A Real Word Study to Evaluate the Safety and Performance of SpaceOAR System When Used to Create Space Between the Rectum and Prostate in Men Undergoing Radiotherapy for Localized T1-T2 Prostate Cancer in China
Phase: NA
Conditions: Localized T1-T2 Prostate Cancer
Sponsor: Boston Scientific Corporation

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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. 
Medical Device Clinical Trial Protocol 
 
Reference Number：U0720 
 
Protocol Title：A real word study to Evaluate the safety and 
performance of SpaceOAR System when used to create space 
between the rectum and prostate in men undergoing 
radiotherapy for localized T1-T2 prostate cancer in China 
（SpaceOAR System RWS） 
 
 
Investigational Device 
SpaceOAR System 
SO-2101/10ml 
Class of device 
Class 3 medical device requiring clinical trials 
Yes□ No☒ 
Same class device within China 
Yes□ No☒ 
Protocol version and 
date 
Ver.A，Oct 12，2021 
Clinical trial sites 
Boao Yiling Life Care Center 
Principal Investigator 
Han Sujun 
Sponsor 
BSC International Medical Trading (Shanghai) 
Co., Ltd, (“BSC China”) 
 
 
 

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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. 
 
 
 
A real word study to Evaluate the safety and performance of 
SpaceOAR System when used to create space between the rectum 
and prostate in men undergoing radiotherapy for localized T1-T2 
prostate cancer in China 
SpaceOAR System RWS 
 
U0720 
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 
 
 
 
 
 
 
 
 
 
 

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Contact Information 
 
Role 
Contact 
Clinical Contact 
BAI Junyang, 
Clinical Trial Manager 
Boston Scientific China 
Part A, 2nd Floor, No.68, Rijing Road, 
Free Trade Zone, 
Shanghai, China 200131 
E-mail: junyang.bai@bsci.com 
Mobile:+86 13671646036 
Tel:+86 21 80317411 
Meidical Writer 
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(s) 
HAN Sujun 
Associate Chief physician 
Boao Yiling Life Care Center 
No.13 Hainan Boao Lecheng International Medical Tourism Pilot 
Zone, Qiong Hai, Hainan, P.R .China 

 
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Original Release: Oct 12,2021 
Current Version: Oct 12,2021 
 
 
 
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2. Protocol Synopsis 
 
A real word study to Evaluate the safety and performance of SpaceOAR System 
when used to create space between the rectum and prostate in men undergoing 
radiotherapy for localized T1-T2 prostate cancer in China 
SpaceOAR System RWS 
Study Objective(s) This study aims to evaluate the safety and performance of SpaceOAR System 
when it is used to create space between the rectum and prostate in men 
undergoing radiotherapy for localized T1-T2 prostate cancer in China via 
collecting the real word data of SpaceOAR System used, to generate local 
clinical evidence on Chinese patients. 
Indication(s) for 
Use 
SpaceOAR System is intended to temporarily position the anterior rectal wall 
away from the prostate during radiotherapy for prostate cancer and in creating 
this space it is the intent of SpaceOAR System to reduce the radiation dose 
delivered to the anterior rectum. 
The SpaceOAR System is composed of biodegradable material and maintains 
space for the entire course of prostate radiotherapy treatment and is completely 
absorbed by the patient’s body over time. 
Study Design 
This study is a retrospective and prospective, single arm, real world study. For 
those patients who have already received the SpaceOAR treatment before study 
kick-off, the data at baseline and the day of procedure will be retrospectively 
collected. For those patients who will receive SpaceOAR treatment after study 
kick-off, the clinical data at baseline, the day of procedure and 30 days post 
procedure will be prospectively collected. 

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Collecting data prospectively 
Collecting data retrospectively 
A real word study to Evaluate the safety and performance of SpaceOAR System 
when used to create space between the rectum and prostate in men undergoing 
radiotherapy for localized T1-T2 prostate cancer in China 
SpaceOAR System RWS 
Baseline- Clinical diagnosis 
and staging 、 Gleason 
score、CT&MRI* etc. 
Procedure-Injection of 
SpaceOAR Hydrogel 
Subject with Pca T1-T2 
Post procedure-CT&MRI# 
Informed consent 
Study 
Follow up at 30days post 
Kick-off 
Before procedure-CT&MRI* 
procedure： 
• 
Assessing and Collecting 
Procedure-Injection of 
AE (If any) 
SpaceOAR Hydrogel 
Post procedure-CT&MRI# 
Follow up via phone at 30days 
post procedure： 
Note: * MRI completed at 30 days before procedure 
• 
Assessing and Collecting 
in other hospital will be allowed 
#MRI completed at 10 days post procedure in 
AE (If any) 
other hospital will be allowed. 
SpaceOAR System RWS Design 
Planned Number 
of Subjects 
Up to 20 subjects with a pathologically confirmed diagnosis of clinical stage T1 
or T2 prostate cancer indicated for radiotherapy will be enrolled, for there are 
chances of missing data in the real world study. A sample of 14 subjects provides 
at least 90% power for the primary objective. 
Planned Number 
of Sites 
1 site, 
Boao Yiling Life Care Center in Hainan BOAO medical tourism pilot zone 
Primary Endpoint Primary Effectiveness Endpoint 
 

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A real word study to Evaluate the safety and performance of SpaceOAR System 
when used to create space between the rectum and prostate in men undergoing 
radiotherapy for localized T1-T2 prostate cancer in China 
SpaceOAR System RWS 
The distance between the posterior prostatic capsule and anterior rectal wall 
post SpaceOAR hydrogel administration. 
Measurement: The distance between the posterior prostatic capsule and 
anterior rectal wall is measured on the axial image slice closest to halfway 
between apex and base, from posterior edge of prostate to inner rectal wall 
via MRI. 
Primary Safety Endpoint 
AEs related to SpaceOAR system and/or procedure within 30 days following 
procedure will be observed. 
Secondary 
Endpoint 
Functional Success 
Defined as creation of at least 7.5mm space between the posterior prostatic 
capsule and anterior rectum wall as assessed via comparative pre and post 
SpaceOAR hydrogel injection MRI scans. 
Follow-up 
Schedule 
Retrospective cohort: For those patients who had been injected with SpaceOAR 
hydrogel before study kick-off, relevent clinical data at baseline and the day of 
procedure will be collected retrospectively, any AE at 30 days post procedure 
will be collected, if applicable. 
Prospective cohort: For those patients who will be injected with SpaceOAR 
hydrogel, informed consent forms will be gained prospectively, then relevent 
data will be collected, follow up at 30 days will be conducted to assess any AEs. 
Study Duration 
The total study duration is estimated to be approximately 3months. 
Participant 
Duration 
The study duration for each subject is expected to be approximately 40 days. 
Inclusion Criteria 
• Subjects has provided the written informed consent, willing to participate 
in clinical data collection and willing to receive visit at 30 days post 
procedure. (for subjects enrolled prospectively) 
• Subjects must have been pathologically confirmed prostate cancer with 
clinical stage T1-T2, and have been treated or will be treated with Space 
OAR Hydrogel in hospital in Hainan Boao Lecheng medical pilot zone. 

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A real word study to Evaluate the safety and performance of SpaceOAR System 
when used to create space between the rectum and prostate in men undergoing 
radiotherapy for localized T1-T2 prostate cancer in China 
SpaceOAR System RWS 
Exclusion Criteria This is a real world study, all patients who have received or are going to receive 
SpaceOAR procedure in Boao Medical Pilot Zone will be enrolled in this study. 
There is no specific exclusion criteria unless the patients refuse to sign the 
informed consent. 
Statistical Methods 
Primary 
Statistical 
Hypothesis 
This is a retrospective and prospective, single arm study with a performance goal 
approach for the primary effectiveness endpoint. The primary effectiveness 
endpoint is the distance between the posterior prostatic capsule and anterior rectal 
wall post SpaceOAR hydrogel administration. As this is real word study with less 
strict I/E criteria, the performance goal was set as 7.5mm, based on the rationales 
in the SpaceOAR EU pilot study, in which the creation of at least a 7.5mm space 
criterion was developed in consult with Augmenix’s Scientific Advisory Board (a 
panel that consists of board-certified radiation oncologists).   If the two-sided 
95% Lower Confidence Interval (LCI) of distance calculated is greater than PG, 
the study primary effectiveness endpoint will be met. 
Statistical Test 
Method 
Descriptive statistics will be used to summarize the study endpoints, such as 
distance between the posterior prostatic capsule and anterior rectal wall post 
SpaceOAR hydrogel administration, functional success. 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. 
This study may allow explorative statistics based on collected data, including but 
not limited to: risk factors associated with functional failure. 
There is no formal interim analysis, but a descriptive summary will be made 
during the study, if needed. 
Sample Size 
Parameters 
The distance was 12.58±3.88mm (N=147) in the Space OAR hydrogel pivotal 
study in USA (IDE study), and it was 15.5±5.7mm (N=48) in pilot study in EU. 
For the sample size estimation, a distance between prostate and rectum of 13 mm 
is expected with a standard deviation of 5.7 mm. 
The sample size is calculated according to below formula: 
 

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A real word study to Evaluate the safety and performance of SpaceOAR System 
when used to create space between the rectum and prostate in men undergoing 
radiotherapy for localized T1-T2 prostate cancer in China 
SpaceOAR System RWS 
n is sample size, PG is assumed as 7.5mm, 13mm is expected distance between 
prostate and rectum, δ = 5.5 mm, σ =5.7 mm, α=0.025, β=0.1（power=90% 
）. Therefore, a sample size of 14 subjects will provide more than 90% power. 
To account for potential missing data in this retrospective and prospective study, 
a final sample size will be up to 20 subjects. 

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3. Table of Contents 
1. 
TITLE PAGE ....................................................................................................................................................... 1 
2. 
PROTOCOL SYNOPSIS ..................................................................................................................................... 5 
3. 
TABLE OF CONTENTS ...................................................................................................................................10 
3.1. Table of Figures ......................................................................................................13 
3.2. Table of Tables ........................................................................................................14 
4. 
INTRODUCTION ...............................................................................................................................................15 
4.1. Background .............................................................................................................15 
4.2. Study Rationale .......................................................................................................18 
5. 
DEVICE DESCRIPTION ..................................................................................................................................18 
5.1. Commercial Device Under Study ...........................................................................18 
5.2. Principle of spaceOAR systerm ..............................................................................19 
5.3. Indication(s) for Use ...............................................................................................19 
5.4. Required Medical Equipment .................................................................................20 
5.5. Relevant Medications ..............................................................................................20 
6. 
STUDY OBJECTIVES AND ENDPOINTS .....................................................................................................20 
6.1. Study Objectives .....................................................................................................20 
6.2. Study endpoints .......................................................................................................20 
7. 
STUDY DESIGN ...............................................................................................................................................21 
7.1. Scale and Duration ..................................................................................................21 
7.2. Treatment Assignment ............................................................................................22 
7.3. Justification for the Study Design ...........................................................................22 
7.4. Method to reduce biases ..........................................................................................22 
8. 
SUBJECT SELECTION ....................................................................................................................................22 
8.1. Study Population and Eligibility .............................................................................22 

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8.2. Inclusion Criteria .....................................................................................................22 
8.3. Exclusion Criteria ....................................................................................................22 
9. 
SUBJECT ACCOUNTABILITY .......................................................................................................................23 
9.1. Point of Enrollment .................................................................................................23 
9.2. Withdrawal ..............................................................................................................23 
9.3. Lost to Follow-Up ...................................................................................................23 
9.4. End-of-Study Definition ..........................................................................................23 
9.5. End of Study Action Plan ........................................................................................23 
10. STUDY METHODS ..........................................................................................................................................24 
10.1. Data Collection ........................................................................................................24 
10.2. Study Candidate Screening .....................................................................................25 
10.3. Informed Consent ....................................................................................................25 
10.4. study visits ...............................................................................................................25 
10.5. Study Completion ....................................................................................................26 
10.6. Source Documents ..................................................................................................26 
11. STATISTICAL CONSIDERATIONS ...............................................................................................................27 
11.1. Endpoints.................................................................................................................27 
11.2. General Statistical Methods ....................................................................................27 
11.3. Data Analyses ..........................................................................................................28 
12. DATA MANAGEMENT ...................................................................................................................................28 
12.1. Data Collection, Processing, and Review ...............................................................28 
12.2. Data Retention .........................................................................................................29 
13. AMENDMENT ..................................................................................................................................................29 
14. DEVIATIONS ....................................................................................................................................................29 
15. COMPLIANCE ..................................................................................................................................................30 

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15.1. Statement of Compliance ........................................................................................30 
15.2. Investigator Responsibilities ...................................................................................30 
15.3. Ethics Committee ....................................................................................................32 
15.4. Sponsor Responsibilities .........................................................................................33 
15.5. Insurance .................................................................................................................34 
16. MONITORING ..................................................................................................................................................34 
17. POTENTIAL RISKS AND BENEFITS ............................................................................................................34 
17.1. Anticipated Adverse Events and Anticipated Adverse Device Effects ...................34 
17.2. Risks associated with Participation in the Clinical Study .......................................35 
17.3. Risk Minimization Actions .....................................................................................35 
17.4. Anticipated Benefits ................................................................................................35 
17.5. Risk to Benefit Rationale ........................................................................................35 
18. SAFETY REPORTING .....................................................................................................................................36 
18.1. Reportable Events by investigational site to Boston Scientific ..............................36 
18.2. Definitions and Classification .................................................................................36 
18.3. Relationship to Study Device(s)(Device Under ) and/or Study Procedure .............39 
18.4. Investigator Reporting Requirements .....................................................................41 
18.5. Device Deficiencies ................................................................................................43 
18.6. Reporting to Regulatory Authorities  ECs / Investigators ......................................43 
19. INFORMED CONSENT ....................................................................................................................................44 
20. COMMITTEES ..................................................................................................................................................45 
20.1. Safety Monitoring Process ......................................................................................45 
20.2. Steering Committee .................................................................................................45 
21. SUSPENSION OR TERMINATION .................................................................................................................45 
22.1 Premature Termination of the Study .......................................................................45 

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22.2 Termination of Study Participation by the Investigator or Withdrawal of EC 
Approval ..................................................................................................................46 
22.3 Requirements for Documentation and Subject Follow-up ......................................46 
22.4 Criteria for Suspending/Terminating a Study Site ..................................................46 
22. STUDY REGISTRATION AND RESULTS ....................................................................................................47 
22.1. Study Registration ...................................................................................................47 
22.2. Clinical Investigation Report ..................................................................................47 
22.3. Publication Policy ...................................................................................................47 
23. REIMBURSEMENT AND COMPENSATION FOR SUBJECTS ...................................................................48 
23.1. Subject Reimbursement ..........................................................................................48 
23.2. Compensation for Subject’s Health Injury ..............................................................48 
24. BIBLIOGRAPHY ...............................................................................................................................................49 
25. ABBREVIATIONS AND DEFINITIONS ........................................................................................................52 
25.1. Abbreviations ..........................................................................................................52 
 
 
 
3.1. Table of Figures 
 
Figure 5-1 SpaceOAR System Components ........................................................................... 19 
Figure 5-2 SpaceOAR delivery system prior to needle attachment ........................................ 19 
Figure 7-1 SpaceOAR System RWS  Design ......................................................................... 21 

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3.2. Table of Tables 
Table 10-1:Data Collection Schedule ..................................................................................... 24 
Table 18-1: Safety Definitions ................................................................................................ 37 
Table 18-2: Criteria for Assessing Relationship of Study Device(s) (Device Under Study) or 
Procedure to Adverse Event ................................................................................ 40 
Table 18-3: Investigator Reporting Requirements .................................................................. 42 
Table 25-1: Abbreviations ...................................................................................................... 52 

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4. Introduction 
4.1. Background 
 
Prostate cancer is one of the most commonly 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 injury caused by direct mucosal damage from ionizing radiation. Since most prostate 
cancers arise in the peripheral zone (PZ) of the gland including that portion adjacent to the 
rectum, the radiation oncologist must expose the rectum to high levels of radiation if the 
tumor is to be effectively treated8. However, rectal mucosa has high radio-sensitivity due to 
rapid cell turnover characteristic of mucosal membranes and, therefore, these tissues are very 
susceptible to injury resulting in what has been referred to as radiation proctitis. It is for this 
reason that radiation oncologists refer to the rectum as the dose-limiting structure in prostate 
cancer radiotherapy. 
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 bleeding9. Occasionally, superficial ulceration causes 
bleeding that may require endoscopic cauterization or medical therapy for anemia including 
transfusion9,10. 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 

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ischemia11,12. 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 exposure11, 13. 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 complications9,10,14,15. Indeed, in an analysis performed by Zelefsky et al. 
the incidence of late GI toxicity in those patients who experienced acute GI toxicity was 
substantially and significantly greater than those that had not experienced acute GI toxicity 
(42% vs. 9% respectively, p<0.0001)16. 
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 
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%, respectively16,22. 
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 toxicity12,17-21. 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 Gy12. Other rectal dose metrics have also been qualified as a risk factor for late 
gastrointestinal symptoms. In particular, for RT prescriptions of 78 Gy or more, higher 
values for rV40Gy through rV60Gy have been associated with a greater incidence of adverse 
gastrointestinal reactions, demonstrating the importance of limiting the volume of rectum 
receiving lower and mid-range doses23. 
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 life15. 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 bleeding24. 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 
evaluated25. 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 

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bowel quality of life (QOL)26 and early quality of life has been reported to be a strong 
predictor of later QOL27. 
Based upon the above review, technologies that can minimize rectal exposure to incidental 
radiation would represent an important tool in modern EBRT therapy. Current technologies 
that have been employed to attain this goal, as described in the literature, include 
administration of space-creating absorbable solutions (i.e., hyaluronic acid, collagen and 
saline) and application of endorectal balloons28-33. Ideally, a technique that may have been 
administered once and be effective throughout the course of radiotherapy treatment would be 
preferred. 
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. 
The SpaceOAR System has been marketed in Australia, Canada, Japan, Europe and USA. A 
pilot study of SpaceOAR System in Europe enrolled 52 subjects. The objective of the Pilot 
Study was to evaluate the initial safety and effectiveness of SpaceOAR System when it is 
injected between the rectum and prostate in adult men undergoing external beam radiation 
therapy for treatment of low-to-mid risk prostate cancer. The space creation effect of 
SpaceOAR hydrogel was assessed via co-primary effectiveness endpoints. Analysis of the 
endpoints for the Per Protocol Population showed that34, Functional Success, defined as the 
creation of at least 7.5 mm space between the prostate (Mid-gland) and rectum measured on 
CT or MRI, was achieved in 46 of 48 subjects (95.8%). Clinical Success, defined as 
reduction in radiation dose to the anterior rectum as measured by a 25% or greater reduction 
in rV70 (i.e., the percent volume of the rectum receiving at least 70 Gy) was achieved in 44 
of 46 subjects (95.7%). There were no unanticipated adverse events associated with the 
SpaceOAR System procedure or the SpaceOAR hydrogel. These results from the Pilot Study 
established initial safety and performance for use of the SpaceOAR System as a means to 
physically separate the rectum from the prostate and reduce the rectal radiation dose. 
The pivotal study of SpaceOAR System in USA aimed to evaluate the safety and 
effectiveness of the SpaceOAR System when it is used in patients with a pathologically 
confirmed diagnosis of clinical stage T1 or T2 prostate cancer who were indicated for a 
course of IMRT. 222 eligible subjects were enrolled and were randomized (2:1) to the 
Treatment group (SpaceOAR System) or Control group after successful fiducial marker 
placement. The study showed that hydrogel placement success rate was 99%; Perirectal 
spaces were 12.6 ±3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. 
There were no device-related adverse events, rectal perforations, serious bleeding, or 
infections within either group. The reduction of rectal V70 in treatment group was 
significantly more than control group (12.4% to 3.3%, P<.0001). Overall acute rectal adverse 
event rates were similar between groups, with fewer spacer patients experiencing rectal pain. 

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Late (3-15 months) rectal toxicity were 2.0%,7.0% in treatment group and control group, 
with a significant reduction and with no late rectal toxicity greater than grade 1 in treatment 
group35. The 3-year incidence of grade ＞1 rectal toxicity were 9.2% , 2.0% in control group 
and treatment group respectively(P=.028), and the 3-year incidence of grade ＞2 rectal 
toxicity were 5.7%, 0% in control group and treatment group respectively(P=.012)36. 
4.2. Study Rationale 
 
Prostate cancer occurs mainly in elderly, and occurs rare in men less than 40, the morbidity 
increase slowly in men more than 40 years old. With the long life expectancy and application 
of PSA test, the morbidity of prostate cancer increase yearly, the amount of prostate cancar 
should not be underestimated considering the large population and aging in China. Treatment 
for prostate cancer varies according to tumor clincal stage,Gleason score etc, external beam 
radiotherapy is recommended for localized prostate cancer, which long term effectiveness is 
comparable to surgical resection. Although IGMT could reduce radiation exposure to normal 
tissues, but damage to the rectum is still inevitable. 
The SpaceOAR System is used to displace the rectum away from the prostate during prostate 
radiotherapy to reduce rectal wall/mucosa radiation exposure, then redurce the rectal damage. 
This medical device has been marketed in US, Europe and many other countries , and its 
safety and effectiveness been confirmed in the previous studies in radiotherapy for prostate 
cancer, it can increase the distance from the rectum to prostate and reduction in radiation 
dose to the anterior rectum was 25% at least. 
The SpaceOAR System is an advanced mecial device, there is no similar device in China. In 
accordance with the policy on licensed medical devices, SpaceOAR has been applied for 
clinical use as a licensed medical device in The Boao Lecang Medical Pilot Zone in Hainan. 
This study is based on clicnial use of SpaceOAR System in real world, will collect clincial 
data related to spacerOAR in patients who has been or will be treated with spceOAR 
retrospectively and prospectively, in order to generate the clinical data in China. This study 
will evaluate the safety and performance of SpaceOAR Hydrogel System, then support its 
widespread use in China. 
 
5. Device Description 
5.1. Commercial Device Under Study 
 
The SpaceOAR System consists of components for the preparation of a synthetic, absorbable 
hydrogel spacer and a delivery system package for single use. 
The SpaceOAR system is sterile provided, SO-2101/10ml is provided. Components and label 
are shown in Figure 5-1 , The assembled delivery system prior to needle attachment is shown 
in Figure 5-2. 

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Figure 5-1 SpaceOAR System 
Components 
Figure 5-2 SpaceOAR delivery system prior 
to needle attachment 
 
5.2. 
Principle of spaceOAR systerm 
 
The SpaceOAR System consists of components for preparation of a synthetic, absorbable 
hydrogel spacer and a delivery system packaged for single use. The in situ formed hydrogel 
spacer creates a temporary space between the prostate and rectum during radiation therapy. 
The spacer is formed by mixing two solutions, the Precursor and the Accelerator. The 
Precursor solution is formed through the mixing of the Diluent solution (Trilysine buffer 
solution) with the PEG powder. The Accelerator solution is a salt buffer solution. When 
mixed together, the solutions cross-link to form a soft hydrogel. The mixing of the solutions 
is accomplished as the materials pass through a static mixer in the Y-Connector prior to 
passing through the injection needle. The SpaceOAR hydrogel implant is MR Safe. 
The hydrogel spacer maintains space for approximately 3 months and is absorbed in about 6 
months, sufficient time to support the intended use. 
 
5.3. Indication(s) for Use 
 
SpaceOAR System is intended to temporarily position the anterior rectal wall away from the 
prostate during radiotherapy for prostate cancer and in creating this space it is the intent of 
SpaceOAR System to reduce the radiation dose delivered to the anterior rectum. 

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The SpaceOAR System is composed of biodegradable material and maintains space for the 
entire course of prostate radiotherapy treatment and is completely absorbed by the patient’s 
body over time. 
 
5.4. Required Medical Equipment 
 
For the SpaceOAR System injection procedure, a real time bi-plane transrectal ultrasound 
(TRUS) and a stepper are required to provide clear, contortion-free images. 
 
5.5. Relevant Medications 
 
The adminstration of prophylactic antibiotics depends on clincial practice in investigation 
site and the patient's condition, which is at discretion of the doctors. 
 
6. Study Objectives and Endpoints 
6.1. Study Objectives 
 
This study aims to evaluate the safety and performance of SpaceOAR System when it is 
used to create space between the rectum and prostate in men undergoing radiotherapy for 
localized T1-T2 prostate cancer in China via collecting the real word data of SpaceOAR 
System used, to generate local clinical evidence on Chinese patients. 
 
6.2. Study endpoints 
 
6.2.1 Primary endpoint 
 
6.2.1.1 Primary effectiveness endpoint 
The distance between the posterior prostatic capsule and anterior rectal wall post SpaceOAR 
hydrogel administration. 
Measurement: The distance between the posterior prostatic capsule and anterior rectal wall is 
measured on the axial image slice closest to halfway between apex and base, from posterior 
edge of prostate to inner rectal wall via MRI. 
6.2.1.2 Primary safety endpoint 
AEs related to SpaceOAR system and/or procedure within 30 days following procedure will 
be observed. 
 
6.2.2 Second endpoints 
 
Functional Success 
Defined as creation of at least 7.5mm space between the posterior prostatic capsule and 
anterior rectum wall as assessed via comparative pre and post SpaceOAR hydrogel injection 
MRI scans. 

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Follow up at 30days post 
procedure： 
• 
Assessing and Collecting 
AE (If any) 
Study Kick- 
off 
7. Study Design 
This study is a retrospective and prospective, single arm, real world study. For those patients 
who have already received the SpaceOAR treatment before study kick-off, the data at 
baseline and the day of procedure will be retrospectively collected. For those patients who 
will receive SpaceOAR treatment after study kick-off, the clinical data at baseline, the day of 
procedure and 30 days post procedure will be prospectively collected. 
All administration of SpaceOAR hydrogel will be performed by trained urologists in the 
hospital in Boao. 
 
 
 
 
 
 
 
 
 
   Subject with Pca T1-T2 
 
 
   Informed consent 
 
 
 
 
 
 
 
 
 
 
 
Note: 
* MRI completed at 30 days before procedure in other 
hospital will be allowed 
#MRI completed at 10 days post procedure in other hospital 
will be allowed. 
 
 
Figure 7-1 SpaceOAR System RWS Design 
 
7.1. Scale and Duration 
 
Up to 20 subjects with a pathologically confirmed diagnosis of clinical stage T1 or T2 
prostate cancer indicated for radiotherapy will be enrolled in this study. This study is based 
on the use of licenced medical device in Hainan BOAO medical tourism pilot zone, the 
enrollment rate may be slow due to limited patients. The enrollment and 30 days follow up 
are expected to completed in 3 months. 
Collecting data prospectively 
Collecting data retrospectively 
Baseline- Clinical diagnosis 
and staging、Gleason score 
* 
、CT&MRI etc. 
Procedure-Injection of 
SpaceOAR Hydrogel 
# 
Post procedure-CT&MRI 
* 
Before procedure-CT&MRI 
Procedure-Injection of 
SpaceOAR Hydrogel 
# 
Post procedure-CT&MRI 
Follow up via phone at 
30days post procedure： 
• 
Assessing and Collecting 
AE (If any) 

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7.2. Treatment Assignment 
 
This is a single arm study without treatment assignment. All subjects will receive injection of 
SpaceOAR hydrogel at the hospital in Hainan BOAO medical tourism pilot zone. 
 
7.3. Justification for the Study Design 
 
SpaceOAR system has received CE Mark in 2010 and FDA approval in April 2015 
respectively, and it is saled in many countries and regions with good safety and effectiveness. 
The pivotal study was a randomized control study, which provided a high level of evidence 
to verify its safety and effectiveness fully. This study aims to generate local clinical evidence 
on Chinese patients via collecting clincia data related to spacerOAR, which is based on the 
use of licenced medical device in Hainan BOAO medical tourism pilot zone. Due to limited 
patient in BOAO, the subjects will be enrolled prospectively and retrospectively, whose data 
will be collected. 
 
7.4. Method to reduce biases 
 
In order to reduce bias of the measurement of the distance between the posterior prostatic 
capsule and anterior rectal, MRI before and post procedure are suggested to be completed in 
same hospital. 
 
8. Subject Selection 
8.1. Study Population and Eligibility 
 
The target population are Patients who have been pathologically confirmed prostate cancer 
with clinical stage T1-T2, and are appropriate for radiotherapy, and have been treated or will 
be treated with SpaceOAR Hydrogel in hospital in Hainan Boao Lecheng medical pilot zone. 
 
8.2. Inclusion Criteria 
 
Subjects who meet all of the following criteria may be given consideration for inclusion in 
this clinical investigation, provided no exclusion criterion is met. 
• 
Subjects has provided the written informed consent, willing to participate in clinical 
data collection and willing to receive visit at 30 days post procedure. (for subjects 
enrolled prospectively) 
• 
Subjects must have been pathologically confirmed prostate cancer with clinical stage 
T1-T2, and have been treated or will be treated with Space OAR Hydrogel in hospital 
in Hainan Boao Lecheng medical pilot zone. 
 
8.3. Exclusion Criteria 
 
This is a real world study, all patients who have received or are going to receive SpaceOAR 
procedure in Boao Medical Pilot Zone will be enrolled in this study. There is no specific 
exclusion criteria unless the patients refuse to sign the informed consent. 

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The indication and health status of subjects are assessed strictly by doctors before use of 
licenced medical device. 
 
9. Subject Accountability 
9.1. Point of Enrollment 
 
For patients who have already received the SpaceOAR treatment, the clinical data can be 
collected retrospectively when he meets the inclusion criteria and the procedure recored is 
complete in reviewing medical recoreds. For patients who will receive the SpaceOAR 
treatment, informed consent will be performed. 
 
9.2. 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. If such withdrawal is due to problems related to device safety 
or performance, the investigator shall ask for the subject’s permission to follow his/her 
status/condition outside of the clinical study. The applicable CRF, including the study end 
form, shall be completed by the time of subject withdrawal.(only for patients enrolled 
porspectively) 
 
9.3. 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 porspectively) 
 
9.4. 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. 
 
9.5. End of Study Action Plan 
 
A subject completes the study when he has recerived spaceOAR treatment and recerived 30 
days follow up vist. In light of first use of the spaceOAR in Chinese patients, it is 
recommended that subjects could participate in the observational study after the injection of 
spcaceOAR, which is following part of this real word study. 

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10. Study Methods 
10.1. Data Collection 
 
The data collection schedule is shown in table 10-1 . 
Table 10-1:Data Collection Schedule 
 
Procedure/Assessment 
Before 
procedure 
Procedure 
Post 
pocedure 
30 days post 
procedure 
（±7days） 
Informed conscent# 
X 
Demographics 
X 
Physical assessment, including 
weight and height 
X 
Clinical diagnosis and clicnial stage 
of turmor、Gleason score 
X 
Medical history（Gerenal disease, 
genitourinary history / treatment 
history ） 
X 
Questionnaires (IPSS, EPIC, QoL) 
X 
Administration of SpaceOAR 
X 
PSA 
X 
CT&MRI* 
X 
X 
Concomitant medication 
X 
X 
Adverse event 
X 
X 
X 
Device Deficiency 
X 
X 
X 
PD# 
X 
X 
X 
X 
Note:# only for patients enrolled prospectively； 
*MRIs conducted in other hospital are allowed, ie, MRI completed in 30 days before procedure and in 10 
days after procedure will be allowed in this study. MRI is required for patients with prostate cancer who 
recerive radiotherapy; techinial success and distance between the prostate and rectum will beevaluated 
based on MRI image. 

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10.2. Study Candidate Screening 
 
After study kick-off, patients who have received treatment of SpaceOAR with a complete 
procedure recored in hospital in BOAO will be enrolled in this study, who compose 
retrospective cohort. 
For patients who have been confirmed Prostate Cancer with clinical stage T1-T2 and will 
receive radiotherapy, is scheduled for SpaceOAR administration in hospital in BOAO will 
be enrolled in this study, who compose prospective cohort. 
 
10.3. Informed Consent 
 
Retrospective cohort: For Patients who have received treatment of SpaceOAR before study 
kick-off, these relevant clinical data will be collected retrospectively. The study will be 
conducted according to study procedure approved by EC. 
Prospective cohort: For patients who will receive treatment of SpaceOAR, the study will be 
conducted as usual prospective study, investigator will introduce study information to 
subject and and get ICF before procedure. Once the ICF is signed, he is considered to be 
participatie in study. If he fails to receive treatment of spaceOAR after ICF signed, the 
subjects is considered to be screening failure. 
 
10.4. study visits 
 
10.4.1. Retrospective cohort 
 
For subjects who have received treatment of SpaceOAR, the relevant clincial data below will 
be collected and be entered in EDC. 
• 
Before procedure: data at baseline will be collect, eg. demographics, physical assessment 
(height, weight), clinical diagnosis and clinical stage, Gleason score, PSA, CT, MRI and 
other related examinations, medical history, urinary history and surgery history 
etc.(Clinical diagnosis and clinical stage, Gleason score, CT and MRI from other 
hospital wthin 30 days before procedure are allowed, as applicable.) 
• 
Procedure : collecting procedure information such as anesthesia, SpaceOAR dosage, 
intraoperative device usage, device defects (if any), complications, etc. 
• 
Post procedure: CT and MRI of subjects will be collected retrospectively; Adverse 
events and device deficiency within 30 days post procedure(if any) will be 
retrospectively collected.(CT and MRI performed in 10 days after surgery are allowed.) 
 
10.4.2. Prospective cohort 
 
For subjects who have been pathologically confirmed prostate cancer with clinical stage T1- 
T2, will receive the treatment of spaceOAR in hospital in BOAO. The radiotherapy plan will 
be made by radiotherapist according to clincial guideline and conditions of subjects. 
1) Informed consent 

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Study objective, schedule and visits will be informed to subjects fully, and the ICF will be 
signed voluntarily. 
2) Before procedure 
The data below will be collected, such as demographics, physical assessment (height, 
weight), clinical diagnosis and clinical stage, Gleason score, PSA, CT, MRI and other related 
examinations, medical history, urinary history and surgery history etc. IPSS score will be 
collected, if any, and questionnaires of EPIC and quality of life (EQ-5D-5L) will be 
completed. (Clinical diagnosis and clinical stage, Gleason score, CT and MRI from other 
hospital within 30 days before procedure are allowed.) 
3) Procedure 
According to regulations of licenced medical device in Hainan, subjects will go to BOAO to 
recerive treatment of SpaceOAR. SpaceOAR is injected between the prostate and rectum via 
TRUS . 
All administration of SpaceOAR hydrogel will be conducted by trained urologists at the 
hospital in Boao. 
Procedure information will be collected, such as anesthesia, SpaceOAR dosage, 
intraoperative device usage, device defects (if any), adverse events, complications, etc. 
4) Post procedure 
CT and MRI will be conducted in 10 days post procedure. AE and device deficiency, as 
applicable, will be assessed. CT and MRI will be conducted for all subjects to complete 
radiotherapy planning. MRI in other hospital will be allowed to avoid duplication 
assessment. 
5) 30 days follow up vist post procedure 
This vists will be conducted vis phone, health status and concommit medication will be 
inquired, AE and device deficiency (if any) will be assessed and collected. 
 
10.5. Study Completion 
 
This is a real world study on licenced medical device. When last subject complete 30 days ( 
±7 days) follow up visit, and all data is collected, this study will come into end. 
 
10.6. 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. 

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11. Statistical Considerations 
11.1. Endpoints 
 
11.1.1. Primary Effectiveness Endpoint 
 
The primary endpoint is The distance between the posterior prostatic capsule and anterior 
rectal wall post SpaceOAR hydrogel administration. 
 
11.1.1.1. Hypotheses 
This is a retrospective and prospective, single arm study with a performance goal approach 
for the primary effectiveness endpoint. The primary effectiveness endpoint is the distance 
between the posterior prostatic capsule and anterior rectal wall post SpaceOAR hydrogel 
administration. As this is real word study with less strict I/E criteria, the performance goal 
was set as 7.5mm, based on the rationales in the SpaceOAR EU pilot study, in which the 
creation of at least a 7.5mm space criterion was developed in consult with Augmenix’s 
Scientific Advisory Board (a panel that consists of board-certified radiation oncologists). If 
the two-sided 95% Lower Confidence Interval (LCI) of distance calculated is greater than 
PG, the study primary effectiveness endpoint will be met. 
 
11.1.1.2. Sample Size 
The distance was 12.58±3.88mm (N=147) in the Space OAR hydrogel pivotal study in USA 
(IDE study), and it was 15.5±5.7mm (N=48) in pilot study in EU. For the sample size 
estimation, a distance between prostate and rectum of 13 mm is expected with a standard 
deviation of 5.7 mm. 
The sample size is calculated according to below formula: 
 
 
n is sample size, PG is assumed as 7.5mm, 13mm is expected distance between prostate and 
rectum, δ = 5.5 mm, σ =5.7 mm, α=0.025, β=0.1（power=90%）. Therefore, a sample 
size of 14 subjects will provide more than 90% power. 
To account for potential missing data in this retrospective and prospective study, a final 
sample size will be up to 20 subjects. 
 
11.2. General Statistical Methods 
 
11.2.1. Analysis Sets 
 
This study is a retrospective and prospective, real world study, in which subjects who 
received the treatment of spaceOAR in hospital in BOAO will be enrolled. The efficacy 
analysis set includes subjects with available distance between prostate and rectum measured 
from MRI post procedure. The safety analysis set includes all subjects who have received 
treatment of SpaceOAR in hospitals in Hainan BOA. 

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11.2.2. Control of Systematic Error/Bias 
 
All patients who receive the treatment of SpaceOAR in hospital in BOAO will be enrolled at 
a given time, no cherry-pick patinets and data to reduce select bias. 
 
11.2.3. The method of handling missing, incorrect data( including subjects withdrawal 
and lost to follow-up) and unreasonable data 
 
Missing data will be excluded for primary analysis in this small sample size study. Incorrect 
and unreasonable data will be clarified before database lock. Imputation where applicable for 
continuous variable, and tipping point analysis where applicable for categorical variable 
might be conducted for sensitivity analysis. 
 
11.3. Data Analyses 
 
Descriptive statistics will be used to summarize the study endpoints, such as distance 
between the posterior prostatic capsule and anterior rectal wall post SpaceOAR hydrogel 
administration, functional success. 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. 
This study may allow explorative statistics based on collected data, including but not limited 
to: risk factors associated with functional failure. 
There is no formal interim analysis, but a descriptive summary will be made during the 
study, if needed. 
Any statistical analysis change will be added in statistical analysis plan before data analysis. 
 
12. Data Management 
12.1. 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 BSC 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. 

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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 can 
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. 
 
12.2. 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. 
 
13. Amendment 
The investigator should adhere to studyprotocol 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. 
 
14. 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. 

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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 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 EC/regulatory authority 
notification, site re-training, or site discontinuation/termination) will be put into place by the 
sponsor. 
Considering that this study is a prospective and retrospective, real world study which is based 
on the ‘pilot program’ of licensed medical device, only collecting data, no intervention. 
For data retrospectively collected, there is an chance of missing data, so missing data and 
undo test is not deemed to be deviations. 
For prospective enrolled subjects who has signed ICF, Deviations must be recored, including 
but not limited to informed consent, inclusion criteria, follow-up visit etc. 
 
15. Compliance 
15.1. 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 chinese laws and regulations. The 
study shall not begin until the required approval/favorable opinion from the 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 
requirements imposed by the EC or regulatory authority shall be followed, if appropriate. 
 
15.2. 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 EC, and prevailing china 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 

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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 course of 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 a 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 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 EC, and supply BSC with any additional requested 
information related to the safety reporting of a particular event. 
• Maintain records of the device,which is used in accordance with this protocol and 
instructions for use. 
• 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). 
• Allow and support regulatory authorities and the EC when performing auditing activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local 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. 
• As applicable, provide the subject with necessary instructions on proper use, handling, 
storage, and return of the device when it is used/operated by the subject. 
• 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 

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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. 
 
15.2.1. 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. 
 
15.3. Ethics Committee 
 
The investigational site will obtain the written and dated approval/favorable opinion of the 
EC for the clinical investigation before recruiting subjects and implementing all subsequent 
amendments, if required. 
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. 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 

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of the study reports and the IRB/EC continuance of approval must be provided to the 
sponsor. 
 
15.4. 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. 
 
15.4.1. Role of Boston Scientific Representatives 
 
At the request of the investigator and while under investigator supervision, BSC personnel 
may assist with the conduct of testing specified in the protocol, provide technical expertise. 
Typical tasks may include the following: 
• Clarifying device behavior, operation or diagnostic output as requested by the 
investigator or other health care personnel 
• Provide technical expertise/support to subjects during office visits and/or during 
teleconference calls/electronic communications with the principal investigator or their 
delegated site staff and the subject. 
 
In addition, 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 
• Discuss a subject’s condition or treatment with a subject 

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• 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 
15.5. 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 compensions 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. 
 
16. 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, mdical recoreds, image(if any), lab tests (if 
any) and SAEs. The Device deficiencies, relationships of AE and medical device/ procedure 
recored in the CRF will be considered as souce 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 souce 
docment can’t be acquired for subjects who went to non-investigation hospital or examined 
by non-investigaor, 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 18. 
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. 
 
17. Potential Risks and Benefits 
17.1. Anticipated Adverse Events and Anticipated Adverse Device Effects 
 
Potential Anticipated adverse events and Anticipated Adverse Device Effects that may be 
associated with the use of SpaceOAR System include, but are not limited to: 
• Pain associated with SpaceOAR hydrogel injection 
• Pain or discomfort associated with SpaceOAR hydrogel 
• Local inflammatory reactions 

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• Infection 
• Urinary retention 
• Mucosal damage, ulcers 
• Bleeding 
• Constipation 
• Urgency(eg urinary and rectal) 
• Allergic reaction 
• Embolism 
• Fistula 
• Penetration 
• Syncope 
17.2. Risks associated with Participation in the Clinical Study 
 
This study is real world 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. Anticipated Adverse event and risks related to medical device are listed in 
IFU. 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. 
 
17.3. 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 research 
procedures and/or follow-ups and by promptly supplying BSC with all pertinent information 
required by this protocol. 
 
17.4. Anticipated Benefits 
 
There are no guaranteed benefits from participation in this study. However, the data collected 
from this study will be used to support SpaceOAR to be approved in china, information 
gained from this study may be of benefit to others with the same medical conditions. 
 
17.5. Risk to Benefit Rationale 
 
The SpaceOAR System is intended to reduce the risk of late Grade 2 or higher GI adverse 
events. The rate of AEs related to the SpaceOAR System procedure and implant are low. The 
SpaceOAR System is intended to temporarily position the anterior rectal wall away from the 
prostate during radiotherapy for prostate cancer and in creating this space it is the intent of 
the SpaceOAR System to reduce the radiation dose delivered to the anterior rectum. 

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18. Safety Reporting 
18.1. 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 the Procedure 
• All Serious Adverse Events related to the Procedure 
• All Device Deficiencies 
• Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects 
• 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 or not 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 of the subject, whether during or subsequent to the procedure, 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 course of 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 18-1 for AE definitions). 
Refer to Instructions for Use for the known risks associated with the commercial device(s). 
 
18.2. Definitions and Classification 
 
Adverse event definitions are provided in Table 18-1. 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. 

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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. 
• 
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 

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Term 
Definition 
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) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
Serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current risk assessment. 
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. 

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Term 
Definition 
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. 
 
18.3. Relationship to Study Device(s)(Device Under ) and/or Study Procedure 
 
The Investigator must assess the relationship of the reportable AE to the study device(s), 
and/or study procedure. See criteria in Table 18-2: 

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Table 18-2: Criteria for Assessing Relationship of Study Device(s) (Device Under 
Study) or Procedure to Adverse Event 
 
Classification 
Description 
Not Related 
Ref: MDCG 2020-10/1 
Relationship to the device, comparator or procedures can be excluded when: 
- the event has no temporal relationship with the use of the study device or the 
procedures related to the use of the study device; 
- 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 or the reduction of the level of 
activation/exposure - 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 
procedure; 
- 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 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/procedures and the serious event. 
Possibly Related 
Ref: MDCG 2020-10/1 
The relationship with the use of the study device or comparator, or the relationship 
with procedures 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, comparator, or the relationship 
with procedures seems relevant and/or the event cannot be reasonably explained by 
another cause. 

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Table 18-2: Criteria for Assessing Relationship of Study Device(s) (Device Under 
Study) or Procedure to Adverse Event 
 
Classification 
Description 
Causal Relationship 
Ref: MDCG 2020-10/1 
The serious event is associated with the study device, comparator or with 
procedures beyond reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or 
of similar devices and procedures; 
- the event has a temporal relationship with the study device use/application or 
procedures; 
- the event involves a body-site or organ that 
-the study device or procedures are applied to; 
-the study device or procedures 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. 
 
18.4. Investigator Reporting Requirements 
 
The communication requirements for reporting to BSC are as shown in Table 18-3. 
Note: For retrospective cohort, there is no specific reporting requirements for retrospective 
study in current laws and regulaions. In view of feasibility of operation and specialty of 
retrospective study, Communication timeline is specified as below. 

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Table 18-3: Investigator Reporting Requirements 
 
Event Classification 
Communication Method 
Communication Timeline 
(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 prospective cohort, within 24 hours of 
first becoming aware of the event. 
• 
For retrospective cohort, 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 
Device Effects 
Complete AE eCRF page 
with all available new and 
updated information. 
• 
For prospective cohort, within 24 hours 
of first becoming aware of the event . 
• 
For retrospective cohort, 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 
tomalfunctions, use errors, 
and inadequacy in 
information supplied by the 
manufacturer, including 
labelling) 
Note: Any Device Deficiency 
that might have led to a 
serious adverse event if 
appropriate action had not 
been taken, intervention had 
not occurred, circumstances 
had been less fortunate is 
considered a reportable event. 
Complete applicable eCRF 
pagewith all available new 
and updated information. 
• 
For prospective cohort, within 24 hours 
of first becoming aware of the event. 
• 
For retrospective cohort, within 5 
business day of the event identified or 
collected during data collection 
• 
Reporting required through the end of the 
study 
Provide all relevant source 
documentation (de- 
identified/ pseudonymized) 
for reported event. 
• 
Upon request of sponsor 

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Event Classification 
Communication Method 
Communication Timeline 
(EU MDR 2017/745, MDCG 2020- 
10/1MEDDEV 2.12/1: 
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
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 for retrospective and 
prospective cohort 
• 
Upon request of sponsor 
Provide all relevant source 
documentation (de- 
identified/ pseudonymized) 
for reported event. 
 
 
18.5. 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. 
 
18.6. Reporting to Regulatory Authorities  ECs / Investigators 
 
BSC is responsible for reporting adverse event information and device deficiency 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 China local 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 the procedure or 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. 
For the retrospective cohort, BSC shall reprot 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. 
For prospective cohort, BSC shall reprot 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. 

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19. Informed Consent 
Subject participation in this clinical study is voluntary. Informed Consent is required from 
each subject or his/her legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to study-required procedures and/or testing, 
or data collection in prospective cohort. 
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 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 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 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. 
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 

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must be reported as deviations to the sponsor and local regulatory authorities (e.g. 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 EC. The new version of the ICF must be approved by the EC. 
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. 
 
20. Committees 
20.1. 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 and oncology 
and with the necessary therapeutic and subject matter expertise to evaluate and classify the 
events into the categories outlined above. 
 
20.2. 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 
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 will be no Clinical Events Committee and Data Monitoring Committee in this study. 
 
21. Suspension or Termination 
22.1 
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 ECs, and regulatory authorities, as applicable, will be 
notified in writing in the event of study termination. 

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22.1.1 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 EC or regulatory authorities to suspend or terminate the clinical 
investigation. 
• An enrollment rate far below expectation that prejudices the conclusion of the study. 
22.2 Termination of Study Participation by the Investigator or Withdrawal of EC 
Approval 
 
Any investigator, or associated 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 ECs, and regulatory authorities, as applicable, 
will be notified in writing in the event of these occurrences. 
 
22.3 
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 
EC 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 EC terminates participation in the study, participating investigators, 
associated 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, if 
supplied by Boston Scientific, unless this action would jeopardize the rights, safety, or 
welfare of the subjects. 
 
22.4 
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, or if the site has multiple or severe protocol violations/noncompliance 
without justification and/or fails to follow remedial actions. 

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The EC and regulatory authorities, as applicable, will be notified. Study participants will be 
contacted, as applicable, and be informed of changes to study visit schedule. 
 
22. Study Registration and Results 
22.1. Study Registration 
 
To comply with applicable laws and regulations, the study will be registered on a publicly 
accessible database. 
 
22.2. 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, 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. 
 
22.3. 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 
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) 

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23. Reimbursement and Compensation for Subjects 
23.1. Subject Reimbursement 
Travel and other expenses incurred by subjects as a result of participation in the study will be 
reimbursed in accordance with pertinent country laws and regulations and per the study site’s 
regulations. （applicable for subjects with ICF signed for the study） 
23.2. 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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24. 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. Chen ME, Johnston DA, Tang K, Babaian RJ, Troncoso P. Detailed mapping of prostate 
carcinoma foci: Biopsy strategy implications. Cancer 2000; 89:1800–1809. 
9. 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. 
10. 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. 
11. 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. 
12. 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. 
13. 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. 
14. 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 
15. 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 
16. Zelefsky MJ, Levin EJ, Hunt M, Yamada Y, Shippy AM, Jackson A, et al. Incidence of 
late rectal and urinary toxicities after three dimensional conformal radiotherapy and 
intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol 
Phys 2008;70:1124–1129. 
17. 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. 

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18. 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 
19. 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. 
20. 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. 
21. Liauw SL, Weichselbaum RR, Rash C, Correa D, Al-Hallaq HA, Pelizzari CA, Jani AB. 
Biochemical control and toxicity after intensity-modulated radiation therapy for prostate 
cancer. Technol Cancer Res Treat. 2009 Jun;8(3):201-6 
22. Al-Mamgani A, Heemsbergen WD, Peeters ST, et al. Role of intensity-modulated 
radiotherapy in reducing toxicity in dose escalation for localized prostate cancer. Int J 
Radiat Oncol Biol Phys 2009; 73:685-691. 
23. Yazamaki H, Nakamura S, Nishimura T et al. Transitioning from conventional 
radiotherapy to intensity-modulated radiotherapy for localized prostate cancer: changing 
focus from rectal bleeding to detailed quality of life analysis. J Radiation Research 2014, 
pp1-15, epub September 8, 2014 
24. Koper PC, Heemsbergen WD, Hoogeman MS, Jansen PP, Hart GA, Wijnmaalen AJ, et 
al. Impact of volume and location of irradiated rectum wall on rectal blood loss after 
radiotherapy of prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:1072–82. 
25. Sanda MG, Dunn RL, Michalski J et al. Quality of Life and Satisfaction with Outcome 
among Prostate-Cancer Survivors NEJM; 2008; 358;1250-1261. 
26. Stenmark MH, Conlon A, Johnson S et al. Dose to the inferior rectum is strongly 
associated with patient reported bowel quality of life after radiation therapy for prostate 
cancer, Radiotherapy and Oncology 2014;110:291-297 
27. Zhao G, Evans J, Daignault S, Sanda M, Michalski J et al. Early Quality of Life (QOL) 
declines correlate with Later QOL after Intensity Modulated, Low Dose Rate 
Brachytherapy, or Stereotactic Radiation for Prostate Cancer, ASTRO 2014 
28. Prada PM, et al; Transperineal Injection of Hyaluronic Acid in Anterior Perirectal Fat to 
Decrease Rectal Toxicity from Radiation Delivered with Intensity Modulated 
Brachytherapy or EBRT for Prostate Cancer Patients, Internal Journal of Radiation 
Oncology-Biology-Physiology, 2007; 69: 95-102 
29. Wilder RB, Barme GA, Gilbert RF, Holevas RE, Kobashi LI, Reed RR, Solomon RS, 
Walter NL, Chittenden L, Mesa AV, Agustin J, Lizarde J, Macedo J, Ravera J,Tokita 
KM. Cross-linked hyaluronan gel reduces the acute rectal toxicity of radiotherapy for 
prostate cancer. Int J Radiat Oncol Biol Phys. 2010;77:824-30. 
30. Wilder RB, Barme GA, Gilbert RF, Holevas RE, Kobashi LI, Reed RR, Solomon RS, 
Walter NL, Chittenden L, Mesa AV, Agustin JK, Lizarde J, Macedo JC, Ravera J, 
Tokita KM. Cross-linked hyaluronan gel improves the quality of life of prostate cancer 
patients undergoing radiotherapy. Brachytherapy. 2011;10:44-50. 

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31. Noyes W, Hosford C, Schultz S. Human collagen injection to reduce rectal dose during 
radiotherapy. 2010. Submitted for publication. 
32. Onik G. Image-Guided Prostate Cryosurgery: State of the Art. Cancer Control 2001; 
8(6):522-531. 
33. Teh BS et al. Rectal wall sparing by dosimetric effect of rectal balloon used during 
intensity-modulated radiation therapy (IMRT) for prostate cancer. Med Dosim, 
2005;30(1):25-30. 
34. Song DY, Herfarth KK, Uhl M, Eble MJ, Pinkawa M, van Triest B, Kalisvaart R, Weber 
DC, Miralbell R, Deweese TL, Ford EC. A multi-institutional clinical trial of rectal dose 
reduction via injected polyethylene-glycol hydrogel during intensity modulated radiation 
therapy for prostate cancer: analysis of dosimetric outcomes. Int J Radiat Oncol Biol 
Phys. 2013 Sep 1;87(1):81-7 
35. Mariados N, Sylvester J, Shah D, et al. Hydrogel Spacer Prospective Multicenter 
Randomized Controlled Pivotal Trial: Dosimetric and Clinical Effects of Perirectal 
Spacer Application in Men Undergoing Prostate Image Guided Intensity Modulated 
Radiation Therapy. Int J Radiat Oncol Biol Phys. 2015;92(5):971-977. 
36. Hamstra DA, Mariados N, Sylvester J, et al. Continued Benefit to Rectal Separation for 
Prostate Radiation Therapy: Final Results of a Phase III Trial. Int J Radiat Oncol Biol 
Phys. 2017;97(5):976-985. 

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25. Abbreviations and Definitions 
25.1. Abbreviations 
 
Abbreviations are shown in Table 25-1. 
 
Table 25-1: Abbreviations 
Abbreviation/Acronym 
Term 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CT 
Computed Tomography 
EBRT 
EBRT 
eCRF 
electronical Case Report Form 
EDC 
Electronic data capture 
FDA 
Food and drug administration 
GCP 
Good clinical practice 
Gy 
Gy 
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 
PZ 
Peripheral zone 
QoL 
Quality of life 
RT 
Radiation therapy 
RTOG 
the Radiation Therapy Oncology Group 
SAE 
Serious adverse event 
UADE 
Unanticipated adverse device effect 
USADE 
Unanticipated serious adverse device effect