Supplement 1 – Study protocol
Protocol: Preservation of the neurovascular bundles improves time to continence
after radical prostatectomy, but not long-term continence rates: Results of a
systematic review and meta-analysis
Objectives
The primary objective of this review is to evaluate if sparing the neurovascular bundle
in men having radical prostatectomy affects postoperative urinary continence
outcomes. The secondary objective is to assess if nerve sparing has an affect on the
timing of return of urinary continence postoperatively.
Methods
Study selection criteria
The study selection criteria and search strategy were based on PICOS framework.
Participants
Adult men having a radical prostatectomy for prostate cancer will be included.
Intervention
Nerve sparing radical prostatectomy will be evaluated. Subcategories of nerve
sparing to be evaluated will include bilateral nerve sparing, unilateral nerve sparing
or nerve-sparing (unspecified).
Comparison
Non-nerve sparing radical prostatectomy will be the control group.
This study will not attempt to evaluate alternative types of nerve sparing techniques.
For example the following interventions will not be compared:
 Intra/interfascial versus “standard”
 Risk stratified nerve spare
 Sural nerve grafting
Studies will not be selected or excluded based on surgical approach (i.e. retropubic,
perineal, laparoscopic and robotic approaches will all be included).
Outcomes
The primary outcome for this review is:
 Post-operative urinary continence rate (as defined by the study authors)
 Urinary Health Related Quality of Life (HRQoL) outcomes where a validated
HRQoL assessment tool has been used
Secondary outcomes for this review are:
 Timing of return of continence (i.e. Does nerve sparing surgery result in
earlier return of continence?)
Study Types
All RCTs or longitudinal controlled studies will be included (i.e. RCT, prospective or
retrospective cohort studies). Single cohort studies (where there is no comparison
group described), case-control studies and cross-sectional studies will not be
included.
Search Strategy
The search will be run in the following electronic databases:
 PubMed
 Medline
 Cochrane Central Register of Controlled Trials
Results will be restricted to publications from 1982 onwards, given that nerve sparing
surgery was not described prior to this time. Studies in languages other than English
will not be included. Results will not be restricted by publication status.
Current and ongoing trials will be searched for using the following website:
 www.clinicaltrials.gov
The reference lists from included publications and relevant reviews will be hand
searched to identify further potentially relevant studies.
Selection of studies
Records identified will be collated and de-duplicated. Two authors will independently
screen search results. The full text of any potentially relevant studies will be reviewed
and studies selected based on the pre-determined inclusion criteria. If discrepancies
are not able to be resolved through discussion, a third author will be consulted.
Data extraction and management
Two authors will develop and pilot a standardized data collection form and
independently undertake data extraction for all studies.
The following data will be extracted for included studies:
 Study details: reference details, country, year, contact details, funding source,
conflicts of interest
 Methods: study design, duration, location, clinical setting, risk of bias
 Participants: sample size, inclusion and exclusion criteria, baseline
characteristics (age, cancer characteristics, BMI, preop continence), surgical
approach
 Intervention: description of nerve sparing status, comparison group(s) and
method for classification
 Outcomes: continence (definition), urinary related HRQoL outcomes
(assessment tool), diagnostic assessment, timing of method of outcome
measurement
 Results: summary data for each intervention group, information on
subgroups, statistical methods used
 References to other potentially relevant publications
Assessment of risk of bias of selected studies
Risk of bias for each study will be assessed independently by two authors using
predefined criteria (Table 1). Risk of bias for each element will be described as high,
low or unclear.
Table 1 Items to assess risk of bias for different study designs
Study design
Item
RCT
Sequence generation
(Adapted from [1]) Allocation concealment
Blinding
Incomplete outcome data
Selective outcome reporting
Other sources of bias
Cohort Study
Study design (prospective/retrospective)
(Adapted from [2]) Cohorts drawn from same population
Assessment of nerve spare
Outcome of interest not present at start of study
Comparability of groups (baseline; co-interventions)
Assessment of outcome
Adequate follow-up of cohorts (number lost to follow-up)
Measures of treatment effect
Risk ratio (with 95% confidence interval) will be calculated for dichotomous variables
(continence rates). Mean difference (with 95% CI) will be calculated for continuous
variables (HRQoL outcomes) where the same scale has been used.
Dealing with missing data
Where there is missing data from included RCTs we will attempt to contact authors.
Where there is missing data from cohort studies, authors will not be contacted. If
there is insufficient data for meta-analysis these studies will be excluded.
Where continence rates are reported as proportions (i.e. percentages) these will be
used to calculate estimated number of continent participants.
Assessment of heterogeneity
Similarity of individual studies will be assessed with respect to clinical and
methodological diversity. The following factors will be considered:
 Baseline characteristics of participants
o e.g. pre-operative continence rate, age, other treatments received
(such as radiotherpy)
 Type of intervention
o Surgical approach
o Author definition/assessment of nerve sparing status
Statistical heterogeneity will be assessed using Chi square analysis and I2 statistic.
Data synthesis
Studies will be grouped according to intervention, comparison and outcomes
evaluated (including timing of outcome reporting).
If studies are judged to be sufficiently similar, meta-analysis will be performed to pool
results. A random effects model will be used to establish a pooled risk ratio. A
sensitivity analysis will be undertaken, evaluating studies of the highest available
evidence.
Statistic analyses will be done using Review Manager software v5.2 (Copenhagen:
The Nordic Cochrane Centre, The Cochrane Collaboration, 2012).
Should a meta-analysis not be possible due to study heterogeneity, we will present
results of individual studies and undertake a narrative synthesis.
Subgroup analyses
The following subgroup analysis will be performed if sufficient data is available:
 Timing of outcome measurement
References
1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews
of Interventions Version 5.1.0 [updated March 2011]. The Cochrane
Collaboration, 2011. Available from www.cochrane-handbook.org
2. The Cochrane Collaboration. Tool to Assess Risk of Bias in Cohort Studies.
http://bmg.cochrane.org/sites/bmg.cochrane.org/files/uploads/Tool%20to%20
Assess%20Risk%20of%20Bias%20in%20Cohort%20Studies.pdf (Accessed
2014)