ≥50 years of age 
2. 
Clinical suspicion of prostate cancer and indicated for prostate biopsy 
3. 
Serum Prostate-specific antigen (PSA) between 4~20 ng/mL 
4. 
Eligible for MRI study 
5. 
Digital rectal examination ≤ cT2 (organ-confined cancer) 
6. 
Able to provide written informed consent. 
 
Exclusion criteria: (any of the followings) 
1. 
Prior prostate biopsy in the 6 months before screening visit 
2. 
Prior diagnosis of prostate cancer  
3. 
Contraindicated to prostate biopsy:  active urinary tract infection, failed insertion of 
transrectal ultrasound probe into rectum (abdominal perineal resection, anal stenosis), 
uncorrectable coagulopathy, antiplatelet or anticoagulant which cannot be stopped 
(continue low-dose aspirin before and after biopsy is permitted) 
4. 
Contraindicated to MRI study: contrast medium allergy, claustrophobia, or other 
contraindications (e.g.: intra-abdominal metal foreign bodies). 
5. 
Patients without histological results of prostate biopsies due to patient refusal for biopsy or 
loss of follow up before biopsy being done 
6. 
Patients have prior treatments for prostate cancers or any kinds of hormone therapy, 
immunotherapy, chemotherapy, radiation therapy of the pelvic cavity. 
7. 
Patients’ withdrawal of informed consents of this study 
 
Withdrawal criteria 
1. 
Patients could not complete the scheduled MRI examinations 
2. 
MRI images of insufficient quality to localized csPCA or to exclude the presence of csPCA 
 
Study Procedures： 
Feasibility in recruiting adequate patients for this trial 
There are estimated 600+ patients diagnosed and treated as prostate cancer in our institute every 
year. We performed about 800+ prostate biopsies in our hospital per year. Assuming 40-50% of men 
agree recruitment to this study, about 200-250 men will be recruited per year, and the recruitment for 
the whole study should complete in 24 months, and the study to complete in 30 months.  
 
Study intervention 
MRI prostate 
Bi-parametric and multi-parametric MRI prostates can be performed using a 3.0 Tesla scanner 
with a pelvic phased array coil with or without contrast. MRI findings will be reported according to 
PI-RADS (Prostate Imaging-Reporting and Data Systems) v2.1 recommendations. (12) MRI will be 
reported by radiologists with experience in MRI prostate reporting. PI-RADS scores 3-5 will be 
regarded as suspicious, and targeted plus systematic biopsy will be performed. 
 
Prostate biopsy 
In patients with suspicious lesion found on MRI (identified as PI-RADS score 3-5 lesions on bp-
MRI or mp-MRI), biopsies will be done via trans-perineal approach under general anesthesia with 3 
cores of targeted biopsy from each lesion, alone with 3 cores of systemic biopsy from right and left 

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lobes respectively. 
In those without identified suspicious lesions on MRI, a standard 12-core systematic biopsy will be 
performed via trans-rectal approach under local anesthesia.  
All biopsies will be performed by Urologists experienced in both targeted and systemic prostate 
biopsy. Targeted biopsies will be done by software-assisted MRI-USG fusion registration. Peri-
biopsy antibiotics are given according to our clinical guidelines.  
 
Post-biopsy management 
Patients will be discharged after prostate biopsy when they can pass urine without significant 
gross hematuria, and clinically stable. They will be followed up in the clinic within 10 days after a 
biopsy to review pathology results and complications. All biopsies will be assessed by experienced 
Urogenital pathologists and reported according to the International Society of Urological Pathology 
(ISUP) consensus. (23) The study period ends after the first clinic follow-up.  
 
 
         
Concomitant Treatments：  ■不適用 
1. Concomitant Therapy： 
      2. Prohibited Therapy： 
Statistical Methods： 
1. Main study Hypothesis： □ Equality  □ Superiority  ■ Non-inferiority  
   ⃞ Equivalence   □ Other ________ 
2. Estimated Sample Size：整個試驗預計納入人數  370  ，整個試驗可評估人數  370   
                                               本中心預計納入人數__370__，本中心可評估人數_370__ 
3. Efficacy assessment group：  □ Intent-to-treat (ITT)   ■ Per-Protocol (PP)   
                                                 □ Other ________ 
附註：意圖治療：Intent-to-treat (ITT)；依計畫書：Per-Protocol (PP)  
4. Interim analysis：  □ Yes    ■ No 
Statistical methods： 
The primary objective of this study is to evaluate the csPCa detection in bp-MRI arm 
versus mp-MRI arm. We hypothesise that bp-MRI is non-inferior to mp-MRI in detecting 

Protocol: BMPFB Trial                                                                                                                        
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csPCa. The baseline characteristics of the two groups will be compared. Continuous 
variables will be evaluated using the student’s t-test and the Mann-Whitney U test. In 
contrast, categorical variables will be analysed using the Chi-squared and Fisher’s exact 
tests, as applicable. The effect size and 95% CI will be presented for secondary outcomes, 
and a 2-sided p-value less than 0.05 will be considered statistically significant. All statistical 
analyses will be performed using SPSS v.24.0 (IBM Corp., Armonk, NY, USA). 
 
5. Handling of Missing Data： 
Analysis would be carried on for available data after exclusion of the missing data. 
 
 
2. Introduction and Rationale 
Prostate cancer (PCa) is the second most commonly diagnosed cancer and the fifth leading cause of 
cancer death in males worldwide [1]. It is traditionally less prevalent in Asia but the incidence has 
increased in the past decades [2-4]. According to the data released by Taiwan Health Promotion 
Administration, Ministry of Health and Welfare Cancer Statistics, Prostate cancer is now the fifth 
most common male cancer in Taiwan [5]. 
Prostate-specific antigen (PSA) is a widely used test for prostate cancer detection. However, 
PSA is highly sensitive but not very specific [6]. Elevated PSA levels typically lead to referrals to 
urologists for further evaluation, including magnetic resonance imaging (MRI) and potentially a 
prostate biopsy. Biopsies carry a risk of complications, with infections at the biopsy site being a 
major concern, leading to sepsis in 2–5% of cases [7]. Concerns about missing clinically significant 
cancer, unnecessary biopsies, and overtreatment of low-risk disease have driven the search for 
improved biopsy methods that are both more accurate in detecting cancer and safer for patients. 
The application of Magnetic Resonance Imaging (MRI) in identifying potentially cancerous 
lesions within the prostate gland dates back to the 1980s [8, 9]. A significant leap forward occurred 
in the 1990s with the introduction of dynamic contrast-enhanced (DCE) and diffusion-weighted 
imaging (DWI) MRI protocols [10, 11]. With the introduction of MRI of the prostate and the 
improvement in PCa detection and localization, an alternative procedure, known as MRI-targeted 
biopsy (MRI-TB), has been shown to have comparable or even higher detection rates of csPCa 
compared to TRUS-system biopsy (SB). Targeted prostate biopsies from MRI-suspicious lesions 
have improved the cancer detection rate (CDR) of csPCa compared with systematic TRUS-guided 
biopsies. The implementation of pre-biopsy multiparametric MRI has effectively reduced the risk 
of both underdiagnosis of clinically significant disease and overdiagnosis of clinically insignificant 
disease, which were previously associated with random prostate sampling. (19) 
Two types of MRIs have emerged for diagnosing PCa: Bi-parametric MRI (bpMRI), which 
combines T2-weighted images with DWI, and multi-parametric MRI (mpMRI), which incorporates 
DCE with or without spectroscopy, into its imaging protocol [12]. The determination of PCa 
utilizing mpMRI relies on the Prostate Imaging Reporting and Data System (PI-RADS) score based 
on PI-RADS versions 2.1 recommendation; however, if DCE is of insufficient quality or not 
available, an alternative PIRADS scores based on mp MRI could be evaluated using modified score 
rules provided by PRIRADS v 2.1 as well [13]. 
In 2015, Rais-Bahrami et al. employed mpMRI with the exclusion of DCE results to analyze 

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biopsy outcomes of individuals. Their research explored the application of bpMRI in diagnosing 
PCa. They found the bpMRI with PCa detection overall accuracy of 80% [14]. Bass et. al. 
conducted a meta-analysis across 44 cohort studies, revealing that the sensitivity, specificity, and 
AUC of bpMRI for csPCa were 87%, 72%, and 87%, respectively [15]. Furthermore, several 
studies have demonstrated that both bpMRI and mpMRI exhibit comparable diagnostic 
effectiveness in detecting PCa and csPCa. The overall sensitivity and specificity for mpMRI were 
76% and 89%, while bpMRI achieved 74% sensitivity and 90% specificity [16]. For patients with 
varying total prostate-specific antigen (tPSA) levels, both mpMRI and bpMRI exhibit identical 
accuracy in detecting PCa or csPCa. However, Pan et al. found that mpMRI detected more cases of 
PCa and csPCa in the tPSA range of 10–20 ng/ml. In contrast, for other tPSA ranges (tPSA < 4 
ng/ml, 4–10 ng/ml, 20–100 ng/ml), the detection rates of PCa and csPCa were similar between 
bpMRI and mpMRI [17]. Collectively, bpMRI proves to be an effective tool for PCa screening and 
diagnosis, with comparable diagnostic accuracy to mpMRI. Additionally, when omitting the DCE 
protocol from the MRI, patients experience reduced costs and shorter imaging times, while 
healthcare providers can offer more tests to their patient population. 
Although these retrospective studies and some meta-analysis shows similar sensitivity and 
specificity for detecting csPCA in Europe and US patients, there is still a lack of randomized 
control trials validating the non-inferiority of bpMRI as compared with mpMRI for detecting and 
guiding targeted biopsies of csPCA in patients of PSA 4-20 ng/ml in the world and Taiwan. Thus, 
we aim to address this questions for Taiwan males suspicious of csPCA, with PSA range of 4-20 
ng/ml by conducting a RCT trial. 
2.1 Investigational product(s) 
 
Not Applicable 
 
2.2 Animal and preclinical study data 
 
Not Applicable 
 
2.3 Clinical data 
 
Not Applicable 
 
2.4 Risks / benefits Assessment 
 
MRI (Magnetic Resonance Imaging) is a commonly used medical imaging technology, 
primarily for detailed observation of internal body structures and functions. Its risks are relatively 
low, but there are still some considerations, while its potential benefits are quite significant. 
 
 
Risks: 
- For patients with cardiac pacemakers, metal implants, or certain types of metal fragments, MRI 
can pose risks. 
- The high-intensity magnetic field may affect or move metal objects inside the body. 
- In very rare cases, the use of contrast agents may cause mild to severe allergic reactions. 
 
Potential Benefits: 
- MRI does not use ionizing radiation, resulting in less exposure to radiation for patients compared 
to X-rays or CT scans. 
- It provides extremely detailed images of soft tissues, which helps in diagnosing various diseases 
such as brain and spinal cord lesions, musculoskeletal injuries, heart diseases, and cancer. 

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- MRI is very useful for long-term tracking and assessing the progression of certain medical 
conditions. 
 
2.5 Regulatory 
 
This study will be conducted in compliance with the protocol approved by the Institutional 
Review Board, and according to Good Clinical Practice standards.  No deviation from the protocol 
will be implemented without the prior review and approval of the IRB except where it may be 
necessary to eliminate an immediate hazard to a research subject.  In such case, the deviation will 
be reported to the IRB as soon as possible. 
Subject data confidentiality is maintained through the use of identification numbers to 
protect the privacy of participants. It ensures that no information about the participants' 
involvement in the study or their personal information is disclosed. Regarding the results and 
diagnoses from participant interviews, the research leader will maintain a confidential stance, 
carefully safeguarding their privacy. 
3.  Objectives and Endpoints 
3.1 Study Objectives:  
3.1.1 Primary objective: 
We aim to address these questions for Taiwan males suspicious of csPCA, with PSA range 
of 4-20 ng/ml by conducting a RCT trial. 
 
3.2 Study endpoints: 
3.2.1 Primary endpoint: 
The proportion of men with clinically significant Prostate cancer(csPCa), defined as 
a diagnosis of ISUP (International Society of Urogenital Pathology) Grade group ≥2 
prostate cancer, in at least one biopsy core. 
 
3.2.2 Secondary endpoints: 
1. The proportion of men with a diagnosis of any PCa 
2. The proportion of men with a diagnosis of clinically insignificant PCa, defined as ISUP 
grade group 1 PCa (ISUP 1 PCa) 
3. The proportion of men with a diagnosis of csPCa 
4. Only in targeted biopsy 
5. Only in systematic biopsy 
6. The proportion of csPCa of all suspicious lesions from bp-MRI and mp-MRI. 
 
 
4. Study Design 
We propose to conduct a phase III randomised controlled trial to evaluate the detection of 
clinically significant prostate cancer (csPCa) by bp-MRI versus mp-MRI before MRI-fusion targeted 
biopsy. Clinically significant prostate cancer (csPCa) is defined as ISUP (International Society of 
Urogenital Pathology) Grade group ≥ 2 prostate cancer.  
Patients who are suspicious of prostate cancers with abnormal digital examination, or abnormal 
ultrasound and having a pre-MRI and were scheduled to receive prostate biopsy will be enrolled in 
this study. Patients will be randomized in a 1:1 manner to bp-MRI and mp-MRI. Patients with clinical 
suspicion of prostate cancer on MRI with PI-RADS (Prostate Imaging-Reporting and Data System, 
version 2.1) [18] score 3-5 will be arranged to receive MRI-Ultrasound fusion biopsy for targeted 
and systemic biopsy. Patients who have no suspicious lesions found on MRI will receive standard 

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systemic biopsy only instead. The study flowchart is provided in Figure 1. The detection rates of 
csPCa will be compared between arms. The study hypothesis is that bp-MRI has similar detection 
rate for csPCa comparing to mp-MRI. 
To formulate the randomization codes and distribution process, we first plan to recruit a total of 
370 participants. Then, we choose a block size of 4 to maintain balance between groups while 
reducing the predictability of the assignment sequence. Utilizing the block randomization method, 
we generate random codes for each block to ensure an equal number of participants in each treatment 
group. Subsequently, a complete table of random codes is created using a random number generator, 
serving as the basis for participant assignment. 
As participants enter the study, they will be assigned to the respective groups according to the 
sequence of the random code table, namely the bp-MRI group or the mp-MRI group. This process 
not only ensures the randomness of the assignments but also helps maintain the fairness and 
transparency of the research. After each assignment, we record the detailed information of the 
participants and the group they are assigned to, ensuring the traceability and transparency of the 
entire process. 
 
4.1 Overall Design 
Study intervention 
MRI prostate 
Bi-parametric and multi-parametric MRI prostates can be performed using a 3.0 Tesla scanner with 
a pelvic phased array coil with or without contrast. MRI findings will be reported according to PI-
RADS (Prostate Imaging-Reporting and Data Systems) v2.1 recommendations. (12) MRI will be 
reported by radiologists with experience in MRI prostate reporting. PI-RADS scores 3-5 will be 
regarded as suspicious, and targeted plus systematic biopsy will be performed. 
 
Prostate biopsy 
In patients with suspicious lesion found on MRI (identified as PI-RADS score 3-5 lesions on 
bp-MRI or mp-MRI), biopsies will be done via trans-perineal approach under general anesthesia with 
3 cores of targeted biopsy from each lesion, alone with 3 cores of systemic biopsy from right and left 
lobes respectively. 
In those without identified suspicious lesions on MRI, a standard 12-core systematic biopsy will be 
performed via trans-rectal approach under local anesthesia.  
All biopsies will be performed by Urologists experienced in both targeted and systemic prostate 
biopsy. Targeted biopsies will be done by software-assisted MRI-USG fusion registration. Peri-
biopsy antibiotics are given according to our clinical guidelines.  
 
Post-biopsy management 
Patients will be discharged after prostate biopsy when they can pass urine without significant 
gross hematuria, and clinically stable. They will be followed up in the clinic within 10 days after a 
biopsy to review pathology results and complications. All biopsies will be assessed by experienced 
Urogenital pathologists and reported according to the International Society of Urological Pathology 
(ISUP) consensus. (23) The study period ends after the first clinic follow-up.  
 
In our medical research, we prioritize protecting participant privacy and confidentiality. 
We use unique research codes to anonymize personal details like names and IDs. The principal 
investigator keeps consultation results and diagnoses confidential, even in published research. 
Participants consent to have their records reviewed by authorized parties for legal and ethical 
compliance, with a promise of maintaining their anonymity. For safety, we may inform 

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participants' other doctors about their trial involvement to manage treatment interactions. 
Overall, these steps ensure participant privacy and safety throughout the research. 
 
Flow Chart (試驗流程圖)：
 
4.1 Number of Patients 
evaluable number 
The sample sizes of 148 in the bp-MRI group and 148 in the mp-MRI group achieve 
80.145% power to detect a non-inferiority margin difference between the group proportions of 
-0.1000. The mp-MRI group proportion is 0.280. Under the null hypothesis of inferiority, the 
bp-MRI proportion is assumed to be 0.180. The power was computed for the case where the 
actual treatment group proportion is 0.280. The test statistic used is the one-sided Z test 
(unpooled), and the significance level of the test is 0.025. We have set the dropout rate at 20%, 
thus the bp-MRI group and mp-MRI group each consist of 185 individuals, resulting in a total 
enrolled number of 370 people. We have set the dropout rate at 20%, thus the mp-MRI 
group and bp-MRI group each consist of 185 individuals, resulting in a total enrolled 
number of 370 people. 
 
enrolled number 
We have set the dropout rate at 20%, thus the mp-MRI group and bp-MRI group each 
consist of 185 individuals, resulting in a total enrolled number of 370 people. 
 
4.2 Schedule of Activities 
Time-Event scheme(評估時程表): 
 
Screening 
Imaging 
Verification 
Post-biopsy 
management 
Category 
Registration 
MRI 
Prostate 
biopsy 
 
Time frame 
Day 1-14 
Day 15-
28 
DAY 29-58 
Day 59-68 
Assessment 
 
 
 
 

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Inform 
consent 
✓ 
 
 
 
History 
taking 
✓ 
 
 
 
PSA level 
✓ 
 
 
 
Digital 
Rectal 
Examination 
✓ 
 
 
 
Abnormal 
Ultrasound 
✓ 
 
 
 
Staging bp-
MRI or mp-
MRI 
 
✓ 
 
 
Biopsy 
 
 
✓ 
 
Hematuria 
 
 
 
✓ 
Pathology 
report 
 
 
 
✓ 
 

 
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5. Study Population 
5.1 Inclusion Criteria 
   
Inclusion criteria: 
1. 
Men ≥50 years of age 
2. 
Clinical suspicion of prostate cancer and indicated for prostate biopsy 
3. 
Serum Prostate-specific antigen (PSA) between 4~20 ng/mL 
4. 
Eligible for MRI study 
5. 
Digital rectal examination ≤ cT2 (organ-confined cancer) 
6. 
Able to provide written informed consent. 
5.2 Exclusion Criteria 
Exclusion criteria: 
1. 
Prior prostate biopsy in the 6 months before screening visit 
2. 
Prior diagnosis of prostate cancer  
3. 
Contraindicated to prostate biopsy:  active urinary tract infection, failed insertion of 
transrectal ultrasound probe into rectum (abdominal perineal resection, anal stenosis), 
uncorrectable coagulopathy, antiplatelet or anticoagulant which cannot be stopped 
(continue low-dose aspirin before and after biopsy is permitted) 
4. 
Contraindicated to MRI study: contrast medium allergy, claustrophobia, or other 
contraindications (e.g.: intra-abdominal metal foreign bodies). 
5. 
Patients without histological results of prostate biopsies due to patient refusal for biopsy 
or loss of follow up before biopsy being done 
6. 
Patients have prior treatments for prostate cancers or any kinds of hormone therapy, 
immunotherapy, chemotherapy, radiation therapy of the pelvic cavity. 
7. 
Patients’ withdrawal of informed consents of this study 
 
5.3 Withdrawal criteria 
1. 
Patients could not complete the scheduled MRI examinations 
2. 
MRI images of insufficient quality to localized csPCA or to exclude the presence of csPCA 
 
6. Treatments 
Not Applicable 
6.1.Treatment Administration 
Not Applicable 
 
6.2. Concomitant Therapy 
Not Applicable 
       
7. Efficacy Assessments 
Not Applicable 
 
8. Safety Assessments 
Allergic Reactions: Some individuals may have allergic reactions to MRI contrast agents 
(usually containing gadolinium). Before administering the contrast agent, medical staff will 
inquire about the patient's allergy history to determine the risk of an allergic reaction. 
 
Renal Function: Contrast agents can affect renal function. Patients with renal impairment 

 
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require a renal function assessment before undergoing an MRI scan with gadolinium-based 
contrast agents. 
 
9. Adverse event reporting 
 
The PI Dr. See-Tong Pang will report SAEs to the IRB of Chang Gung Medical Foundation 
according to the Serious Adverse Event Reporting Procedures and Guidelines as posted in the 
Clinical Trials Resource on the website of Chang Gung Medical Foundation IRB. SAE reports 
to the IRB should include the following information when calling the Medical Monitor: 
• Date and time of the SAE 
• Date and time of the SAE report 
• Name of reporter 
• Call back phone number 
• Affiliation/Institution conducting the study 
• Protocol number 
• Title of protocol 
• Description of the SAE, including attribution to drug and expectedness    
 
 
9.1 Definitions and reports of Adverse Events 
All adverse events that occur after the informed consent is signed (including run-in) must be 
recorded on the adverse event CRF (paper and/or electronic) whether or not related to study 
agent. AE Data Elements including: 
• AE reported date 
• AE Verbatim Term 
• CTCAE Term (v 5.0) 
• Event onset date and event ended date 
• Severity grade 
• Attribution to study agent (relatedness) 
• Whether or not the event was reported as a Serious Adverse Event (SAE) 
• Action taken with the study agent 
• Outcome of the event 
• Comments 
 
Identify the adverse event using the NCI Common Terminology Criteria for Adverse Events 
(CTCAE) version 5.0.  The CTCAE provides descriptive terminology and a grading scale for 
each adverse event listed. 
 
AEs will be assessed according to the CTCAE grade associated with the AE term.  AEs that 
do not have a corresponding CTCAE term will be assessed according to their impact on the 
participant’s ability to perform daily activities as follows: 
 
 
Grade 
Severity 
Description  
1 
Mild 
• 
Barely noticeable, does not influence functioning 
• 
Causing no limitations of usual activities 

 
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2 
Moderate 
• 
Makes participant uncomfortable, influences functioning 
• 
Causing some limitations of usual activities 
3 
Severe 
• 
Severe discomfort, treatment needed 
• 
Severe and undesirable, causing inability to carry out 
usual activities 
4 
Life threatening 
• 
Immediate risk of death 
• 
Life threatening or disabling 
5 
Fatal 
• 
Causes death of the participant 
 
The possibility that the adverse event is related to study drug will be classified as one of the 
following:  not related, unlikely, possible, probable, definite. 
  
DEFINITION of Serious Adverse Events: ICH Guideline E2A and GCP of Taiwan define 
serious adverse events as those events, occurring at any dose, which meet any of the following 
criteria: 
➢ 
Results in death 
➢ 
Is life threatening (Note: the term life-threatening refers to an event in which 
the patient was at risk of death at the time of the event; it does not refer to an 
event which hypothetically might have caused death if it were more severe). 
➢ 
Requires inpatient hospitalization or prolongation of existing hospitalization 
➢ 
Results in persistent or significant disability/incapacity 
➢ 
Is a congenital abnormality/birth defect 
➢ 
Events that may not meet these criteria, but which the investigator finds very 
unusual and/or potentially serious, will also be reported in the same manner. 
 
9.2 Adverse event follow-up 
All AEs, including lab abnormalities that in the opinion of the investigator are clinically 
significant, will be followed according to good medical practices and documented as such. Site 
staff should send follow-up reports as requested when additional information is available.  
Additional information should be entered on the IRB of Chang Gung Medical Foundation of 
SAE form in the appropriate format.  Follow-up information should be sent to Chang Gung 
Medical Foundation IRB as soon as possible according to IRB’s Serious Adverse Event 
Reporting Procedures and Guidelines.  
 
10. Criteria for the termination of the trial 
Following CGMH’s Management of Study Termination guideline, the trail shall be 
terminated by the investigator or the CGMH IRB when deemed necessary after evaluation. 
Incidents that may cause the termination of the trail include the encounter of life-threatening 
AE, fatal AE, etc. The PI will send in an application via CGMH HRPMS system to file for the 
termination of the trial.   
 
11. Statistical Considerations 
11.1 Sample size Determination 
The sample sizes of 148 in the bp-MRI group and 148 in the mp-MRI group achieve 
80.145% power to detect a non-inferiority margin difference between the group proportions of 
-0.1000. The mp-MRI group proportion is 0.280. Under the null hypothesis of inferiority, the 
bp-MRI proportion is assumed to be 0.180. The power was computed for the case where the 
actual treatment group proportion is 0.280. The test statistic used is the one-sided Z test 
(unpooled), and the significance level of the test is 0.025. We have set the dropout rate at 20%, 

 
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thus the bp-MRI group and mp-MRI group each consist of 185 individuals, resulting in a total 
enrolled number of 370 people. We have set the dropout rate at 20%, thus the mp-MRI 
group and bp-MRI group each consist of 185 individuals, resulting in a total enrolled 
number of 370 people. 
 
11.2 Planned Statistical methods of analysis 
Statistical analysis  
The primary objective of this study is to evaluate the csPCa detection in bp-MRI arm versus 
mp-MRI arm. We hypothesise that bp-MRI is non-inferior to mp-MRI in detecting csPCa. The 
baseline characteristics of the two groups will be compared. Continuous variables will be 
evaluated using the student’s t-test and the Mann-Whitney U test. In contrast, categorical 
variables will be analysed using the Chi-squared and Fisher’s exact tests, as applicable. The 
effect size and 95% CI will be presented for secondary outcomes, and a 2-sided p-value less 
than 0.05 will be considered statistically significant. All statistical analyses will be performed 
using SPSS v.24.0 (IBM Corp., Armonk, NY, USA). 
 
11.2.1 Efficacy analysis 
 Not applicable 
 
11.2.2 Safety analysis 
 Not applicable 
 
11.2.3 Additional analysis 
 Not applicable 
 
11.2.4 The level of significance 
A p-value less than 0.05 was considered significant and was denoted by * and p-value 
less than 0.001 was denoted by **. 
 
11.3 Analysis Population 
Not applicable 
 
11.4 Procedure for accounting for missing, unused and spurious data 
The incomplete clinical data and sequencing data with poor quality will be excluded in 
the study. 
 
11.5 Procedures for reporting any deviation(s) from the original statistical plan 
If deviation(s) from the original statistical plan is identified, the investigator will follow the 
guideline of CGMH IRB to record and report such incident. The PI may login to the CGMH 
HRPMS system to report and IRB will proceed with further review.  
 
12. Direct access to source data/documents 
Investigators permit IRB to access to the source data of experiment for trial-related 
monitoring, audits and regulatory inspection. 
 

 
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13. Ethical considerations 
This study will be conducted according to Taiwan and international standards of Good 
Clinical Practice for all studies.  Applicable government regulations and Chang Gung 
Medical Foundation research policies and procedures will also be followed. 
 
This protocol and any amendments will be submitted to the Chang Gung Medical Foundation 
Institutional Review Board (IRB) for formal approval to conduct the study.  The decision of 
the IRB concerning the conduct of the study will be made in writing to the investigator.   
All subjects for this study will be provided a consent form describing this study and 
providing sufficient information for subjects to make an informed decision about their 
participation in this study.  This consent form will be submitted with the protocol for review 
and approval by the IRB.  The formal consent of a subject, using the IRB-approved consent 
form, will be obtained before that subject is submitted to any study procedure.  This consent 
form must be signed by the subject or legally acceptable surrogate, and the investigator-
designated research professional obtaining the consent.  
 
14. Data handling and keeping 
Clinical samples will be collected in Chang Gung Medical Foundation. The sequencing data 
will be stored in computers of laboratory with an electronic encryption. The clinical and source 
data can only be assessed by clinical doctors and investigators of the study. 
 
15.  Financing and Insurance 
The Ministry of Health and Welfare will provide sufficient funding for this clinical study. 
 
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