1

ROBOSLING: DOES AN AUTOLOGOUS VASCULARISED BLADDER NECK SLING IMPROVE CONTINENCE OUTCOMES

FOLLOWING ROBOTIC RADICAL PROSTATECTOMY?

Scott LESLIE

BSc (Med) MBBS (Hons) FRACS (Urology)

Senior Lecturer Robotic Surgery & Program Lead

The Institute of Academic Surgery at RPA

The University of Sydney

This thesis is submitted in requirements for the Degree of

MASTERS OF PHILOSOPHY

DISCIPLINE OF SURGERY

UNIVERSITY OF SYDNEY

February 2021

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ABSTRACT

Prostate cancer is commonly diagnosed in Australian men owing to widespread

use of PSA testing. In appropriate patients, radical prostatectomy is an effective

treatment option with good long-term oncological outcomes. However, the

morbidity associated with functional complications including urinary

incontinence and sexual dysfunction remain a significant concern for men when

deciding between surgery or other treatment options.

Although recovery of continence 12 months following radical prostatectomy is

high (60-93%), early continence rates are significantly lower (32-84%) and can

negatively impact quality of life. Post-operative incontinence is predominantly a

result of damage to the urethral sphincter due to surgical dissection, cautery and

traction on the continence mechanisms with subsequent intrinsic sphincter

deficiency. Improved understanding of operative pelvic anatomy has allowed

better preservation of these continence mechanisms and there are a large

number of publications describing various intraoperative surgical techniques to

reduce incontinence.

One such surgical concept is the use of Slings at the time of radical

prostatectomy to promote continence post-operatively. Chapter 1 of my thesis is

a systematic review and meta-analysis of the current literature on the use of

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intraoperative slings at the time of radical prostatectomy. This review was

registered with PROSPERO and written in accordance with PRISMA-P (Preferred

Reporting Items for Systematic Reviews and Meta-Analysis Protocols). Five

randomised controlled trials and five retrospective cohort studies were included

with various sling material used including, rectus fascia, small intestinal

submucosa, vas deferens, Denonvillier’s fascia, median umbilical ligament and

retrotrigonal muscular layer. The meta-analysis concluded that intraoperative

sling procedures during radical prostatectomy may promote early return of

continence compared to having no sling, however there are no long-term

differences.

Chapter 2 of my thesis describes the technique and preliminary outcomes of a

novel intraoperative sling developed to improve post-prostatectomy continence.

This sling, the RoboSling, differs from previously described slings in that it is an

autologous, fascial sling harvested from the well-vascularised peritoneum on the

posterior aspect of the bladder, then placed underneath the bladder neck and

hitched to the inguinal ligaments of Cooper with v-loc sutures. By tensioning the

RoboSling, the bladder neck, perineal body and urethrovesical anastomosis are

supported in order to improve post-operative continence. In this non-

randomised cohort study, using prospectively collected data from the prostate

cancer database at Royal Prince Alfred Hospital (RPAH), we compared the

outcomes of 30 patients who had the novel RoboSling performed at the time of

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robotic-assisted radical prostatectomy (RARP) with 163 patients who

underwent robotic-assisted radical prostatectomy without the sling. This study

found that improved rates of continence were achieved in the RoboSling group

both at 3 months as well as 12 months. Furthermore, this was without a higher

complication rate and there was no deleterious effect on oncological outcomes.

These promising results were the impetus for developing a randomised

controlled trial (RCT) in order to provide Level 1 evidence on the outcomes of

the novel RoboSling technique. Chapter 3 of my thesis is the protocol of the

RoboSling RCT that was approved by the Sydney Local Health District Human

Research Ethics Committee in 2018. The study aims to recruit 120 patients with

localised prostate cancer undergoing RARP at Royal Prince Alfred Hospital. At

the time of submitting this thesis, 40 patients have been enrolled in the study.

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ACKNOWLEDGEMENTS

Many people have contributed to this work. I would firstly like to thank the

members of the urology departments of Royal Prince Alfred Hospital and

Concord Repatriation General Hospital who have supported this study and

contributed their own patients for enrolment. My thanks to Professor Lewis

Chan for his expertise in functional urology that has helped immeasurably with

study design, particularly for the randomised controlled trial. The preoperative

and post-operative functional assessment for our patients would not have been

possible without the wonderful work of Virginia Ip (RPAH) and Beth Whittaker

(Concord), urology nurse specialists in the Sydney Local Health District. Thank

you to Dr Nariman Ahmadi and Associate Professor Ruban Thanigasalam who

have been a great sounding board in the development of the RoboSling

technique, and contributed significantly to the cohort study as well as the RCT.

This thesis could not have been completed without the hard work and support

from all the individuals associated with the Institute of Academic Surgery (IAS)

at Royal Prince Alfred Hospital. Particular thanks to Dr Danielle van Diepen

(Robotics Fellow), Dr Jeremy Fallot (Robotics Fellow), Julia Stanbury (Robotics

Research Officer) and Christina Stanislaus (Robotics Research Officer) at the IAS

who have assisted immensely with data management and statistical analysis. I

would also like to thank Dr Daniel Steffens, Surgical Outcomes Research Centre

(SOuRCe), for his statistical input and support with all aspects of the thesis.

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Special mention to Dr Eunice Lim for her hard work and contributions with the

systematic review and to Beth Croce for the wonderful illustrations of the

RoboSling technique.

Special thanks must go to my supervisor Professor Michael J Solomon, Chairman

IAS and Professor of Surgical Research, University of Sydney, who has always

supported my academic pursuits.

Finally, my gratitude and respect for the patients who entrusted me with their

care.

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TABLE OF CONTENTS

CHAPTER PAGE

Title Page 1

Abstract 2

Declaration 5

Acknowledgements 6

Authorship Attribution Statement 10

Abbreviations 11

Chapter 1: Systematic Review and Meta-analysis 13

1.1 Introduction 13

1.2 Materials and Methods 14

1.3 Results 17

1.4 Discussion 29

1.5 Conclusion 31

1.6 References 32

Chapter 2: RoboSling Technique and Cohort Study 36

2.1 RoboSling Technique 36

2.2 Materials and Methods 42

2.3 Results 44

2.4 Discussion 50

2.5 Conclusion 55

2.6 References 56

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2.7 Appendices 58

Chapter 3: Randomised Controlled Trial Protocol 60

3.1 Introduction 60

3.2 Methodology and Design 60

3.3 Statistical Analyses 67

3.4 Benefits and Risks of the Study 68

3.5 Safety Monitoring 69

3.6 Data Handling and Record Keeping 69

3.7 Ethical Considerations 71

3.8 References 72

3.9 Appendices 75

Chapter 4: Conclusions 97

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Abbreviations ASA American Society of Anaesthesiologists

BMI Body Mass Index

CI Confidence Interval

CNC Clinical Nurse Consultant

CRGH Concord Repatriation General Hospital

CT Computed Tomography

DSMB Data and Safety Monitoring Board

EBL Expanded Prostate Cancer Index Composite

GRADE Grading of Recommendations Assessment, Development and

Evaluation

HREC Human Research Ethics Committee

IAS Institute of Academic Surgery

ICIQ-SF Incontinence Questionnaire short-form

ICU Intensive Care Unit

IIEF International Index of Erectile Function

IPSS International Prostate Symptom Score

LOS Length of Stay

MCS Mental Component Summary

MD Mean Difference

mpMRI multi-parametric Magnetic Resonance Imaging

NOS Newcastle-Ottawa Scale

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NPRS Numerical Pain Rating Score

PCI Pelvic Cavity Index

PCS Physical Component Summary

PFUS Pelvic Floor Ultrasound

PSA Prostate Specific Antigen

PRISMA-P Preferred Reporting Items for Systematic Reviews and Meta-

Analysis Protocols

PV Prostate Volume

RARP Robotic-Assisted Radical Prostatectomy

RCT Randomised Controlled Trial

ROSE Robotic and Open Surgery for Prostate Cancer database

RPAH Royal Prince Alfred Hospital

RR Relative Risk

RRP Retropubic Radical Prostatectomy

SD Standard Deviation

SF-36 Short Form – 36

SIS Small Intestinal Submucosa

SLHD Sydney Local Health District

SOuRCe Surgical Outcomes Research Centre

SSA Site Specific Assessment

UTI Urinary Tract Infection

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CHAPTER ONE: SYSTEMATIC REVIEW AND META-ANALYSIS

1.1 Introduction

Prostate cancer is the second most common malignancy in men worldwide, with 1.3 million

new cases in 2018.(1) Radical prostatectomy is an effective and commonly performed

treatment option for localized prostate cancer.(2) However, urinary incontinence remains a

major adverse event following radical prostatectomy, with 12 months postoperative urinary

incontinence rate ranging from 4% to 31%.(3) Urinary incontinence can have a severe impact

on the patient’s quality of life and thus remains a deterrent for many patients when deciding

treatment for their prostate cancer.(3)

Multiple aetiologies have been proposed for the development of postoperative incontinence

with the major factor attributed to intraoperative damage of the urethral sphincter with

accompanying intrinsic sphincter deficiency.(4) Other possible causes include detrusor over

and under-activity, bladder outlet obstruction due to anastomotic strictures and damage to

pelvic nerves that potentially supply the sphincter mechanism. As such, several intraoperative

techniques aiming to reduce postoperative urinary incontinence have been described;

including surgical techniques to preserve anatomical structures (i.e. bladder neck,

neurovascular bundle or puboprostatic ligaments) and different surgical approaches

including anterior and posterior reconstruction and the Retzius-sparing technique.(5, 6)

However, the role of these intraoperative techniques in reducing incontinence remains

unclear; with many of these techniques not externally validated in a multicentre setting.(7-9)

Recent studies suggest that the use of intraoperative sub-urethral sling techniques during

prostatectomy may reduce the incidence of postoperative urinary incontinence.(10) Sling

suspension technique involves the placement of a sling to support the proximal urethra and

bladder neck to provide compressive force on the urethra, increase the functional length of

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the urethra and maintain adequate urethral closure. (5) Sling techniques are commonly used

in the setting of postoperative urinary incontinence when non-invasive therapies such as

pelvic floor muscle training and pharmacologic treatments fail.(11) Performing a sling

procedure intra-operatively at the time of prostatectomy may prevent the development of

urinary complications, improving postoperative quality of life and reducing overall cost by

minimising the likelihood of patients having to undergo secondary surgery for incontinence

following radical prostatectomy.

Different surgical techniques and sling materials have been explored with varying results.

Therefore, the purpose of this study is to conduct a systematic review and meta-analysis to

evaluate the effectiveness of intraoperative slings compared with no sling procedure in

reducing postoperative urinary incontinence and complication rates in patients undergoing

radical prostatectomy.

1.2 Materials and Methods

This systematic review and meta-analysis was registered with PROSPERO

(https://www.crd.york.ac.uk/PROSPERO/, CRD42017078878) prior to commencement of the

review. The protocol followed the methods recommended by the Cochrane Handbook for

Systematic Reviews of Interventions(12) and was written in accordance with PRISMA-P

(Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols)

statement.(13)

Search Strategy

A sensitive search was performed from inception to November 2020 in MEDLINE via OVID,

EMBASE via OVID, Pubmed (www.ncbi.nlm.nih.gov/pubmed) and Cochrane Central Register

Clinical Trials (CENTRAL) via the Cochrane Library, using key words related to ‘prostate

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cancer’, ‘prostatectomy’, ‘sling’ and ‘urinary incontinence’ (Supplementary Table 1). No

language restrictions were applied. In addition, reference lists of all included studies were

screened.

One reviewer inspected the titles and abstracts of all identified studies to generate a list of

potentially eligible studies. Full-text articles were reviewed by two review authors for

eligibility. Consensus between the two reviewers was used to resolve any disagreement.

Inclusion and exclusion criteria

The studies included in this review reported data on localized prostate cancer patients who

underwent radical prostatectomy at any age. Study types included randomized controlled

trials and non-randomized comparative studies. Exclusion criteria includes animal studies,

conference abstractions or poster publications, and descriptive commentaries

Outcome measures

The main outcomes of interest were urinary incontinence and other adverse events or

complications. Length of hospital stay, length of operation, quality of life and cost were also

investigated. Postoperative outcome data were extracted at 4 time points: 1, 3, 6 and 12

months.

Data extraction

Two review authors used a pre-piloted data extraction sheet to extract data from the included

studies. Consensus between the two reviewers were used to resolve any disagreement. An

attempt was made to contact authors from studies where data was unclear or not available in

the published manuscript. For each included study the following data were extracted: sample

characteristics (country, study design, surgical procedure, sling position, sling material, age,

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body mass index, prostate specific antigen (PSA)), name of sling procedure used, and all

outcome measures from all time points.

Risk of bias assessment and strength of the evidence

Cochrane Collaboration’s tool was used to assess the methodological quality of randomized

controlled trials.(12) Each study was assessed as having high, low or unclear risk of bias by

two reviewers. Methodological quality of comparative studies was assessed via the

Newcastle-Ottawa Scale (NOS), which was endorsed by the Cochrane handbook for quality

appraisal of observational studies.(14, 15) Each study was given a score between zero and

nine, by considering three factors that consist of nine items in total: (1) Selection of study

groups, (2) Comparability and (3) Outcome of interest.(14). Our review considered a study

with a score of 7 as having high quality and low risk of bias, as there are no established

standardized criteria for the interpretation of the NOS scores currently. Grading of

Recommendations Assessment, Development and Evaluation (GRADE) approach was used to

assess strength of evidence from high to very-low-quality for each outcomes.(16)

Statistical Analysis

For dichotomous outcomes, we extracted the number of patients in each group who

experienced the outcome of interest and the number of patients assessed at endpoint in each

treatment arm at the end of the pre-specified follow-up, in order to estimate a relative risk

and its 95% confidence interval. For continuous outcomes, we extracted the final value and

standard deviation of the outcome of interest and the number of patients assessed at the

endpoint in each treatment arm at the end of follow-up. Where appropriate, we calculated the

mean difference and 95% confidence interval.

Outcome measures from individual trials were combined through a meta-analysis where

possible using a random-effects model, via the Comprehensive Meta-Analysis software.(17)

When a meta-analysis was not possible, results were described qualitatively. Included studies

were grouped by outcome measures (e.g. continence defined as zero pad/day), followed by

time frame (1, 3, 6 and 12 months) to provide a homogenous subset for meta-analysis. Time

points (1, 3, 6 and 12 months) were selected based on the available results. Studies included

in the meta-analysis were ordered chronologically.

1.3 Results

Literature search

The search identified 179 citations after the removal of duplicates. Following the elimination

of irrelevant references, 31 full-text articles were screened for eligibility. 21 articles were

excluded due to the following reasons: conference abstracts (n=2); ineligible study design

(n=3); and no outcome of interest (n=16). Therefore, ten studies(10, 18-26) were included in

this systematic review (n=1447) (Fig. 1).

Records identified through database searching

Cochrane = 32 Medline = 36 Embase = 45

PubMed = 142

Scre

en

ing

Iden

tifi

cati

on

Additional records identified through other sources (Screening of references of included studies)

(n = 2)

Records after duplicates removed (n = 179)

Records screened (n = 179)

Records excluded (n = 148)

Full-text articles assessed for eligibility

(n = 31)

21 Full-text articles excluded

2 Conference abstracts 3 Ineligible study design 16 No outcome of interest

Elig

ibili

ty

22

Sling procedure did not reduce the time taken to achieve continence with zero pad/day

definition (20, 25)(n= 296) (MD: 1.29; 95%CI: -0.54 to 3.13) (Fig.3). Study by Bahler et al was

not included in this meta-analysis as the study did not report confidence interval for the data,

however the study coincides with our finding (18)(n=104) (MD: -0.4; p=0.61; 95% CI: not

reported). However, with 1pad/day definition, sling group achieved continence 0.5 week

earlier than the no-sling group (MD: 0.5; 95%CI: 0.1 to 0.9).(25)

Furthermore, sling procedure did not reduce the number of pads required per day (n=60) at 5

days (MD: -0.2; 95%CI: -0.9 to 0.5) and 10 days postoperatively (MD: -0.5; 95% CI: -1.2 to 0.2).

Yet, there was a low-quality evidence demonstrating reduced pad use in the sling group at 1

month (MD: -0.7; 95%CI: -1.2 to -0.2).(19) There was a low-quality evidence that sling

procedure does not result in more patients achieving immediate continence after catheter

removal (n= 59) (RR: 1.31; 95%CI: 0.69 to 2.51).(20)

Figure 2. Forrest plot of continence outcomes when continence is defined as using 0 pad versus 1 pad or as using 1 pad versus >1 pad

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Figure 3. Forrest plot of time taken to achieve continence (months)

Continence defined by pad weight via 1-hour pad test (21)

There is a very-low-quality evidence that sling procedure reduces the mean pad weight gain

at 1 month (MD: 21.55; 95%CI: 12.58 to 30.52) but not at 3 months (MD: 0.00; 95%CI: -4.12

to 4.12) and 6 months (MD: 0.41; 95%CI: -0.79 to 1.91) postoperatively (n= 57).(21)

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Patient Reported Outcomes Measures (21, 26)

A significant difference in International Consultation on Incontinence Questionnaire short-

form (ICIQ-SF) favoring the sling group was found at 3 months (MD: 2.25; 95%CI: 1.26 to

3.24) but not at 1 month (MD: 2.77; 95%CI: -1.54 to 7.08) (Fig.4) or 6 months (MD: 0.5;

95%CI: -0.63 to 1.63). For Expanded Prostate Cancer Index Composite (EPIC-U) results, a

significant difference favoring sling procedures is seen at 1 month (MD: 15.35; 95%CI: 11.37

to 19.33), 3 months (MD: 5.30; 95%CI: 1.21 to 9.39) but not at 6 months (MD: 4; 95%CI: -0.04

to 8.04) postoperatively. In addition, a significant difference in International Prostate

Symptom Score (IPSS) favoring the sling group was found at 1 month (MD: 4.75; 95%CI: 3.67

to 5.83) and 3 months (MD: 1.44; 95%CI: 0.14 to 2.74) but found to favor the no-sling group at

6 months (MD: -0.94; 95%CI: -1.77 to -0.11).

Figure 4. Forrest plot of International Consultation on Incontinence Questionnaire short form score at 1 month

Adverse events and complications

There is a very-low-quality evidence that sling does not reduce the incidence of bladder neck

contracture (n=177) (RR: 0.34; 95%CI: 0.04 to 3.12) and moderate-quality evidence of no

effect on pelvic abscess formation (n=318) (RR; 2.63; 95%CI: 0.50 to 13.70). However, there is

a low-quality evidence of reduced incidence of urethral stricture (n=348) (RR: 2.35; 95%CI:

1.33 to 4.13) and very-low-quality evidence of reduced incidence of urinary

retention(n=297)(RR: 2.09; 95%CI: 1.26 to 3.48)(24, 25) in the sling group (Fig. 5).

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Figure 5. Forrest plot of adverse events

Length of hospital stay, length of operation, Quality of life and Cost

Cestari et al.(19) reported that sling procedure does not reduce hospital length of stay (MD:

0.0; p value not reported; 95% CI not reported) (n=60). Sling procedure however resulted in

increase in the length of operation (MD: -6.13, 95%CI: -9.18 to -3.07)(Fig. 6). Our search did

not find any study investigating differences in quality-of-life outcomes and cost.

Figure 6. Forrest plot of operative time (minutes)

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Continence - 6

months ( 1 pad

versus >1 pad)

[Jorion, 1997;

Westney, 2006;

Bahler, 2011;

Nguyen, 2017]

513 (2 RCTs /

2 comparative

studies)

RR: 1.01

(0.95 to 1.07) -1 -1 None

⨁⨁◯◯

Low

Continence - 12

months ( 1 pad

versus >1 pad)

[Jorion, 1997;

Westney, 2006;

Bahler, 2011]

310 (1 RCT/2

comparative

studies)

RR: 1.02

(0.93 to 1.13) -1 -1 None

⨁⨁◯◯

Low

Time to achieve

continence, months

(0 pad versus 1

pad) [Altinova,

2009; Punnen,

2014]

296 (1 RCT; 1

comparative

study)

MD: -1.29 (-

3.13 to 0.54) -1 -1 -1

⨁◯◯◯

Very low

Time to achieve

continence, months

(0 pad versus 1

pad) [Bahler, 2011]

104 (1 RCT)

MD: -0.4

(95%CI Not

reported),

p=0.61

-1 -1 -1 ⨁◯◯◯

Very low

Time to achieve

continence, months

( 1 pad versus >1

pad)

[Punnen, 2014]

237 (1

comparative

study)

MD: 0.5 (0.1

to 0.9) -1 -1 -1

⨁◯◯◯

Very low

Number of pads

required - 5 days

[Cestari, 2015]

60 (1 RCT) MD: -0.2 (-0.9

to 0.5) None -1 -1

⨁⨁◯◯

Low

Number of pads

required - 10 days

[Cestari, 2015]

60 (1 RCT) MD: -0.5 (-1.2

to 0.2) None -1 -1

⨁⨁◯◯

Low

Number of pads

required - 1 month

[Cestari, 2015]

60 (1 RCT) MD: -0.7 (-1.2

to -0.2) None -1 -1

⨁⨁◯◯

Low

Achieving

immediate

continence after

catheter removal

(0 pad versus 1

pad) [Altinova,

2009]

59 (1 RCT) RR: 1.31

(0.69 to 2.51) None -1 -1

⨁⨁◯◯

Low

1-hour pad test - 1

month [Kojima,

2014]

57 (1 RCT)

MD: 21.55

(12.58 to

30.52)

-1 -1 -1 ⨁◯◯◯

Very low

1-hour pad test - 3

months [Kojima,

2014]

57 (1 RCT) MD: 0.00 (-

4.12 to 4.12) -1 -1 -1

⨁◯◯◯

Very low

1-hour pad test – 6

months [Kojima,

2014]

57 (1 RCT) MD: 0.41 (-

0.79 to 1.91) -1 -1 -1

⨁◯◯◯

Very low

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1.4 Discussion Our systematic review demonstrates that there is a low-moderate certainty evidence that

intraoperative sling procedures are generally favorable for short-term improvement but have

no difference in long-term continence outcomes compared to having no sling procedures

(Table 4). Early return of continence in the sling group is seen in patient-reported

questionnaires for up to 3 months (IPSS, ICIQ-SF, EPIC-U) postoperatively. Furthermore,

significant improvement is seen in the sling group at 1 month for pad weight test, number of

pads used per day and number of continent patients with zero pad/day definition, although

no difference is discerned at longer term.

However, sling procedure does not increase the number of continent patients at any time

point with 1 pad/day definition. As such, it is evident that variability in results is introduced

by the difference in continence definition and methods. Similarly, sling procedure reduces the

time taken to achieve continence with 1 pad/day definition but not with zero pad/day

definition.

Our meta-analysis also demonstrated that intraoperative sling may reduce the incidence of

postoperative complications such as urethral stricture and urinary retention, however no

explanation as to why this is the case was provided in the included studies. Sling procedure

increased the operative time but did not affect the length of hospital stay.

Strengths and Limitations of the study

The strengths of this systematic review include strict adherence to the Cochrane

Collaboration guideline and PRISMA guidelines, registration of the protocol on PROSPERO,

utilization of a highly sensitive search strategy with no language and date restriction,

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inclusion of RCTs, strict assessment of quality with the Cochrane risk of bias tool and

Newcastle-Ottawa Scale and use of the GRADE approach for evidence appraisal.

This review has some limitations. Firstly, intraoperative sling procedure is a relatively new

technique in the literature, and thus only five RCTs were identified and included in our

analysis.(10) Moreover, the inclusion of non-randomized comparative studies and difficulty in

standardizing the tension of the sling, surgical technique and sling material may have

influenced the results. This systematic review also does not include data from ongoing

studies, studies published as abstract only and unpublished RCTs. Furthermore, variability in

continence measurements resulted in very-low-quality evidence of data due to inability to

perform meta-analyses for many continence outcomes.

Comparison with other studies and future directions

To our knowledge, this is the first systematic review and meta-analysis that evaluates the

effectiveness of intraoperative sling procedures compared to having no sling procedures on

post-prostatectomy continence outcomes. Our review demonstrates the importance of

standardizing the definition of continence for utilization in future studies. Although defining

continence via pad number is a common clinical practice, it is not a reliable measure of urine

leakage as it is largely affected by pad size and type as well as the variability of individual

patient’s perception of when to change the pads.(27) Thus, pad weight measurement via 24-

hour pad test is a more objective assessment of urinary incontinence for use in future

studies.(27, 28) Additionally, questionnaires are objective assessment tools that also allow the

evaluation of patient’s postoperative quality of life and thus provide a better assessment of sling

effectiveness.(27)

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Furthermore, our review demonstrates that current studies in the field of intraoperative sling

technique have very-low to moderate quality, identifying the need for future studies with high-

quality evidence.

Our review also suggests that future studies assessing the effectiveness of intraoperative sling

must consider the type of sling material used. The sling materials used in all studies included

in our review are biological absorbable graft materials, and as they are known to degrade very

quickly, this may be one reason for poor outcome. Our review demonstrates that there is no

significant difference in continent patients between the sling and no sling group beyond 6

months postoperatively. This may be influenced by the fact that biological sling materials are

absorbed after 6 months.

1.5 Conclusion

Overall, our study demonstrates that intraoperative sling procedures do not decrease long

term urinary incontinence rate, however may have potential to promote early return of

continence. Currently, our evidence is limited by the lack of high-quality studies and

variability in definitions, and as thus our study details how future clinical research in this field

can be improved in order to verify the effect of intraoperative slings more effectively.

32

1.6 References

1. Globocan. Prostate cancer: World Health Organization; 2018 [Available from:

http://gco.iarc.fr/today/data/factsheets/cancers/27-Prostate-fact-sheet.pdf.

2. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU

Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with

Curative Intent—Update 2013. European Urology. 2013;65(1):124-37.

3. Ficarra V, Novara G, Rosen RC, Artibani W, Carroll PR, Costello A, et al. Systematic

Review and Meta-analysis of Studies Reporting Urinary Continence Recovery After Robot-

assisted Radical Prostatectomy. European Urology. 2012;62(3):405-17.

4. Singla N, Singla AK. Post-prostatectomy incontinence: Etiology, evaluation, and

management. Turkish journal of urology. 2014;40(1):1-8.

5. Kojima Y, Takahashi N, Haga N, Nomiya M, Yanagida T, Ishibashi K, et al. Urinary

incontinence after robot‐assisted radical prostatectomy: Pathophysiology and intraoperative

techniques to improve surgical outcome. International Journal of Urology. 2013;20(11):1052-

63.

6. Lim SK, Kim KH, Shin TY, Han WK, Chung BH, Hong SJ, et al. Retzius‐sparing robot‐

assisted laparoscopic radical prostatectomy: combining the best of retropubic and perineal

approaches. BJU international. 2014;114(2):236-44.

7. Reeves F, Preece P, Kapoor J, Everaerts W, Murphy DG, Corcoran NM, et al.

Preservation of the Neurovascular Bundles Is Associated with Improved Time to Continence

After Radical Prostatectomy But Not Long-term Continence Rates: Results of a Systematic

Review and Meta-analysis. European Urology. 2014;68(4):692-704.

8. Ma X, Tang K, Yang C, Wu G, Xu N, Wang M, et al. Bladder neck preservation improves

time to continence after radical prostatectomy: a systematic review and meta-analysis.

Oncotarget. 2016;7(41):67463.

33

9. Rocco B, Cozzi G, Spinelli MG, Coelho RF, Patel VR, Tewari A, et al. Posterior

Musculofascial Reconstruction After Radical Prostatectomy: A Systematic Review of the

Literature. European Urology. 2012;62(5):779-90.

10. Westney OL, Scott S, Wood C, Eddings T, Johnson MM, Taylor JM, et al. Suburethral

sling at the time of radical prostatectomy in patients at high risk of postoperative

incontinence. BJU international. 2006;98(2):308-13.

11. Bauer RM, Bastian PJ, Gozzi C, Stief CG. Postprostatectomy Incontinence: All About

Diagnosis and Management. European Urology. 2008;55(2):322-33.

12. Higgins J GS. Cochrane handbook for systematic reviews of interventions 2011

[Available from: www.cochrane-handbook.org.

13. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic

reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.

14. GA Wells BS, D O'Connell, J Peterson, V Welch, M Losos, P Tugwell,. The Newcastle-

Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.

15. Higgins JPT GS. The Cochrane Collaboration. Section 13.5.2.3. Tools for assessing

methodological quality or risk of bias in non-randomized studies. 2011.

16. Atkins D, Eccles M, Flottorp S, Guyatt GH, Henry D, Hill S, et al. Systems for grading the

quality of evidence and the strength of recommendations I: critical appraisal of existing

approaches The GRADE Working Group. BMC health services research. 2004;4(1):38.

17. Borenstein M, Hedges, L., Higgins, J., & Rothstein, H. Comprehensive Meta-Analysis

Version 3. 2013.

18. Bahler CD, Sundaram CP, Kella N, Lucas SM, Boger MA, Gardner TA, et al. A Parallel

Randomized Clinical Trial Examining the Return of Urinary Continence after Robot-Assisted

Radical Prostatectomy with or without a Small Intestinal Submucosa Bladder Neck Sling. The

Journal of urology. 2016;196(1):179-84.

34

19. Cestari A, Ferrari M, Ghezzi M, Sangalli M, Zanoni M, Fabbri F, et al. Retropubic

Intracorporeal Placement of a Suburethral Autologous Sling During Robot-Assisted Radical

Prostatectomy to Improve Early Urinary Continence Recovery: Preliminary Data. Journal of

endourology. 2015;29(12):1379-85.

20. Altinova S, Demirci DA, Ozdemir AT, Akbulut Z, Atmaca AF, Caglayan A, et al.

Incorporation of anterior rectus fascial sling into radical retropubic prostatectomy improves

postoperative continence. Urologia internationalis. 2009;83(1):19-21.

21. Kojima Y, Hamakawa T, Kubota Y, Ogawa S, Haga N, Tozawa K, et al. Bladder neck sling

suspension during robot-assisted radical prostatectomy to improve early return of urinary

continence: a comparative analysis. Urology. 2014;83(3):632-9.

22. Nguyen HG, Punnen S, Cowan JE, Leapman M, Cary C, Welty C, et al. A Randomized

Study of Intraoperative Autologous Retropubic Urethral Sling on Urinary Control after

Robotic Assisted Radical Prostatectomy. The Journal of urology. 2017;197(2):369-75.

23. Jones JS, Vasavada SP, Abdelmalak JB, Liou L, Ahmed ES, Zippe CD, et al. Sling may

hasten return of continence after radical prostatectomy. Urology. 2005;65(6):1163-7.

24. Jorion JL. Rectus Fascial Sling Suspension of the Vesicourethral Anastomosis After

Radical Prostatectomy. The Journal of urology. 1997;157(3):926-8.

25. Punnen S, Clint Cary K, Glass A, Cowan J, Carroll P. Autologous retro-pubic urethral

sling: a novel, quick, intra-operative technique to improve continence after robotic-assisted

radical prostatectomy. Journal of Robotic Surgery. 2014;8(2):99-104.

26. Zanoni ML, Grizzi F, Maffei D, Vota P, Frego N, Toia G, et al. Retrotrigonal muscular

layer sling associated with total anatomical reconstruction in robot-assisted radical

prostatectomy and early continence. World J Urol. 2020.

27. Syan RN, V. Post-prostatectomy Incontinence Initial Evaluation2016.

35

28. Tsui JF, Shah MB, Weinberger JM, Ghanaat M, Weiss JP, Purohit RS, et al. Pad Count is a

Poor Measure of the Severity of Urinary Incontinence. Journal of Urology, The.

2013;190(5):1787-90

Supplementary Table 1. Search strategy

Search Strategy

#1 Prostate cancer OR Prosta* carcinoma OR Prostat* tumour

#2 Prostatectomy OR radical prostatectomy OR RARP OR MIRP OR RRP OR

LRP

#3 Suburethral Sling OR Sling OR suspension OR intraoperative sling

#4 Urinary incontinence OR Incontinen* OR Continen* OR Leak* OR Urin*

#1 AND #2 AND #3 AND #4

36

CHAPTER TWO: ROBOSLING TECHNIQUE AND COHORT STUDY

2.1 RoboSling Technique

To our knowledge, there are no surgical techniques yet demonstrated during RARP which

have used a vascularised, autologous sling which supports the bladder neck and

vesicourethral anastomosis. I developed a straightforward technique utilising a concurrent

retropubic vascularised fascial (flap) sling, placed during RARP. The objective of this study

was to detail our technique, and to assess its efficacy on urinary continence after robotic

prostatectomy.

RoboSling placement utilises an autologous vascularized fascial flap of peritoneum placed

underneath the urethrovesical anastomosis and suspended to the inguinal ligament of Cooper

(pectineal ligament) with v-loc barbed sutures (Medtronic®, Minneapolis, USA) creating a

supportive sling incorporated into the perineal body and bladder neck. RARP is performed via

a transperitoneal approach with standard 4 robotic-port, and 2 assistant-port positioning.

Once within the peritoneal cavityand the robot docked, a rectangular shaped vascularised flap

of peritoneum on the posterior aspect of the bladder is first marked and then dissected off the

detrusor muscle (Figure 1). The flap is mobilised with a broad base to maintain its vascularity

and care given not to button hole the flap. As the flap is dissected off the bladder, the vas

deferens and seminal vesicles on either side are revealed. The posterior plane between

denonvilliers fascia and the prostate is then dissected towards the apex of the prostate.

37

Figure 1. Mobilisation of the vascularised flap of peritoneum from the posterior wall of the

bladder

Following this initial step of creating the vascularised flap of peritoneum, attention is then

turned to performing the standard steps of the RARP procedure. After the prostate and

seminal vesicles have been removed, any lymph node dissection carried out as required and

haemostasis achieved, the peritoneal flap is then transferred underneath the bladder (Figure

2), and incorporated into the perineal body and bladder neck as a ‘modified Rocco Stitch’

using a 3-0 v-loc suture (Figure 3).

38

Figure 2. Tunnelling of the peritoneal flap under the bladder following prostatectomy

39

Figure 3. Incorporating the RoboSling flap into the perineal body and posterior bladder neck

with v-loc sutures.

The vesicourethral anastomosis is completed in usual fashion. Sequentially, at each corner of

the flap a 3-0 v-loc suture is passed and hitched to the inguinal ligament of Cooper on each

side (Figure 4) – these are tensioned by pulling on the suture and securing with two Hem-o-

lok clips (Teleflex®, Philadelphia, USA) (Figure 5). As the v-loc sutures are tensioned, the

40

bladder neck, perineal body and urethrovesical anastomosis are lifted upwards and

supported by the RoboSling.

Figure 4. Corners of RoboSling flap sutured to the ligament of Cooper on each side.

41

Figure 5. The flap is tensioned and secured with two hem-o-lok clips on each side completing

the RoboSling.

The illustrations in Figures 1-5 were based on my hand-drawn sketches of the key steps of the

RoboSling technique. Beth Croce, an anatomical illustrator, created the final detailed drawings

for this thesis. The Medical Art Commission Agreement is attached (Appendix 1).

42

2.2 Materials and Methods

Study Patient Selection

In order to assess the utility and safety of the novel RoboSling technique a prospective, non-

randomised cohort study was undertaken. The da Vinici Xi robot has been used to perform

urological procedures at Royal Prince Alfred Hospital (RPAH) since December 2016.

Demographic, oncological and functional outcomes have been prospectively collected since

the beginning of the robotic program at RPAH. The outcomes of the first 193 men who

underwent RARP between December 2016 and September 2019 were analysed. This

consisted of 163 patients (control group) who underwent the standard RARP procedure and

30 patients (intervention group) who had the novel RoboSling technique performed

concurrently with their robotic prostatectomy. RPAH is a tertiary referral centre and public

teaching hospital and therefore has a number of accredited urology registrars and robotic

surgery fellows who performed large parts of the procedure, mentored closely by the urology

consultants to whom the patients were admitted under. This non-randomised study compares

the outcomes of patients who underwent RARP with the concurrent retropubic vascularised

fascial sling (RoboSling) to the group of control patients who did not undergo RoboSling

placement. All basic prostatectomy steps were identical in the control and sling groups except

for the RoboSling-specific steps required for harvesting, mobilisation, incorporation into the

bladder neck and placement of the sling as described in detail above. Operative decisions on

bladder neck preservation, nerve-sparing and lymph node dissection were not influenced by

the RoboSling technique, but rather individualised for each case based on tumour factors,

patient factors and surgeon preference. Preoperative characteristics and clinical information

were collected via a baseline study questionnaire and existing records of clinical data. Men 18

years and over, undergoing prostatectomy at RPAH, and clinically suitable for robotic

prostatectomy were included in the study. Men with patient or tumour factors precluding

43

robotic surgery were excluded. All patients who participated provided written informed

consent under ethical approval of the Sydney Local Health District Human Research Ethics

Committee.

Primary Outcomes

Primary outcomes of pad usage were evaluated at 3- and 12-months post operatively. Pad

usage at each time point was measured as average pad use per day for the preceding week.

Patients filled in the Expanded Prostate Cancer Composite (EPIC)-urinary domain

questionnaire (1) at 3- and 12- months post-operatively. This is a validated self-assessment

questionnaire composed of 12 questions that address continence, as well as haematuria,

dysuria and other voiding problems. In addition to ascertaining objective answers (e.g. pad

number used daily), the EPIC also allows for subjective answers, such as “frequent” and

“occasional”. The EPIC score ranges from 0 to 100 points with higher scores signifying a

better quality of urination. However, it is important to appreciate that the EPIC score lacks a

clear, uniform definition that differentiates continence from incontinence. One study

indicated that an EPIC score 85 is closely associated with men being satisfied with their

degree of urinary continence and therefore this EPIC score cut-off of 85 was also used to

compare urinary continence outcomes between the RoboSling group and the control group

(2).

Secondary Outcomes

Secondary outcomes included quality of life (QoL), operative time, positive surgical margins,

length of stay, blood loss and complication rate. The Short Form - 36 (SF-36) questionnaire is

utilised to assess QoL for all patients undergoing robotic surgery at Royal Prince Alfred

Hospital. The SF-36 questionnaire is filled out at 6 weeks and 12 months, however not at the

44

3-month time point post-operatively. Therefore the 6-week SF-36 was used to assess early

post-operative QoL and the 12-month questionnaire to assess QoL in the longer term.

Statistical Analysis

Clinically relevant baseline variables were tabulated and compared between groups.

Categorical variables were compared between groups using the chi-squared test (frequencies

and proportions). Continuous variables were compared using t-test (means) or Wilcoxon 2-

sample test (median). All statistical analysis was performed using SPSS version 22 (SPSS Inc.,

Chicago, IL, USA).

2.3 Results

The study consisted of 30 patients who underwent RARP with concurrent RoboSling, and 163

without the RoboSling. Baseline characteristics did not differ between the two groups (Table

1).

46

outcomes in the RoboSling group was also reflected by a larger percentage of patients having

an EPIC score of 85 or greater (28%) at 3-months, compared to the control group where only

7% of patients at 3-months had an EPIC 85 (p=0.007).

With longer follow-up, the continence outcomes of the two groups improved as expected

(Figure 5). There was convergence in continence outcomes between the two groups. At 12

months, the mean EPIC scores were not significantly different between the two groups, 73 for

the RoboSling group versus 65 for the control group (p=0.237). The number of patients with

EPIC 85 were also similar between the two groups at 1 year. However, although there was

no significant difference in the EPIC scores at 1 year, the number of patients in the RoboSling

group who were using 0-pads was again significantly higher compared to the control group.

At 12 months, 72.2 % of men who had the RoboSling did not require any pads, whereas only

44.7% of patients in the control group were pad free (p=0.029).

3 months 12 months

RoboSling (n=18)

No RoboSling (n=133)

p- value RoboSling (n=18)

No RoboSling (n=123)

p-value

No Pad (%) 8 (44.4) 22 (16.5) 0.005

13 (72.2) 55 (44.7) 0.029

≥1 Pad (%) 10 (55.6) 111 (83.5) 5 (27.8) 68 (55.3)

EPIC Score Mean (SD) 62 (33) 43 (27) 0.008 73 (15) 65 (27) 0.237

EPIC 85 (%) 5 (28) 9 (7) 0.007

8 (47) 38 (39) 0.520

EPIC 85 (%) 13 (72) 113 (93) 9 (53) 60 (61)

Table 2. Continence outcomes

49

Mean (SD) p-value

6 Weeks PCS

RoboSling (n=25)

46.6 (13.1)

0.316

Control (n=134)

43.1 (16.1)

1 Year PCS

RoboSling (n=14)

51.4 (10.9)

0.766

Control (n=93)

52.1 (6.8)

6 Weeks MCS

RoboSling (n=25)

46.9 (13.7)

0.085

Control (n=134)

40.7 (17.1)

1 Year MCS

RoboSling (n=14)

50.8 (6.2)

0.457

Control (n=93)

48.8 (9.9)

Table 5 – SF-36 Quality of life outcomes (PCS – Physical Component Summary, MCS – Mental

Component Summary

50

2.4 Discussion

This prospective study assesses the effect of the RoboSling – a novel, autologous

vascularised fascial sling placed during RARP, and its effects on post-operative urinary

incontinence. The evidence provided in this study suggests that placement of a

RoboSling provides a significant beneficial effect on pad usage and continence rates at 3

months and 12 months. Significantly, there was no increase in complications or positive

surgical margin rate due to sling placement.

The rationale for the use of a vascularised autologous sling positioned during RARP is to

assist the restoration of vesicourethral and pelvic anatomical support, with prevention

of bladder descent, and improvement of outlet resistance via a reduced posterior

urethrovesical angle and increased exposure to intra-abdominal pressure and this

hypothesis could be supported by our initial results.

Jorian et al first described concurrent autologous sling placement during radical

retropubic prostatectomy in 1997 (3). Utilising a rectus fascial sling, continence rates

were significantly higher for the sling cohort at 2 months, compared with non-sling

control (93% vs 70%; P=0.04). Westney et al conducted a similar retrospective study

with rectus fascia, finding no difference in pad usage at 6 and 12 months, though with a

statistically significant increase in urethral stricture (35% vs 14%; p=0.001) for the

sling group (4). It is suggested however that this may have been driven by discordant

population characteristics – in particular, a significantly higher proportion of men in the

sling group who had had previous radiation therapy (0.017). More recently a

retrospective RARP study using autologous slings made of median umbilical

51

ligament/vas deferens by Punnen et al demonstrated no effect on time to one pad (p =

0.24) or no pads (p = 0.20) (5). It is similarly suggested by the authors that population

characteristics of the intervention group (older, p<0.01; less nerve sparing surgery,

p<0.01; and trend to larger prostate, p = 0.06) may explain this higher risk of post-

operative incontinence due to the impact of non-nerve sparing, larger bladder necks,

and shorter urethral lengths – factors associated with worse incontinence (6). Zanoni et

al’s 2020 study demonstrated a novel RARP sling technique using the retrotrigonal

muscular layer, with significant improvement in early continence rates at 1 (p = 0.0049)

and 4 weeks (p = 0.035) favouring the sling group, and no differences in operative times

or complication rate.

A final small retrospective study in 2005 by Jones et al examined the use of a non-

autologous sling during radical retropubic prostatectomy (RRP) (7). Fifteen men

underwent placement of either porcine small intestine submucosa or polyglactin mesh

underneath the anastomosis. Four weeks after catheter removal, 10 sling patients

(67%) were completely continent compared with 6 (40%) controls. At 12 weeks, 14

sling patients (93%) were continent vs. 7 controls (47%). All patients followed up,

except for one control patient, were continent at both 12 and 24 months.

Randomised controlled trials (RCT) have illustrated benefit with a non-vascularised

autologous technique in more recent years. In 2009, Altinova et al conducted the first

RCT examining use of an anterior rectus fascial sling during RRP (8). The incontinence

rate was 17.5% in the sling group and 43.5% for controls (p = 0.010). Incontinence

duration for each group were also significantly different, with mean time to achieve full

continence 1.4 and 3.8 months for sling and control group, respectively (p = 0.026).

52

Cestari et al conducted the first RCT of RARP with concurrently placed autologous sling,

using vas deferens, finding significant improvement in the sling cohort, with number of

pads used per day (0.4 vs 1.1; P=0.01), International Consultation on Incontinence

Questionnaire-Urinary Incontinence-Short Form score (1.8 vs 4.8; P=0.01), and 0 pad

rate (76% vs 46%; P=0.03) significantly improved at 30 days (9). Notably, 0-pad rates

were also significantly improved for the sling cohort at 3,6 and 12 months. Contrary to

these positive results, a randomised RARP study by Nguyen et al did not demonstrate

any benefit in post-operative continence at 1, 3 or 6 months when utilising an

autologous sling also fashioned from vas deferens (10).

RCTs utilising non-autologous slings have produced mixed results. Kojima et al

conducted the first RCT demonstrating feasibility of non-autologous sling use during

RARP, utilising a single suspended vicryl suture after double layered posterior

rhabdosphincter reconstruction (11). Both patient perception and objective data of

urinary incontinence 4 weeks after RARP were better in the sling group than in the non-

sling cohort. Furthermore, mean operative time, estimated blood loss, prostate weight,

and catheter removal between the groups showed no difference. Comparatively, Bahler

et al used non-autologous porcine small intestinal submucosa as a bladder neck sling,

and secured to the pubic bone (12). The sling failed to demonstrate any statistically

significant improvement in urinary continence.

Our study describes the novel RoboSling technique which involves the first reported use

of an autologous fascial flap of peritoneum utilised as a prophylactic sling during RARP.

Compared to the previous published techniques, the RoboSling is unique as the sling

material is vascularised and supports the bladder neck, urethrovesical anastomosis and

53

greater pelvic floor over a broad surface area by incorporating the sling to the perineal

body and vertical detrusor fibres of the bladder neck with v-loc sutures as a ‘modified-

Rocco’ stitch.

With this technique 0-pad use was significantly improved in the RoboSling group both

at 3-months follow-up and 12 months. At 3–months 0-pad use was 44.4% in the

RoboSling group versus 16.5% in the control group (p=0.011). This was also reflected

with better EPIC scores, with the mean EPIC score in the RoboSling group 62, versus a

mean score of 43 in the control group (p=0.008). With longer follow-up, there was

convergence of continence rates between the two groups and there was no difference in

the EPIC score. However, at 12-months there was still significantly higher 0-pad use in

the RoboSling group, 72.2%, versus 44.7% in the control group (p=0.029). This

demonstrates that concurrent use of the RoboSling at the time of RARP not only

improved continence outcomes in the short term but the benefit also extended to longer

follow-up at 1 year after surgery. Furthermore, the RoboSling was not difficult for the

trainees to perform and did not result in any increased rate of complications in the sling

cohort. Importantly there were no cases of ureteric injury, bladder injury or urinary

retention. Urinary tract infection occurred once in the RoboSling group and once in the

control group.

One of the unexpected benefits of the RoboSling technique was significantly reduced

blood loss. Mean EBL in the RoboSling group was 232 mL versus 373 mL in the control

group (p=0.008). A possible explanation for this finding is the early posterior dissection

behind the bladder and prostate that is necessitated by the initial formation of the

vascularised peritoneal flap. The posterior bladder neck dissection is arguably the most

54

challenging part of the RARP procedure as the surgeon can easily find themselves

within the prostate or peri-prostatic veins with subsequent problematic bleeding that

can further exacerbate an already difficult dissection. In the RoboSling cohort, as the

posterior dissection behind the prostate has already been initiated with the vas

deferens and seminal vesicles exposed on each side before the bladder neck dissection,

the trainees in turn found that the posterior bladder neck dissection was made

significantly easier resulting in less blood loss.

There are several limitations which should be noted for this study. Confounders such as

prostate volume to pelvic volume ratio, preoperative urethral length and angle, and

bladder neck size may affect continence outcomes and were not assessed in this cohort

of patient. Second, while questionnaires were provided prospectively, patients were

completing these with retrospective recall of the preceding period, with potential for

associated bias. Mitigating this risk however, is the use of the validated EPIC-urinary

domain questionnaire. Third, in our study, the rates of continence, particularly in the

control group, are lower than other rates published in the literature (1), however it

should be noted that a strict definition of ‘zero-pads’ was used to define continence and

furthermore as a public teaching hospital these cases were predominantly performed

with the trainee or fellow as the primary surgeon on the console. Furthermore, there

continues to be no clear consensus on a measurable definition of continence, and the

use of ‘pad number’ as a measure of the degree of incontinence may not be reliable. For

example, an incontinent patient who loses urine but refuses to wear pads could hardly

be considered continent. Conversely, a careful man who hardly leaks, but changes his

pads multiple times daily to maintain hygiene, may be misinterpreted to be reliant on

pads when he is actually not. Therefore, a more accurate measure of incontinence is 24-

55

hour pad weight as it better quantifies the amount of leakage. 24-hour pad weight in

combination with quality of life measures (EPIC, SF-36) would be the optimal tools for

any future studies to quantify urinary incontinence outcomes following prostate

surgery (13).

2.5 Conclusion

In summary, the RoboSling technique is a novel, easily performed intra-operative sling

at the time of RARP that demonstrates improved rates of continence both in the short

term and at 1-year following surgery without a higher complication or positive surgical

margin rate. A randomised controlled study is now underway at Royal Prince Alfred

Hospital to further assess the benefits of this technique.

56

2.6 References

1. Wei JT, Dunn RL, Litwin MS, Sandler HM, Sanda MG. Development and validation

of the expanded prostate cancer index composite (EPIC) for comprehensive assessment

of health-related quality of life in men with prostate cancer. Urology. 2000;56(6):899-

905.

2. Bossert K, Ramakrishnan VM, Seifert B, Lehmann K, Hefermehl LJ. Urinary

Incontinence-85: An Expanded Prostate Cancer Composite (EPIC) Score Cutoff Value for

Urinary Incontinence Determined Using Long-term Functional Data by Repeated

Prospective EPIC-Score Self-assessment After Radical Prostatectomy. Int Neurourol J.

2017;21(4):302-8.

3. Jorion JL. Rectus fascial sling suspension of the vesicourethral anastomosis after

radical prostatectomy. The Journal of urology. 1997;157(3):926-8.

4. Westney OL, Scott S, Wood C, Eddings T, Johnson MM, Taylor JM, et al.

Suburethral sling at the time of radical prostatectomy in patients at high risk of

postoperative incontinence. BJU Int. 2006;98(2):308-13.

5. Punnen S, Clint Cary K, Glass AS, Cowan JE, Carroll PR. Autologous retro-pubic

urethral sling: a novel, quick, intra-operative technique to improve continence after

robotic-assisted radical prostatectomy. J Robot Surg. 2014;8(2):99-104.

6. Arroua F, Toledano H, Gaillet S, Saidi A, Breton X, Delaporte V, et al. [Radical

prostatectomy with bladder neck preservation: surgical margins and urinary

continence]. Progr Urol. 2008;18(5):304-10.

7. Jones JS, Vasavada SP, Abdelmalak JB, Liou L, Ahmed ES, Zippe CD, et al. Sling

may hasten return of continence after radical prostatectomy. Urology.

2005;65(6):1163-7.

57

8. Altinova S, Demirci DA, Ozdemir AT, Akbulut Z, Atmaca AF, Caglayan A, et al.

Incorporation of anterior rectus fascial sling into radical retropubic prostatectomy

improves postoperative continence. Urol Int. 2009;83(1):19-21.

9. Cestari A, Ferrari M, Ghezzi M, Sangalli M, Zanoni M, Fabbri F, et al. Retropubic

Intracorporeal Placement of a Suburethral Autologous Sling During Robot-Assisted

Radical Prostatectomy to Improve Early Urinary Continence Recovery: Preliminary

Data. J Endourol. 2015;29(12):1379-85.

10. Nguyen HG, Punnen S, Cowan JE, Leapman M, Cary C, Welty C, et al. A

Randomized Study of Intraoperative Autologous Retropubic Urethral Sling on Urinary

Control after Robotic Assisted Radical Prostatectomy. The Journal of urology.

2017;197(2):369-75.

11. Kojima Y, Hamakawa T, Kubota Y, Ogawa S, Haga N, Tozawa K, et al. Bladder neck

sling suspension during robot-assisted radical prostatectomy to improve early return of

urinary continence: a comparative analysis. Urology. 2014;83(3):632-9.

12. Bahler CD, Sundaram CP, Kella N, Lucas SM, Boger MA, Gardner TA, et al. A

Parallel Randomized Clinical Trial Examining the Return of Urinary Continence after

Robot-Assisted Radical Prostatectomy with or without a Small Intestinal Submucosa

Bladder Neck Sling. The Journal of urology. 2016;196(1):179-84.

13. Liss MA, Osann K, Canvasser N, Chu W, Chang A, Gan J, et al. Continence

definition after radical prostatectomy using urinary quality of life: evaluation of patient

reported validated questionnaires. The Journal of urology. 2010;183(4):1464-8.

58

2.7 Appendices

Appendix 1: Medical Art Commission Agreement

60

CHAPTER THREE: RANDOMISED CONTROLLED TRIAL PROTOCOL

3.1 Introduction

With the encouraging results seen in the prospective cohort study, a randomised

controlled trial protocol was developed to further assess the merits of this novel

RoboSling technique. The protocol was given ethics approval on 10th October 2018 with

the HREC letter of approval attached as Appendix 1.

3.2 Methodology and Design

Study Design

This is a prospective, 2 group, 1:1 randomised controlled trial assessing urinary

function following RARP in patients with and without a concurrent RoboSling

procedure. Two surgeons performing RARP at Royal Prince Alfred Hospital will take

part in the study, both of whom are beyond their learning curve. Patients will be blinded

as to whether the RoboSling procedure is performed for them, as will the research

officers collecting the post- operative data on urinary function.

To reduce participant burden, this study will use the clinical data already collected by

the Robotic and Open Surgery for Prostate Cancer (“ROSE”) study (existing approved

protocol: No. X16-0294 & HREC/16/RPAH/377).

Primary Aim

The primary aim of this study is to determine if incorporating the RoboSling procedure

with RARP improves early (3 months) and late (1 year) post-operative urinary

continence compared to RARP alone.

61

Secondary Aims

(i) Identify urinary functional parameters (by uroflow, urodynamics and dynamic 3D

pelvic floor ultrasound) which may differ between the RoboSling group and the control

group

(ii) Identify differences in perioperative complications.

(iii) Identify anatomic features on pre-op imaging (MRI scan/ 3D pelvic floor ultrasound

scan) which may result in poorer post-operative functional outcome post RARP

(prostate volume; pelvic volume; urethral length; BMI).

(iv) Prospectively assess:

(a) Clinical outcomes

(b) Quality of life

(c) Health economic outcomes

(d) Decision-regret

Selection of Subjects

Inclusion Criteria -To be eligible to enter the study all patients must satisfy the

following criteria:

1. Adult men aged 18 years and over

2. Undergoing prostatectomy for prostate cancer at RPA hospital

3. Clinically suitable for robotic prostatectomy

4. Cognitively able to give written informed consent for participation

5. Elective procedure

Exclusion Criteria -Patients will be excluded if they present the following exclusion

criteria:

1. The patient lacks the ability to consent for themselves

62

2. Patient or tumour factors precluding robotic surgery

Patient Recruitment

This study aims to recruit 120 consecutive patients with clinically localised prostate

cancer who have chosen to undergo RARP under the care of SLHD urologists. Eligible

patients will be informed about the study by their surgeon during preoperative

counselling and given a study pack containing a written consent form (Appendix 2),

patient information sheet (Appendix 3) and baseline study questionnaire (Appendix 4)

to complete and return to the study coordinator (Virginia Ip - Urology CNC at RPAH or

Beth Whitaker – Prostate care CNC at CRGH) in a reply-paid envelope. On receipt of the

consent form, the study coordinator will contact the patient to provide additional

information about the study, answer any questions and to confirm consent to

participate independent of the treating surgeon.

Consenting patients will be allocated a unique study identification number. The list that

matches individual patients with study identification numbers will be kept securely by

the study coordinator in a separate excel file on a password protected computer within

the Department of Urology at RPAH. Study data will be entered into a REDCap database

with individuals identified by their study identification number (i.e. in re-identifiable

format). Only the study coordinator and study investigators will have access to these

data.

Preoperative assessment

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Patients will be invited to attend the hospital (RPAH or CRGH, whichever is more

convenient for the patient) for functional diagnostic assessment for the purposes of this

study, which includes:

1. Urodynamics (to study bladder storage function, voiding function and continence);

2. Pelvic floor ultrasound (to assess pelvic floor contraction and urethral mobility and

measure urethral sphincter length);

3. Uroflow assessment (to assesses bladder and sphincter function and to test for urine

obstructions)

Urodynamic testing will occur at pre-operative and 12-months post-operative. Uroflow

and Pelvic floor ultrasound assessments will occur at pre-operative, 6 weeks, 3 months,

6 months and 12 months post-operative. These tests will be carried out in in a 15

minute to 1- hour clinic visit.

Quality of life (QoL) data using the SF-36 questionnaire will be collected from all

participants. This QoL measure is an internationally recognised, widely used QoL

instrument that can generate utility-based quality of life scores that will be used in

future health economic analyses (baseline, 2 and 6 weeks, 3, 6 and 9 months, and 1 year

post surgery).

Follow up assessments

The study measurements and time points of collection are outlined in Table 1. All

patients participating will be contacted by an authorised member of the study team at, 2

weeks, 6 weeks, 3 months, 6 months, 9 months, and 1-year post –operatively, either via

telephone, post or email and asked to complete a follow-up questionnaire that will be

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emailed or posted to them (with a reply-paid envelope), according to the patient’s

preference. Patients will have the option of completing the questionnaire by telephone

if this is more convenient. Decision regret scale is a validated questionnaire to assess

the degree of regret after a treatment choice and will be collected at 6 weeks, 3 months

and 1 year.

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Randomisation

Assignment to the RoboSling procedure or to standard RARP technique will be

randomly determined by computer generated code. Random assignment will be

generated just prior to the operation. Patients, data collectors and study personnel will

be blinded to randomisation assignments.

Outcome Measures

The primary outcome measures will be continence defined as 0 pads per day at 3

months post-operatively. Secondary outcomes will be 24-hr pad weight, EPIC & ICIQ

scores, time to return of continence, SF-36 scores and decision regret scale. Uroflow,

Urodynamic parameters (Qmax, Detrusor Leak point pressure, bladder compliance) and

pelvic floor contraction and mobility on 3D pelvic floor ultrasound (PFUS) will be

recorded preoperatively and post-operatively. Anatomic factors to assess functional

outcomes: sphincter length, prostate size and configuration, pelvic dimensions on

MRI/CT/PFUS, operative factors.

The study coordinator in each Hospital will collect the participant data from different

sources. Age, BMI, PSA, mpMRI, clinical stage, margin involvement, and extracapsular

extension will be collected from PowerChart. Operation time, console time,

complications, conversion rate, blood loss, length of hospital staying, transfusions,

lymph nodes harvested, PCI and PV will be collected from the Medical Records. Study

questionnaires, such as SF-36v2 QoL questionnaire IPSS, IIEF, ICIQ-UI and EPIC will be

given or mailed to participants by the study coordinators pre- and post-operatory (i.e.

pre-operatory, 2 weeks, 6 weeks, 3 months, 6 months, 9 months and 1 year post-

operatively).

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3.3 Statistical Analyses

Clinically relevant baseline variables will be tabulated and compared between groups.

Categorical variables will be compared between groups using the chi-squared test

(frequencies and proportions). Continuous variables will be compared using t-test

(means) or Wilcoxon 2-sample test (median). Unadjusted rates of continence will be

compared between groups with the Fisher exact test. All data will be stored in a REDCap

database and statistical analysis will be performed using SPSS version 22 (SPSS Inc.,

Chicago, IL, USA).

Sample size

Urinary continence at 3 months was the primary outcome used for power and sample

size calculation. In this prospective RCT, based on previous studies and on the authors

own experience and data (including the ROSE study data), the rate of no urinary pad use

(continence) at 3 months post-surgery between robotic prostatectomy with and

without the RoboSling procedure is approximately 50% and 20%, respectively. If the

true urinary continence rate for experimental (RARP + RoboSling) subjects is 50% at 3

months, we will need to study 51 experimental subjects and 51 control (RARP only)

subjects to be able to reject the null hypothesis that the urinary continence rates for

experimental and control groups are equal with probability 90% power and type I error

probability 0.05. We will use an uncorrected Chi-square statistic to evaluate this null

hypothesis. The sample size was calculated using Power and Sample Size Calculations

software (Vanderbilt University, version 3.0).

We anticipate that around 2 procedures (1 RoboSling and 1 without RoboSling) will be

performed each week, approximately 100 per year. Assuming a maximum drop-out rate

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of 15%, a total of at least 120 patients (60 in each group) will be accrued over

approximately 1.5 years and followed-up for disease progression and continence.

3.4 Benefits and Risks of this Study

Benefits

The primary benefit of the study will to scientifically evaluate whether a novel sling

procedure will improve post-operative continence following RARP. If early and late

continence rates are improved with the RoboSling then improved quality of life could

also be expected in men following surgery for their prostate cancer.

Risks

The risks of the study are the surgical risks of the robotic radical prostatectomy

operation and the novel RoboSling procedure. Specific to the RoboSling, possible risks

include intraoperative complications such as bladder and ureteric injury. Post-operative

complications may include urinary retention, urinary tract infection and diminished

urinary flow. All eligible participants will be under the care of specialist urological

surgeons at the time of research. There will be regular interaction between medical staff

and the investigators to ensure that any issues are raised and addressed. The research

will not proceed without the ongoing support of the treating clinicians and medical staff.

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3.5 Safety Monitoring

The Data and Safety Monitoring Board (DSMB) will be the Royal Prince Alfred Institute

of Academic Surgery (RPAIAS) Surgical Robotic Steering Committee. The senior surgeon

investigators of the trial (Dr Scott Leslie and Associate Professor Ruban Thanigasalam)

independent senior clinicians, including Prof Michael Solomon and Prof Paul Bannon, as

well as RPAIAS Executive Director Kate McBride, form this board. Two external data

monitors will work with the DSMB. Summarised and de-identified data will be

periodically reported to them or when requested.

Similarly, data will be reported to the HREC when requested. Should any unforeseen

circumstances or concerns arise, the Principal Investigators will report these to the

HREC as well.

3.6 Data Handling and Record Keeping

Data recording

Data will be stored on the Sydney Local Heath District (SLHD) REDCap Installation

during the study. This is a SLHD run research database with appropriate security

measures and backup in place. Data management will be performed with the same rigor

and security measures that have been used in the past.

Once the study is complete the data will be exported to a DVD, which will be locked in a

cabinet in the Data Management office. DVD’s will be kept for 15 years following

completion of the study after which they will be confidentially destroyed. Data will be

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stored using re- identifiable coding to permit follow-up data collection and quality

checks if there are any concerns regarding the data.

Data reporting

Throughout the study, results (summarised and de-identified) will be reported monthly

to the RPA Institute of Academic Surgery (RPAIAS) Surgical Robotic Steering

Committee. Similarly, reports will be provided to the ethics department for annual

reporting. Final reporting of this study will occur in the form of publications in specialty

specific peer- reviewed journals. Any data published will be de-identified completely.

This study will also provide key data elements to the Robotic Research Database (BEST)

(protocol no X16-0182, LNR/16/RPAH/223 & LNRSSA/16/RPAH/460), administered

by the RPAH Institute of Academic Surgery (IAS). BEST serves as an ongoing

comprehensive database capturing information from the Robotic Surgical Programs of

participating specialties including surgical outcomes, patient quality of life and costings

measures. The purpose of BEST is to provide data for internal monitoring and reporting

of all robotic procedures undertaken at the RPAH; support quality improvement

activities within the Robotic Program; and identify potential areas for and assist with

the development of further research within the Robotic Program.

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3.7 Ethical Considerations

General duties

This study will be conducted within the framework of local and national Human

Research and Ethics guidelines, and with the approval of relevant authorities. Ultimate

responsibility for approval and compliance of the study with the above lies with the

Principal Investigator.

Consent and Human Research Ethics Committee

Ethical approval was sought from the SLHD (RAPH Zone) Human Research Ethics

Committee (EC00113) and approval given on 10th October 2018 (Appendix 1) Site

specific assessments (SSAs) were submitted to RPAH and Concord Hospitals for

research governance. Consent will be sought from patients using the Patient

Information and Signed Consent Forms (Appendix 2 and 3).

Patient confidentiality

All investigators are health professionals who have previously signed documents

ensuring confidentiality for patients at Sydney Local Health District facilities.

Additionally, patient confidentiality is a required agreement for all registering bodies of

the involved health professionals.

Data will be re-identifiable for the duration of the study and de-identified prior to

statistical analysis. No participant will be identified in any publications. Confidentiality

is ensured as published data will be aggregate.

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3.8 References

1. Australian Institute of Health and Welfare. Australian Cancer Incidence and

Mortality books: Prostate cancer Canberra: 2014 [13/03/2014]. Availableat

www.aihw.gov.au/acim-books [Accessed 5 February 2015].

2. Roberts G, Xatzipsalti M, Borrego LM, et al. Paediatric rhinitis: Position paper of

the European Academy of Allergy and Clinical Immunology. Allergy: European

Journal of Allergy and Clinical Immunology 2013;68:1102-16.

3. Sharma R, Sharma A, Prasher B. Introduction to adhesions and their prevention.

International Journal of Pharmacy and Technology 2013;5:2465-76.

4. Katz G, Rodriguez R. Changes in continence and health-related quality of life after

curative treatment and watchful waiting of prostate cancer. Urology

2007;69:1157-60.

5. Ficarra V, Novara G, Artibani W, et al. Retropubic, laparoscopic, and robot-

assisted radical prostatectomy: a systematic review and cumulative analysis of

comparative studies. Eur Urol 2009;55:1037-63.

6. Rocco B, Gregori A, Stener S, et al. Posterior reconstruction of the

rhabdosphincter allows a rapid recovery of continence after transperitoneal

videolaparoscopic radical prostatectomy. Eur Urol 2007;51:996-1003.

7. Menon M, Muhletaler F, Campos M, Peabody JO. Assessment of early continence

after reconstruction of the periprostatic tissues in patients undergoing computer

assisted (robotic) prostatectomy: results of a 2 group parallel randomized

controlled trial. J Urol 2008;180:1018-23.

8. Ahlering TE, Gordon A, Morales B, Skarecky DW. Preserving continence during

robotic prostatectomy. Curr Urol Rep 2013;14:52-8.

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9. Lee SR, Kim HW, Lee JW, Jeong WJ, Rha KH, Kim JH. Discrepancies in perception

of urinary incontinence between patient and physician after robotic radical

prostatectomy. Yonsei Med J 2010;51:883-7.

10. Kundu SD, Roehl KA, Eggener SE, Antenor JA, Han M, Catalona WJ. Potency,

continence and complications in 3,477 consecutive radical retropubic

prostatectomies. J Urol 2004;172:2227-31.

11. Coakley FV, Eberhardt S, Kattan MW, Wei DC, Scardino PT, Hricak H. Urinary

continence after radical retropubic prostatectomy: relationship with

membranous urethral length on preoperative endorectal magnetic resonance

imaging. J Urol 2002;168:1032-5.

12. . Link BA, Nelson R, Josephson DY, et al. The impact of prostate gland weight in

robot assisted laparoscopic radical prostatectomy. J Urol 2008;180:928-32.

13. Boczko J, Erturk E, Golijanin D, Madeb R, Patel H, Joseph JV. Impact of prostate

size in robot-assisted radical prostatectomy. J Endourol 2007;21:184-8.

14. Chang JI, Lam V, Patel MI. Preoperative Pelvic Floor Muscle Exercise and

Postprostatectomy Incontinence: A Systematic Review and Meta-analysis. Eur

Urol 2016;69:460-7.

15. Trinh QD, Bjartell A, Freedland SJ, et al. A systematic review of the volume-

outcome relationship for radical prostatectomy. Eur Urol 2013;64:786-98.

16. Samadi DB, Muntner P, Nabizada-Pace F, Brajtbord JS, Carlucci J, Lavery HJ.

Improvements in robot-assisted prostatectomy: the effect of surgeon experience

and technical changes on oncologic and functional outcomes. J Endourol

2010;24:1105-10.

17. Zorn KC, Wille MA, Thong AE, et al. Continued improvement of perioperative,

pathological and continence outcomes during 700 robot-assisted radical

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prostatectomies. Can J Urol 2009;16:4742-9; discussion 9.

18. Patel VR, Coelho RF, Palmer KJ, Rocco B. Periurethral suspension stitch during

robot-assisted laparoscopic radical prostatectomy: description of the technique

and continence outcomes. Eur Urol 2009;56:472-8.

19. Cestari A, Ferrari M, Ghezzi M, et al. Retropubic Intracorporeal Placement of a

Suburethral Autologous Sling During Robot-Assisted Radical Prostatectomy to

Improve Early Urinary Continence Recovery: Preliminary Data. J Endourol

2015;29:1379-85.

20. Takenaka A, Tewari AK, Leung RA, et al. Preservation of the puboprostatic collar

and puboperineoplasty for early recovery of urinary continence after robotic

prostatectomy: anatomic basis and preliminary outcomes. Eur Urol

2007;51:433-40; discussion 40.

21. Ficarra V, Novara G, Rosen RC, et al. Systematic review and meta-analysis of

studies reporting urinary continence recovery after robot-assisted radical

prostatectomy. Eur Urol 2012;62:405-17.

22. Nguyen HG, Punnen S, Cowan JE, et al. A Randomized Study of Intraoperative

Autologous Retropubic Urethral Sling on Urinary Control after Robotic Assisted

Radical Prostatectomy. J Urol 2017;197:369-75.

23. Bahler CD, Sundaram CP, Kella N, et al. A Parallel Randomized Clinical Trial

Examining the Return of Urinary Continence after Robot-Assisted Radical

Prostatectomy with or without a Small Intestinal Submucosa Bladder Neck Sling.

J Urol 2016;196:179-84.

24. Yaxley JW, Coughlin GD, Chambers SK, et al. Robot-assisted laparoscopic

prostatectomy versus open radical retropubic prostatectomy: early outcomes

from a randomised controlled phase 3 study. Lancet 2016;388:1057-66.

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Appendix 2: Participant Consent Form

ROBOSling MASTER Participant Consent Form Version 1 25Aug17 1 RPAH Participant Consent Form Version 1 12Oct2018

RANDOMISED STUDY ASSESSING URINARY CONTINENCE FOLLOWING ROBOTIC RADICAL PROSTATECTOMY WITH OR WITHOUT AN INTRAOPERATIVE

RETROPUBIC VASCULARISED FASCIAL SLING (ROBOSLING)

Protocol No. X17-0339 and HREC/17/RPAH/518 and SSA/18/RPAH/XXX

RPAH PARTICIPANT CONSENT FORM I, ……………………………………………………………………………………………………[name] of ………………………………………………………………………………………….........[address] have read and understood the Participant Information Sheet on the above named study,

and have discussed it with ...............................................................................................[name] .....................................................................................[relationship] I have been made aware of the procedures involved in the study, including any known or expected inconvenience, risk, discomfort or potential side effect and of their implications as far as they are currently known by the researchers. I understand that my participation in this study will allow the researchers and others, as described in the Participant Information Sheet, to have access to my medical record, and I agree to this. I understand that my identity will never be revealed at any time and that the research study is strictly confidential. I freely choose to participate in this study and understand that I can withdraw at any time. I hereby agree to participate in this research study. NAME: ................................................................................................................... SIGNATURE: .......................................................................................................... DATE: ........... / ........... / .................. Best phone number to contact me on: ...................................................................

Best time of day to contact me: Morning Afternoon Any time

My Email Address: ………………………………………………………………………... To email your study questionnaires ONLY NAME OF WITNESS: .............................................................................................. SIGNATURE OF WITNESS ....................................................................................

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Appendix 3: Participant Information Sheet

MASTER Participant Information Sheet - Version 3 11Oct2018 Page 1 RPAH Participant Information Sheet - Version 1 12Oct2018

RANDOMISED STUDY ASSESSING URINARY CONTINENCE FOLLOWING ROBOTIC

RADICAL PROSTATECTOMY WITH OR WITHOUT AN INTRAOPERATIVE

RETROPUBIC VASCULARISED FASCIAL SLING (ROBOSLING)

Protocol No. X17-0339 and HREC/17/RPAH/518 and SSA/18/RPAH/633

PARTICIPANT INFORMATION SHEET

This information sheet is 4 pages long. Please make sure you have all the pages. This information

sheet is for you to keep.

Invitation to participate in the study

You are invited to take part in a research study evaluating the effectiveness of a new procedure,

called “Robo-Sling” which is performed during your robotic-assisted radical prostatectomy surgery.

The new procedure involves using your own tissue from behind the bladder during the radical

prostatectomy operation to form a tissue ‘sling’ to support the urethra to reduce the leakage of

urine (incontinence) following the surgery. The study aims to find out if including the Robo-Sling

procedure during radical prostatectomy improves urinary continence after robotic surgery for

prostate cancer.

You will be participating in a randomised controlled trial. This is a type of study where we compare

a new treatment with the current standard treatment to see if one is better. You will be allocated by

chance (this is called randomisation) to having the standard robotic assisted radical prostatectomy

operation or having the Robo-Sling procedure in addition to the radical prostatectomy operation.

You will have equal chance of receiving either the new procedure or the standard procedure.

Your clinical assessment and treatment both before and after the surgery will proceed as usual.

Participation in this study will not affect your decision whether or not to have surgery or your

treatment plan.

The study is being conducted at Royal Prince Alfred Hospital (RPAH) by:

• Dr Scott Leslie, Department of Urology, RPAH

• A/Prof Ruban Thanigasalam, Institute of Academic Surgery, RPAH

• Sr Virginia Ip, Department of Urology, RPAH

• Dr Daniel Steffens, Surgical Outcomes Research Centre, RPAH

• Ms Julia Stanbury, Surgical Outcomes Research Centre, RPAH

• Ms Christina Stanislaus, Surgical Outcomes Research Centre, RPAH

None of the investigators involved in the study have any conflicts of interest to declare. The study

investigators have no financial relationships with the robotic manufacturer to disclose.

Study Procedures

We aim to include approximately 120 patients in this research study. In addition to the surgery, this

study involves the collection of clinical data, the administration of questionnaires and 2 physical

assessments. The information collected will remain confidential at all times and will only be

identifiable by those directly conducting the research.

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Appendix 4: Participant Study Questionnaire

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CHAPTER 4: CONCLUSIONS

This thesis explores a novel technique to improve the functional outcomes

for men undergoing prostatectomy for prostate cancer. Although there

have been substantial improvements in surgical techniques over the last 20

years from better understanding of pelvic anatomy to the introduction of

robotic technology, long-term stress urinary incontinence still occurs in 5-

25% of patients following radical surgery. Even for those men that regain

full continence with time, the early post-operative incontinence can be

substantial, preventing return to work or restrict their social and leisure

activities, therefore significantly impacting on quality of life.

The systematic review and meta-analysis summarises the different types of

intra-operative slings that have been used at the time of radical

prostatectomy to improve post-operative continence. The current

literature suggests that intraoperative sling procedures may promote early

return of continence, however there was no long-term benefit seen.

The RoboSling, is a novel intra-operative continence technique which uses

a vascularised flap of peritoneum positioned as a bladder neck sling and

hitched to the pubic bone to improve functional outcomes. This

prospective, non-randomised cohort study demonstrated improved 3-

month and 12-month continence outcomes compared to the non-sling

cohort.

A randomised control trial is currently underway at Royal Prince Alfred

Hospital with the aim to recruit 120 patients to provide level 1 evidence as

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to the benefits of the RoboSling. As of the time of thesis submission

(February 2021), 40 patients have been enrolled in the RCT.