Randomized Clinical Trial of an Early vs Late Patient Empowerment Program for Men Undergoing Curative Treatment for Prostate Cancer
Phase: NA
Conditions: Prostate Cancer
Sponsor: Nova Scotia Health Authority

Official Title 
PC-PEP: Randomized Clinical Trial of an Early vs 
Late Patient Empowerment Program for Men 
undergoing Curative Treatment for Prostate Cancer  
 
 
NCT Number:  
 
NCT03660085 
 
 
Document Date: 
 
December 8, 2020 
 

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PC PEP Protocol v6.0 December 8, 2020 
PC–PEP CLINICAL TRIAL PROTOCOL 
PC-PEP: Randomized Clinical Trial of an Early vs Late Patient Empowerment 
Program for Men undergoing Curative Treatment for Prostate Cancer  
Status:  
Version 6 
Date:  
December 8, 2020 
Prepared by: Drs. Gabriela Ilie and Rob Rutledge 
Document #: PC_PEP_RCT_Protocol_Version_6_December_8_2020 
This study is being conducted in compliance with the Tri-Council Policy Statement, and 
applicable regulatory guidelines. 
Principal Investigator: Gabriela Ilie 
Co-Investigators: Rob Rutledge, Greg Bailly, David Bell, Ross Mason, Ricardo Rendon, 
Joseph Lawen, David Bowes, Derek Wilke, Nik Patil, Jeffery Zahavich, Mike 
Kucharczyk 
Additional Team Members: Cody MacDonald, Jessica Davis, Getty Vasista, Barbara 
Ross-Campbell 
PROTOCOL SYNOPSIS 
Title 
PC-PEP: Randomized Clinical Trial of an Early vs Late Patient 
Empowerment Program for Men undergoing Curative Treatment for 
Prostate Cancer 
Funder 
Dalhousie Medical Research Foundation, Soillse Research Fund and 
Research Nova Scotia (#2215) 
Primary 
Objective 
To determine if a six-month comprehensive empowerment program 
(physical exercises, meditation, and social support) with use of 
information technology improves the mental health in men 
scheduled for curative prostate cancer treatment.  
Secondary 
Objectives 
1. To compare urinary function, sexual function, quality of life
related to hormonal treatment, relationship satisfaction,
functional, emotional, and social well-being, general
physical and mental/cognitive quality of life and
psychological needs, and health care utilization – between
the early intervention group and the late (wait-list control)
group at the six month point.

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PC PEP Protocol v6.0 December 8, 2020 
2. To compare assessments of fitness and cardiovascular risks 
measured by the six-minute walk test and sit to stand 
assessment, BMI, strength, flexibility and balance, diastolic 
and systolic blood pressure – between the early intervention 
group and the late (wait-list control) group at the six-month 
point.  
3. To compare assessments of stress levels measured by EEG 
and heart rate variability – between the early intervention 
group and the late (wait-list control) group at the six-month 
point.  
4. To evaluate patient and program contextual factors and 
mechanisms that account for differences in outcomes among 
participants in the program.   
 
Number patients 
140 
 
Enrollment 
Criteria 
-Patients must be scheduled for potentially curative prostate cancer 
treatment including radical prostatectomy or radical radiotherapy 
(external beam radiation and/or brachytherapy) or both. Hormone 
therapy is permitted if given along with surgery or radiotherapy. 
(Exclusion - Men on active surveillance, hormone therapy only, or 
those with metastatic disease) 
-Age >18 
-Deemed safe to participate in a low to moderate exercise program  
-Able to read English and access daily emails for six months 
-Willing to travel to Halifax at baseline, six and 12 months 
- Have access to a computer/phone/iPad/tablet with internet access 
for training and program communication 
 
Efficacy 
Assessments 
 
Mental health will be ascertained via a self-administered online 
questionnaire (K10 - Kessler Psychological Distress Scale).  
 
Primary Endpoint 
 
Mental distress (K10 score > 20) at six months from 
randomization (at the end of intervention for the early group and 
before the late group starts the program). 
 
Other Evaluations Evaluation of all men in the early and late intervention groups 
occur at baseline, six months and one year. 
a. Comprehensive set of validated questionnaires including 
International Prostate Symptom Scale (IPSS), Expanded 
Prostate Cancer Index Composite, EPIC-26, Dyadic 
Assessment Scale (DAS), Screening for Distress 
Questionnaire (SDQ), Quality of life (SF-12 and FACT-P), 
self-reported health care utilization  
b. Standardized six-minute walk test, sit to stand assessment, 
BMI, strength, flexibility, balance, diastolic and systolic 

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PC PEP Protocol v6.0 December 8, 2020 
blood pressure,standardized six-minute walk test, sit to 
stand assessment, strength, flexibility, balance, diastolic 
and systolic blood pressure. 
c. EEG (alpha, beta, delta, gamma, and theta activity 
measured every 30 seconds for 10 minutes pre-and post-
intervention), heart rate variability using HeartMath 
monitors.  
Rationale for 
number of 
patients 
This is a 1:1 randomized wait-list controlled trial of men 
scheduled for curative treatment for prostate cancer. Eligible and 
consented participants will be randomized with equal probability 
to either immediate (early) six-month comprehensive patient 
empowerment program or to the wait-list control (late) arm 
starting at six months. Men will be stratified by treatment type 
(surgery vs radiotherapy vs both), whether they are or will be on 
hormone treatment, and mental distress at baseline. 
 
Assuming 30% of all participants will score positive on the K10  
(screen positive for mental distress) at baseline (rationale 
described in Sample Size Calculation heading under the Statistical 
Considerations section), and assuming the wait list control (late) 
group will continue to have the same rate of mental distress (30% 
screen positive) at six months, and assuming the intervention 
(early) group will drop their distress rate to 10% screening positive 
at six months, the sample size required is 124 to detect these 
difference with a power of 0.8 and an alpha of 0.05. With a 5% 
drop out rate (an additional 6 patients) and some missed 
assessments due to COVID-19 (additional 10 patients) the total 
number of participants needed for this trial is 140. 
 
Statistical 
Analysis Plan for 
Primary Endpoint 
An intent-to-treat approach will be used to analyze the percentage 
of men screening positive for mental distress (K10>20) at the six-
month point.  Conditional Logistic Regression Statistical analyses. 
 
Duration of 
Patient 
Participation and 
Duration of Trial 
 
All study participants must commit to three in-person visits in 
Halifax for assessment over one year, and multiple online survey 
assessments. Particpants will also be invited to attend a focus 
group or one-on-one exit interview at the end of the ntervention, 
which will occur via videoconference. The trial will extend over 
an estimated 2-3 years to complete accrual and follow up. 
 
 
 
 
 

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PC PEP Protocol v6.0 December 8, 2020 
LIST OF ABBREVIATIONS 
 
AE – Adverse Event 
 
BMI – Body Mass Index 
 
CEP – Certified Exercise Physiologist 
 
COVID-19 – An acronym that stands for coronavirus disease of 2019. 
 
EEG – Electro-encephalogram 
 
HRV – Heart Rate Variability 
 
HT – Hormone Therapy 
 
K10 - Kessler Psychological Distress Scale 
 
 
PC – Prostate Cancer 
 
PEP – Patient Empowerment Program 
 
PC–PEP – Prostate Cancer Patient Empowerment Program  
 
QOL – Quality of Life 
 
RC – Research Coordinator 
 
RCT – Randomized Control Trial 
 
RP – Radical Prostatectomy 
 
RT - Radiotherapy 
 
SP – Study Physician 
 
 
 

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PC PEP Protocol v6.0 December 8, 2020 
TABLE OF CONTENTS 
1 BACKGROUND .................................................................................................................................................... 8 
1.1 RATIONALE .................................................................................................................................................................... 8 
1.2 SCIENTIFIC BASIS FOR A PATIENT EMPOWERMENT PROGRAM ........................................... 9 
1.2.1 Development of the PC-PEP Feasibility Program ............................................................................................ 9 
1.2.2 Building on Pre-habilitation Prior to Radical Prostatectomy (RP) ........................................................ 9 
1.2.3 Benefits of Pelvic Floor Muscle Exercise .............................................................................................................. 9 
1.2.4 Stress Reduction thorough Meditation and Relaxation Exercises (and biofeedback) ................. 10 
1.3 PC-PEP FEASIBILITY TRIAL DESCRIPTION AND RESULTS ........................................................ 10 
1.3.2 PC-PEP Timeline ......................................................................................................................................................... 11 
1.2.3 Compliance .................................................................................................................................................................... 12 
1.2.4 Pelvic Floor Training ................................................................................................................................................ 13 
1.2.5 Stress Reduction - Meditation Training ............................................................................................................ 13 
1.2.6 Preliminary Results ................................................................................................................................................... 13 
1.2.7 Overall Summary of the PC-PEP Feasibility Study ....................................................................................... 14 
2 STUDY OBJECTIVES AND OUTCOMES ................................................................................................. 15 
2.1 PRIMARY OBJECTIVE ........................................................................................................................................... 15 
2.2 SECONDARY OBJECTIVES ................................................................................................................................. 15 
3 SELECTION AND ENROLLMENT OF PARTICIPANTS .................................................................... 16 
3.1 ELIGIBILTY CRITERA ........................................................................................................................................... 16 
3.1.1 Inclusion Criteria ........................................................................................................................................................ 16 
3.1.2 Exclusion Criteria ....................................................................................................................................................... 16 
3.2 RECRUITMENT, SCREENING, AND ENROLLMENT PROCEDURES ........................................ 17 
3.2.1 Recruitment Methods and Timeline ................................................................................................................... 17 
3.2.2 
Screening and Consent Procedure ................................................................................................................. 17 
3.3 RANDOMIZATION AND STRATIFICATION ..................................................................................... 18 
3.3.1 Sequence Generation ................................................................................................................................................ 19 
3.3.2 Randomization Assignment and Concealment Mechanism ..................................................................... 19 
4 CLINICAL INTERVENTION (PATIENT EMPOWERMENT PROGRAM) .................................... 21 
4.1 INTERVENTIONS AND ADMINSTRATION ................................................................................................ 21 
4.1.1 Aerobic Training Recommendations ................................................................................................................. 21 
4.1.3 Pelvic Floor Muscle Training ................................................................................................................................. 22 
4.1.4 Meditation Instruction ............................................................................................................................................. 23 
4.1.5 Healthy Lifestyle Promotion .................................................................................................................................. 23 
4.1.6 Connection and Relationship Teaching ............................................................................................................ 24 
4.1.7 Social Support .............................................................................................................................................................. 24 
4.1.8 Monthly Videoconferencing with active PEP participants ....................................................................... 24 
4.1.9 Using Technology for Support .............................................................................................................................. 26 
4.2 DESCRIPTON OF ARM A – ‘EARLY’ INTERVENTION ....................................................................... 27 
4.2.1 Education Phase for ‘EARLY’ ARM  ‘A’ Prior to Day 1 ................................................................................ 27 
4.2.2 Intervention Phase for EARLY ARM  (days 1-180) ....................................................................................... 27 
4.2.3 Post Intervention Assessment Phase for EARLY ARM (Day 181) ........................................................... 28 
4.2.4 End of trial Assessment for EARLY ARM (Day 360) ..................................................................................... 29 
4.3.1 Education phase for LATE ARM (Just prior to Day 180) ........................................................................... 29 
4.3.2 Intervention Phase for ‘LATE’ ARM  (Days 180-360) ................................................................................. 30 
4.3.3 Post Intervention Assessment Phase for LATE ARM (Day 360) ............................................................. 30 

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PC PEP Protocol v6.0 December 8, 2020 
5 CLINICAL EVALUATIONS .......................................................................................................................... 31 
5.1 PRIMARY ENDPOINT (MENTAL DISTRESS) EVALUATION ......................................................... 31 
5.2 SECONDARY ENDPOINT EVALUATIONS .................................................................................................. 31 
5.3 SCHEDULE OF EVALUATIONS .............................................................................................................. 32 
5.4 PRE- AND POST-INTERVENTION MEASUREMENTS ......................................................................... 32 
5.4.1 Physical Fitness Assessment ................................................................................................................................... 32 
5.4.2 RELAXATION – BRAIN ACTIVITY ASSESSMENT ............................................................................................... 33 
5.4.3 Online Questionnaires .............................................................................................................................................. 33 
5.4.4 Measuring Compliance ............................................................................................................................................. 34 
6 STATISTICAL CONSIDERATIONS ........................................................................................................... 34 
6.1 SAMPLE SIZE AND ACCRUAL ........................................................................................................................... 34 
6.2 STATISTICAL ANALYSES .................................................................................................................................... 35 
6.2.1 General Considerations ............................................................................................................................................ 35 
6.2.2 Comparisons ................................................................................................................................................................. 35 
6.2.3 Primary Analyses ........................................................................................................................................................ 36 
6.2.4 Qualitative Analysis ................................................................................................................................................... 36 
6.2.5 Secondary Analyses ................................................................................................................................................... 37 
7 ADVERSE EVENTS AND REPORTING REQUIREMENTS ............................................................... 37 
7.1.1 Adverse Events ............................................................................................................................................................. 37 
7.1.2 Indications for Stopping Exercise ........................................................................................................................ 38 
7.1.3 Reporting Requirements ......................................................................................................................................... 38 
9 WITHDRAWAL OF PARTICIPANTS ........................................................................................................ 39 
9.1.1 Protocol Violation ...................................................................................................................................................... 39 
9.1.2 Withdrawal of Participants ................................................................................................................................... 39 
11 PROTECTION OF HUMAN SUBJECTS ................................................................................................. 39 
11.1.1 Harms ............................................................................................................................................................................ 39 
11.1.2 Benefits ......................................................................................................................................................................... 40 
11.2.3 Liability ........................................................................................................................................................................ 40 
11.2.4 Confidentiality ........................................................................................................................................................... 40 
11.2.5 Disclosure of Any Financial Compensation .................................................................................................. 41 
12.1 DISSEMINATION PLAN ................................................................................................................................................. 41 
12 REFERENCES ................................................................................................................................................. 43 

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PC PEP Protocol v6.0 December 8, 2020 
1 BACKGROUND 
1.1 RATIONALE 
Each year over 20,000 men are diagnosed with prostate cancer (PC) in Canada with the 
majority undergoing radical surgery and/or radiotherapy (1). One in seven men will be 
diagnosed with PC in their lifetime (1). Survival rates for newly diagnosed cases of 
prostate cancer are very high, with an expected 5 survival rate of 95% (1). However, of 
those treated with curative intent, 90% will suffer significant treatment-related side 
effects with respect to their psychological well-being, urinary and erectile dysfunction 
(2,3). Nova Scotia has the third highest new cancer rate, with PC representing the highest 
incidences of cancer for males (95 per 100,000) but it has the highest relative survival 
rate for PC in the country (1,4,5). Based on a survey which assessed 100 PC survivors 
from Nova Scotia who completed a comprehensive on-line quality of life survey 
(between May 2017 to March 2018), we identified that a high percentage of survivors 
reported urinary symptoms, intimacy concerns, isolation, insomnia and many other health 
problems (6). Overall 17% of these survivors screened positive for mental health issues, 
yet very few were on medication to address these mental health issues. Fewer than 20% 
have ever attended a prostate cancer support group (6). Since then, almost 400 men have 
taken the survey, but this estimate has not changed. The high incidence and long survival 
rates of PC along with treatment related side effects has resulted in a silent epidemic 
among thousands of Nova Scotian men needlessly suffering alone. Low attendance to 
support groups among PC survivors throughout Canada (including PC survivors from 
NS), problems with intimacy/sexuality, fatigue and depression have also been noted 
elsewhere (7). 
Our program of research aims to address the most critical needs for PC patients and 
survivors: the development and evaluation of interventions to address the quality of life 
impact of PC.  Based on our survey of 400 PC patients and survivors, a review of 
scientific evidence, and extensive consultation with patients and their families, and health 
care providers, our team has developed and pilot tested a unique, comprehensive Patient 
Empowerment Program for patients with PC (PC-PEP) aimed at educating and teaching 
the men life skills/habits in order to improve their mental health issues, fitness levels and 
overall quality of life, and to decrease treatment related side effects. The program 
includes aerobic, strength and pelvic floor exercise, meditation, relationship teaching, and 
peer support - based on the best of health promotion science. Building on a feasibility 
trial which we recently completed, this trial will aim to rigorously evaluate the 
effectiveness of the program to improve mental health issues and physical outcomes. As 
well, we aim to conduct a rigorous evaluation process, using realist methods, that will 
guide program refinement to better accommodate the diverse needs of PC patients and 
survivors in the future, and facilitate its uptake and spread to other settings. 

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PC PEP Protocol v6.0 December 8, 2020 
1.2 SCIENTIFIC BASIS FOR A PATIENT EMPOWERMENT PROGRAM 
1.2.1 Development of the PC-PEP Feasibility Program  
The PC-PEP program was developed based on our patient surveys, extensive input from 
patients and health care providers, and scientific evidence. In April 2018 our team 
convened a Maritime-wide prostate cancer integrative care conference in Halifax, 
attended by 60 people (mostly from NS), including 28 patients, 10 patients’ partners, 6 
Urologists, 8 Radiation Oncologists, and a range of other health care professionals 
including nurses, administrators (e.g., Cancer Care Nova Scotia), residents, and MSc. 
students.  At this Conference we shared the results of our patient survey (6) and asked 
conference attendees to contribute ideas towards improving these quality of life 
outcomes, especially mental health issues. The group strongly endorsed the idea of a 
comprehensive patient empowerment program to be offered to all newly diagnosed 
prostate cancer patients, to educate and teach the men and their partners life skills/habits 
which are aimed to improve their mental health, fitness levels and overall quality of life, 
and to decrease treatment related side effects.  PC-PEP was designed by drawing on ideas 
presented from the April 2018 conference, more than 25 years of experience leading 
support groups for cancer patients by members of our team, and a review of the scientific 
evidence in support of potential program components. 
 
1.2.2 Building on Pre-habilitation Prior to Radical Prostatectomy (RP) 
Participating in preoperative exercise programs, and/or having a higher level of health 
and fitness immediately prior to surgery, appears to facilitate a quicker recovery and 
fewer complications in patients undergoing many operations including radical 
prostatectomy (RP) (8-12). Men undergoing RP who participated in moderate exercise for 
60 minutes, 3-4 times a week, for 4-8 weeks preoperatively reported better quality of life 
outcomes including less anxiety before and six months after surgery, and superior six-
minute walk test scores 4 weeks post operation, compared to the more sedentary control 
group (8).  In an Australian feasibility study (n=10) that provided 6 weeks of an aerobic 
exercise program prior to surgery to recently diagnosed men, the results were similar, and 
no adverse effects were reported (12).  
 
1.2.3 Benefits of Pelvic Floor Muscle Exercise 
In a recent systematic review looking at pre- and post-operative pelvic floor muscle 
exercise (PFME) it was shown that preoperative PFME improved early (3 months but not 
six month) postoperative urinary incontinence post RP. Overall pelvic floor programs 
have been shown to improve sexual function and urinary continence post-prostate surgery 
compared to ‘usual care’ void of this training (13). 
 

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PC PEP Protocol v6.0 December 8, 2020 
1.2.4 Stress Reduction thorough Meditation and Relaxation Exercises (and 
biofeedback) 
Anxiety tends to be the most often experienced mental health issue for men with prostate 
cancer (14). Men may also report irritability or depression (15-16). 
Participating in a meditation or mindfulness program has been consistently reported to 
reduce stress symptoms (16-21), mood disturbance (16-17, 22) anger (20), and fatigue 
(19) as well as improve quality of sleep (21), facilitate post-traumatic growth (19), 
promote spirituality (19,23) and enhance quality of life (22) in survivors of various types 
of cancer. Men with PC who are under medical surveillance reported significantly greater 
resilience and less anxiety after receiving an intervention of mindfulness meditation (22). 
Another study showed combining mindfulness therapy with Kegel exercises resulted in 
significantly improved continence for men after RP (95.6% achieved continence), 
compared to men who only did Kegel exercises without mindfulness therapy (71.6% 
achieved continence) (23).  
 
The implementation of meditation biofeedback training using heart rate variability (HRV) 
has been shown to improve the quality of life in study participants experiencing many 
conditions such as diabetes (24), hypertension (25), asthma (26-27), PTSD (28), and 
chronic pain (29). HRV biofeedback training appears to decrease emotional and 
physiological stress levels (30), symptoms of burnout, anxiety and depression (30-32) 
and to increase working and episodic memory (33) and emotional well-being (28,34-35). 
 
1.3 PC-PEP FEASIBILITY TRIAL DESCRIPTION AND RESULTS 
  
1.3.1 Addressing Feasibility Concerns 
 
After ethics approval, Privacy Council clearance from NSHA, and registration in 
clinicaltrials.org, on January 4, 2019 we began a pilot Patient Empowerment Program of 
30 PC survivors to assess the following concerns: 
1. Recruitment – would patients be interested and participate in this type of 
programming? 
2. Participant adherence and dropout rates with an intense program (70 
minutes of programmed activity daily over 28 days) 
3. Would participants complete a 28 days program of this type? Would there 
be any attrition and if so, how big of a drop out will a program of this type 
incur? 
4. Feasibility of intensive pre- and post- intervention testing.  
5. Will there be any safety issues arising from teaching strength training in a 
group format and prescribing home-based strength and aerobic exercise 
training? 
6. How will patients judge the helpfulness of such a program and each of its 
individual components? 
7. Will patients recommend such program to other patients undergoing active 
or non-active forms of treatment at the end of the program? 

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PC PEP Protocol v6.0 December 8, 2020 
8. Will the research team be competent and be deemed competent by the 
participants in delivering such a program? 
9. Will the technology developed (an app to alert participants to do their daily 
exercises) be suitable and effective for this program? 
 
1.3.2 PC-PEP Timeline 
 
The PC-PEP pilot program ran for 28 straight days from January 12, 2019 to February 
10, 2019 for 30 men with a history of non-metastatic prostate cancer. Subjects (n=30) 
ranged in age from 56-83 years of age, 90% were married, and 67% had a university 
education. The men varied in their time since diagnosis (four men were less than 7 
months, four were between 7 to 12 months, and 22 were greater than 2 years). 
Participants’ treatment history for their prostate cancer diagnosis at pre-intervention was 
divided between Active Surveillance (10%), Radical Prostatectomy (33%), Radiation 
External Beam, Brachy or seed implementation (10%), Radiation and Hormonal 
Treatment (20%), Radical Prostatectomy and Hormonal manipulation (20%), Radical 
Prostatectomy and Hormonal Manipulation (10%) and Radical Prostatectomy, Radiation 
and Hormonal manipulation (17%).  
 
All 30 participants completed pre-intervention assessments including: 
a) 30 minute quality of life online multidimensional survey which included 
standardized measures for urinary, bowel, sexual, hormonal function [measured 
through the International Prostate Symptom Score (I-PSS)], the Expanded 
Prostate Cancer Index Composite (EPIC-26), mental health assessment (Kessler 
Psychological Distress Scale-K10), health and well-being (SF-12), current 
stressors/needs (Screening Distress Scale), relationship Satisfaction (Dyadic 
Assessment Scale – DAS), overall quality of life (Functional Assessment of 
Cancer Therapy - Prostate Cancer, FACT-P), demographics (marital status, age, 
household income, education, occupation) and support group participation. 
b) Fitness cardiovascular risks testing (6-minute walk, sit to stand, flexibility, 
balance, grip strength, height, weight and girth, blood pressure) (see Figure 1). 
c) Assessment of stress levels through EEG and heart rate variability monitoring 
(Heart Math assessment) (see Figure 1).  
d) Dietary assessment using a self-reported 24-hour food record. 
 
(These same measurements a-d will be used in this randomized trial) 
 
 
 
 
 
 
 
 
 
 

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PC PEP Protocol v6.0 December 8, 2020 
Figure 1. Fitness, EEG, and Heart Rate Variability Testing in the 28-day PC-PEP pilot 
program from January 12 to February 10, 2019. 
 
 
All 30 men first attended a half day education session/intervention which included five 
sessions taught by professionals:  
1. The Science behind PEP taught by a Clinician who treats PC 
2. Pelvic floor training by a registered Physiotherapist 
3. Mediation instruction by a Psychotherapist 
4. Connection/Intimacy by a Professor who taught University courses on Aging and 
Sexuality 
5. Strength training by a Certified Exercise Physiologist (CEP) 
1.2.3 Compliance 
During the intervention, the men received three daily alerts to do their exercises (either 
via an app which one of our team members developed for PC-PEP specifically, android 
and iPhone – 26 participants received app alerts; 4 received text alerts sent by our study’s 
coordinator). They also received a daily video message by email with a list of the daily 
habits/lifestyle changes recommendations from the PI and the Study Physician. These 
video messages were between 2-3 minutes long and their usefulness was rated 9.15/10 by 
PC-PEP participants. Participants were also paired with 2 buddies (also PC-PEP 
participants) and were encouraged to call each other once a week. This recommendation 
was highly successful and achieved 100% compliance. The lectures were all videotaped 
and made available to the participants to use during the program. In the randomized trial, 
all PEP participants will watch these videos prior to starting the program. The men have 
graded the didactic and training components of the program as an average of 9.1 out of 
10 (lowest scored component was 8.7/10) and the competence of the research team as an 
average of 9.47 out of 10.  

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PC PEP Protocol v6.0 December 8, 2020 
1.2.4 Pelvic Floor Training  
Our Specialized Physiotherapist provided a 45-minute overview and live demonstration 
of pelvic floor anatomy and training. Participants were asked to practice their ‘Kegel’ 
exercises three times a day by following an 8-10 minute video we have produced and 
uploaded for the study participants on the PI’s Lab website. The Kegel video instructions 
changed each week (all uploaded on the website), increasing in intensity during the trial 
period. Feasibility results of the a-priori repeated measures ANOVA evaluating pre-post 
mean differences in urinary and sexual function (using the Expanded Prostate Cancer 
Index Composite, EPIC–Urinary & Sexual domain) found significant improvements in 
bowel function (p < 0.05) and marginal significance in urinary function despite the low 
statistical power in the feasibility study. 
1.2.5 Stress Reduction - Meditation Training 
A meditation instructor trained in Mindfulness-based stress reduction with over 30 years 
of experience, prepared a video of simple mindfulness of body and breath meditations 
that was made available to the participants. In addition, participants received biofeedback 
training (30 minutes) during the pre-intervention assessment. Change in pre-post 
assessment of theta brain wave activity (indicating a meditative brain state) was assessed. 
No statistically significant results emerged in the analysis of brain waves pre- post 
intervention (p=.056). However, a trend in the improvement direction was observed.  
 
1.2.6 Preliminary Results 
Effect on current mental health assessment during the feasibility trial.  The results we 
obtained assessing the effect of the PC-PEP intervention on the pre-post change in mental 
health status of participants, as measured by a well validated instrument (described below 
in the methods) showed a statistically significant difference (p=.031), despite the small 
sample size.  
 
Relationship satisfaction: Analyses of relationship satisfaction showed no statistically 
significant improvement 28 days post intervention. 
 
Strength training: A trained Physiologist evaluated each man and individually prescribed 
either a low, intermediate, or high-level strength program modified according to the 
limitations of each man and recommend it to be performed twice per week. An a-priori 
repeated measures ANOVA revealed statistically significant weight loss, reduced 
diastolic blood pressure, better endurance sit to stand, and improved hamstring and 
shoulder flexibility, at post-test comparted to pre-test. The men also agreed to contact two 
other participants by phone each week. As mentioned earlier, most men received a three-
times-a-day reminder text via an app developed by our team or by manual text from our 
research coordinator (Appendix 10).  
 

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PC PEP Protocol v6.0 December 8, 2020 
All training sessions for strength, Kegels, meditation, connection training/ 
recommendations were videotaped and uploaded to our lab’s website at: 
http://soillseprostatecancerqualityofliferesearch.che.dal.ca/wordpress/index.php/pc-pep-
educational-materials/. Weekly compliance to the program was measured via a weekly 
self-report online survey.  All 30 men completed the post-intervention assessments. No 
participants dropped out from the program. We collected compliance data (the exact 
number of days, minutes per day and intensity of engagement in the various aspects of 
the program). Compliance was consistent among the four weeks with little variation 
(mostly NS) noted. Overall, the order of compliance for the various aspects of the 
program (from the highest to the least compliance): strength and aerobic exercises, 
Kegels, meditation, and intimacy/connection exercises. The buddy system showed 
maximum compliance. Twenty-five men participated in one of the three focus group 
sessions held after the program. No adverse events (e.g., injury) occurred. In addition to 
confirmation of the evaluation results post intervention, the most significant message 
received during the focus group was the participants’ strong indication that they would 
like the program to have survivors representation so that they may continue to remain 
enrolled in the program and also help other men and motivate them to do the program as 
they thought it would be highly beneficial for patients as they go through treatments and 
afterwards. For this reason, we have 5 men (former PC-PEP members) represented in this 
grant application; although, we have a list of 20 men (PC-PEP participants) who provided 
consent and would like to partake in the RCT in some capacity.  
 
1.2.7 Overall Summary of the PC-PEP Feasibility Study 
After 28-days of intensive training, the group showed some physical (e.g., weight loss – 3 
lbs. weight loss overall, lower diastolic blood pressure, increased flexibility) and 
improved current mental health assessment as measured by validated self-report 
questionnaires. The K10 assessment results indicated the presence of screening positive 
for current mental health issues in 6 men at baseline and in only 2 one month later. Asked 
whether they would recommend this same program for all new PC patients the men gave 
an average score of 9.8 out of 10. Self-reported compliance measured weekly was very 
high throughout the 4 weeks. The feedback from the focus groups was overwhelmingly 
positive.  Some men benefited tremendously from the program more so than what was 
picked up by assessing group averages. We hope that the reviewing committee for this 
application would consider viewing one of the 10 patient testimonials we collected by 
following this link (5 minute length): 
https://www.youtube.com/watch?v=rAQqejhiXYg&feature=youtu.be. In an interview 
with the Canadian Press this is what 5 of the participants in our study had to say about the 
program: https://www.ctvnews.ca/health/unmet-need-new-program-for-men-with-
prostate-cancer-shows-promising-results-1.4328403 (36). The results of the feasibility 
study clearly demonstrate the viability of PC-PEP, and document the interest and 
commitment of patients and survivors in the program. Our hypothesis is that a 
comprehensive program such as PC-PEP will improve the mental health of men 
scheduled for curative PC treatment six months after starting the program compared to 
standard of care. Our hope is to empower the men at diagnosis and through their 

15 
 
PC PEP Protocol v6.0 December 8, 2020 
treatment and recovery period, mitigate against treatment related side effects (e.g., 
urinary incontinence, fatigue), improve their relationships, and ultimately improve quality 
of life. 
 
 
 
 
2 STUDY OBJECTIVES AND OUTCOMES 
 
2.1 PRIMARY OBJECTIVE 
 
1. To determine whether a comprehensive six-month Prostate Cancer Patient 
Empowerment Program started prior to treatment, improves the mental health six 
months later of men undergoing curative treatment for PC, compared to a control 
group receiving usual care. (All participants receive standard medical care). 
 
2.2 SECONDARY OBJECTIVES 
 
1. Secondarily, we will determine whether PC-PEP also improves the following 
outcomes relative to controls for:  
a. Urinary function;  
b. Sexual function;  
c. Quality of life related to hormonal treatment;  
d. Fitness and cardiovascular risks;  
e. Relationship satisfaction;  
f. Functional, emotional and social well-being;  
g. General physical and mental/cognitive quality of life and psychological 
needs;  
h. Diet; 
i. Health care utilization. 
 
2. To determine whether a six-month comprehensive Prostate Cancer Patient 
Empowerment Program (PC-PEP), delivered to men starting at the six month 
point improves the one-year point mental health of men who had curative 
treatment for PC, compared to a control group who received the PC-PEP program 
during the first six months. We will also compare outcomes relative to controls 
who did not participate in this trial on secondary outcomes (a) – (h) from 
Objective 1.  
 
3. To evaluate patient and program contextual factors and mechanisms that account 
for differences in outcomes among participants in the PC-PEP program.   
 
 
 

16 
 
PC PEP Protocol v6.0 December 8, 2020 
3 SELECTION AND ENROLLMENT OF PARTICIPANTS 
 
3.1 ELIGIBILTY CRITERA 
 
All potential study participants will be screened by the Research Coordinator and Study 
Physician (Dr. Rob Rutledge) to ensure that they meet the following eligibility criteria:   
3.1.1 Inclusion Criteria 
• Age >18 
• History of a PC diagnosis 
• Scheduled for a Radical Prostatectomy (RP) , or curative intent Radiotherapy (RT 
= external beam and/or brachytherapy), or adjuvant or salvage RT post RP and 
complete treatment within 6 months post study enrolment. Patient on hormone 
therapy (HT) or scheduled to start HT are eligible if they are scheduled to undergo 
RP or radical RT and complete prostate cancer treatment by 6 months past study 
randomization.  
• Approval from Study Physician that they are safe to exercise. Participants who 
have recovered from a minor stroke or heart condition in the past will require 
approval from their Family Physician or Cardiologist to participate in the study. 
• Existing (or willingness to create) email account  
• Access to a computer/smartphone/tablet with internet access 
• Willingness to access and use daily email and/or text messages 
• Ability to follow website links to watch YouTube videos  
• Ability to understand and speak English 
• Ability to participate in low to moderate levels of physical activity 
• Willingness to travel to Halifax for an in-person assessment at baseline, six 
months and one year. 
3.1.2 Exclusion Criteria 
• Patients treated with hormone therapy only at 6 months post randomization 
• Patients on active surveillance (not scheduled for a curative intervention) at 6 
months post randomization 
• Patients deemed unfit to participate in low level exercise e.g. including but not 
limited to a myocardial infarction or stroke within the last year, without approval 
from their Family Physician or Cardiologist that they are safe to exercise. 
• Patient with uncontrolled blood pressure. Systolic > 160 or Diastolic > 90. 
• Unable to travel to Halifax without incurring travel and accommodation costs for 
three study visits unless the participant requests to participate in the study and is 
willing to pay for these expenses in order to participate in the study 

17 
 
PC PEP Protocol v6.0 December 8, 2020 
• Unable to access the internet and/or lack of a computer/smartphone/tablet to 
receive emails required for the study intervention, or unable to click on a link to 
successfully watch a YouTube video. 
3.2 RECRUITMENT, SCREENING, AND ENROLLMENT PROCEDURES 
3.2.1 Recruitment Methods and Timeline 
Recruitment of potential participants will occur through posters, support groups, and 
education sessions held for PC patients scheduled for curative treatments. Posters 
(Appendix 1) will be placed within the Departments of Urology and Radiation Oncology, 
Urologists offices and Cancer Centre’s (Radiation Oncology Clinics) throughout the 
Maritimes. The poster will be available at PC support groups in all three provinces and to 
Prostate Cancer Canada. In addition to self-referrals, individuals can be referred to the 
study by their physician or a healthcare provider from their oncology team. Lastly, we 
will offer this trial to all patients joining an education session to be heald online monthly 
via telehealth and shared to all patients scheduled for surgery or curative radiotherapy in 
Nova Scotia. Potential and interested participants will be instructed to contact the 
Research Coordinator (RC). 
 
At our centre, in Halifax alone, 150 men undergo a radical prostatectomy each year (Dr. 
Baillie, Head of Urology, personal communication). An additional 250 men receive PC 
radiotherapy with curative intent. This represents approximately 400 potential 
participants per year being treated at our centre alone. We have strong support from both 
the Heads of Urology and Radiation Oncology (leading both Halifax and Sydney 
Radiation teams). Many non-Halifax Urologists were trained at Dalhousie University and 
likely will be supportive of this program. Realistically, we aim to accrue 140 (as 
explained below in section) participants and complete the accrual in 2.5 years (40, 55, 
and 35 participants per year). A smaller percentage of men who are being treated in New 
Brunswick or Prince Edward Island and who may will be willing to travel to Halifax for 
the requisite three (possible 4 visits if they agree to participate in the focus groups and/or 
face-to-face exit interviews) visits over one year may also be eligible for the study. 
However, these participants will be informed that their travelling expenses to arrive to 
Halifax (including related expenses, e.g., accommodation) will not be reimbursed. With 
their participation, the overall accrual time may be shortened. 
3.2.2 Screening and Consent Procedure 
1. 
The Study Physician will explain the study to interested participants via telephone or 
videohealth. The Study Physician will attempt to screen the participant for eligbility 
in the trial (Appendix 2) at this time. The RC will provide participants who are 
interested and eligible with a link to an online REDCap consent form that includes 
both the study consent form and the Personal Health Information Act (PHIA) 
Consent form. The PHIA will allow potential participants to give knowledgeable 
implied consent and details including their name, phone number, and email address. 
If a potential participant makes initial contact by calling or emailing the RC directly 

18 
 
PC PEP Protocol v6.0 December 8, 2020 
(by obtaining study information from posters, urology nurses, or other written/verbal 
information) the RC will assume knowledgeable implied consent to discuss their 
eligibility and continue with the screening. Knowledgeable implied consent will be 
assumed to make it more convenient for the patient. This may save some patients a 
trip to the hospital and avoid unnecessary in-person visits. Since we aim to recruit 
participants from the three Maritime provinces, assuming implied consent when 
patients make initial contact via phone/email only may allow for the accrual of a 
larger demographic of participants who would not have made an in person visit to 
learn about the study. This process may also improve patient comfort, as participants 
will all be newly diagnosed cancer patients who may be experiencing distress and 
who may feel more comfortable talking over the phone. The PHIA consent form will 
also be made available to Nurses in the Urology Department of the QEII Health 
Sciences Centre who may introduce the study to patients at the same time as they are 
providing other standard-of-care education, thus no additional patient contact will 
occur solely for research purposes. During the COVID-19 pandemic when no in-
person recruitment or contact will occur for research purposes, participants will be 
asked to sign a PHIA consent form on-line at the time they are invited to participate 
in the study. No candidates will be contacted without voluntarily initiating contact 
themselves or signing the PHIA form. 
2. 
The Study Physician (RR) will contact the candidates who have signed the PHIA 
form but have not yet been screen for elgibility criteria to confirm their treatment 
type and treatment date, interview them for their suitability to engage in low to 
moderate exercise using the Physical Activity Readiness Questionnaire for Everyone 
(PAR-Q+; Appendix 3; 37), and screen for other contraindications to exercise. 
Participants with significant co-morbidities (e.g., moderate or severe cardiovascular 
disease) will be asked to get a signed letter from their Primary or Specialist 
Physician clearing them to participate in the program before they can become 
eligible for the study. Instead of in-person blood pressure assessment, the Study 
Physcian will obtain their most recent record from their medical records. All 
potential participants are patients diagnosed with cancer, so they will all have visited 
a clinic recently and have blood pressure measurements on file. Participants who are 
eligible, including being able to join a videoconference and deemed safe to exercise 
will be emailed a link to an electronic version of the informed consent form residing 
on the NSHA platform, for their review prior to their day 1 assessment or start of the 
program.  
3. 
All participants who have passed the eligibility criteria and who have completed the 
online consent forms will be scheduled for a baseline in-person study visit. 
 
 
 
 
 
 

19 
 
PC PEP Protocol v6.0 December 8, 2020 
 
 
 
3.3 
RANDOMIZATION AND STRATIFICATION 
3.3.1 Sequence Generation 
To minimize the chance of having unbalanced groups, participants will be randomized 
according to a fixed block design (block length 4), stratifying on the following 
characteristics: (RP= Radical Prostatectomy, RT = Radiotherapy)  
a. Type of curative treatment (RP vs primary RT vs adjuvant/salvage RT post RP) 
b. Whether or not they have started or are scheduled to receive hormone therapy. 
(Note: men scheduled for RP are not expected to start HT) 
c. Whether they score positive or negative for mental distress on the K10 
questionnaire. (Note: men will have already completed this questionnaire as part 
of the online survey prior to randomization) 
 
 
Example Fixed Block (block length 4) Table 
‘A’ represents randomization to early PEP 
‘B’ represents randomization to later PEP 
 
RP and K10 neg – ABBA, BBAA, AABB, BABA, ABAB, BAAB, and so on 
RP and K10 pos – BAAB, AABB, BBAA, ABAB, BABA, ABBA, and so on 
 
RT and K10 neg and no HT – BAAB, ABAB, BABA, AABB, ABBA, BBAA, and … 
RT and K10 neg and HT – ABBA, ABAB, BABA, ABBA, AABB, BBAA, and … 
 
RT and K10 pos and no HT – ABBA, BABA, ABAB, BAAB, AABB, BBAA, and … 
RT and K10 pos and HT – BAAB, ABAB, BABA, AABB, ABBA, BBAA, and … 
 
RP + RT, K10 neg and no HT - BAAB, ABAB, BABA, AABB, ABBA, BBAA, and … 
RP + RT, K10 neg and HT - ABBA, BBAA, AABB, BABA, ABAB, BAAB, and … 
 
RP + RT, K10 pos and no HT – ABBA, BABA, ABAB, BAAB, AABB, BBAA, and … 
RP + RT, K10 pos and HT – BAAB, ABAB, BABA, AABB, ABBA, BBAA, and … 
 
Only one member of the team (the Principal Investigator), will have access to the 
randomization table. The PI will not be involved in the consent process (delivered by the 
RC and CEP).  
3.3.2 Randomization Assignment and Concealment Mechanism 
Once the participant completes the comprehensive survey, the RC will let the PI know 
the participant’s treatment type, whether they are on or scheduled for HT, and their K10 

20 
 
PC PEP Protocol v6.0 December 8, 2020 
score.  The PI will then let the RC know the next available assignment on the 
randomization chart (i.e. ‘A’ for early PEP, and ‘B’ for late PEP starting at six months). 
 
The participant will be booked for physical assessments and EEG/HRV testing on Day 0 
in Halifax (Figure 2). Neither the participant nor the CEP will know their assignment 
(early vs late) until after the initial assessments have been done.  
 
The participants randomized to the Early PEP program (A) will then be asked to stay 
with the CEP to undergo a full exercise assessment and receive a prescribed home-based 
exercise program.  
 
The participants randomized to Late PEP (B) will be told (after they complete their initial 
assessment) to follow the instructions provided by the medical system, and that they will 
be scheduled to meet with the research team again in 6 months time.  
 
 
 
 
Figure 2. Study Overview Timeline; Early Arm versus Late Arm 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility: 
Screening + 
Consent
Comprehensive 
survey
Baseline 
physical 
assessments 
incl. 
EEG + HRV
* Daily PEP activities can be 
found on a separate graphic 
RANDOMIZATION
12 month 
assessment: 
•
comprehensive  
survey
•
Physical
•
EEG / HRV
Strength & 
meditation 
training + 
educational videos 
+ Pelvic Floor 
Specialist training 
+ cell phone setup
Day 180
Usual medical care 
AND daily PEP 
activities* + weekly 
compliance + 
monthly 
videoconference + 
monthly AE 
assessment
Day 1 - 179
6 month 
assessment:
•
comprehensive 
survey
•
physical 
•
EEG / HRV
Exit interview
Day 0
Usual 
medical care
Day 180 -359
Day 360
Arm A: “Early”
Day 180 - 359
Day 0 - 179
Usual medical care
Usual medical 
care AND
daily PEP 
activities* + 
weekly 
compliance + 
monthly 
videoconfere
nce + monthly 
AE 
assessment 
Day 180
12 month 
assessment:
•
comprehensive 
survey 
•
Physical 
•
EEG / HRV
Exit interview
6 month 
assessment: 
•
comprehensive 
survey
•
Physical
•
EEG / HRV
Strength & 
meditation training 
+ educational videos 
+ Pelvic Floor 
Specialist training + 
cellphone setup
Day 360
Arm B: “Late”
Day 180 -359

21 
 
PC PEP Protocol v6.0 December 8, 2020 
 
4 CLINICAL INTERVENTION (Patient Empowerment Program) 
 
The PC-PEP program includes the following components: 
1. Specific training and instructions on how to follow a “home-based” individualized 
aerobic program aiming to achieve 150 minutes of exercise per week; 
2. Specific training and instructions on how to follow an “at home” individualized 
strength program twice per week as part of the 150 minutes of weekly exercise; 
3. Specific training and instructions on how to engage in pelvic floor strengthening 
exercises and follow an “at home” program three times a day; 
4. Specific training and instructions on how to meditate and follow an “at home” 
program for a minimum of 10 minutes per day; 
5. Specific training and instructions on how to use other healthy lifestyle habits 
related to diet, sleep, and social connection and make them part of routine living. 
6. Additional social support by being asked to call two other participants each week 
during the 6-month intervention period. Participants will also be encouraged to 
join a confidential videoconference hosted monthly by the PI, Study Physician 
and PC survivor ‘Mentors’. 
 
 
 
4.1 INTERVENTIONS AND ADMINSTRATION 
4.1.1 Aerobic Training Recommendations 
The SP will provide a medical overview to the CEP for every participant.  The CEP will 
assess each participant and create an individualized aerobic exercise plan for the six-
month period based on the safe training principles (e.g. slowly increasing intensity and 
duration of workouts over time). If possible, the participants will try to work their way up 
to the recommended 150 minutes per week. Participants will be encouraged to exercise 
daily via emails and short videos and to choose fun and social activities to maximize 
adherence.  
4.1.2 Strength Training Recommendations 
The CEP will also assess each participants ability to follow a home-based strength 
program using elastic bands for some exercises. The CEP will teach the proper technique 
and prescribe a set of exercises for each participant including the number of reps, sets and 
intensity (work: rest ratio) of each exercise (see Appendix 8 for an example handout).  
The CEP will relay the prescription to the Research Team who will create a YouTube 
video specific for that participant. The video reinforces the correct technique of each 
exercise and encourages the men to stay within their physical limits. The men are asked 
to do their strength training program twice per week with a target of 30 minutes per 
session as part of the 150 minutes of aerobic exercise. Over time they can increase the 

22 
 
PC PEP Protocol v6.0 December 8, 2020 
intensity of the program on their own by increasing elastic band tension or number of sets 
or reps, or duration of session. The CEP will be available as a resource to the men 
throughout the study duration. 
 
Participants Undergoing Radical Prostatectomy (RP) 
Men undergoing RP, a pelvic surgery, will need to adjust their exercise program.  The 
Research Coordinator will remind the men to taper down their exercise regimen four days 
prior to the surgical date (note the daily email system will be set up according to surgical 
dates). Once the men are admitted to Hospital for their surgery, they will follow the 
directions of their Health Care Professionals about when and how to reinstitute an 
exercise program (typically six weeks after their operation).  Gentle aerobic activities 
(e.g. walking) will start first, and only after they have been cleared by their Urologist can 
they restart the strength training sessions, for instance by starting with the upper body 
exercises. 
Participants Undergoing Radiotherapy (Brachytherapy or External Beam) 
Brachytherapy entails placing radioactive sources directly in the prostate gland through 
needles inserted in the perineum. Men have swelling and tenderness in the lower pelvis 
for at least a month. Men can exercise lightly throughout the recovery period. However, 
they will be instructed to follow the directions of their Radiation Oncologist before 
reinstituting their strength training exercises. 
Participants undergoing external beam radiotherapy can continue with the aerobic and 
strength exercises without modification.  If / when they develop fatigue or other issues, 
they will take instruction from their health care team. 
4.1.3 Pelvic Floor Muscle Training 
All participants will be encouraged to follow pelvic floor training (Appendix 7) three 
times a day during the intervention period.  They will be taught the concepts and 
techniques by: 
a) Watching a video explaining the anatomy and physiology of the pelvic floor and 
the rationale for the exercises, as well as practical exercises they can use to 
decrease the likelihood of leaking. 
b) Meeting with a Pelvic Floor Specialist via videohealth or telephone for a one-hour 
individualized teaching session.  
c) During the six-month intervention they will receive a daily email. On the email is 
a link to a 5-10 minute video outlining the pelvic floor exercise for that day.  
Every two weeks the video changes, slowly increasing in intensity, and teaching 
different techniques. They are expected to follow the video instructions three 
times a day. 
 
NOTE:  As per standard of care, all men who undergo surgery will meet with a Pelvic 
Floor Specialist 3-4 weeks after surgery for up to 6 weekly training sessions or as per 
their Urologist’s recommendations.    

23 
 
PC PEP Protocol v6.0 December 8, 2020 
4.1.4 Meditation Instruction 
Participants will receive a heart rate variability (HRV) monitor produced by the 
HeartMath Institute to use at home throughout the 6-month intervention. This will allow 
them to have consistent biofeedback and further help them learn how to relax (increase 
their HRV). The monitor can be a stand-alone hand-held unit, or as a Bluetooth 
compatible free unit synched to the patients iPhone or android device. The HeartMath 
Institute monitors were chosen based on their hardware and software’s reliable and 
frequent use in other clinical studies (30, 32, 38). Over 300 peer-reviewed studies have 
used HeartMath products and the technology is based on 25 years of scientific research 
(34). The monitors were also well received by participants during the feasibility study. 
Each patient connects a small probe to their earlobe which is painless and non-invasive. 
The probe detects their heart rate pattern and sends the signal to the device. The software 
produces an ongoing read out of the HRV and a display of a slow breathing pattern.  
Those who are using their cell phones will be encouraged to send a summary of their 
session to the RC.  Summary includes length of session and average heart rate coherence. 
These data will be deidentified and housed on NSHA servers.  
 
 
Patients will receive instruction on how to meditate (and increase their HRV) by: 
a) Watching a video produced by the HeartMath Institute (slow breathing, coupled 
with positive emotional image, and visualization of warming up the heart region) 
b) Daily emails will include a link to a 5- or 10-minute meditation sequence 
c) The start of each pelvic floor exercise video starts with two minutes of simple 
meditation instruction 
4.1.5 Healthy Lifestyle Promotion 
Participants will be encouraged to follow a healthy lifestyle by: 
a) Watching a video of the science underlying the PEP program (includes the 
modifiable risk factors for PC including diet, smoking, obesity, and sleep. Men 
who are smoking will be asked to contact their provincial smoking cessation 
program) 
b) Joining an in-person or videoconference session at the start of the program with 
the Study Physician 
c) Daily emails and short videos include reminders to adhere to the recommended 
lifestyle habits including dietary tips. 
d) Monthly videoconference sessions led by the Study Physician, other participants, 
and others (PI, Mentors) 
 
4.1.5.1 Smoking Cessation  
 
In the online baseline questionnaire, participants will be asked about their smoking habits 
(Appendix 4). Participants who indicated that they currently smoke or consume tobacco 
products will be directed to Tobacco Free Nova Scotia (TFNS). TFNS offers free, 
confidential, personalized support to help people quit smoking and stay quit. Participants 

24 
 
PC PEP Protocol v6.0 December 8, 2020 
will be asked to call 8-1-1 to register with the service at the beginning of their 6-month 
intervention period after they watch the educational videos and receive other health 
promotion advice (Day 0 for ‘Arm A: Early Intervention’ or Day 180 for ‘Arm B: Late 
Intervention). Participants from provinces outside of Nova Scotia will still be asked to 
call 8-1-1 while at the QEII Hospital for their first study visit, after which TFNS will 
refer them to their specific provincial smoking cessation program. A 2016 study found 
that Canadian provinces with smoking cessation initiatives for cancer patients offered a 
referral to 22-80% of ambulatory cancer patients who screened positive for smoking and 
21-45% of those patients accepted the referral (39). Therefore, participants may be 
referred to smoking cessation services through standard medical care, in which this will 
act as extra support to further encourage acceptance of referral to TFNS or other 
provincial service. 
 
4.1.6 Connection and Relationship Teaching 
Participants will learn about and be encouraged to increase the multidimensional 
connection and intimacy in their lives by: 
a) Watching a video produced by the PI 
b) Joining an in-person or videoconference session at the start of the program with 
the Study Physician 
c) Daily emails and short videos include reminders to express and ask for more 
connection in their lives.  For instance, every Sunday the pilot participants were 
asked to call a family member or friend who lives at a distance 
d) Monthly videoconference sessions led by the Study Physician, other participants, 
and others (PI, Mentors) 
4.1.7 Social Support 
To maximize compliance with an intense program and to improve the depth and breadth 
of social support we’re asking all participants to 
a) Call two other co-participants each week. Co-participants are matched by 
demographic features. They are instructed to ask their ‘Buddies’ how they are 
doing with the program and to report their own compliance. 
b) Join a monthly videoconferencing session 
 
4.1.8 Monthly Videoconferencing with active PEP participants 
The www.Zoom.us platform is an easy-to-access platform to allow distant participants to 
join in on a videoconference.  Participants will be encouraged watch or listen to the 
videoconference, and if they feel so inclined, to join in on the conversation. The 
conference will occur for one hour on the first Tuesday of each month at 7pm AST/ADT 
and will be available to the participants in the active phase of the protocol. This 
conference will provide an opportunity to discuss issues arising on the trial and include 
tips on how to address health concerns and on how to maintain compliance with the 

25 
 
PC PEP Protocol v6.0 December 8, 2020 
protocol. Participants who are willing will be encouraged to share their experience of 
going through treatment. 
 
The Study Physician and PI will host the meetings and will be joined by PC survivors 
who have been screened. The survivors will act as ‘Mentors’ by providing stories of their 
personal experiences. Mentors may offer their contact information during the conferences 
or on the study’s website, and participants can choose to reach out to the Mentors for 
ongoing support. The Mentors will not be offering medical advice. Mentors will be 
registered as “volunteers” with the NSHA and thus they will be required to sign an 
NSHA Pledge of Confidentiality agreement. Any action considered as a breach of 
confidentiality will result in immediate termination of their role as “Mentor/Volunteer”. 
 
Participants themselves will be offered the opportunity to become mentors after a 
minimum of one year of follow up from time of their randomization.  
Maintaining Privacy during Videoconferences 
 
The Zoom videoconferencing software has a number of privacy features including: 
a) Only participants who have a password can access a meeting.  Each meeting has 
its own unique password 
b) Participants can join by telephone only and ‘listen’ to the conversation, with the 
option of speaking. 
c) The RC can provide a unique username to each person like a 4-digit number. The 
username is what appears as the participants name for those who decide to join by 
videoconference. 
d) Each participant can mute their microphone and turn off or cover their camera.  
e) Once the appropriate participants have joined a meeting the meeting can be 
‘locked’ so that no one else can join the meeting 
f) The Zoom software does not capture any personal information of the participant. 
Each person simply goes to a webpage and enters in the meeting-specific 
password. 
g) The videoconferences will not be recorded. 
h) Participants will be reminded to maintain the confidentiality of all other 
participants both at the start and end of each meeting. 
 
 
 

26 
 
PC PEP Protocol v6.0 December 8, 2020 
Figure 3. Schedule of weekly PEP activities during the 6-month intervention period. 
 
 
4.1.9 Using Technology for Support 
 
To increase compliance with this intense program, participants will receive a daily email 
outlining the activities recommended by the program for each day. These email notices 
will point out different resources (including video links) to help the men with their 
implementation of the program’s recommendations. Participants who use a smart 
 phone will also receive a text three times per day reminding them to do their pelvic floor 
exercises. Participants who do not have a smart phone will choose their preferred 
platform for their three times a day reminder (e.g. text message, or email). Smartphones 
will not be provided to participants as part of the study.  
 
Bank of Emails and Videos 
 
To standardize the program for all participants (for both early and late groups, and over 
the entire accrual period), we will create a bank of 180 emails for each day of the six 
months of intervention.  Each email will have an accompanying 2-4-minute YouTube 
video. 
 
Once a participant has watched all day 0 educational videos and spoken with the Study 
Physician, they will be asked to start the program.  Each day the RC will email each 
  
MON 
TUES 
WED 
THUR 
FRI 
SAT 
SUN 
Meditation  
(minimum 10 min/day) 
ü 
 
ü 
ü 
ü 
ü 
ü 
ü 
Pelvic Floor Exercises* 
 (8-10 min/day) 
ü 
ü 
ü 
ü 
ü 
ü 
ü 
Aerobic Exercises 
(30 min/day or as total 
time; allowed to miss a 
day) 
 
 
ü 
 
 
Somethi
ng 
different 
 
Strength training 
Work 
out #1 
Work 
out #2 
Connection suggestions 
Call 2 
co-
particip
ants 
ü 
ü 
ü 
ü 
Fun 
activity 
of 
choice 
Call 
some 
one at a 
distance 
Compliance survey 
 
 
 
 
 
 
ü 

27 
 
PC PEP Protocol v6.0 December 8, 2020 
participant who is on the active phase of the trial.  At the end of active phase, the 
participants will no longer receive emails and no longer be invited to join the monthly 
videoconferences. 
 
 
4.2 DESCRIPTON OF ARM A – ‘EARLY’ INTERVENTION 
 
All participants prior to randomization will have taken the comprehensive online survey 
(Appendix 4) and completed the physical assessments (Appendix 5) with the CEP and the 
EEG/HRV with the RC.  
 
Participants will learn about their randomization assignment at the end of the pre-
intervention assessment by the CEP. Those randomized to ‘Early’ PEP will stay with the 
CEP for the strength training session.  The schedule for Arm A participants is as follows: 
 
 4.2.1 Education Phase for ‘EARLY’ ARM  ‘A’ Prior to Day 1 
a. Strength training session The CEP will create an individualized strength training 
program (one session to be done every Monday, and a different session to be done 
every Thursday).  A YouTube video of these two sessions will be produced by the 
Research Team who will send the links and a paper copy of the list of exercises to 
the participant. The strength training session can be conducted while maintianging 
2 meters distance at all times and participants use new exercises bands that have 
not been used by any other people. 
b. At the pre-intervention session the CEP will also offer advice and a suggested 
weekly aerobic exercise regimen. 
c. The participant will by given an appinment with the Pelviv Floor Specalist.  who 
will provide individualized PFME teaching. This will be done via videohealth or 
telephone. 
d. The participant will be directed to watch three videos (total 1 hour viewing time) 
and given a chance to ask any questions the participant may have at that time: 
i. Science behind PEP 
ii. Pelvic Floor training 
iii. Meditation 
iv. Connection 
e. A research staff member will review the PEP program with the participant. Once 
the participant is satisfied with their instructions, they will start the intervention 
phase. 
4.2.2 Intervention Phase for EARLY ARM  (days 1-180) 
The men randomized to the Early intervention will complete the following activities 
during the first six months at home: 

28 
 
PC PEP Protocol v6.0 December 8, 2020 
1. Between the strength and aerobic program to try to achieve or work towards 150 
minutes/week of exercise**.  They will be encouraged to do some form of 
exercise every day, even if it is just easy walking. 
2. Do an “at home” individualized strength program twice per week, one program on 
Monday and a different program on Thursday.** Men can choose to deviate from 
these specified programs by doing more than twice per week strength training, 
working out in a gym alone (+/- with the advice of a personal trainer) as long as 
they do strength training twice per week. 
3. Engage in pelvic floor strengthening exercises three times a day, for 8-10 minutes 
per session 
4. Meditate for a minimum of 10 minutes per day 
5. Read an email and listen to a video (embedded in the email) every day which 
includes healthy lifestyle habit suggestions and social connection teaching. 
6. Call two other participants each week.  
7. Join a monthly confidential videoconference hosted by the PI, Study Physician 
and PC survivor ‘Mentors’. 
8. Fill out their compliance survey (5min) weekly (Appendix 6). 
**Men undergoing surgery will be instructed to decrease their exercise and strength 
program the 3 days prior to the procedure, and to slowly increase their aerobic 
component after the surgery on the advice of their Urologist.  Men undergoing RP or 
Brachytherapy will not restart their strength training until they have been given 
permission by their Urologist or Radiation Oncologist, for instance six weeks after 
surgery.  
 
All men undergoing surgery will see a Pelvic Floor Specialist starting 3-4 weeks after 
their surgery and weekly for six weeks to undergo PFME teaching. 
 
4.2.3 Post Intervention Assessment Phase for EARLY ARM (Day 181)  
The men randomized to the Early intervention (Arm A) will complete the following 
assessments during a single visit on Day 181 (+/- 2 days): 
1. Comprehensive online survey (same as the pre-invention survey) 
2. Program evaluation survey 
3. In-person audiotaped interview evaluating the program 
4. Physical Assessments with the CEP 
5. EEG/HRV assessment 
During the assessment, research staff members will wear a new pair of medical gloves 
and a new disposable medical mask. Participants will also be required to wear a mask. 
Only one participant will be present during each assessment. Staff will be required to 
maintain a distance of 2 meters from each other and from particiapnts whenever possible. 
Equipment will be sanitized thoroughly after ever use. These procedures will occur 
during every study visit. 
 

29 
 
PC PEP Protocol v6.0 December 8, 2020 
Arm A men will then follow usual care as prescribed by the medical system until day 
359. 
4.2.4 End of trial Assessment for EARLY ARM (Day 360)  
On Day 360 (or within a few days) the Early’ men will come in for a single visit to 
complete  
1. Comprehensive online survey (same as the pre-invention survey) 
2. Physical Assessments with the CEP 
3. EEG/HRV assessment 
 
Please refer to Figure 2 for a timeline diagram of ‘EARLY ARM’ schedule. 
 
4.3 DESCRIPTON OF ARM B - ‘LATE’ INTERVENTION 
Participants will learn about their randomization assignment at the end of the initial 
physical assessment with the CEP.  Those randomized to ‘Late’ PEP will be told to 
follow the instructions provided by the medical system. All men undergoing surgery will 
see a Pelvic Floor Specialist starting 3-4 weeks after their surgery and weekly for six 
weeks to undergo PFME teaching. 
Late arm men will receive no further instruction about how to empower themselves until 
they meet again with the CEP for assessment on day 180 (or within a few days) for a 
strength training.  During that visit the men will complete. 
1. Comprehensive online survey (same as the pre-invention survey) 
2. Physical Assessments with the CEP 
3. EEG/HRV assessment 
4.3.1 Education phase for LATE ARM (Just prior to Day 180) 
a. Strength training session.  The CEP will create an individualized strength 
training program (one session to be done every Monday, and a different 
session to be done every Thursday) for the participant after assessment of 
their health by the study’s physician just prior to day 180.  The study’s 
physician and CEP will ensure the exercise program offered/recommended 
is suitable for the level of fitness of the participant.  A YouTube video of 
these two sessions will be produced by the Research Team who will send 
the links and a paper copy of the list of exercises to the participant 
b. At the same session the CEP will also offer advice and a suggested weekly 
aerobic exercise regimen. 
c. The participant will be directed to watch three videos (total 2 hour viewing 
time) 
i. Science behind PEP 
ii. Pelvic Floor training 
iii. Meditation 
iv. Connection 

30 
 
PC PEP Protocol v6.0 December 8, 2020 
d. After they watch the videos the participant will videoconference or 
telephone call the Study Physician and/or PI to discuss information 
provided on the videos and ask questions. The SP/PI will review the PEP 
program. Once they are satisfied with their instructions, they will start the 
intervention phase. 
4.3.2 Intervention Phase for ‘LATE’ ARM  (Days 180-360) 
The men randomized to the Late intervention will complete the following activities 
between 6 to 12 months post diagnosis, at home: 
1. Between the strength and aerobic program try to achieve or work towards 150 
minutes/week of exercise.  They will be encouraged to do some form of exercise 
every day even if just easy walking. 
2. Do a “at home” individualized strength program twice per week, one program on 
Monday and a different program on Thursday. Men can choose to deviate from 
these specified programs e.g. do more than twice per week strength training, work 
out in a gym alone or with the supervision of a personal trainer as long as they do 
strength training twice per week. 
3. Engage in pelvic floor strengthening exercises three times a day. 
4. Meditate for a minimum of 10 minutes per day 
5. Read an email and listen to a video (embedded in the email) every day which 
includes healthy lifestyle habit suggestions and social connection teaching. 
6. Call two other participants each week.  
7. Join a monthly confidential videoconference hosted by the PI, Study Physician 
and PC survivors ‘Mentors’. 
8. Fill out their compliance survey (5min) weekly (Appendix 6). 
4.3.3 Post Intervention Assessment Phase for LATE ARM (Day 360) 
The men randomized to the Late intervention will complete the following assessments 
during a single visit on Day 360 (or within a few days): 
1. Comprehensive online survey (same as the pre-invention survey) 
2. Program evaluation survey 
3. In-person audiotaped interview evaluating the program 
4. Physical Assessments with the CEP 
5. EEG/HRV assessment 
Please refer to Figure 2 for a timeline diagram of ‘LATE ARM’ schedule. 
 
 
 
 
 

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PC PEP Protocol v6.0 December 8, 2020 
5 CLINICAL EVALUATIONS 
 
5.1 PRIMARY ENDPOINT (MENTAL DISTRESS) EVALUATION 
 
The primary outcome is current mental health status as measured by the Kessler 
Psychological Distress Scale-K10 assessment at the six-month point self-administered by 
all participants- at the end of the intervention period for Early men and prior to the Late 
men starting the program. K-10 is a 10-item questionnaire intended to yield a global 
screening measure of current mental health illness based on questions about anxiety, 
depressive symptoms and psychological distress that a person has experienced in the 
most recent 4-week period (40). Scores on K-10 range from 10 to 50.  Scores of 20 or 
above indicate the presence of a mental health illness ranging from mild (20-24), 
moderate (25-29) or severe (30 or above). This is a screening instrument that practitioners 
consider to help them make a clinical judgement as to whether a person needs mental 
illness treatment (41). K-10 has been widely implemented, including in the World 
Health Organization World Mental Health Survey, Center for Addiction and Mental 
Health (Toronto, Ontario), as it is widely used all over the world in epidemiology and 
clinical research (42) and prior research has shown the K-10 to be an excellent 
screening tool for mental health illness (43-44). In a study (n=3,697) assessing the 
screening for mental health illness among older adults (65 years old and plus), the K10 
was found to exhibit sensitivity to internalizing disorders as they occur across the lifespan 
(45). 
 
If the sum of the ten questions is greater than 20 on the K10, the participant is deemed to 
screen positive for mental distress, and those whose total is 20 or less are deemed to 
screen negative for mental distress. 
The Study Physician will contact those who have screened positive for mental distress 
and will recommend or refer them to the psychosocial cancer team at the Nova Scotia 
Cancer Centre. 
 
5.2 SECONDARY ENDPOINT EVALUATIONS 
 
Secondary outcome measures will include physical fitness assessments, relaxation brain-
waves activity (EEG) measurement (alpha, beta, delta, theta, gamma averages over 
listening to 10 minutes relaxation music and instructions), Heart Rate Variability, and 
quality of life patient reported survey outcomes pre- and post- PC-PEP. Three a-priory 
hypotheses will examine changes between pre and post physical strength, EEG brain 
activity during meditation and quality of life patient reported outcomes. We predict 
improved physical and quality of life outcomes in those randomized to the ‘early’  
intervention arm compared to those randomized to the ‘late’ intervention. 
 
 
 
 

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PC PEP Protocol v6.0 December 8, 2020 
5.3 SCHEDULE OF EVALUATIONS 
 
XA = applies to participants in ‘ARM A Early’ only 
XB = applies to participants in ‘ARM B Late’ only 
 
Note: Compliance surveys will be administered weekly during the intervention part of the 
study (Day 0 – 180 for Arm A Early and Day 180 – 360 for Arm B Late). Assessment of 
AEs will occur monthly throughout these intervention periods. 
 
 
5.4 PRE- AND POST-INTERVENTION MEASUREMENTS 
5.4.1 Physical Fitness Assessment  
All physical fitness assessments will be performed by a CEP. Measurements will be 
recorded for weight, height, hip, and waist. Body composition and abdominal obesity will 
be assessed via calculating body mass index (BMI) from weight and height 
measurements, and waist-to-hip circumference (WHR). According to recommendations 
from the World Health Organization, abdominal obesity is defined as a BMI >30.0 and 
WHR >0.90 for males (46). Aerobic fitness will be determined using the six-minute walk 
test (47). Static postural and balance control will be assessed using the one-legged stance 
test (48) while the timed sit-to-stand test will be used to evaluate lower limb strength 
(49).  
 
 
 
Evaluation 
Screening 
 
 
(Day -7 to -1) 
Baseline/ 
Study Visit 
1 
(Day 0) 
Study Visit 
2 
 
(Day 180  
± 3) 
Study Visit 
3 
 
(Day 360)  
± 3) 
Inclusion/exclusion criteria  
X 
 
 
 
Contact information + planned date of PC treatment 
X 
 
 
 
PAR-Q+ assessment 
X 
 
 
 
Medical history 
X 
 
 
 
Informed consent 
 
X 
 
 
Comprehensive online questionnaire 
X 
 
X 
X 
Physical assessments 
 
X 
X 
X 
EEG/HRV assessments 
 
X 
X 
X 
Randomization 
 
X 
 
 
Adverse Events 
 
 
X 
X 
Exit Interview 
 
 
XA 
XB 

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PC PEP Protocol v6.0 December 8, 2020 
5.4.2 Relaxation – Brain Activity Assessment 
 
EEG assessment of the relaxation state will be measured using the MuseTM (InteraXon, 
Inc., SCR_014418, Toronto, Ontario, Canada) neurofeedback device (Appendix 9). It is a 
headband that detects and measures brain activity via seven dry sensors located at various 
points across the forehead and behind the ears. These measures of brain activity will be 
used as an indication of skill of mindfulness and meditation. The MuseTM device has been 
used in previous research studies related to treatment of traumatic brain injury in civilian 
and military populations (50). A validation study reported that the MuseTM device 
accurately captured event related potential components during rapid tests, demonstrating 
its application in clinical studies (51). Furthermore, the MuseTM takes minimal time to 
set-up compared to larger electrode EEG devices, costs significantly less to purchase and 
administer, is portable, non-invasive, and user-friendly (51). The MuseTM device was 
chosen because it will allow us to collect EEG data from a large number of participants at 
a low cost.  The analysis from the MuseTM data will provide the results we are interested 
in: how many restful periods were achieved, how frequently, and how many times during 
the 10 minute session was the individual able to bring their attention back to the present 
moment and relax (go into theta brain activity). MuseTM  captures in an excel file its own 
data which is exported to the study data base housed on the NSHA servers. 
5.4.3 Online Questionnaires 
All online questionnaires will be administered via Research Electronic Data Capture 
(REDCap) and they will include the evaluation of the following areas (please see 
Appendix 4 for a complete list of online questions): 
1. Demographics – e.g., education, household income, relationship status, etc. 
2. General Health Questions – e.g., presence of health conditions, medication usage, 
etc. 
3. Cancer-Specific Questions – e.g., date of diagnosis, cancer stage, Gleason score, 
etc.  
4. Urinary Tract Symptoms: For the assessment of lower urinary tract symptoms and 
impact on quality of life, participants will be asked to complete the Expanded 
Prostate Index Composite (EPIC-26) (52) questionnaire and the International 
Prostate Symptom Score (IPSS) (53, 54). The EPIC is a validated questionnaire 
that was derived from the UCLA-Prostate Cancer Index (UCLA-PCI) (55) to 
assess health-related quality of life after treatment for cancer. The 26-item 
domain-specific patient-reported questionnaire has been tested on patients treated 
with RP and it has demonstrated satisfactory results in both validation analyses 
and respondent compliance with survey completion (52).  
5. Modified Charlson Comorbidity Index questionnaire (CCI): The CCI is based on 
a history of concomitant disease (e.g., diabetes, renal failure, cardiovascular 
disease, etc.) and malignancy and it was a tool initially developed and validated in 
women being treated for breast cancer (56). However, since its inception, it has 
gone on to be used in various clinical populations and has been widely 
administered to predict short-term outcomes (57 – 62).  

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PC PEP Protocol v6.0 December 8, 2020 
6. Quality of Life (QoL): Questions taken from several questionnaires will be used to 
assess the different components of QoL: 
 
a) Functional Assessment of Cancer Therapy-Prostate (FACT-P) – This 
questionnaire has been shown to be one of the best psychometric tools for 
measuring the psychosocial (e.g., emotional distress, social functioning, 
etc.) aspect of QoL in patients with PC (63).  
b) Short Form 12 (SF-12) Health Survey – This questionnaire will be used to 
assess general health QoL (64, 65). The SF-12 has been considered the 
most superior generic instrument for measuring health related QoL in 
individuals with PC (55, 65, 67). 
c) Kessler Psychological Distress Scale (K10) – The K10 is a validated and 
widely used clinical instrument for the assessment of psychological 
symptoms, which has demonstrated high factorial and construct validity 
(68, 69). 
 
5.4.4 Measuring Compliance 
Each week the participants will self-report the number of times they did aerobic exercise, 
strength exercise, pelvic floor exercises, and meditation – and the average number of 
minutes they spent during each session - by completing an online survey (please see 
Appendix 6 for a list of questions for the compliance survey sent out weekly via email). 
 
6 STATISTICAL CONSIDERATIONS 
 
6.1 SAMPLE SIZE AND ACCRUAL 
 
A meta-analysis of 4494 PC patients reported in 27 articles shows the incidence of pre-
treatment anxiety to be 27% and of pre-treatment depression to be 18% (69). Kessler 
Psychological Distress Scale-K10 (our primary outcome questionnaire) picks up both 
depression and anxiety so the rate of clinical positive K10 score at diagnosis is likely lower 
than 45% (the sum of 27% and 18%). In our feasibility study of a diverse group of 30 
prostate cancer survivors (22 of which having been treated more than 2 years since their 
diagnosis) 6 men scored positive for mental distress (K10 measurement) at baseline (20%). 
We hypothesize, based on literature findings, our participants’ mental health status will 
likely be poorer at the time of their diagnosis, likely higher than 20%. So, as a conservative 
estimate (between 20% and 45%) we predict that the rate of screening positive on K10 for 
mental distress will be 30% of all our study participants at baseline.   
 
At the six-month time point we expect the control group (Late arm) will maintain a 30% 
positive distress rate as they will be dealing with the long-term side effects of their 
treatment and multiple other stressors. Supporting this assertion comes from two trials 

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PC PEP Protocol v6.0 December 8, 2020 
showing that up to 23% of men who undergo PC treatment continue to screen positive for 
mental health issues 12 months after and onwards (71-72). Screening positive for mental 
distress are likely to be even more prevalent at the six-month point than at 12 the month 
point, again supporting an estimate of 30% distress rate in the control group (Late arm) at 
six months (71-72). 
We expect those in the intervention arm (Early Arm) to have improved their mental 
health status at six months because the intervention is designed to address multiple issues 
(in the physical, cognitive, and social realms) that lead to depression and anxiety. In our 
feasibility study, the K10 distress rate decreased from 20% to 6% (a 66% reduction) in 
just 28 days.  If in the proposed trial the estimated improvement is a similar 2/3 reduction 
in distress rates, we calculate the distress rates will drop from 30% at baseline down to 
10% at six months.  To summarize, at six months we expect 30% of the control group to 
score positive for mental distress compared with 10% in the intervention group. With a 2-
sided test, an alpha level of 0.05, and estimated power of .80 power analysis based on an 
anticipated incidence of screening positive for mental health issues among men 
diagnosed with prostate cancer six months after diagnosis of 30% (control arm) vs 
incidence of 10% (intervention arm) indicated a total of 124 participants is needed to 
detect a minimum effect (F = 0.35), which is considered to be meaningful (60-62). 
Although during the PC-PEP feasibility study there were no dropouts (n=30), we will 
accrue an extra 6 participants to account for any possible dropouts. The COVID-19 
pandemic has presented additional challenges in accrual. We expect a small number of 
participants to miss 6-month or 12-month follow-up assessments due to concerns 
regarding the virus. We also originally planned to acrue a small number of participants 
from New Brunswick and Prince Edward Island, however due to restrictions in travel 
across provinces, it is difficult for these participants to arrange and commit to all study 
visits in Halifax. We plan to accrue an additional 10 participants to account for these 
participants missing assessments. Therefore, the total number of participants we plan to 
accrue is 140.  
 
 
6.2 STATISTICAL ANALYSES 
6.2.1 General Considerations  
General description of the statistical methods is outlined below. A more detailed 
statistical analysis plan (SAP) will be developed early in the study which includes details 
on coding, data handling, output tables and figures, and technical specifics on all 
variables. All SAP associated documents will be finalized without knowledge of any 
emerging results from the study.  
6.2.2 Comparisons 
Following our design, we will conduct three sets of analyses comparing outcomes for (1) 
the intervention (early) group versus control (late) group in the first half year (PC-PEP vs 
usual care); (2) Late group (i.e. late intervention) versus the post early group period in the 
second half year following diagnosis; and (3) difference in outcomes for early versus late 

36 
PC-PEP. This provides assessments of the effectiveness of early PC-PEP versus usual 
care (Obj. 1), late PC-PEP versus men who have already completed PC-PEP (Obj. 2), and 
late versus early PC-PEP (Obj. 2).    
6.2.3 Primary Analyses 
Descriptive analyses will first be conducted to assess the extent of balance between 
intervention and control groups with respect to treatment modalities and base-line 
characteristics. As a consequence of our blocked randomization, analyses of primary and 
secondary outcomes need to account for potential clustering of the data and accrue the 
benefits of blocking on baseline variables. Accordingly, conditional-fixed effect, 
generalized linear regression models will be used. Appropriate link and error distributions 
will be employed, as appropriate, for each dependent variable. An intent-to-treat 
approach will be used, as we wish to assess effectiveness. Adjustment for prognostic 
covariates will be employed to address observed imbalances between randomized groups. 
Post-hoc analyses to describe heterogeneity in treatment effects will also be conducted to 
support our Objective 3 investigation. Statistical analyses will be performed using R ver. 
3.6.0 and SPSS ver. 24.  
6.2.4 Qualitative Analysis 
Face-to-face interviews will be conducted with two purposively selected subjects in each 
of the treatment and control arms of 3 randomization blocks (see yellow bars in Table 1, 
for a total of 12 interviews). We anticipate that one of the two will be a man who had 
high perceived benefit of PC-PEP, and the other a man who had lower perceived benefit; 
however, we will also draw on results from post-hoc analyses and results from previous 
interviews to guide subject selection. In addition, two focus groups will be conducted 
with personnel delivering PC-PEP (at months 14 and 22). All interviews/focus groups 
will be audiotaped and transcribed verbatim before being reviewed and coded by 
members of the research team. Analysis will be guided by realist evaluation processes 
based on a cycle of hypothesis generation, testing and refinement of Context-Mechanism- 
Outcome (C-M-O) configurations (73-74). In keeping with this approach, we will 
generate C-M-O configurations using both qualitative and quantitative data (post-hoc 
analyses) . Patient interview materials will be qualitatively analyzed by two members of 
the research team, independent of each other. They will generate preliminary codes based 
on 4 patient interviews, then meet to compare and develop a coding framework to code 
the remaining data. A detailed coding procedure will be followed, and codes will be 
compared among the raters and re-coded if necessary, to identify and capture patterns and 
trends rooted in the data. Data will be stored, managed, and coded with the latest NVivo 
qualitative software.  
Additional thematic analyses or analyses informed by the abovementioned critical 
paradigm may also be performed. A series of tables and summaries will be constructed to 
highlight key results across data sources for each age group and treatment type and 
develop detailed case reports to facilitate knowledge mobilization of study findings at 
local and provincial levels.  
PC PEP Protocol v6.0 December 8, 2020 

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PC PEP Protocol v6.0 December 8, 2020 
6.2.5 Secondary Analyses 
Secondary outcomes will be assessed through descriptive statistics: adherence counts, 
frequencies, means, standard deviations, range of responses, proportion of participants 
who adhered to the various aspects of the program (engaging in the exercises prescribed 
at the rate prescribed).  
 
A series of a-priori repeated measures t-tests will be used to assess pre- and post-physical 
strength and relaxation secondary outcomes. We hypothesize that if the program is 
successful, there will be differences (e.g. improved physical fitness and ability to relax). 
Urinary and mental health symptoms will also be assessed using repeated measures t-
tests. We hypothesize that if the program is successful, there will be differences (e.g., 
improved urinary continence and less psychological distress). Analyses will be assessed 
using R ver. 3.6.0 and SPSS ver. 24.  
 
 
7 ADVERSE EVENTS AND REPORTING REQUIREMENTS 
7.1.1 Adverse Events 
A clinical adverse event (AE) is any unfavourable or unintended sign or symptom 
associated with the study intervention and occurring in a participant assigned to the 
intervention. Participants will be able to self-report AEs to the study team at any time 
throughout the study. The chance of an adverse event on this study is expected to be low 
and very likely related to aerobic or strength training. All reported AEs will be recorded 
for type, severity, relationship to exercise program (aerobic, strength), expectedness, 
serious AE (yes/no), timing, action taken (if any) and outcome.  
 
All AEs reported from the date of informed consent until 28 days after the end of the 
intervention are considered. Men randomized to the ‘late’ group from the time they 
complete their initial physical assessment until the start of the intervention at the six-
month point. AEs are also assessed by CEP at the time of each physical assessment 
(baseline, six months and one year) and during strength training.   
The risk of an adverse event from pelvic floor exercises, meditation, or social support is 
so low, that no AEs related to these activities are anticipated. 
The study intervention does include home-based aerobic and strength exercises, which 
pose some possible AEs. Notwithstanding, this is a relatively low-risk group of men (who 
also have been deemed fit to undergo potentially curative surgery and/or radiotherapy) 
and all potential candidates will have been screened by the study physician by review of 
their medical history and through in-person assessment by the CEP to assess 
cardiovascular contraindications to exercise. Our approach should systematically identify 
and screen out any individual for whom this study is contraindicated.    
It is possible that the participants may experience the following expected non-serious 
adverse events as a result of participating in this study:  musculoskeletal injury (sprain, 
strain), joint pain, falls, and/or muscle soreness. These will also be listed in the informed 

38 
 
PC PEP Protocol v6.0 December 8, 2020 
consent form and discussed with the participant prior to their signed consent. Participants 
will be instructed to contact us immediately if the experience symptoms/events beyond 
what is typically expected from exercising.  
Rare but serious AEs are also possible, however unlikely. Those that may occur during 
either physical assessment (six-minute walk, sit to stand test, etc.), during the strength 
training session with the CEP, or during the home-based program include myocardial 
infarction (heart attack), stroke, unconsciousness, bone fracture or other serious injury. 
These serious AEs, along with unanticipated adverse events not listed in the protocol or 
consent form but still believed to be as a result of participation in this study, will be 
reported according to section 7.1.3. 
Events during physical assessment and strength training are rare (<1/100,000 in well men 
and 1/10,000 in sick men). The CEP will monitor the participants closely in a location 
with an automatic external defibrillator, five minutes away from the emergency 
department. 
The CEP will provide advice about home-based exercise including the principles of 
staying within personal physical limits, slowly increasing the intensity of the program 
over time, and reviewing the warning symptoms of heart attack and stroke. 
7.1.2 Indications for Stopping Exercise 
The participants will be instructed about when to stop exercising.  Absolute Indications to 
Stop Exercising (during assessment): Suspicion of myocardial infarction, onset of angina 
(chest pain), signs of poor perfusion (pallor, cyanosis (blue skin), or cold and clammy 
skin), severe or unusual shortness of breath, central nervous system problems 
(incoordination, dizziness, confusion, visual problems), participants request to stop, 
extreme fatigue, skeletal fracture 
Relative Indications to Stop Exercising (at home): Increasing chest pain, shortness of 
breath, wheezing, leg cramps (intermittent claudication), fatigue, signs or symptoms of 
exercise overload. 
 
7.1.3 Reporting Requirements 
All AEs and SAEs whether reported by the participant, discovered during questioning, 
directly observed, or detected by other means must be recorded in the patient’s medical 
record and in the study’s database. Participants will be asked to ensure they have been or 
will be seen by a physician for full assessment and documentation of the event. All AEs 
will be reviewed by the Study Physician and PI. The PI is responsible for notifying the 
REB about the AEs in accordance with local regulations. 
Reporting Deaths. All deaths on study will be reported through and including from time 
of consent for 13 months. The Study Physician will investigate the circumstances of the 
death and include a description of the adverse event in sufficient detail to allow for a 
complete medical assessment of the case and independent determination of the possible 
causality. The Study Physician and PI will promptly report these findings to the REB. 

39 
 
PC PEP Protocol v6.0 December 8, 2020 
Statistically Analysis of Adverse Events:  Adverse event rates will be summarized with 
frequency and percentage within each arm and across arms.  The men randomized to the 
‘late’ arm will have a one-time assessment of AE during their first six month ‘waiting’ 
period. 
 
9 WITHDRAWAL OF PARTICIPANTS 
9.1.1 Protocol Violation 
Participants who do not comply with activities outlined in the intervention arm will 
remain on trial. They will be highly encouraged to complete the six- and 12-month 
assessments and provide their feedback on the exit interview.  
9.1.2 Withdrawal of Participants 
Participants are free to withdraw from the trial at any stage without providing a reason 
and without consequence. If a man withdraws from the study, any data collected on him 
up to that point in the study will go forward for study analysis.  If a man withdraws from 
the intervention but provides consent to complete subsequent follow up measurements, he 
will continue to attend study assessments and data will be used for intention-to-treat 
analysis.  
 
11 PROTECTION OF HUMAN SUBJECTS 
11.1.1 Harms 
The majority of the practices in the protocol have no possible harms, except exercise. 
However, exercise has been shown to be a safe and effective means of preventing and 
improving a multitude of physical and psychological treatment and disease-related side-
effects across the cancer trajectory (e.g., on and off treatment). For example, research has 
shown that cancer survivors who exercise not only have a reduced risk of disease 
recurrence (75) and all-cause/cancer mortality (75, 76) but also have reduced side-effects 
of their cancer and/or its treatment such as fatigue (77-79), anxiety (80,81), depression 
(79, 81), and cancer-related pain (82). Thus, while there is always the risk of increased 
short-term fatigue, stiffness muscle soreness, and injury with any exercise program, 
exercise has been shown to be a safe supportive care intervention for cancer patients and 
survivors and the potential benefits (e.g., improved physical, social and emotional 
functioning and overall quality of life) outweigh the risks. Furthermore, each participant 
will be required to have a physician’s approval to participate, and our CEP will design an 
individualized program to minimize risk. 
 
Participants will be asked to fill out several questionnaires regarding their health, 
substance use, etc. Some participants might find some of these questions uncomfortable, 

40 
 
PC PEP Protocol v6.0 December 8, 2020 
distressing, or upsetting to answer. Participants can choose not to answer any questions 
that they do not wish to answer. 
 
There are no known risks with having one’s brain waves measured, but some may find 
the head band around their head uncomfortable. We will do our best to adjust the head 
band so that it is comfortable on the participant’s head. The head band will not cut or 
mark the skin. 
 
Some participants may also find the procedure of having the muscle activity in their 
pelvic floor measured with the medical biofeedback apparatus embarrassing or 
uncomfortable. We will provide participants with a hospital gown to protect their 
modesty. If participants feel uncomfortable with the procedure, they are free to withdraw 
from the study at any time without penalty. 
 
In addition, the participants will be told to alert the PI, SP or RC of the study via email or 
telephone call of any unexpected adverse effects (e.g., exercise induced, mental stress or 
disease progression may develop).  Contact information will be provided to the 
participants on the first day of the study. Participants will also be encouraged at the 
training sessions to call and discuss their feelings being unearthed by the process if they 
feel they want to.  
11.1.2 Benefits 
As a result of following the 180-day study intervention, participants may experience 
improved physical fitness, quality of life, lifestyle changes, and social connection. In 
addition, findings from the current study will improve our understanding of PC and this 
information will be used to improve the care at NSHA.   
11.2.3 Liability 
There are no statements in any documents that attempt to limit the liability to which the 
investigators or affiliated institutions are subject.  
 
11.2.4 Confidentiality  
The data will be stored on a secure server with NSHA. Data will be downloaded for 
analyses by the Principal Investigators, Research Coordinator, and analyzed by a Data 
Analyst. The computers used for data analyses are password protected and stored in 
locked offices within the hospital. After study closure, all study related information will 
be transferred and stored within the Department of Research Services for 7 years. At the 
end of the retention period, the Department of Research Services will arrange for 
destruction in accordance with applicable standards. 
 

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PC PEP Protocol v6.0 December 8, 2020 
11.2.5 Disclosure of Any Financial Compensation 
Participation in the study is completely voluntarily. Participants will be given no 
monetary compensation for taking part in this study. Participants will be reimbursed 
$14.50 for parking for 4 study visits to the hospital. 
 
 
12 PUBLICATION OF RESEARCH FINDINGS 
 
12.1 Dissemination Plan 
We will produce an Interim Annual report on the data collected a year before trial 
completion and a Complete Annual Report at the end of the trial, release the results of the 
study to public and media outlets. This is in addition to producing scientific manuscripts 
on the evaluation of the PC-PEP and the contextual psychosocial determinants of QOL in 
community members, policy makers and support group representatives. The Soillse 
Scientist’s lab will post updates on a website and allow the free dissemination of Annual 
reports resulting from this initiative. The members of the research team have 
demonstrated effective knowledge translation and exchange practices in previous work. 
We will publish the results of the proposed study in high impact journals and present the 
results to international conferences. We will train one MSc graduate and one 
Undergraduate student with the proposed methods and data of this study

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