An Observational Study to Evaluate the Safety and Effectiveness of Radiotherapy for Localized T1-T2 Prostate Cancer in China After Injection of SpaceOAR Hydrogel
Conditions: Prostate Cancer
Sponsor: Boston Scientific Corporation

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Medical Device Clinical Trial Protocol 
 
 
 Reference Number：U0745 
 
Protocol Title：An observational study to evaluate the safety 
and effectiveness of radiotherapy for localized T1-T2 prostate 
cancer in China after injection of SpaceOAR Hydrogel 
(An observational study of radiotherapy after injection of SpaceOAR Hydrogel) 
Protocol version and 
date： 
Ver. B，January 25, 2022 
 
Clinical trial sites： 
Shanxi Provincial Cancer Hospital  
Principal 
Investigator： 
Professor XING Nianzeng   
Sponsor: 
BSC International Medical Trading (Shanghai) 
Co., Ltd, (“BSC China”) 
 
 
 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. It should be held 
confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
 

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An observational study to evaluate the safety and effectiveness of 
radiotherapy for localized T1-T2 prostate cancer in China after 
injection of SpaceOAR Hydrogel 
 
An observational study of radiotherapy after injection of 
SpaceOAR Hydrogel  
 
 
U0745 
CLINICAL INVESTIGATION PLAN 
 
 
 
 
Sponsored By 
BSC International Medical Trading (Shanghai) Co., Ltd, (“BSC 
China”)  
Part A, 2nd Floor, No.68, Rijing Road,  
Free Trade Zone,  
Shanghai, China 200131 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
 
 
 
 
 
 

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Contact Information 
Role 
Contact  
Clinical Contact 
YUE Taimin, 
Clinical Trial Manager  
Boston Scientific China  
Part A, 2nd Floor, No.68, Rijing Road,  
Free Trade Zone, Shanghai, China 200131  
E-mail:Taimin.Yue @bsci.com 
Mobile:+86 18911590729 
Coordinating Principal 
Investigator(s) 
CHENG Huanlian  
Medical affairs manager  
Boston Scientific China   
Part A, 2nd Floor, No.68, Rijing Road,  
Free Trade Zone,  Shanghai, 200131, P.R .China  
Email：Huanlian.Cheng@bsci.com  
Mobile:+86 13426268201 
Principal Investigator 
Professor  XING Nianzeng   
Shanxi Provincial Cancer Hospital  
NO. 3 Zhigongxinjie, Xinghualing District, Taiyuan, Shanxi, 
China 
 
 
 

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                                                                    SpaceOAR Observation-China , 92808273, Rev/Ver B 
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Original Release: October 28,2021 
Current Version: January 25,2022 
 
 
 
Revision Version 
Protocol Date 
Template 
number and 
version 
Protocol 
Section 
Modified 
Summary of Changes 
[note: confirm with Reg as to level of detail 
needed (e.g. verbatim or summary)] 
Justification for 
Modification 
[note: Include any 
potential impact on the 
performance, 
effectiveness, safety or 
other endpoints).  
Please also update the 
impacted sections of 
the protocol as 
applicable.] 
Ver A 
Oct 28,2021 
92120219_R
ev/Ver G 
NA 
NA 
Original release 
Ver B 
Jan 25,2022 
92120219_R
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7.1 
Add introduction of “association study- 
SpaceOAR real world study in Hainan’ 
Based on EC’s opinion 
Ver B 
Jan 25,2022 
92120219_R
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7.2 
Add ’The target population in this study are 
patients diagnosed with localized prostate cancer  
who took part in SpaceOAR RWS in Hainan 
(U0720)’.  
Based on EC’s opinion 
Ver B 
Jan 25,2022 
92120219_R
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Modified the wording in ‘study candidates 
screening’ 
Based on EC’s opinion 
Ver B 
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92120219_R
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9.4 
Add process of SpaceOAR real world study 
briefly. 
Based on EC’s opinion 
Ver B 
Jan 25,2022 
92120219_R
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Cover & 
Contact 
Information  
PI was changed to Professor Xing, and hospital 
was changed to Shanxi Provincial Cancor hospital 
Company Strategy 
updated  
 
 
 

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2. Protocol Synopsis 
An observational study to evaluate the safety and effectiveness of 
radiotherapy for localized T1-T2 prostate cancer in China after 
injection of SpaceOAR Hydrogel 
An observational study of radiotherapy after injection of SpaceOAR Hydrogel  
Study Objective(s) 
This observational study aims to evaluate the safety and effectiveness of 
radiotherapy for subjects with localized T1-T2 prostate cancer in China who were 
injected with SpaceOAR Hydrogel, via collecting clinical data related to 
radiotherapy. 
Study design 
This study protocol is for the second part of SpaceOAR real world study in which 
long term follow-up visits will be performed (up to 1 year) outside Boao Medical 
Tourism Pilot Zone. The SpaceOAR real world study is a retrospective and 
prospective, single arm, observational study (Ptotocol of SpaceOAR RWS 
Windchill#: 92743236). Subjects with localized T1-T2 prostate cancer who have 
already been injected with the SpaceOAR and have received radiotherapy or will 
receive radiotherapy will be enrolled, and clinical data related to radiotherapy 
will be collected. 
For subjects who have already completed radiotherapy before study kick-off, 
clinical data will be collected retrospectively, such as data related to 
radiotherapy, AE (if any) and MRI (if any). Follow up vist will be completed if 
applicable. 
For subjects who receive therapy after study kick-off, follow up visits at 2 weeks, 
6weeks, 3 months and 10 months after radiotherapy will be scheduled to assess 
bowel, urinary and sexual function and quality of life. 
 

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An observational study to evaluate the safety and effectiveness of 
radiotherapy for localized T1-T2 prostate cancer in China after 
injection of SpaceOAR Hydrogel 
An observational study of radiotherapy after injection of SpaceOAR Hydrogel  
Space OAR observational Study Design 
Planned Number of 
Subjects 
Up to 20 eligible subjects will be enrolled to generate data including 14 subjects 
at least. 
Planned Number of 
Sites / Countries 
1 site，Shanxi Provincial Cancer Hospital 
 
 
After injection-CT & MRI 
Before injection- CT&MRI 
Informed consent  
Study   
Kick- off 
After injection-CT & MRI 
Radiotherapy (RT) 
Radiotherapy (RT) 
Injection of SpaceOAR 
Follow-ups (if applicable) : 
1.
2 weeks post RT -EPIC, EQ-
5D-5L, AE 
2.
6 weeks post RT -MRI,EPIC, 
EQ-5D-5L,AE 
3.
3 months post RT -EPIC, 
EQ-5D-5L, AE 
4.
10 months post RT -MRI, AE 
Before injection- CT&MRI 
Injection of SpaceOAR 
Follow-ups： 
1.
2 weeks post RT -EPIC, EQ-
5D-5L, AE 
2.
6 weeks post RT -MRI, EPIC, 
EQ-5D-5L, AE 
3.
3 months post RT -EPIC, EQ-
5D-5L, AE 
4.
10 months post RT -MRI, AE 
Before RT-EPIC 
Before RT-EPIC 
Collecting data retrospectively 
Collecting data prospectively 

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An observational study to evaluate the safety and effectiveness of 
radiotherapy for localized T1-T2 prostate cancer in China after 
injection of SpaceOAR Hydrogel 
An observational study of radiotherapy after injection of SpaceOAR Hydrogel  
Primary Endpoint 
Reduction of dose volume of rectum receiving x Gy as specified below, 
which is measured from CT simulation scans acquired pre and post 
SpaceOAR hydrogel injection，that is Vx Gy : 
• For conventionally fractionated regimen: V70Gy 
• For moderately hypofractionated regimen: V46Gy, V37Gy 
• For ultrahypofractionated regimen：V29 Gy, V18. 1 Gy, V36 Gy 
Dose to the anterior rectum is quantified by computing a rectal dose-volume 
histogram (DVH).  
Second Endpoints 
1. EPIC bowel and urinary assessment composite score at 2 weeks, 6 weeks, 
and 3 months post radiotherapy  
2. EPIC sexual assessment composite score at 2 weeks, 6 weeks, and 3 
months post radiotherapy 
3. Quality of Life at 2 weeks, 6 weeks, and 3 months post radiotherapy 
(QOL) 
4. Whether there is SpaceOAR hydrogel between the posterior prostatic 
capsule and the anterior rectal wall at 6 weeks post radiotherapy. 
5. Whether the SpaceOAR hydrgel between the prostate and the anterior 
rectal wall is absorbed in 10 months post radiotherapy. 
6. Rectal adverse event (CTCAE) 
7. AEs/SAEs related to SpaceOAR hydrogel 
Follow-up Schedule Follow ups at 2 weeks, 6 weeks, 3 months, and 10 months after radiotherapy will 
be scheduled prospectively, if applicable. 
Study Duration 
The total study duration is estimated to be approximately 15 months. 
Participant 
Duration 
The study duration for subject enrolled prospectively is expected to be 
approximately 12 months. 
Inclusion Criteria 
• Subjects have provided the written informed consent, are willing to 
participate in clinical data collection and willing to comply with study 
procedure. (for subjects enrolled prospectively) 

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An observational study to evaluate the safety and effectiveness of 
radiotherapy for localized T1-T2 prostate cancer in China after 
injection of SpaceOAR Hydrogel 
An observational study of radiotherapy after injection of SpaceOAR Hydrogel  
• Subjects must have been pathologically confirmed prostate cancer with 
clinical stage T1-T2, and have been treated with Space OAR Hydrogel, 
and have received or will receive radiotherapy. 
Exclusion Criteria 
This is an observational study, all subjects have received radiotherapy or will 
receive radiotherapy, who have injected with SpaceOAR hydrogel in Boao 
Medical Pilot Zone. There is no specific exclusion criteria unless the patients 
refuse to sign the informed consent. 
Statistical Methods 
Statistical 
Hypothesis 
There are no hypotheses for this second stage of the SpaceOAR Real World 
study. All the endpoints are descriptive in nature.   
Statistical Test 
Method 
Descriptive statistics will be used to summarize the study endpoints, which 
include, but not limited to,dose volume of rectum receiving x Gy, EPIC 
cpmposite score, and AEs.  Continuous variables will be tabulated with mean, 
median, standard deviation, minimum, maximum, when appropriate. 
Categorical variables be tabulated with frequencies, percentages along with the 
95% confidence intervals when appropriate. 
There is no formal interim analysis, but a descriptive summary of the study data 
may be made during the study, if needed. 
 
 
 

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3. Table of Contents 
1. 
TITLE PAGE  .........................................................................................................................1 
2. 
PROTOCOL SYNOPSIS ...........................................................................................................5 
3. 
TABLE OF CONTENTS ...........................................................................................................9 
3.1. Table of Figures ......................................................................................................11 
3.2. Table of Tables ........................................................................................................12 
4. 
INTRODUCTION ..................................................................................................................13 
4.1. Background .............................................................................................................13 
4.2. Study Rationale .......................................................................................................15 
5. 
STUDY OBJECTIVES AND ENDPOINTS .................................................................................15 
5.1. Study Objectives .....................................................................................................15 
5.2. Study endpoints .......................................................................................................15 
6. 
STUDY DESIGN ..................................................................................................................16 
6.1. Scale and Duration ..................................................................................................17 
6.2. Treatment Assignment ............................................................................................17 
6.3. Justification for the Study Design ...........................................................................18 
6.4. Method to reduce biases ..........................................................................................18 
7. 
SUBJECT SELECTION ..........................................................................................................18 
7.1. Association study-SpaceOAR Real World Study in Hainan（U0720） ...............18 
7.2. Study Population and Eligibility .............................................................................18 
7.3. Inclusion Criteria .....................................................................................................19 
7.4. Exclusion Criteria ....................................................................................................19 
8. 
SUBJECT ACCOUNTABILITY ...............................................................................................19 
8.1. Point of Enrollment .................................................................................................19 
8.2. Withdrawal ..............................................................................................................19 
8.3. Lost to Follow-Up ...................................................................................................19 
8.4. End-of-Study Definition ..........................................................................................20 
9. 
STUDY METHODS ..............................................................................................................20 
9.1. Data Collection ........................................................................................................20 

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9.2. Study Candidate Screening .....................................................................................20 
9.3. Informed Consent ....................................................................................................20 
9.4. study visits ...............................................................................................................21 
9.5. Study Completion....................................................................................................22 
9.6. Source Documents ..................................................................................................22 
10. STATISTICAL CONSIDERATIONS .........................................................................................22 
10.1. Study hypotheses .....................................................................................................22 
10.2. General Statistical Methods ....................................................................................23 
10.3. Data Analyses ..........................................................................................................23 
11. DATA MANAGEMENT ........................................................................................................24 
11.1. Data Collection, Processing, and Review ...............................................................24 
11.2. Data Retention .........................................................................................................24 
12. AMENDMENT .....................................................................................................................25 
13. DEVIATIONS ......................................................................................................................25 
14. COMPLIANCE .....................................................................................................................25 
14.1. Statement of Compliance ........................................................................................25 
14.2. Investigator Responsibilities ...................................................................................26 
14.3. Institutional Review Board/ Ethics Committee .......................................................28 
14.4. Sponsor Responsibilities .........................................................................................28 
14.5. Insurance .................................................................................................................29 
15. MONITORING .....................................................................................................................29 
16. POTENTIAL RISKS AND BENEFITS ......................................................................................29 
16.1. Anticipated Adverse Events and Anticipated Adverse Device Effects of 
SpaceOAR system ...................................................................................................29 
16.2. Risks associated with Participation in the Clinical Study .......................................30 
16.3. Risk Minimization Actions .....................................................................................30 
16.4. Anticipated Benefits ................................................................................................30 
17. SAFETY REPORTING ...........................................................................................................31 
17.1. Reportable Events by investigational site to Boston Scientific ..............................31 
17.2. Definitions and Classification .................................................................................31 

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17.3. Relationship to Study Device(s) (Device Under Study and Comparator Device, if 
applicable) and/or Study Procedure ........................................................................34 
17.4. Investigator Reporting Requirements .....................................................................36 
17.5. Device Deficiencies ................................................................................................37 
17.6. Reporting to Regulatory Authorities / IRBs / ECs / Investigators ..........................37 
18. INFORMED CONSENT .........................................................................................................38 
19. COMMITTEES .....................................................................................................................39 
19.1. Safety Monitoring Process ......................................................................................39 
19.2. Steering Committee .................................................................................................39 
20. SUSPENSION OR TERMINATION ..........................................................................................40 
20.1. Premature Termination of the Study .......................................................................40 
20.2. Termination of Study Participation by the Investigator or Withdrawal of IRB/ EC 
Approval ..................................................................................................................40 
20.3. Requirements for Documentation and Subject Follow-up ......................................40 
20.4. Criteria for Suspending/Terminating a Study Site ..................................................41 
21. STUDY REGISTRATION AND RESULTS ................................................................................41 
21.1. Study Registration ...................................................................................................41 
21.2. Clinical Investigation Report ..................................................................................41 
21.3. Publication Policy ...................................................................................................41 
22. REIMBURSEMENT AND COMPENSATION FOR SUBJECTS .....................................................42 
22.1. Subject Reimbursement ..........................................................................................42 
22.2. Compensation for Subject’s Health Injury ..............................................................42 
23. BIBLIOGRAPHY ..................................................................................................................43 
24. ABBREVIATIONS AND DEFINITIONS ...................................................................................45 
24.1. Abbreviations ..........................................................................................................45 
 
3.1. Table of Figures 
Figure 6-1 Space OAR observational Study Design ............................................................... 17 
 

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3.2. Table of Tables 
Table 9-1: Data Collection Schedule ...................................................................................... 20 
Table 17-1: Safety Definitions ................................................................................................ 31 
Table 17-2: Criteria for Assessing Relationship of Study Device or RT to Adverse Event ... 35 
Table 17-3: Investigator Reporting Requirements .................................................................. 36 
Table 24-1: Abbreviations ...................................................................................................... 45 
 

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4. Introduction 
4.1. Background 
Prostate cancer is one of the most diagnosed noncutaneous human malignancies, and is 
second only to lung cancer as the leading cause for cancer mortality among men1. According 
to the Surveillance, Epidemiology and End Results Program (SEER) of the NCI, within the 
United States alone it is anticipated that there will be 233,000 new cases of prostate cancer 
diagnosed in 2014, with an approximate 29,480 deaths resulting2. In China, prostate cancer 
has became the most common urinary tumor in male since 2008, with a morbidity of 
9.8/100,000 and a mortality of 4.22/100,000 in 2014 3.Gu Xiuying et al. found that the 
incidence of prostate cancer increased by 11.5% per year on average according China tumor 
registry data 4.The amount of prostate cancer may increase greatly due to the increase of life 
expectancy and aging in China.  
Reported prostate cancer incidence has increased with introduction of the prostate-specific 
antigen (PSA) blood test. Application of the PSA test has allowed for earlier detection of 
prostate cancer and earlier intervention such that disease-specific mortality rates have  
declined5. Treatment options for prostate cancer include surgical resection (radical 
prostatectomy), radiation (brachytherapy (BT) or external beam radiotherapy (EBRT)), 
cryotherapy,  hormonal therapy (androgen deprivation) or “watchful waiting”/active 
surveillance involving no immediate treatment but yearly or biannual biopsies or medical 
monitoring. The choice of treatment is based on a multidisciplinary approach, taking into 
account tumor staging, Gleason score, baseline PSA, patient age, comorbidity, life 
expectancy and quality of life. In localized prostate cancer (i.e. T1c-T2c), external radiation 
therapy is commonly recommended, particularly for young patients who refuse surgical 
intervention or for patients who are not good surgical candidates6. An increasing number of 
men choose radiotherapy for the treatment of localized prostate cancer because of the 
perception that there is a lower risk of impotence and incontinence7. 
Although each of the treatment options have associated risks and benefits, one of the more 
significant concerns associated with radiation therapy (RT) is the potential for acute and late 
rectal injuries caused by direct mucosal damage from ionizing radiation. Acute radiation 
gastrointestinal (GI) injury is typically characterized as that which occurs during and within 
the immediate twelve weeks after completion of therapy. Toxicity can be manifested as 
diarrhea, pain, a sense of rectal distention with cramping, rectal urgency or tenesmus, 
mucous production and bleeding. Occasionally, superficial ulceration causes bleeding that 
may require endoscopic cauterization or medical therapy for anemia including transfusion8,9. 
Late effects include rectal dysfunction requiring surgical intervention, necrosis, perforation 
and life threatening bleeding. Late toxicity is attributable to progressive epithelial atrophy 
and fibrosis associated with obliterative endarteritis and chronic mucosal ischemia10,11. 
Symptoms usually are persistent in nature, and may take up to 6-12 months to appear but can 
occur any time post-irradiation up to 30 years after exposure10, 12. Of note, several researchers 
have documented a positive correlation between acute and late GI toxicity demonstrating that 
late complications are more likely to occur in patients who also experienced acute 
complications8,9,13,14.  
There have been several advancements in the delivery of external beam radiotherapy (EBRT) 
including improvement in accelerator equipment used for the delivery of RT, improved 

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imaging and planning algorithms, and target localization through the use of Image Guided 
Radiotherapy (IGRT). Despite the improvements in RT delivery, acute and chronic 
gastrointestinal toxicity remains a concern. With dose-escalation (e.g., ≥78 Gy), rates of 
acute and chronic Grade ≥ 2 rectal toxicity associated with Intensity Modulated Radiation 
Therapy (IMRT), the most contemporary form of RT, have been documented to range from 
3-50% and 5-24%, respectively15,20. 
It is well documented that the volume of normal rectal tissue exposed to varying radiation 
dose levels represents the most significant factor affecting the development of acute and late 
rectal toxicity11,15-29. Specifically, it has been noted that patients with greater than 25% of the 
rectum irradiated to 70 Gy had a significantly higher risk of developing Grade 2 or higher 
rectal toxicity scored using physician reported toxicity RTOG criteria for GI toxicity. 
Furthermore, all Grade 3 complications occurred when greater than 30% of the rectum 
received ≥70 Gy11. Other rectal dose metrics have also been qualified as a risk factor for late 
gastrointestinal symptoms.  
Although traditionally GI toxicity has been evaluated based on the physician’s assessment, 
recently there has been a transition to change focus to patient-reported outcomes using 
detailed quality of life analysis. When evaluating toxicity from a patients’ perspective, IMRT 
has an associated acute and late GI toxicity that has been demonstrated to have an important 
impact on quality of life14. A patient self-assessment questionnaire analysis performed by 
Koper et al., revealed that soiling and fecal loss (both surrogates for fecal incontinence) and 
mucus discharge were the most bothering complaints and of greater patient concern than 
rectal bleeding21. In a study published by Sanda et al, radiotherapy was associated with a 
reduced quality of life related to bowel function early after treatment, and the change lasted 
for a year or more. Rectal urgency, frequency, pain, fecal incontinence, or hematochezia 
caused distress related to bowel function in 9% of patients one year after radiotherapy and 
moderate to severe (i.e., “big”) bowel and rectal function was reported in 11% of patients 
evaluated22. These studies lead to the conclusion that non -physician scored toxicity criteria 
(i.e., parameters not necessarily considered when applying the RTOG toxicity criteria) have a 
substantial impact on quality of life. Consistent with physician-scored toxicity, increased 
rectal doses has been demonstrated to have a significant negative impact on patient reported 
bowel quality of life (QOL)23 and early quality of life has been reported to be a strong 
predictor of later QOL24.  Therefore, technologies that can minimize rectal exposure to 
incidental radiation would represent an important tool in modern EBRT therapy. 
The SpaceOAR System is an in-situ formed absorbable hydrogel that is administered 
transperineally (with transrectal ultrasound guidance) between the prostate and rectum 
(posterior to Denonvilliers' fascia and anterior to the fascia propria of the rectum). The 
formed hydrogel displaces the rectum away from the prostate during prostate radiotherapy 
and thereby has the potential to reduce rectal wall/mucosa radiation exposure. The 
SpaceOAR hydrogel material is designed to maintain rectal displacement away from the 
prostate for three months ensuring a stable relationship between the prostate and rectum 
during the typical nine week radiotherapy protocol. SpaceOAR hydrogel then slowly absorbs 
via hydrolysis and is cleared from the implant site in approximately six months. It’well 
documented that the volume of rectum was reduced during radiotherpy when the SpaceOAR 
System is used as a means to physically separate the rectum from the prostate in previos 

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studys25, 26. The 3 year incidence of grade 1+ and grade 2+ rectal toxicity was reported to 
reduce significantly when the spaceOAR were used in follow up study (2% vs 9.2%, 0% vs 
5.7%)26. 
4.2. Study Rationale 
The SpaceOAR System is designed to create space between the rcetum and prostate to reduce 
rectal wall/mucosa radiation exposure during prostate radiotherapy, then reduces the rectal 
damage. This medical device has been marketed in US, Europe and many other countries, 
and its safety and effectiveness have been confirmed in the previous studies in radiotherapy 
for prostate cancer, and Incidence of grade 1+ and grade 2+ rectal toxicity reduced 
significantly. 
The SpaceOAR System is an advanced mecial device, and there is no similar device in 
China. In accordance with the policy on special innovative medical devices, SpaceOAR can 
be used in  clinical practice as a special innovative medical device in The Boao Lecang 
Medical Pilot Zone in Hainan. This study will collect relevant clinical data of Chinese 
patients who received radiotherapy after SpaceOAR hydrogel is administrated, to evaluate its 
safety and performance during radiotherapy in a real world setting. 
5. Study Objectives and Endpoints 
5.1. Study Objectives 
This observational study aims to evaluate the safety and effectiveness of radiotherapy for 
subjects with localized T1-T2 prostate cancer in China who were injected with SpaceOAR 
Hydrogel, via collecting clinical data related to radiotherapy. 
5.2. Study endpoints 
5.2.1. Primary endpoint 
Reduction of dose volume of rectum receiving x Gy as specified below, which is measured 
from CT simulation scans acquired pre and post SpaceOAR hydrogel injection(i.e.Vx Gy): 
• 
For conventionally fractionated regimen: V70Gy 
• 
For moderately hypofractionated regimen: V46Gy, V37Gy 
• 
For ultrahypofractionated regimen：V29 Gy, V18. 1 Gy, V36 Gy 
Dose to the anterior rectum is quantified by computing a rectal dose-volume histogram 
(DVH).  
5.2.2. Second endpoints 
1. EPIC bowel and urinary Assessment composite score at 2 weeks, 6 weeks and 3 
months post radiotherapy  

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2. EPIC Sexual Assessment composite score at 2 weeks, 6 weeks, and 3 months post 
radiotherapy 
3. Quality of Life at 2 weeks, 6 weeks and 3 months post radiotherapy (QOL) 
4. Whether there is SpaceOAR hydrogel between the posterior prostatic capsule and the 
anterior rectal wall at 6 weeks post radiotherapy. 
5. Whether the SpaceOAR hydrgel between the prostate and the anterior rectal wall is 
absorbed in 10 months post radiotherapy. 
6. Rectal adverse event (CTCAE) 
7.  AEs/SAEs related to SpaceOAR hydrogel 
6. Study Design 
The SpaceOAR real world study is a retrospective and prospective, single arm study, and this 
study protocol is for the second part of the SpaceOAR real world study in which long term 
follow-up will be performed (up to 1 year) outside Boao Medical Tourism Pilot Zone. Subjects 
with localized T1-T2 prostate cancer who have already been injected with the SpaceOAR and 
have received radiotherapy or will receive radiotherapy will be enrolled, and clinical data 
related to radiotherapy will be collected. 
For subjects who have already completed radiotherapy before study kick-off, clinical data will 
be collected retrospectively, such as data related to radiotherapy, AE (if any) and MRI (if any), 
and follow up will be performed, if applicable.  
For subjects who receive therapy after study kick-off, radiotherapy relevant clinical data will 
be collected, and follow up visits after radiotherapy will be scheduled to assess urinary, bowel, 
sexual functions and AE. 
All administration of SpaceOAR hydrogel will be completed by trained urologists in the 
hospital in Boao. 
All radiotherapy planning will be made according to clinical practice and stage of Pca at 
discretion of the doctors. 

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Figure 6-1 Space OAR observational Study Design 
6.1. Scale and Duration 
Up to 20 subjects with localized Pca will be enrolled in this study and followed by  
radiotherapy after injection of SpaceOAR. This study is based on the use of special medical 
device in Hainan BOAO medical tourism pilot zone, the enrollment may be slow due to 
limited patient pool. Together, the study enrollment, radiotherapy, and follow up visits are 
expected to be completed in 15 months.   
6.2. Treatment Assignment 
This is a single arm, observational study without treatment assignment. All subjects receive 
radiotherapy in sites when they were treated with SpaceOAR hydrogel at the hospital in 
Hainan BOAO. 
 
  
  
After injection-CT & MRI 
Before injection- CT&MRI 
Informed consent  
Study  
Kick-off 
After injection-CT & MRI 
Radiotherapy (RT) 
Radiotherapy (RT) 
Injection of SpaceOAR 
Follow-ups (if applicable) : 
1.
2 weeks post RT -EPIC, EQ-
5D-5L, AE 
2.
6 weeks post RT -MRI, EPIC, 
EQ-5D-5L,AE 
3.
3 months post RT -EPIC, 
EQ-5D-5L, AE 
4. 10 months post RT -MRI, AE 
Before injection- CT&MRI 
Injection of SpaceOAR 
Follow-ups： 
1.
2 weeks post RT -EPIC, EQ-
5D-5L, AE 
2.
6 weeks post RT -MRI, EPIC, 
EQ-5D-5L, AE 
3.
3 months post RT -EPIC, EQ-
5D-5L, AE 
4.
10 months post RT -MRI, AE 
Before RT-EPIC 
Before RT-EPIC 
Collecting data retrospectively 
Collecting data prospectively 

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6.3. Justification for the Study Design 
SpaceOAR system has been firstly used in Hainan BOAO as a special medical device, while 
there is no evidence about the radiotherapy after SpaceOAR hydrogel injection in China. As 
a result, an observational study is conducted to gather the relevant clinical data in Chinese 
patients with localized PCa who receive radiotherapy after SpaceOAR hydrogel is injected. 
Due to limited patient pool in BOAO, the subjects will be enrolled prospectively and 
retrospectively to speed up the study recruitment.. 
6.4. Method to reduce biases 
To reduce bias of primary endpoints, objective endpoints, Vx Gy, are used. They are 
obtained by computing a rectal dose-volume histogram (DVH) in the same hospital. 
7. Subject Selection  
7.1. Association study-SpaceOAR Real World Study in Hainan（U0720） 
SpaceOAR Real World Study is conducted based on the use of special medical devices in the 
Boao Lecheng Medical Pilot Zone in Hainan.  Patients who have been diagnosed with stage 
T1-T2 prostate cancer and are scheduled to receive radiation therapy will be recommended to 
participate in the SpaceOAR RWS after informed consent is done fully.  If patients 
voluntarily participate in the study, they can go Boao Yiling Life Care Center in Hainan to 
receive SpaceOAR gel injection.   
The injection of SpaceOAR hydrogel is performed by trained urologists, via rectal ultrasound 
guided under general anesthesia or local anesthesia and sedation.  Subjects will go back 
Local hospital, where simulated mapping CT and MRI examination will be performed to 
make radiotherapy treatment plan in time post-discharge (Shanxi Provincial Cancer Hospital 
is recommended).   
Subjects will be called by phone at 30 days after discharge to collect adverse events and 
Device Deficiency (if applicable) to assess patient health.  The relevant clinical data 
generated in another hospital (e.g., Local hospital where subjects have been examined) will 
be collected when applicable.   
In addition, the study will retrospectively collect the clinical data of patients who had 
completed SpaceOAR hydrogel injection before the study kick-off.  
7.2. Study Population and Eligibility  
The target population in this study are patients diagnosed with localized prostate cancer who 
took part in SpaceOAR RWS in Hainan (U0720) and have been treated with SpaceOAR 
Hydrogel in hospital in Hainan Boao, are receive or will receive radiotherapy in this site.   

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7.3. Inclusion Criteria 
Subjects who meet all the following criteria may be given consideration for inclusion in this 
clinical investigation, provided no exclusion criterion is met.  
• Subjects have provided the written informed consent, are willing to participate in 
clinical data collection and willing to comply with study procedure. (for subjects 
enrolled prospectively) 
• Subjects must have been pathologically confirmed prostate cancer with clinical stage 
T1-T2, and have been treated with Space OAR Hydrogel, and have received or will 
receive radiotherapy. 
7.4. Exclusion Criteria 
There are no specific exclusion criteria unless the patients refuse to sign the informed 
consent. 
8. Subject Accountability 
8.1. Point of Enrollment 
During screening, patients who have received or will receive radiotherapy will be identified. 
These who have been injected with SpaceOAR hydrogel will be enrolled. For patients who 
have already received radiotherapy, the clinical data can be collected retrospectively, and 
informed consent will be performed (If follow up visits can be conducted prospectively). For 
patients who will receive radiotherapy, informed consent will be gained. 
8.2. Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study) 
shall be accounted for and documented. If a subject withdraws from the clinical 
investigation, the reason(s) shall be reported. The applicable CRF(s), including the end of the 
study form, shall be completed at the time of subject withdrawal. 
8.3. Lost to Follow-Up 
A subject will be considered lost to follow-up if he fails to complete 30 days follow-up visits 
and is unable to be contacted by the study site staff after at least three documented attempts, 
at which point an End of Study form should be completed.  Before a participant is deemed 
lost to follow up, the investigator or designee will make every effort to regain contact with 
the participant (where possible, 3 telephone calls and, if necessary, a certified letter to the 
participant’s last known mailing address or local equivalent methods).  These contact 
attempts should be documented in the participant’s medical record or study file. (only for 
patients enrolled prospectively). 

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8.4. End-of-Study Definition  
A subject is considered to have completed the study if he has completed all phases of study 
including the last visit or last scheduled procedure shown in the data collection schedule. 
A clinical trial is considered completed when participants are no longer being examined or 
the last participant’s last study visit has occurred.  
9. Study Methods 
9.1. Data Collection 
The data collection schedule is shown in Table 9-1. 
Table 9-1: Data Collection Schedule 
Procedure/Assessment 
Before RT 
RT 
After RT 
2W (±
3days) 
6W (±
7days) 
3M (±
15days) 
10M (±
30 days) 
Informed consent  
X 
 
 
 
 
 
PSA 
X 
 
 
X 
 
X 
CT 
X* 
 
 
 
 
 
MRI 
X* 
 
 
X 
 
X 
Radiotherapy  
 
X 
 
 
 
 
EPIC questionnaire 
X 
 
X 
X 
X 
 
EQ-5D-5L questionnaire 
X 
 
X 
X 
X 
 
Concomitant medication 
X 
X 
X 
X 
X 
X 
Adverse event 
X 
X 
X 
X 
X 
X 
Protocol Deviation 
X 
X 
X 
X 
X 
X 
Device Deficiency# 
X 
X 
X 
X 
X 
X 
NOTE:1. Data at baseline such as demography, medical history, Pca, etc. refer to SpaceOAR RWS 
(U0720).  
2.*CT&MRI for mapping, which used to make RT planning, 2 times. 
3.# DD of Space OAR hydrogel. 
 
9.2. Study Candidate Screening 
Patients diagnosed with localized prostate cancer who have been injected with SpaceOAR 
hydrogel in SpaceOAR RWS in Hainan (U0720) will be invited to participate in this study. 
9.3. Informed Consent 
For patients who receive radiotherapy after SpaceOAR injected, investigator will introduce 
study information to subject and get ICF. Once the ICF is signed, he is enrolled in study. If 
he fails to receive radiotherapy after ICF signed, the subjects are screening failure. 

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9.4. study visits 
The subject of  SpaceOAR RWS are going to participate in this study when he completed last 
visit. the process of SpaceOAR RWS is summarized below. 
• Patients who diagnosed with T1-T2 prostate cancer and scheduled to recerive RT will be 
screened and recommended to participate in SpaceOAR RWS in Hainan. After informed 
consent is done fully, Mapping CT and MRI will be conducted. (Shanxi Provincial 
Cancer Hospital is preferred.) 
• Subjects go to Boao Yiling Life Care Center in Hainan to receive SpaceOAR gel 
injection voluntarily, which is completed by trained and qualified urologist. 
• After discharge, subjects will recerive Mapping CT and MRI to make RT plan, then 
recerive RT. (Shanxi Provincial Cancer Hospital is preferred, i.e., enrolled in this study) 
• At 30 days after SpaceOAR injection, a phone visit will be completed. Then subject 
complete all visits. 
Subjects who have been injected with SpaceOAR in Hainan BOAO return to participate in 
this observational study. subjects receive radiotherapy per site’s clinical practice, then will be 
followed in 2 weeks, 6 weeks, 3 months and 10 month after RT. 
1) Before RT 
RT planning before and after SpaceOAR hydrogel injection will be made (such as 
planning type of EBRT, planning RT regimen, CTV, PTV and constraint of risk 
organs, etc.). The RT planning of the subjects will be determined by the investigators 
based on the current clinical practice and PCa staging and conditions of the subjects.  
The questionaries of EPIC and EQ-5D-5L will be completed, adverse event and 
Device Deficiency (if applicable) will be assessed and collected.  
Note: The subject's demographic, medical history, genitourinary history, prostate 
treatment, PCa therapies, PCa staging, Gleason score, etc., are collected in the 
SpaceOAR RWS(U0720). 
2) RT 
RT is conducted according to RT planning after SpaceOAR injection; adverse event 
and Device Deficiency will be collected, if applicable. 
3) Follow-ups after RT 
2 weeks post RT: the questionaries of EPIC and EQ-5D-5L will be completed to 
assess the functions of urinary, rectum and health related Quality of life; Adverse 
event and Device Deficiency will be collected, if applicable. 
6 weeks post RT: the questionaries of EPIC and EQ-5D-5L will be completed to 
assess the functions of urinary, rectum and health related Quality of life; Adverse 
event and Device Deficiency will be collected, if applicable; MRI will be performed. 

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3 months post RT: the questionaries of EPIC and EQ-5D-5L will be completed to 
assess the functions of urinary, rectum and health related Quality of life; Adverse 
event and Device Deficiency will be collected, if applicable. 
10 months post RT:  MRI will be performed; Adverse event and Device Deficiency 
will be collected, if applicable. 
NOTE: For subjects who have received RT (after SpaceOAR injection), applicable 
follow up will be performed after participation in this study to assess adverse event 
and device deficiency, if any, then to collect clinical data. The clinical data before 
participation will be collected retrospectively at same time.  
9.5. Study Completion 
When last subject complete follow up visit at 10 months post RT and data collection is 
complete, this study will come to an end. 
9.6. Source Documents 
It is preferable that original source documents are maintained, when available. In lieu of 
original source documents, certified copies are required to be maintained.  A certified copy is 
a copy (irrespective of the type of media used) of the original record that has been verified 
(i.e., by a dated signature or by generation through a validated process) to have the same 
information, including data that describe the context, content, and structure, as the original.    
10. Statistical Considerations 
10.1. Study hypotheses 
There are no hypotheses for this second stage of SpaceOAR Real World study. All the 
endpoints are descriptive in nature. The endpoints in the study include the following: 
 
Primary endpoint 
 
Reduction of dose volume of rectum receiving x Gy as specified below, which is measured 
from CT simulation scans acquired pre and post SpaceOAR hydrogel injection, (i.e.Vx 
Gy): 
• For conventionally fractionated regimen: V70Gy 
• For moderately hypofractionated regimen: V46Gy, V37Gy 
• For ultrahypofractionated regimen：V29 Gy, V18. 1 Gy, V36 Gy 
Dose to the anterior rectum is quantified by computing a rectal dose-volume histogram 
(DVH). 
 
Secondary endpoints 
 

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1. EPIC bowel and urinary assessment composite score at 2 weeks, 6 weeks, and 3 months 
post radiotherapy  
2. EPIC sexual assessment composite score at 2 weeks, 6 weeks, and 3 months post 
radiotherapy 
3. Quality of Life at 2 weeks, 6 weeks, and 3 months post radiotherapy (QOL) 
4. Whether there is SpaceOAR hydrogel between the posterior prostatic capsule and the 
anterior rectal wall at 6 weeks post radiotherapy. 
5. Whether the SpaceOAR hydrgel between the prostate and the anterior rectal wall is 
absorbed in 10 months post radiotherapy. 
6. Rectal adverse event (CTCAE) 
7. AEs/SAEs related to SpaceOAR hydrogel 
10.2. General Statistical Methods 
10.2.1. Analysis Sets 
The effectiveness set, and safety set include all subjects who have radiotherapy after injection 
of SpaceOAR hydrogel. 
10.2.2. Control of Systematic Error/Bias 
 All patients who receive RT at the BOAO site after injection of SpaceOAR will be invited to 
enroll at a given time, to minimize selection bias. The primary endpoint is an objective 
measure, which is computed via DVH to reduce assessment bias. 
10.2.3. The method of handling missing, incorrect data (including subjects’ withdrawal 
and lost to follow-up) and unreasonable data 
Missing data will not be imputed for primary analysis. Incorrect and unreasonable data will 
be clarified before database lock. Imputation with mean or median may be performed where 
applicable for the primary endpoint as a sensitivity analysis.  
10.3. Data Analyses 
Descriptive statistics will be used to summarize the study endpoints, such dose volume of 
rectum receiving x Gy, EPIC composite score, AEs.  Continuous variables will be tabulated 
with mean, median, standard deviation, minimum, maximum. Categorical variables will be 
tabulated with frequencies, percentages along with the 95% confidence intervals when 
appropriate. 
Any statistical analysis changes for the study endpoints will be described in the statistical 
analysis plan before the data analysis.  

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11. Data Management 
11.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) 
system.  
The clinical database will reside on a production server hosted by Medidata EDC System. All 
changes made to the clinical data will be captured in an electronic audit trail and available for 
review by the sponsor or its representative. The associated Rave software and database have 
been designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. A written signature on printouts 
of the eCRFs must also be provided if required by local regulation. Changes to data 
previously submitted to the sponsor require a new electronic signature by the Investigator 
acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the Medidata EDC system 
and will be issued to the site for appropriate response. Site staff will be responsible for 
resolving all queries in the database. 
All access to the clinical database will be changed to “Read only” after all data is either 
“Hard Locked” or “Entry Locked”. Once acceptance of the final report or finalization of 
publications (as applicable) is received, final database storage and archiving activities may 
begin. Once all of the closeout activities are completed a request to IT is submitted to have 
the “Database Locked” or Decommissioned and all database access revoked. 
11.2. Data Retention 
The Principal Investigator or his/her designee or Investigational site will maintain all 
essential study documents and source documentation that support the data collected on the 
study subjects in compliance with applicable regulatory requirements. Documents must be 
retained for 10 years after the formal discontinuation of the clinical investigation of the 
product or retained for a long time in accordance with site’s reqiurements . These documents 
will be retained by BSC until the product/device is no longer in use in compliance with local 
regulations. 
The Principal Investigator or his/her designee will take measures to prevent accidental or 
premature destruction of these documents. If for any reason the Principal Investigator or 
his/her designee withdraws responsibility for maintaining these essential documents, custody 
must be transferred to an individual who will assume responsibility and BSC must receive 
written notification of this custodial change. Sites are required to inform Boston Scientific in 
writing where paper or electronic files are maintained in case files are stored off site and are 
not readily available. 

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12. Amendment 
The investigator should adhere to clinical trial protocol approved by EC. Any Amendment to 
the protocol (management information or study process modification, etc.) should be 
completed and reviewed by the sponsor during the study, then should be submitted to the EC 
for approval via the investigator. Only the amendment of protocol is approved by EC, the 
amended ptotocol should be implemented. 
13. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An investigator shall notify the 
sponsor and the reviewing IRB/EC, and the regulatory authority if applicable of any 
deviation from the investigational plan to protect the life or physical well-being of a subject 
in an emergency, and those deviations which affect the scientific integrity of the clinical 
investigation. Such notice shall be given as soon as possible, but no later than 5 working days 
after the emergency occurred, or per prevailing local requirements, if sooner than 5 working 
days.  
All deviations from the investigational plan, with the reason for the deviation and the date of 
occurrence, must be documented and reported to the sponsor using EDC. Sites may also be 
required to report deviations to the IRB/EC, and the regulatory authority, per local guidelines 
and national/government regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including  but not limited to IRB/EC, regulatory authority 
notification, site re-training, or site discontinuation/termination) will be put into place by the 
sponsor. 
Since this study is a prospective and retrospective, real world study without intervention 
based on standard medical care, missing data and tests are not deemed as study deviations for 
the restrospectively collected data. For prospectively collected data, deviations should be 
recorded, including but not limited to informed consent, inclusion criteria, follow-up visit etc.  
14. Compliance 
14.1. Statement of Compliance 
This clinical investigation is financed by the study sponsor. Before the investigational site 
can be “Authorized to Enroll,” the investigational site must enter into a Clinical Study 
Agreement with the sponsor that details the financing of the study as well as the rights and 
obligations of the investigational site and the investigator. This study will be conducted in 
accordance with ISO 14155, ICH-GCP, ethical principles that have their origins in the 
Declaration of Helsinki, and applicable individual country laws and regulations. The study 
shall not begin until the required approval/favorable opinion from the IRB/EC and/or 
regulatory authority has been obtained, if appropriate. Also, the study shall not begin prior to 
issuance of the site Authorization to Enroll, as provided by the sponsor. Any additional 

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requirements imposed by the IRB/EC or regulatory authority shall be followed, if 
appropriate.  
14.2. Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the study 
is conducted in accordance with the Clinical Study Agreement, the clinical investigation 
plan/, the spirit of ISO 14155, ethical principles that have their origins in the Declaration of 
Helsinki, any conditions of approval imposed by the reviewing IRB/EC, and prevailing local 
and/or country laws and/or regulations, whichever affords the greater protection to the 
subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• Prior to beginning the study, sign the Clinical Study Agreement and comply with the 
Investigator responsibilities as described in such Agreement.   
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the site team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
• Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation from the 
approved protocol that occurred during the clinical investigation. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the CRFs and in all required reports. 
• Record, report, and assess (seriousness and relationship to the device/procedure) every 
adverse event as applicable per the protocol and observed device deficiency. For 
prospective cohort, investigator will analyze cause of adverse events and write an 
analysis report with sponsor, then provide suggestion such as continuation, suspension, or 
termination of study according to China GCP. All will be reviewed by EC. 
• Report to sponsor, per the protocol requirements, all reportable events. 
• Report to the IRB/EC and regulatory authorities any SAEs and device deficiencies that 
could have led to a SADE and potential/USADE or UADE, if required by applicable laws 
or regulations or this protocol or by the IRB/EC, and supply BSC with any additional 
requested information related to the safety reporting of a particular event. 
• Allow the sponsor to perform monitoring and auditing activities, and be accessible to the 
clinical research monitor or auditor and respond to questions during monitoring visits or 
audit(s). 

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• Allow and support regulatory authorities and the IRB/EC when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB/EC requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical study in the case of adverse events, as described in the Informed Consent Form 
(ICF). 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 
treatment, including decoding procedures for blinded/masked clinical investigations, as 
needed. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 
• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together with 
identification and compliance information for concomitant treatment measures (contact 
address and telephone numbers shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation. 
All investigators will provide their qualifications and experience to assume responsibility 
for their delegated tasks through up-to-date curriculum vitae or other relevant 
documentation and disclose potential conflicts of interest, including financial, that may 
interfere with the conduct of the clinical study or interpretation of results. 
14.2.1. Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal Investigator is responsible for providing 
appropriate training, are competent to perform the tasks they have been delegated and 
adequate supervision of those to whom tasks are delegated. Where there is a sub investigator 
at a site, the sub investigator should not be delegated the primary supervisory responsibility 
for the site. The investigator is accountable for regulatory violations resulting from failure to 
adequately supervise the conduct of the clinical study.  

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14.3. Institutional Review Board/ Ethics Committee 
The investigational site will obtain the written and dated approval/favorable opinion of the 
IRB/EC for the clinical investigation before recruiting subjects. 
A copy of the written IRB/EC and/or competent authority (CA) approval of the protocol (or 
permission to conduct the study) and ICF, must be received by the sponsor before 
recruitment of subjects into the. Prior approval must also be obtained for other materials 
related to subject recruitment or which will be provided to the subject. 
Any amendment to the protocol will require review and approval by the IRB/EC before the 
changes are implemented to the study.  All changes to the ICF will be IRB/EC approved; a 
determination will be made regarding whether a new ICF needs to be obtained from 
participants who provided consent, using a previously approved ICF. Annual IRB/EC 
approval and renewals will be obtained throughout the duration of the study as required by 
applicable local/country laws or regulations or IRB/EC requirements. Copies of the study 
reports and the IRB/EC continuance of approval must be provided to the sponsor.  
14.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC and will be kept confidential in accordance with all 
applicable laws and regulations. Only authorized BSC personnel and/or a BSC representative 
including, but not limited to Contract Research Organization (CRO), will have access to this 
information. Authorized regulatory personnel have the right to inspect and copy all records 
pertinent to this study. Study data collected during this study may be used by BSC for the 
purposes of this study, publication, and to support future research and/or other business 
purposes, such as overseeing and improving the performance of its device, new medical 
research and proposals for developing new medical products and procedures. All data used in 
the analysis and reporting of this study or shared with a third-party researcher will be without 
identifiable reference to specific subjects. 
Information received during the study will not be used to market to subjects; subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
14.4.1. Role of Boston Scientific Representatives 
BSC personnel may perform certain activities to ensure study quality. These activities may 
include the following. 
• Observing testing or medical procedures to provide information relevant to protocol 
compliance 
• Reviewing collected data and study documentation for completeness and accuracy 
 
Boston Scientific personnel will not do the following.  
• Practice medicine 
• Provide medical diagnosis or treatment to subjects 

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• Discuss a subject’s condition or treatment with a subject  
• Independently collect critical study data (defined as primary or secondary endpoint data) 
• Enter data in electronic data capture systems or on paper case report forms 
14.5. Insurance  
Where required by applicable regulation in China, BSC will provide insurance coverage for 
subjects in the study. If any study related health injury occurs, claims and compensation will 
be made, where required, and BSC will assume the responsibility per insurance procedure, 
except in the case that damages are incurred due to deviation of the protocol, intentional or 
serious negligence at the site. 
15. Monitoring 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, the clinical research monitor verifies that 
study records are adequately maintained, that data are reported in a satisfactory manner with 
respect to timeliness, adequacy, and accuracy, and that the Principal Investigator continues to 
have sufficient staff and facilities to conduct the study safely and effectively. The source 
documents include but not limit to signed ICF, medical records, image (if any), lab tests (if 
any) and SAEs. The Device deficiencies, relationships of AE and medical device/ procedure 
recorded in the CRF will be considered as source documents in this study. The sponsor will 
put a plan in place to document the specific monitoring requirements.  
The Principal Investigator/institution guarantees direct access to original source documents 
by BSC personnel, their designees, and appropriate regulatory authorities. If the source 
document can’t be acquired for subjects who went to non-investigation hospital or examined 
by non-investigator, the certified copies should be got and maintained. Source document 
related to SAE should be copied (if applicable) and sent to BSC safety, as specified in 
chapter 17. 
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
16. Potential Risks and Benefits 
16.1.  Anticipated Adverse Events and Anticipated Adverse Device Effects of 
SpaceOAR system 
All subjects were treated with SpaceOAR system, which were implanted between prostate 
and anterior rectum before participation in this study. It slowly absorbs via hydrolysis and is 
cleared from the implant site in approximately six months. Anticipated adverse events and 
Anticipated Adverse Device Effects of SpaceOAR system are specified as below: 

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• Pain associated with SpaceOAR hydrogel injection  
• Pain or discomfort associated with SpaceOAR hydrogel  
• Local inflammatory reactions  
• Infection  
• Urinary retention  
• Mucosal damage, ulcers  
• Bleeding  
• Constipation  
• Urgency (e.g., urinary and rectal) 
• Allergic reaction 
• Embolism 
• Fistula  
• Penetration  
• Syncope  
16.2. Risks associated with Participation in the Clinical Study 
This study is an observational study, that the medical data generated in the clinical practice 
will be used, no new or additional intervention will be imposed on the subjects, no foreseen 
additional risks. But the risks of PCa and treatment may not be reduced when subjects take 
part in this study. During the data collection in the study, no private information that can 
identify the subject will be collected, such as, name, ID number, hospital number, telephone 
number, address etc. 
16.3. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject 
selection criteria, close monitoring of the subject's physiologic status during follow-ups and 
by promptly supplying BSC with all pertinent information required by this protocol. 
16.4. Anticipated Benefits 
There are no guaranteed benefits from participation in this study. However, information 
gained from this study may be of benefit to others with the same medical conditions. 

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17. Safety Reporting 
17.1. Reportable Events by investigational site to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of following categories: 
• All adverse events 
• All serious adverse events 
• All Adverse Events related to Study Device  
• All Serious Adverse Events related to Study Device  
• All Adverse Events related to RT 
• All Serious Adverse Events related to RT 
• Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects 
• All Device Deficiencies  
• New findings/updates in relation to already reported events 
When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms. 
If it is unclear whether an event fits one of the above categories, or if the event cannot be 
isolated from the device or procedure, it should be submitted as an adverse event and/or 
device deficiency. 
Any reportable event, experienced by the study subject after informed consent, whether prior 
to, during or after RT, must be recorded in the eCRF. 
Underlying diseases and chronic conditions are not reported as AEs unless there is an 
increase in severity or frequency during the investigation. Death should not be recorded as an 
AE, but should only be reflected as an outcome of one (1) specific SAE (see Table 17-1 for 
AE definitions). 
17.2. Definitions and Classification 
Adverse event definitions are provided inTable 17-1. Administrative edits were made on the 
safety definitions from applicable regulations and guidance including (but not limited to) 21 
CFR Part 812, ISO 14155 and EU MDR 2017/745/MDCG 2020-10/1 Guidance on Safety 
Reporting in Clinical Investigations for clarification purposes. 
Table 17-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons, in the context of a clinical investigation, 
whether or not related to the study medical device and whether anticipated 
or unanticipated.  

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Table 17-1: Safety Definitions 
Term 
Definition 
 
 
 
 
• 
This includes events related to the study medical device or 
comparator. 
• 
This definition includes events related to the procedures involved. 
NOTE: For users or other persons, this definition is restricted to events 
related to the study medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
 
Adverse event related to the use of the study medical device 
• 
This includes any adverse event resulting from insufficiencies or 
inadequacies in the instructions for use, the deployment, the 
implantation, the installation, the operation, or any malfunction of the 
study medical device. 
• 
This definition includes any event resulting from use error or from 
intentional misuse of the study medical device. 
• 
This includes ‘comparator’ if the comparator is a medical device. 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
 
Adverse event that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, users or other persons 
as defined by either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
including chronic diseases, or  
3) in-patient hospitalization or prolongation of existing 
hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
c) foetal distress, foetal death, or a congenital abnormality or birth defect 
including physical or mental impairment. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the clinical investigational plan, without a serious 
deterioration in health, is not considered a serious adverse event.  
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
 
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
 
Unanticipated Adverse Device 
Effect (UADE) 
 
Ref: 21 CFR Part 812 
 
Any serious adverse effect on health or 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 application (including a 
supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or 
welfare of subjects.   
Unanticipated Serious Adverse 
Device Effect (USADE) 
Serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current risk assessment. 

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Table 17-1: Safety Definitions 
Term 
Definition 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
 
 
NOTE 1: Anticipated serious adverse device effect (ASADE) is an effect 
which by its nature, incidence, severity or outcome has been identified in 
the risk assessment. 
Serious Health Threat 
 
Ref: ISO 14155 
 
Signal from any adverse event or device deficiency that indicates an  
imminent risk of death or a serious deterioration in the health in subjects, 
users or other persons, and that requires prompt remedial action 
for other subjects, users or other persons. 
NOTE 1: This would include events that are of significant and unexpected 
nature such that they become alarming as a potential serious health hazard 
or possibility of multiple deaths occurring at short intervals. 
Device Deficiency 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
 
An inadequacy of a medical device related to its identity, quality, 
durability, reliability, usability, safety or performance.  
NOTE 1: Device deficiencies include malfunctions, use errors, and 
inadequacy in the information supplied by the manufacturer including 
labelling. 
NOTE 2: This definition includes device deficiencies related to the device 
under study. 
The following definitions will be used for defining hospitalization or prolongation of hospitalization for SAE 
classification purposes: 
Hospitalizations  
Hospitalization does not include: 
• 
emergency room visit that does not result in in-patient admission  
Note: although an emergency room visit does not itself meet the 
definition for hospitalization, it may meet other serious criteria 
(e.g. medical or surgical intervention to prevent permanent 
impairment or damage) 
• 
elective and pre-planned treatment/surgery for a pre-existing 
condition that is documented in the subject’s record at the time of 
consent/enrollment 
• 
admission for social reasons and/or respite care in the absence of 
any deterioration in the subject’s general condition (e.g. subject is 
homeless, caregiver relief) 
• 
pre-planned, protocol-specified admission related to the clinical 
study (e.g. procedure required by protocol) 
Note 1: If complications or AEs occur during an elective/planned (i.e., 
planned prior to signing ICF) hospitalization after signing ICF, the 
complications and AEs must be reported as AEs or SAEs if they meet the 
protocol-specified definitions, However, the original elective/planned 
hospitalization(s) itself should not be reported as an SAE. 
Prolongation of hospitalization  
In-patient admission to the hospital that is prolonged beyond the expected 
standard duration for the condition under treatment. 
Note: new adverse events occurring during the hospitalization are 
evaluated to determine if they prolonged hospitalization or meet another 
SAE criteria. 

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Table 17-1: Safety Definitions 
Term 
Definition 
 
 
17.3. Relationship to Study Device(s) (Device Under Study and Comparator Device, 
if applicable) and/or Study Procedure 
The Investigator must assess the relationship of the reportable AE to SpaceOAR hydrogel, 
and/or radiotherapy. See criteria in Table 17-2:  

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Table 17-2: Criteria for Assessing Relationship of Study Device or RT to Adverse 
Event 
Classification 
Description 
Not Related 
Ref: MDCG 2020-10/1 
Relationship to the device, comparator or RT can be excluded when: 
-  the event has no temporal relationship with the use of the study device or the RT 
- the serious event does not follow a known response pattern to the medical device 
(if the response pattern is previously known) and is biologically implausible; 
- the discontinuation of medical device application/RT or the reduction of the level 
of activation/exposure/RT - when clinically feasible – and reintroduction of its use 
(or increase of the level of activation/exposure), do not impact on the serious event; 
- the event involves a body-site or an organ that cannot be affected by the device or 
RT;  
- the serious event can be attributed to another cause (e.g. an underlying 
or concurrent illness/ clinical condition, an effect of another device, drug, treatment 
or other risk factors); 
- the event does not depend on a false result given by the study device/RT used for 
diagnosis, when applicable; 
- In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/RT and the serious event. 
Possibly Related 
Ref: MDCG 2020-10/1 
The relationship with the use of the study device or RT, or the relationship with RT 
is weak but cannot be ruled out completely. Alternative causes are also possible 
(e.g. an underlying or concurrent illness/ clinical condition or/and an effect of 
another device, drug or treatment). Cases where relatedness cannot be assessed or 
no information has been obtained should also be classified as possible. 
Probably Related 
Ref: MDCG 2020-10/1 
The relationship with the use of the study device or, or the relationship with RT 
seems relevant and/or the event cannot be reasonably explained by another cause. 
Causal Relationship 
Ref: MDCG 2020-10/1 
The serious event is associated with the study device or with RT beyond reasonable 
doubt when: 
- the event is a known side effect of the product category the device belongs to or 
of similar devices and RT; 
- the event has a temporal relationship with the study device use/application or RT; 
- the event involves a body-site or organ that 
-the study device or RT are applied to; 
-the study device or RT have an effect on; 
- the serious event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment) have been adequately ruled 
out; 
- harm to the subject is due to error in use; 
- the event depends on a false result given by the study device used for diagnosis, 
when applicable; 
- In order to establish the relatedness, not all the criteria listed above might be met 
at the same time, depending on the type of device/procedures and the serious event. 

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17.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 17-3.  
Note: For data collected retrospectively, there is no specific reporting requirements for 
retrospective study in current laws and regulations. In view of feasibility of operation and 
specialty of retrospective study, Communication timeline is specified as below. 
Table 17-3: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline post-market 
studies*  
(EU MDR 2017/745, MDCG 2020-
10/1MEDDEV 2.12/1:  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Unanticipated Adverse 
Device Effect / Unanticipated 
Serious Adverse Device 
Effect  
 
Complete AE eCRF page 
with all available new and 
updated information.  
• 
For data collected prospectively: within 
24 hours of first becoming aware of the 
event.  
• 
For data collected retrospectively, within 
5 business day of the event identified or 
collected during data collection 
• 
Terminating at the end of the study. 
 
 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
• 
Upon request of sponsor.  
Serious Adverse Event 
including serious adverse 
effects 
Complete AE eCRF page 
with all available new and 
updated information.  
• 
For data collected prospectively: within 
24 hours of first becoming aware of the 
event.  
• 
For data collected retrospectively, within 
5 business day of the event identified or 
collected during data collection 
• 
 Reporting required through the end of 
study 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
• 
Upon request of sponsor 
Device Deficiencies 
(including but not limited to 
malfunctions, use errors, and 
inadequacy in information 
supplied by the manufacturer, 
including labelling) 
Note:  Any Device Deficiency 
that might have led to a 
Complete eCRF page with 
all available new and 
updated information.  
• 
For data collected prospectively: within 
24 hours of first becoming aware of the 
event.  
• 
For data collected retrospectively, within 
5 business day of the event identified or 
collected during data collection 
• 
Reporting required through the end of the 
study 

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Event Classification 
Communication Method  
Communication Timeline post-market 
studies*  
(EU MDR 2017/745, MDCG 2020-
10/1MEDDEV 2.12/1:  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
serious adverse event if 
appropriate action had not 
been taken, intervention had 
not occurred, circumstances 
had been less fortunate is 
considered a reportable event. 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event. 
• 
Upon request of sponsor  
Adverse Event including 
Adverse Device Effects 
Complete AE eCRF page, 
which contains such 
information as date of AE, 
treatment of AE resolution, 
assessment of seriousness 
and relationship to the 
device.  
• 
In a timely manner but recommend within 
10 business days after becoming aware of 
the information  
• 
Upon request of sponsor 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
 
17.5. Device Deficiencies 
Device deficiencies will be documented and reported to BSC. If possible, the device(s) under 
study should be returned to BSC for analysis. The return instructions of the device refer to 
the return process of the product after market. It shall be returned by the supplier and relevant 
personnel of the hospital's instrument department. If these device can’t be returned, the 
reason and final deposal will be documented. Device deficiencies and failure to function 
properly shall also be recorded in the subject's medical record. 
Device deficiencies are not adverse events. However, an adverse event that results from a 
device deficiency, would be recorded as an adverse event on the appropriate eCRF. 
17.6. Reporting to Regulatory Authorities / IRBs / ECs / Investigators 
BSC is responsible for reporting adverse event information to all participating Principal 
Investigators, IRBs/ECs and regulatory authorities, as applicable.  
The Principal Investigator is responsible for informing the IRB/EC, and regulatory 
authorities of UADEs and SAEs as required by Chinese regulations. 
BSC shall notify all participating study centers if SAEs/SADEs or Device Deficiencies occur 
which imply a possible increase in the anticipated risk of use of the device or if the 
occurrence of certain SAEs/SADEs demands changes to the protocol or the conduct of the 
study in order to further minimize the unanticipated risks. 

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For data collection retrospectively, BSC shall report all SAEs and device deficiencies that 
may lead to SAE to the regulatory authorities in Shanghai and Hainan within 10 working 
days within the events identified or collected, and shall notify ECs in a timely manner during 
data collecting. 
For data collection prospectively, BSC shall report all SAEs and device deficiencies that may 
lead to SAE to the regulatory authorities in Shanghai and Hainan within 5 working days upon 
receipt of such information, and shall notify investigators/investigation site and ECs in a 
timely manner. 
18. Informed Consent 
Subject participation in this clinical study is voluntary.  The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to study-required procedures and/or testing, 
or data collection for subjects enrolled prospectively. For subjects enrolled retrospectively, 
informed consent process of the protocol specified approved by EC will be followed. 
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and 
local Ethics Committee and/or Regulatory authority, as applicable. The ICF must be accepted 
by BSC or its delegate (e.g. CRO), and approved by the site’s IRB/EC, or central IRB, if 
applicable. 
Boston Scientific will provide a study-specific template of the ICF to investigators 
participating in this study. The ICF template may be modified to meet the requirements of the 
investigative site’s IRB/EC.  Any modification requires acceptance from BSC prior to use of 
the form.  The ICF must be in a language understandable to the subject and if needed, BSC 
will assist the site in obtaining a written consent translation. Translated consent forms must 
also have IRB/EC approval prior to their use.  Privacy language shall be included in the body 
of the form or as a separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations and guidelines: 
• be conducted by the Principal Investigator or designee authorized to conduct the process,  
• include a description of all aspects of the clinical study that are relevant to the subject’s 
decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing subjects throughout the 
clinical study.  

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The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the subject shall be asked to provide informed 
consent for continued participation as soon as his/her medical condition allows. The original 
signed ICF will be retained by the site and a copy of the signed and dated document and any 
other written information must be given to the person signing the form.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory 
authority according to their requirements. Any violations of the informed consent process 
must be reported as deviations to the sponsor and local regulatory authorities (e.g. IRB/EC), 
as appropriate. 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written form 
via a revised ICF or, in some situations, enrolled subjects may be requested to sign and date 
an addendum to the ICF. In addition to new significant information during the course of a 
study, other situations may necessitate revision of the ICF, such as if there are amendments 
to the applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB/EC. The new version of the ICF must be approved by 
the IRB/EC/REB. Acceptance by Boston Scientific is required if changes to the revised ICF 
are requested by the site’s IRB/EC. The IRB/EC will determine the subject population to be 
re-consented. 
19. Committees 
19.1. Safety Monitoring Process 
The BSC personnel from the Medical Safety and Safety Trial Operation group review safety 
data as it is reported by the sites throughout the duration of the study. During scheduled 
monitoring activities, clinical research monitors further support this review through their 
review of source documents and other data information. The BSC Medical Safety and Safety 
Trial Operations team include health care providers with expertise in urology, Radiation 
Oncology and with the necessary therapeutic and subject matter expertise to evaluate and 
classify the events into the categories outlined above. 
19.2.  Steering Committee 
A Steering Committee composed of the sponsor's Clinical Management and the 
study 
Coordinating Principal Investigator(s) may be convened. Responsibilities may 
include 
oversight of the overall conduct of the study with regard to protocol development, 
study 

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progress, subject safety, overall data quality and integrity as well as 
disseminating any study 
results through appropriate scientific sessions and publications. Steering 
Committee members 
may participate in the review and approval of all requests for data analysis, 
abstract and 
manuscript preparation, and submission.  
There are no Clinical Events Committee and Data Monitoring Committee in this study. 
20. Suspension or Termination 
20.1. Premature Termination of the Study 
Boston Scientific reserves the right to terminate the study at any stage but intends to exercise 
this right only for valid scientific or business reasons and reasons related to protection of 
subjects.  Investigators, associated IRBs/ECs, and regulatory authorities, as applicable, will 
be notified in writing in the event of study termination. 
20.1.1. Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the 
following: 
• Suspicion of an unacceptable risk, including serious health threat. In this case, the 
sponsor shall suspend the clinical investigation while the risk is assessed. The sponsor 
shall terminate the clinical investigation if an unacceptable risk which cannot be 
controlled is confirmed. 
• Instructions by the IRB/EC/REB or regulatory authorities to suspend or terminate the 
clinical investigation. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
20.2. Termination of Study Participation by the Investigator or Withdrawal of IRB/ 
EC Approval 
Any investigator, or associated IRB/EC or regulatory authority may discontinue participation 
in the study or withdraw approval of the study, respectively, with suitable written notice to 
Boston Scientific. Investigators, associated IRBs/ECs, and regulatory authorities, as 
applicable, will be notified in writing in the event of these occurrences. 
20.3. Requirements for Documentation and Subject Follow-up 
In the event of premature study termination, a written statement as to why the premature 
termination has occurred will be provided to all participating sites by Boston Scientific. The 

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IRB/EC/REB and regulatory authorities, as applicable, will be notified. Detailed information 
on how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB/EC terminates participation in the study, participating investigators, 
associated IRBs/ECs, and regulatory authorities, as applicable, will be notified in writing. 
Detailed information on how enrolled subjects will be managed thereafter will be provided 
by Boston Scientific. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 
to transfer Principal Investigator responsibility; detailed information on how enrolled 
subjects will be managed thereafter will be provided by Boston Scientific. 
The Principal Investigator or his/her designee must return all study-related documents and 
devices, if supplied by Boston Scientific, unless this action would jeopardize the rights, 
safety, or welfare of the subjects. 
20.4. Criteria for Suspending/Terminating a Study Site 
Boston Scientific reserves the right to stop the inclusion of subjects at a study site at any time 
after the study initiation visit if no subjects have been enrolled for a period beyond 6 months 
after site initiation. 
In the event of termination of site participation, The IRB/EC and regulatory authorities, as 
applicable, will be notified. Study participants will be contacted and followed, as applicable. 
21. Study Registration and Results 
21.1. Study Registration 
To comply with applicable laws and regulations, the study will be registered on a publicly 
accessible database. 
21.2. Clinical Investigation Report 
Study results will be made available in accordance with the legal requirements and the 
recognized ethical principles, in accordance with the Boston Scientific Policy. A Clinical 
Investigation Report will be made available to all investigators, IRB/EC and regulatory 
authorities, as applicable in accordance with the Boston Scientific Policy and local 
requirements.  As applicable an abbreviated Clinical Investigation Report will be made 
available on a publicly accessible database. 
 
21.3. Publication Policy 
BSC requires disclosure of its involvement as a sponsor or financial supporter in any 
publication or presentation relating to a BSC study or its results. BSC may submit study 
results for publication (regardless of study outcome) following the conclusion or termination 
of the study. Boston Scientific adheres to the Contributorship Criteria set forth in the 

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Uniform Requirements of the International Committee of Medical Journal Editors (ICMJE; 
http://www.icmje.org). In order to ensure the public disclosure of study results in a timely 
manner, while maintaining an unbiased presentation of study outcomes, BSC personnel may 
assist authors and investigators in publication preparation provided the following guidelines 
are followed:  
• All authorship and contributorship requirements as described above must be followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy should 
be discussed with the Coordinating Principal Investigator(s) and/or Executive/Steering 
Committee at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  
The data, analytic methods, and study materials for this clinical trial may be made available 
to other researchers in accordance with the Boston Scientific Data Sharing Policy 
(https://www.bostonscientific.com/en-US/data-sharing-requests.html)  
22. Reimbursement and Compensation for Subjects 
22.1. Subject Reimbursement 
Travel and other expenses incurred by subjects because of participation in the study will be 
reimbursed in accordance with pertinent country laws and regulations and per the study site’s 
regulations (only for subjects with ICF signed and dated). 
22.2. Compensation for Subject’s Health Injury 
Boston Scientific will purchase an insurance policy to cover the cost of potential health 
injury for study subjects, if required by applicable law.  
 
 

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23. Bibliography 
1. Cooperberg MR et al. Time Trends and Local Variation in Primary Treatment of Localized 
Prostate Cancer. J Clinical Oncology: 2010; 28: 1117-1123.  
2. http://seer.cancer.gov/statfacts/html/prost.html, accessed on September 25, 2014  
3. 前列腺癌诊疗规范，2018版》 
4. 顾秀瑛, 郑荣寿, 张思维, 等.  2000—2014年中国肿瘤登记地区前列腺癌发病趋势及
年龄变化分析 [J]. 中华预防医学杂志,2018,52( 6 ): 586-592. 
5. Cancer Institute website at http://www.cancer.gov/cancertopics/types/prostate accessed 
January 11, 2011.  
6. NCCN Guidelines for Prostate Cancer: 2010  
7. Bucci MK, Bevan A, Roach M. Advances in radiation therapy: Conventional to 3D, to 
IMRT, to 4D, and beyond. CA Cancer J Clin 2005; 55:117-134.  
8. Lesperance RN, Kjorstadt RJ, Halligan JG, Steele SR., Colorectal complications of 
external beam radiation versus brachytherapy for prostate cancer. Am J. Surg 
2008;195:616-20.  
9. Michalski JM, Gay H, Jackson A et al. Radiation dose-volume effects in radiation-induced 
rectal injury. Int. J. Radiation Oncology Biol. Phys., 2010;76:A123-129.  
10. Schultheiss TE; Lee WR; Hunt MA; Hanlon AL; Peter RS; Hanks GE; Late GI and GU 
complications in the treatment of prostate cancer. Int J Radiat Oncol Biol Phys 1997;37:3-
11.  
11. Huang EH, Pollack A, Levy L, et al. Late rectal toxicity: dose-volume effects of conformal 
radiotherapy for prostate cancer. IJROBP 2002; 54:1314-1321.  
12. Gilinsky NH; Burns DG; Barbezat GO; Levin W; Myers HS; Marks IN; The natural 
history of radiation-induced proctosigmoiditis: an analysis of 88 patients. Q J Med 
1983;52:40-53.  
13. Heemsbergen WD, Peeters ST, Loper PC, et al. Acute and late gastrointestinal toxicity 
after radiotherapy in prostate cancer patients: Consequential late damage. Int J Radiat 
Oncol Biol Phys 2006;66:3-10  
14. Pinkawa M, Holy R, Piroth MD et al. Consequential late effects after radiotherapy for 
prostate cancer-a prospective longitudinal quality of life study. Radiation Oncology 
2010,5:27  
15. Nguyen PL, Chen RC, Hoffman KE et al. Rectal dose-volume histogram parameters are 
associated with long-term patient-reported gastrointestinal quality of life after 
conventional and high-dose radiation for prostate cancer: A subgroup analysis of a 
randomized trial. Int J Radiation Oncology Bio Phys 2010;78:1081-1085.  
16. Vargas C, Martinez A, Kestin LL, Yan D, Grills I, Brabbins DS, et al. Dose-volume 
analysis of predictors for chronic rectal toxicity after treatment of prostate cancer with 
adaptive image guided radiotherapy. Int J Radiat Oncol Biol Phys 2005;62:1297–308  
17. Fiorino C, Cozzarini C, Vavassori V, et al. Relationships between DVHs and late rectal 
bleeding after radiotherapy for prostate cancer: Analysis of a large group of patients 
pooled from three institutions. Radiother Oncol 2002;64:1–12.  

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18. Peeters ST, Lebesque JV, Heemsbergen WD, et al. Localized volume effects for late rectal 
and anal toxicity after radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 
2006;64:1151–1161.  
19. Liauw SL, Weichselbaum RR, Rash C, Correa D, Al-Hallaq HA, Pelizzari CA, Jani AB. 
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24. Abbreviations and Definitions  
24.1. Abbreviations 
Abbreviations are shown inTable 24-1.   
Table 24-1: Abbreviations 
Abbreviation/Acronym 
Term 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CT 
Computed Tomography 
DVH 
Dose Volume Histogram 
EBRT 
External beam radiation therapy 
eCRF 
electronical Case Report Form 
EDC 
Electronic data capture 
EPIC 
The Expanded Prostate Cancer Index Composite 
FDA 
Food and drug administration 
GCP 
Good clinical practice  
ICF 
Informed consent form 
ICH 
International Conference on Harmonization  
IGRT 
Image Guided Radiotherapy 
IMRT 
Intensity Modulated Radiation Therapy 
LCI 
Lower Confidence Interval 
MRI 
Magnetic Resonance Imaging 
NCI 
National Cancer Institute 
PEG 
polyethylene glycol 
PSA 
Prostate-specific antigen 
QoL 
Quality of life 
RT 
Radiation therapy 
CTCAE 
Common Terminology Criteria for Adverse Events  
SAE 
Serious adverse event  
UADE 
Unanticipated adverse device effect 
USADE 
Unanticipated serious adverse device effect