Assessing the Detection of Clinically Significant Prostate Cancer Using Magnetic Resonance Imaging-Guided Transperineal Targeted Biopsy Compared to Standard Transrectal Biopsy Outcomes Study: The ASTROS Trial
Phase: NA
Conditions: Prostate Cancer, Magnetic Resonance Imaging, Target Lesion, Fusion Biopsy, Clinically Significant Prostate Cancer, Transperineal
Sponsor: The University of Texas Medical Branch, Galveston

 
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Assessing the Detection of Clinically 
Significant Prostate Cancer using Magnetic 
Resonance Imaging-Guided Transperineal 
Targeted Biopsy Compared to Standard 
Transrectal Biopsy Outcomes Study: The 
ASTROS Trial (NCT03044197) 
 
 
 
 
Stephen B. Williams M.D., Assistant Professor 
The University of Texas Medical Branch 
Department of Surgery, Division of Urology 
301 University Blvd., Galveston, TX 77555 
 
 
 
 
 
 
 
 

 
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Table of Contents: 
 
Study Schema 
1.0 
Background 
2.0 
Rationale and Specific Aims 
3.0 
Inclusion/Exclusion Criteria 
4.0 
Enrollment/Randomization 
5.0 
Study Procedures 
6.0 
Study Product Description 
7.0 
Reporting of Adverse Events or Unanticipated Problems involving Risk to 
Participants or Others 
8.0 
Study Withdrawal/Discontinuation 
9.0 
Statistical Considerations 
10.0 
Ethical Considerations and Privacy/Confidentiality Issues 
11.0 
Record Retention 
12.0 
References 
 
 
 
 

 
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SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal 
regulations and ICH guidelines. 
 
Site Investigator:* 
Stephen B. Williams M.D. 
Signed: 
 
Date: 
 
 
Name Stephen B. Williams M.D. 
Title:  Assistant Professor 
 
 
 
 
* The protocol should be signed by the local investigator who is responsible for the study 
implementation at his/her specific site; i.e., if Investigational New Drug study, the 
individual who signs the Form FDA 1572. 

 
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1.0 
Background 
 
 
Prostate cancer (PCa) is the most common non-cutaneous malignancy and the second 
leading cause of death among men.1 Transrectal ultrasound guided rostate biopsies are 
currently the gold standard for the diagnosis of PCa which can be categorized as 
clinically significant or indolent PCa. Clinically significant prostate cancer (csPCa) is 
deemed cancer which warrants treatment and is defined according to previously 
published studies as biopsy Gleason score ≥7 or maximum cancer core length ≥5mm.2 
Indolent PCa is considered cancer which does not require treatment with patients placed 
on active surveillance and is defined by the modified Epstein criteria as biopsy Gleason 
score ≤6, PSA density ≤0.15, ≤2 positive cores, and unilateral cancer).2,3 Given concerns 
regarding the overtreatment of indolent PCa, efforts to improve the diagnosis of csPCa 
and limit diagnosis of indolent disease are needed.4 
 
Standard in-office prostate biopsies using transrectal ultrasound guidance are random, 
non-diagnostic and imprecise in detecting PCa. Moreover, standard biopsies may miss 
csPCa. With multi-parametric magnetic resonance imaging (mpMRI), we now have a 
way of increasing the detection of csPCa while decreasing the detection of indolent 
disease. Using the mpMRI and scoring methodology called the prostate imaging 
reporting and data system (PIRADS v2), lesions suspicious for PCa and csPCa can be 
categorized as: 1: very low, 2: low, 3: intermediate, 4: high, and 5: very high risk of 
csPCa.5 Studies using mpMRI recommend prostate biopsy of mpMRI lesions with 
PIRADS ≥3.2,5,6 
 
The Division of Urology has introduced a powerful new solution for analysis, planning 
and targeted biopsy of the prostate. This consists of using DynaCAD for Prostate mpMRI 
and the UroNav fusion biopsy system- a comprehensive solution which offers a cutting 
edge imaging option for many patients with clinical suspicion for harboring PCa mainly 
by elevated and/ or rising prostate specific antigen (PSA) levels. Targeted 
MRI/Ultrasound biopsy is poised to become the new standard in PCa diagnosis at 
UTMB. 
 
Presently at UTMB, if patients have a mpMRI and region of interest identified (usually 
mpMRI obtained after prior negative biopsy or in patients deemed to have indolent 
disease by standard prostate biopsy and to be placed on active surveillance) then they are 
referred for consideration of targeted biopsy with UroNav. 
 
No study has compared UroNav transperineal mpMRI-targeted versus standard 
transrectal ultrasound guided prostate biopsy in the detection of prostate cancer. A recent 
trial compared transperineal/transrectal mpMRI-targeted versus TRUS systematic biopsy 
in biopsy naïve men and noted improved detection of csPCa.7 Specifically, the overall 
(50.5% vs 29.5%, p=0.002) and csPCa (43.9% vs 18.1%, p<0.001) detection rates were 
significantly higher in the targeted versus the standard transrectal ultrasound guided 
prostate biopsy group, respectively.7 While this trial provided the first level one evidence 
in support of mpMRI-targeted biopsy in biopsy naïve men, the study used a device not 

 
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commercially available in the United States and allowed both transperineal or transrectal 
mpMRI-targeted prostate biopsies to be performed in the targeted biopsy arm of the 
study.  
 
 
In this prospective randomized trial, the investigators will assess the detection rates of 
csPCa diagnosis of standard transrectal ultrasound guided prostate biopsy compared to 
computer targeted system (UroNav - InVivo corp) to sample suspicious areas (PIRADS 
≥3) identified on mpMRI.  
 
The hypothesis being tested is that computerized fusion guided biopsy (UroNav) will 
increase detection of csPCa compared to standard transrectal ultrasound guided prostate 
biopsy alone. 
 
 
2.0 
Rationale and Specific Aims 
 
Transrectal prostate biopsy with multiple samples using a standardized template under 
transrectal ultrasound (TRUS) guidance is the current standard diagnostic approach in 
suspicion of PCa as recommended by the European Association of Urology (EAU) and 
American Urological Association (AUA).8,9 With the introduction of mpMRI we now 
have an effective way to localize cancer and direct our biopsies more effectively.6 
mpMRI guided biopsies have shown to have high negative predictive values, especially 
in men with prior negative mapping results.10,11 mpMRI-targeted biopsy and systemic 
biopsies are comparable in their detection rates of PCa, with mpMRI showing increasing 
csPCa detection in biopsy-naive patients, thus decreasing the detection of indolent PCa.  
 
The mpMRI-targeted biopsy system UroNav allows for the fusion of mpMRI images 
with live TRUS feed to target lesions noted on mpMRI. Studies have demonstrated men 
undergoing biopsy for suspected PCa, targeted MR/ultrasound fusion biopsy (using the 
transrectal UroNav prostate biopsy device), compared with standard extended-sextant 
TRUS-guided biopsy, was associated with increased detection of high-risk PCa and 
decreased detection of indolent disease.6 
 
The mpMRI-targeted devices used in prior studies have been either the UroNav 
transrectal machine or used a combination of transrectal and transperineal techniques 
using devices not available in the United States.6,7 Based on these prospective studies and 
limited randomized trials there is increasing support of the utility of using mpMRI-
targeted prostate biopsy in the detection of PCa.  
 
The present study will assess a transperineal device (UroNav) currently available in the 
United States and thus will not only directly assess the impact of transperineal prostate 
detection of csPCa but provide the first United States trial assessing the utility of this 
platform. UTMB has the only commercially available UroNav transperineal mpMRI-
targeted device in the state of Texas. Thus, this trial has the leverage of a large academic 
primary care referral network combined with a novel device to provide important clinical 

 
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information discerning the improved detection of csPCa in a relatively short period of 
time (approximately one year). 
 
 
The UroNav fusion biopsy system until recently only allowed targeted prostate biopsy to 
be performed transrectally. With over 200 devices sold in the United States, UroNav is 
the most commonly used targeted biopsy system and has been extensively studied by the 
National Institutes of Health (NIH). UroNav requires pre-biopsy mpMRI for lesion(s) 
delineation, real-time TRUS registered to the mpMRI and electromagnetic tracking of 
biopsy needles for precise guidance. The actual working elements of the UroNav fusion 
biopsy system includes the UroNav mobile workstation cart, ultrasound cart and the 
electromagnetic field generator which connects to the patient bed by a mobile arm. The 
electromagnetic field generator in combination with a navigation sensor mounted to the 
TRUS transducer merges the mpMRI images with live TRUS guidance to accurately 
biopsy the prostate. As previously mentioned, UroNav provides support for transrectal 
biopsy procedures but now has the capability to perform biopsy via a transperineal 
approach. The UroNav fusion-guidance for transperineal biopsy requires the transperineal 
stepper which holds the TRUS probe and a standard biopsy grid plate equipped with 
UroNav universal sensors to precisely perform biopsies. Invivo supports both UroNav 
and DynaCad which UTMB has recently acquired and the Department of Radiology 
currently has been working with for many years, respectively. DynaCad is a software 
used in the radiology suite which exports diagnostic 3D information from a prior mpMRI 
exam to discern the prostate gland and MR-suspicious lesions. The transperineal 
approach (skin halfway between scrotum and anus) essentially eliminates the risk of 
sepsis and/or infection associated with transrectal prostate biopsy samples obtained 
through feces and rectal mucosa. Sepsis occurs in up to 3% of patients who undergo 
transrectal prostate biopsy (Table 1).12  
 
Table 1. Signs and Symptoms of Sepsis12 
 
General 
Fever (>38.3°C) 
Hypothermia (<36°C) 
Tachycardia >90/min 
Tachypnea 
Hypotension (SBP<90 mmHg) 
Altered mental status 
Significant edema or positive fluid balance 
Oliguria 
Ileus 
Altered mental status/lethargy 
 
Laboratory 
Normal WBC with >10% immature forms 
Creatinine increase >0.5 mg/dL 
INR >1.5 or aPTT >60 secs 

 
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Thrombocytopenia (platelet count <100,000/mm3) 
Hyperglycemia (plasma glucose >120 mg/dL) in the absence of 
diabetes 
Hyperlactatemia (>1 mmol/L) 
 
No study has compared UroNav transperineal mpMRI-targeted versus standard 
transrectal prostate biopsy in the detection of prostate cancer.   
 
The hypothesis being tested is that computerized fusion guided biopsy (UroNav) will 
increase detection of csPCa compared to standard biopsy (SB) (transrectal) alone. The 
primary end point will be the comparison of detection rates csPCa between arm A 
mpMRI+ and arm B (refer to figure on page 9). csPCa will be defined according to the 
Standards of Reporting for MRI-targeted Biopsy Studies (START) criteria for targeted 
biopsy Gleason Score ≥ 7 or maximum cancer core length (CCL) ≥ 5 mm and the 
updated Epstein criteria for SB (Gleason score ≥ 7, PSA density ≥ 0.15, Gleason score ≥ 
2 positive cores, and bilateral cancer).2,3 The secondary end points will be (1) comparison 
of the overall detection rate of PCa and csPCa between arm A mpMRI+, arm A mpMRI–, 
and arm B and (2) comparison of complication rates (Table 2) between arm A mpMRI+ 
and arm B. 
 
Considering 10% of patients will be lost to follow-up, the total sample size needed will 
be 80 patients (See Section 9.1 Statistical Considerations). The clinical trial is enrolled in 
clinicaltrials.gov (ClinicalTrials.gov Identifier NCT03044197). 
 
If the primary end point is reached, the study will continue and remain ongoing to 
examine the remaining secondary end points. 
 
Specific Aims: 
1. Determine if UroNav increases the detection of csPCa between arm A mpMRI+ than 
arm B standard transrectal biopsy. 
 
2. Determine if UroNav increases the overall detection of PCa between arm A mpMRI+ 
versus arm A mpMRI- and arm B standard transrectal biopsy. 
 
3. Determine if UroNav decreases rates of complications between arm A mpMRI+ than 
arm B standard transrectal biopsy.  
 
 
3.0 
Inclusion/Exclusion Criteria 
 
Subjects must meet all of the inclusion criteria in order to be eligible to participate 
in the study. 
 
1. Males aged 18-75 years old 
2. PSA >1 ng/ml but <15 ng/ml 
3. Negative DRE 

 
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4. Subject has provided informed consent in a manner approved by the IRB and is willing 
and able to comply with the trial procedures. 
 
Subjects meeting any of the exclusion criteria at baseline will be excluded from 
study participation. 
 
1. Previous prostate biopsy or prostate surgery 
2. Previous prostate mpMRI 
3. Contraindication to mpMRI: Patient has implanted metal clips or wires of the type 
which may concentrate radiofrequency fields or cause tissue damage from twisting in a 
magnetic field. Examples include: aneurysm clip, implanted neural stimulator, implanted 
cardiac pacemaker or autodefibrillator, cochlear implant, ocular foreign body (e.g., metal 
shavings), any implanted device (pumps, infusion devices, etc), shrapnel injuries. 
4. Patients in the Texas Department of Criminal Justice (prisoners)  
5. Patients with acute urinary symptoms including urinary retention and urinary tract 
infection   
6. Patient has dialysis dependent renal failure or baseline serum creatinine level > 
2.0mg/dL 
 
4.0 
Treatment Assignment/Randomization 
 
Enrollment into the study is defined as following randomization. Patients who fulfills all 
eligibility criteria and have provided written consent will be randomized to undergo 
mpMRI followed by targeted biopsies (arm A mpMRI+) or TRUS transrectal biopsy 
(arm-B) by the PI and authorized study collaborators. 
, study coordinator, will 
have access to randomization, generated by an electronic randomization system provided 
by REDCap.  
 
Sequence generation 
Patients will be randomly assigned to arm A or arm B following a 1:1 simple 
randomization procedure according to a computer-generated randomization list provided 
by REDCap. 
 
 study coordinator, and a designated back-up will be the only 
persons to have access of the REDCap randomization list. 
 
   
 
5.0 
Study Procedures 
 
Study population and design: 
 
Eligible patients referred to the Division of Urology will be randomly assigned to one of 
the following arms: arm A (mpMRI+ group), mpMRI prior to transperineal mpMRI-
targeted prostate biopsy; arm B (Standard group), TRUS-guided transrectal 12-core 
prostate biopsy.  
In arm A, all patients with positive mpMRI evidence of lesions suspicious for PCa, i.e. PI 
RADS ≥ 3 will be submitted to transperineal MRI-targeted prostate biopsy (arm A 
mpMRI+). In cases of negative mpMRI results i.e. PI RADS<3, arm A patients will 

 
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undergo TRUS-guided transrectal 12-core prostate biopsy (arm A mpMRI–)(refer to 
figure on page 9). 
 
The present randomized clinical trial will compare the outcomes between the two arms. 
 
Primary End-Points: The primary end point will be the comparison of detection rates 
csPCa between arm A mpMRI+ and arm B. csPCa will be defined according to the 
Standards of Reporting for MRI-targeted Biopsy Studies (START) criteria for targeted 
biopsy Gleason Score ≥ 7 or maximum cancer core length (CCL) ≥ 5 mm and the 
updated Epstein criteria for standard biopsy (Gleason score ≥ 7, PSA density ≥ 0.15, 
Gleason score ≥ 2 positive cores, and bilateral cancer).2,3 Patients will be enrolled in an 
intention to treat trial (See Section 9.1 Statistical Considerations). 
 
Secondary End-Points: The secondary end points will be: 
i. 
 Comparison of the overall detection rate of PCa and csPCa between arm A 
mpMRI+, arm A mpMRI–, and arm B and 
ii. 
 Comparison of complication rates (Table 2) between arm A mpMRI+ and arm B. 
 
If the primary end point is reached, the study will continue and remain ongoing to 
examine the remaining secondary end points. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Astros Trial 
     Patient meeting eligibility criteria 
Randomization 
Arm A 
mpMRI Group 
Arm B 
Standard Group 
12 cores 
TRUS BIOPSY 12 
Cores 
12 cores 
mpMRI ordered 
TARGETED 
BIOPSY 
3-6 cores 
PI RADS ≥ 3 
        PI RADS<3 
Arm A 
mpMRI+ 
Arm A 
mpMRI- 

 
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Patients will be consented by Urology providers (IRB approved Co-Investigators and 
collaborators). 
 
Randomization and data collection will be done by 
 
 (study coordinator) into a 
REDCap generated case form (SEE APPENDIX). Study coordinator will provide de-
identified data for statistical data analysis and will have master file, in password protected 
computer, which will link the PHI to subject ID (will be assigned by the study 
coordinator). After the completion of statistical analysis the master file will be deleted 
permanently.  
  
Data analysis will be done by Yong Shan (Department of Surgery analyst) supervised by 
Dr. Stephen Williams (PI) and statistical analysis collaborators (Dr. Yong-Fang Kuo, IRB 
approved). Data to be analyzed will be de-identified will have no protected health 
information (PHI) including patient name, medical record number or date of birth.  
  
PRE-PROCEDURE EVALUATION (within 2 months from study enrollment) 
 
Patients are going to be evaluated at the time of office appointment by the PI and Study 
Collaborators 
 
 Screening-Patients with elevated level of Prostate-specific antigen (PSA >1 ng/ml but 
<15 ng/ml), will be screened for research study participation by the urology providers 
(Co-Investigators) and Stephen B. Williams, MD (PI). 
 Inclusion/ Exclusion Criteria 
 Consent- Patient having all the inclusion and no exclusion criteria for eligibility will be 
approached with research consent for participation by the urology providers (Co-
Investigators) and Stephen B. Williams, MD (PI). 
 Demographics 
 Medical History 
 Surgical History 
 Clinical Stage/ Digital Rectal Exam 
 Vital Signs 
 Physical Exam  
 MRI PI-RAD Score (Grade System to classifying prostate cancer , using Pre-Procedure 
MRI (within 2 months from consenting & randomization))- only required for arm A  
 Gland Volume (Calculated from the mpMRI and/or Ultrasound -within 2 months from 
consenting & randomization) 
 Prostate specific antigen (PSA) 
 
 
 
PROCEDURE EVALUATION (Surgical procedure) 
Patient will undergo prostate biopsy in arm A or arm B as assigned by the randomization 
card  
 

 
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A. Transperineal mpMRI-targeted prostate biopsy (arm A mpMRI+) (Procedure 
will be performed in operating room): mpMRI-targeted prostate biopsy is standard 
of care and will be performed using the UroNav transperineal fusion system by a 
single urologist (Stephen Williams, MD). Dr. Williams has >1 yr experience in 
performing mpMRI-targeted prostate biopsies. All patients will receive one dose of 
Ancef intravenous antibiotic at time of surgery (Vancomycin 1gm intravenous for 
penicillin/cephalosporin allergies or prior history of orthopedic hardware implanted 
within 2 years) to cover skin flora and may add additional antibiotic if prior 
documented UTI(s) in past then antibiotic may be tailored according to those 
culture(s) sensitivities) to cover enteric flora as well. All patients will receive an 
enema until result to be performed the morning of prostate biopsy. 
 
The gland and the regions of interest will be contoured, and the prostate contour will 
be fused in real time with the TRUS image. Biopsies will be performed via a 
transperineal approach in the operating room. The patient will be placed in dorsal 
lithotomy position. mpMRI-targeted biopsies will be performed on regions of interest, 
and three to six cores will be obtained for biopsy from each lesion and is standard of 
care according to START criteria for targeted biopsy. 
 
Multiparametric magnetic resonance imaging (mpMRI) 
All of the patients in arm A will undergo mpMRI according to the European Society of 
Urogenital Radiology guidelines. The Prostate Imaging–Reporting and Data System (PI-
RADSv2) classification (1-5) will be used to describe the lesions found: 1: very low, 2: 
low, 3: intermediate, 4: high, and 5: very high risk of csPCa. 5 The mpMRI will be 
performed at two centers with a 3-T scanner using a 32-channel phase array coil or four-
channel phase array coil. Two experienced radiologists will analyze the mpMRI findings. 
Lesions with a PI-RADS score of ≥3 will be considered suspicious for PCa. 
 
In cases of negative mpMRI results, arm A patients will undergo TRUS-guided 
transrectal 12-core prostate biopsy (arm A mpMRI–) in an identical fashion as described 
in arm B. Urologists (PI and Co-Investigators) will obtain SOC informed consent and 
perform the TRUS biopsies. 
 
Dr. Williams will collect the biopsy sample in case of positive mpMRI results (arm A 
mpMRI+) and it will be sent out to pathology lab at UTMB for analysis, as SOC. 
 
Please Note: Patients having positive mpMRI results will be referred to Dr. Williams, by 
their primary urology (Co-Investigators and collaborators) providers, only after patients 
provide written consent to participation. Primary Urology (Co-Investigators and 
collaborators including Dr. Williams) providers will consent the patients. 
 
 
B. TRUS-guided transrectal prostate biopsy (arm B) (Procedure will be performed 
in Clinic): TRUS-guided transrectal prostate biopsy will be performed using a 
disposable 18-gauge biopsy gun with a specimen size of 18–22 mm (Bard Medical, 
Covington, GA, USA) by Urology providers (Co-Investigators and Dr. Williams 

 
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(PI)). All patients will receive one dose fluoroquinolone antibiotic to be taken the 
morning of prostate biopsy (if fluoroquinolone allergy then may substitute Bactrim 
DS, if prior documented UTI(s) in past then antibiotic may be tailored according to 
those culture(s) sensitivities) to cover enteric flora. All patients will receive an enema 
until result to be performed the morning of prostate biopsy. 
 
Urologists will obtain SOC informed consent and perform the TRUS biopsies. 
 
The 12 cores will be obtained from 12 separate anatomical regions of the prostate 
which is standard practice in performing TRUS-guided transrectal prostate biopsy: left 
medial apex, left lateral apex, left medial midgland, left lateral midgland, left medial 
base, left lateral base, right medial apex, right lateral apex, right medial midgland, 
right lateral midgland, right medial base and right lateral base. 
 
For arm A and arm B biopsy, 
 (the study research coordinator) , Stephen B. 
Williams, MD and Eduardo Orihuela, MD (Chairman, Division of Urology and study 
co-investigator), will monitor safety and any possible Unanticipated Adverse Device 
Events (UADEs). Serious Adverse Events (SAEs), Adverse Events (AEs) and UADEs 
assessment will be done by Eduardo Orihuela, MD. 
 
For Arm A and Arm B biopsy, the procedure will be performed and the sample will be 
sent to the Pathology lab for analysis. Dr. Williams and other urology providers will not 
be involved with the sample analysis and biopsy report data and results. Once the report 
/ data is available on Epic for review, the study coordinator will extract data from 
patient records/ Epic into an electronic data sheet (REDCap case form, SEE 
APPENDIX) on which the patient will be identified by a subject ID assigned to them, 
no PHI information will be present. The data analysis will be performed in aggregate. 
A master file linking the patient to Subject ID will remain with the study coordinator for 
data entry purposes and once the data analysis is complete, the master file will be 
securely stored and password protected.  
 
 Adverse event assessment (Tables 2 and 3) 
 
POST-PROCEDURE EVALUATION/ END OF STUDY- (Follow-up can be done 
by telephone or clinical visit) 
 
 Diagnosis of csPCa- Based on the biopsy report will be available 2-4 weeks post-
procedure 
 Gleason score ((Grade System to classifying PCa)- Based on the biopsy report will be 
available 2-4 weeks post-procedure 
 Total cancer core length (mm)- Based on the biopsy report will be available 2-4 
weeks post-procedure 
 Maximum cancer core length (mm)- Based on the biopsy report will be available 2-4 
weeks post-procedure 
 Adverse event assessment- Can be done by telephone or clinical visit, usually 2-4 
weeks post biopsy procedure 

 
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Table 2. Schedule of Events 
 
Variables (Both Arm A and Arm 
B) 
Pre-Study 
(within 2 months from 
consent 
and 
randomization) 
Biopsy 
Post-Biopsy Follow-
up/Study End (within 
2-4 wks from biopsy) 
Follow-up 
can 
be 
done by telephone or 
clinical visit) 
 
Informed consent* 
X 
 
 
Demographics 
X 
 
 
Medical History 
X 
 
 
Surgical History 
X 
 
 
Clinical Stage/digital rectal exam 
X 
 
 
Vital signs 
X 
 
 
Height 
X 
 
 
Weight 
X 
 
 
PSA 
X 
 
 
MRI PI-RADS ( Arm A) 
X 
X 
 
Gland volume (MRI- Arm A or 
US- Arm B) 
X 
X 
 
Diagnosis of Prostate Cancer 
 
 
X 
Serum creatinine*** 
X 
 
 
Diagnosis of Clinically Significant  
Prostate Cancer** 
 
 
X 
Gleason score 
 
 
X 
Total cancer core length (mm) 
 
 
X 
Maximum 
cancer 
core 
length 
(mm) 
 
 
X 
UADE* 
 
X 
X 
* Indicates study-only activity.  
All other procedures/tasks are standard of care.  Prostate specific antigen (PSA), Digital rectal 
examination (DRE), Prostate Imaging Reporting and Data System (PI-RADS), transrectal 
ultrasound (TRUS), Unanticipated Adverse Device Event 
**Clinically significant PCa defined as targeted biopsy Gleason Score ≥ or maximum CCL ≥ 
5 mm and the updated Epstein criteria for SB. 
*** The serum creatinine assessment will be performed no more than one month prior to 
randomization.  
 
 
 
6.0 
Study Product Description 
 

 
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The actual working elements of the UroNav fusion biopsy system includes the UroNav 
mobile workstation cart, ultrasound cart and the electromagnetic field generator which 
connects to the patient bed by a mobile arm. The electromagnetic field generator in 
combination with a navigation sensor mounted to the TRUS transducer merges the 
mpMRI images with live TRUS guidance to accurately biopsy the prostate. As previously 
mentioned, UroNav provides support for transrectal biopsy procedures but now has the 
capability to perform biopsy via a transperineal approach. The UroNav fusion-guidance 
for transperineal biopsy requires the transperineal stepper which holds the TRUS probe 
and a standard biopsy grid plate equipped with UroNav universal sensors to precisely 
perform biopsies. Invivo supports both UroNav and DynaCad which UTMB has recently 
acquired and the Department of Radiology currently has been working with for many 
years, respectively. DynaCad is a software used in the radiology suite which exports 
diagnostic 3D information from a prior mpMRI exam to discern the prostate gland and 
MR-suspicious lesions. 
 
A detailed UroNav Brochure is attached with IRB submission for review and will be 
provided to patients (SEE APPENDIX). 
 
 
7.0 
Adverse Events or Unanticipated Problems involving Risk to Participants or 
Others 
Table 3. Complications associated with prostate biopsy 
 
Common (greater than 1 in 
10) 
 
Occasional (between 1 in 
10 and 1 in 50)  
 
Rare (less than 1 in 50) 
 
•Blood in your urine for up to 
10 days. 
 •Blood in your semen for up 
to 6 weeks; this is harmless 
and poses no risk to you or 
any sexual partners. 
•Bruising in your perineal 
area.  
•Urinary 
infection 
(10% 
risk).  
•Sensation of discomfort due 
to bruising.  
•Haemorrhage(bleeding) 
preventing you from passing 
urine (2% risk).  
 
 
•Blood 
infection 
(septicaemia) 
needing 
hospitalisation (2% risk).  
•Haemorrhage 
(bleeding) 
needing hospitalisation (1% 
risk). 
•Failure 
to 
detect 
a 
significant cancer of the 
prostate. 
 •The procedure may need 
to 
be 
repeated 
if 
the 
biopsies are inconclusive or 
your 
PSA 
level 
rises 
further. 
•Inability to pass urine 
(retention of urine).  
 
 
•Hospital-acquired 
infection 
•Colonisation with MRSA 
(0.9% - 1 in 110).  
•MRSA 
bloodstream 
infection (0.02% - 1 in 
5000).  
•Clostridium 
difficile 
bowel infection (0.01% - 1 
in 10,000).  
Please note: The rates for 
hospital-acquired infection 
may be greater in “high-
risk” patients. This group 
includes, 
for 
example, 
patients 
with 
long-term 
drainage 
tubes, 
patients 
who have had their bladder 
removed due to cancer, 
patients who have had a 

 
Version 02:  11 Dec 2017 
long stay in hospital or 
patients who have been 
admitted to hospital many 
times. 
 
 
Complications associated with MR-Gadolinium: 
 
The contrast material used in MRI called gadolinium is less likely to produce an allergic 
reaction than the iodine-based materials used for x-rays and CT scanning. Very rarely, 
patients are allergic to gadolinium-based contrast materials and experience hives and 
itchy eyes. Reactions usually are mild and easily controlled by medication. Severe 
reactions are rare. 
Nephrogenic systemic fibrosis (NSF), a thickening of the skin, organs and other tissues, 
is a rare complication in patients with kidney disease that undergo an MR with contrast 
material. Gadolinium-based contrast material may be withheld in some patients with 
severe kidney disease. 
Adverse Event: 
 
For the purposes of this study, pre-planned interventions noted at baseline are not 
considered AEs. 
 
Adverse Events (AEs) collected in this study will be limited to death post biopsy 
procedure, serious injury (life threatening, results in permanent impairment of body 
functions or permanent damage to a body structure, or necessitates medical or surgical 
intervention to preclude permanent impairment of body functions),    
Any unanticipated adverse device event will be recorded and reported to the IRB within 
10 business days. 
 
AE/SAE information must be collected up until subject’s completion of the study. In the 
case of death or serious injury, Investigator or study coordinator must report to IRB as 
soon as possible within 10 business days after first learning the event. 
 
Collection of all AEs, to be reported as follows:  
 
i) all serious adverse events and/or unanticipated problems involving subjects will 
be reported as required per the UTMB IRB Policies and Procedures, Section 8; 
and  
 
ii) All other adverse events will be recorded on an excel spreadsheet and submitted 
with each continuing review. 
 
 
Serious Adverse Event (SAE):  
 

 
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An SAE is defined as an AE that meets one of the following conditions: 
 
Death during the period of protocol defined surveillance 
 
Life-threatening event (defined as a subject at immediate risk of death at the time of 
the event) 
 
An event requiring inpatient hospitalization or prolongation of existing 
hospitalization during the period of protocol defined surveillance  
 
Results in congenital anomaly or birth defect 
 
Results in a persistent or significant disability/incapacity 
 
Any other important medical event that may not result in death, be life threatening, or 
require hospitalization, may be considered a serious adverse experience when, based 
upon appropriate medical judgment, the event may jeopardize the subject and may 
require medical or surgical intervention to prevent one of the outcomes listed above. 
Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug dependency or drug 
abuse. 
 
All SAEs will be: 
 
recorded on the appropriate SAE CRF 
 
followed through resolution by a study clinician 
 
reviewed and evaluated by a study clinician 
 
Unanticipated Adverse Device Events (UADEs): 
An UADE is “any serious adverse effect on health and safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, problem, or 
death was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or protocol., or any other unanticipated serious problem 
associated with a device that relates to the right, safety, or welfare of subjects. (21 
CFR 812.3(s)).”The principal investigator will submit to the reviewing IRB a report 
of any UADE occurring during an investigation as soon as possible, but in no event 
later than ten (10) days after the investigator learns of the effect. All UADEs must be 
documented by the investigator including the date of consent, a complete description 
of the event, possible reason(s) for the event, severity, duration, concurrently with 
appropriate CRF. 

 
Version 02:  11 Dec 2017 
Reporting Procedures 
 
Any AE considered serious by the PI (Dr. Williams) or Co-PI (Dr. Orihuela) or which 
meets the aforementioned criteria must be submitted on the SAE form to the IRB in 
accordance with IRB policies and procedures. 
 
The study PI (Dr. Williams) or Co-PI (Dr. Orihuela) will complete Serious Adverse 
Event Assessment Form within the following timelines:   
 
All deaths and immediately life-threatening events, whether related or unrelated, will 
be recorded on the Serious Adverse Event Form within 72 hours of awareness.  
 
Serious adverse events other than death and immediately life-threatening events, 
regardless of relationship, will be reported within 10 days of becoming aware of the 
event.  
 
All SAEs will be followed until satisfactory resolution or until the PI (Dr. Williams) or 
Co-PI (Dr. Orihuela) deems the event to be chronic or the patient to be stable.  
 
Study related risks include loss of confidentiality.  
 
 
8.0 
Study Withdrawal/Discontinuation 
 
A study subject will be discontinued from participation in the study if any of the 
following occur: 
 Unacceptable adverse event (AE)  
 Intercurrent illness, or other medical condition or situation occurs such that 
continued participation in the study would not be in the best interest of the subject 
in the opinion of the treating investigator 
 Development of any exclusion criteria  
 Subject withdrawals consent to continue in the research for any reason 
 
Handling of Withdrawals 
 
Subject will be followed as per standard of care, after withdrawal from study. 
 
Termination of Study  
 
Possible reasons for discontinuation of the study include poor study accrual and/or IRB 
request for study closure after review of reported adverse event(s) in the required timeline 
as above. 
 
9.0 
Statistical Considerations 
 
 

 
Version 02:  11 Dec 2017 
This is an un-blinded, single center, randomized controlled trial. The associations 
between categorical variables and the arms will be analyzed with fisher’s exact test; 
Mann-Whitney and Kruskal-Wallis tests for continuous variables. p values will be 
obtained by the two-sided exact method at the conventional 5% significance level. Using 
an intention to treatment power analysis for Aim 1, a sample size of 62 patients (31 per 
arm) will be required to detect a 30% absolute increase in the detection rate of csPCa, 
with a one-sided 0.05 significant level, a type II error of 0.20, and the rate of csPCa being 
18.1% from standard biopsy,7 based on two-sample test for proportions. For Aim 2, 
assuming about 25% of Arm A is MRI- and rate of csPCa was 4% in MRI- and 48% in 
MRI+ (based on the results from paper published by Porpiglia et al 7) and using one-way 
ANOVA test, it will require 72 patients (36 per arm) to detect this different with power of 
80%. Considering 10% of patients will be lost to follow-up, the total sample size needed 
will be 80 patients. No interim analyses will be planned, and all procedures will be 
performed on an intention-to-treat basis for Aim 1 as our main analyses. Non-intent to 
treat analyses under Aim 2 will be treated as sensitivity analyses. All analyses will be 
performed with SAS version 9.4 (SAS Institute, Cary, NC). 
 
 
10.0 
Ethics and the Protection of Human Subjects 
The investigator will ensure that this study is conducted in full conformity with the 
principles set forth in The Belmont Report: Ethical Principles and Guidelines for the 
Protection of Human Subjects of Research of the US National Commission for the 
Protection of Human Subjects of Biomedical and Behavioral Research (April 18, 1979) 
and codified in 45 CFR Part 46 and/or the ICH E6; 62 Federal Regulations 25691 (1997).   
The investigator must provide for the review and approval of this protocol and the 
associated informed consent documents and recruitment material by an appropriate 
independent ethics committee (IEC) or IRB registered with the OHRP. Any amendments 
to the protocol or consent materials must also be approved before they are placed into 
use. In the United States and in other countries, only institutions holding a current US 
Federalwide Assurance issued by OHRP may participate. 
Informed consent is a process that is initiated prior to the individual’s agreeing to 
participate in the study and continuing throughout the individual’s study participation. 
Extensive discussion of risks and possible benefits of this therapy will be provided to the 
subjects and their families. Consent forms describing in detail the study 
interventions/products, study procedures, and risks are given to the subject and written 
documentation 
of 
informed 
consent 
is 
required 
prior 
to 
starting 
intervention/administering study product. Consent forms will be IRB-approved and the 
subject will be asked to read and review the document. Upon reviewing the document, 
the investigator will explain the research study to the subject and answer any questions 
that may arise. The subjects will sign the informed consent document prior to any 
procedures being done specifically for the study. The subjects should have the 
opportunity to discuss the study with their surrogates or think about it prior to agreeing to 

 
Version 02:  11 Dec 2017 
participate. The subjects may withdraw consent at any time throughout the course of the 
trial. A copy of the informed consent document will be given to the subjects for their 
records. The rights and welfare of the subjects will be protected by emphasizing to them 
that the quality of their medical care will not be adversely affected if they decline to 
participate in this study. 
 
Privacy/Confidentiality Issues 
 
Subject confidentiality is strictly held in trust by the participating investigators, their 
staff, and the sponsor(s) and their agents. This confidentiality is extended to cover testing 
of biological samples and genetic tests in addition to the clinical information relating to 
participating subjects. 
 
The study protocol, documentation, data, and all other information generated will be held 
in strict confidence. No information concerning the study or the data will be released to 
any unauthorized third party without prior written approval of the Principal investigator. 
 
Individuals authorized to view study records will be identified to the study subject on the 
informed consent but may include a study monitor or other authorized representatives of 
the sponsor or funding agency or federal or local agencies that regulate research 
including representatives from the Food and Drug Administration, Office of Human 
Research Protections, or the Institutional Review Board.  Study records may also be 
made available for internal compliance reviews and quality assurance representatives. 
These individuals may inspect all documents and records required to be maintained by 
the investigator, including but not limited to, medical records (office, clinic, or hospital) 
and pharmacy records for the subjects in this study. The clinical study site will permit 
access to such records. 
 
In accordance with the Food and Drug Administration Amendment Act of 2007 
(FDAAA) and The International Committee of Medical Journal Editors (ICMJE) member 
journals trials-registration policy as a condition for publication, this study will be 
registered in the public trials registry ClinicalTrials.gov, which is sponsored by the 
National Library of Medicine.  Results will be published to clinicalTrial.gov when 
available but will not identify individual subjects. 
 
11.0 
Record Retention 
 
Consent forms and other study related documents will be retained for a minimum of 6 
years from study closure with IRB, 
 
 The specific location of the data and where/how the data will be stored  
The gathered data will be stored on an IBM General Parallel File System (GPFS) in our 
institution. GPFS is a high-performance, shared-disk file management system that can 
provide faster, more reliable access to a common set of file-based data. The GPFS allows 
multiple applications or users to share access to a single file simultaneously while 
maintaining file-data integrity. Currently, our department in the Sealy Center for Aging 

 
Version 02:  11 Dec 2017 
has 78 terabytes of storage space on the GPFS, and it can be expanded to 2 petabytes if 
needed. All the data can be accessed through an SAS server. This SAS server is a Red 
Hat Enterprise Linux server configured with two 8-core 2.9-GHz processors and 160 GB 
of DDR3 RAM memory. Both the GPFS and the SAS server are housed in a tier-4 data 
center located on the institution’s main campus.  
 
 
How the data will be protected from unauthorized access   
     Clinical research staff will have access to the GPFS and SAS server is password 
protected. The passwords are created by the information technology (IT) team in our 
institution. The IT team manages the passwords through Active Directory Group Policies. 
The principal investigator (PI), Dr. Stephen Williams, will not have access to any 
knowledge of the participants in the study, however, authorized co-investigators, and 
authorized statistical analysts can access the data via desktop computers provided by our 
institution. Only investigators and analysts who are approved and working directly on the 
projects will be provided access.  All the co-investigators and statistical analysts who are 
authorized by the PI to have access to the data will need to sign an internal data use 
agreement (DUA). The PI will store those signed DUAs in the office and keep a list of all 
staff members who have access to the data. The password will be updated every three 
months. If a staff member leaves the project or our institution, he or she will be removed 
from the server and will no longer have access to the data. All the desktop computers are 
located in offices that can be locked to prevent authorized access. The computers log off 
and enter a screensaver mode after a period of inactivity to protect the data. Several of 
our analysts have home computers provided by our institution. They can use these 
personal computers with the supported institution’s VPN to link to their desktop 
computers to work with the prospectively gathered data saved on the server from home. 
All data generated using the gathered data will be stored on the GPFS in our institution’s 
server behind the institutional firewall. 
 
 
Information on the storage/protection of the media you receive containing the 
original files  
    The media received containing the original files will be stored in a locked file cabinet 
in a locked office, Room 6.622 of Rebecca Sealy Building on The University of Texas 
Medical Branch campus. The office building is secured by police and/or security guards, 
and off-hours access to the building is available only to staff with a The University of 
Texas Medical Branch badge who work within the building. 
 
 
Assurances that no attempt will be made to identify individual patients, hospitals, 
or physicians 
     We will educate/train our co-investigators and statistical analysts to not attempt to 
identify   patients, their physicians, or the treating hospital.  
 
 
Assurances that publications and presentations of the data will not allow 
identification of patients, hospitals or physicians.  
    We will make sure that all the results reported in the publications or presentations 
contain no information that can be used to identify patients, hospitals, or physicians. 
 

 
Version 02:  11 Dec 2017 
 
 
 
12.0 
References 
 
1. 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: a cancer journal for 
clinicians. 2016;66(1):7-30. 
2. 
Moore CM, Kasivisvanathan V, Eggener S, et al. Standards of reporting for MRI-
targeted biopsy studies (START) of the prostate: recommendations from an 
International Working Group. European urology. 2013;64(4):544-552. 
3. 
Kryvenko ON, Carter HB, Trock BJ, Epstein JI. Biopsy criteria for determining 
appropriateness for active surveillance in the modern era. Urology. 
2014;83(4):869-874. 
4. 
Chamie K, Williams SB, Hu JC. Population-Based Assessment of Determining 
Treatments for Prostate Cancer. JAMA oncology. 2015;1(1):60-67. 
5. 
Vargas HA, Hotker AM, Goldman DA, et al. Updated prostate imaging reporting 
and data system (PIRADS v2) recommendations for the detection of clinically 
significant prostate cancer using multiparametric MRI: critical evaluation using 
whole-mount pathology as standard of reference. European radiology. 
2016;26(6):1606-1612. 
6. 
Siddiqui MM, Rais-Bahrami S, Turkbey B, et al. Comparison of MR/ultrasound 
fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate 
cancer. Jama. 2015;313(4):390-397. 
7. 
Porpiglia F, Manfredi M, Mele F, et al. Diagnostic Pathway with Multiparametric 
Magnetic Resonance Imaging Versus Standard Pathway: Results from a 
Randomized Prospective Study in Biopsy-naive Patients with Suspected Prostate 
Cancer. European urology. 2016. 
8. 
Mohler JL, Armstrong AJ, Bahnson RR, et al. Prostate Cancer, Version 1.2016. J 
Natl Compr Canc Netw. 2016;14(1):19-30. 
9. 
Heidenreich A, Aus G, Bolla M, et al. EAU guidelines on prostate cancer. 
European urology. 2008;53(1):68-80. 
10. 
Futterer JJ, Briganti A, De Visschere P, et al. Can Clinically Significant Prostate 
Cancer Be Detected with Multiparametric Magnetic Resonance Imaging? A 
Systematic Review of the Literature. European urology. 2015;68(6):1045-1053. 
11. 
Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-
parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired 
validating confirmatory study. Lancet (London, England). 2017;389(10071):815-
822. 
12. 
Liss MA, Ehdaie B, Loeb S, et al. American Urological Association White Paper 
on the Prevention and Treatment of the More Common Complications Related to 
Prostate Biopsy Update. J Urol. 2017.