Systematic review and meta-analysis of the clinical effectiveness of

bipolar compared with monopolar transurethral resection of the prostate

(TURP)

To compare monopolar and bipolar transurethral resection of the prostate

(TURP) for clinical effectiveness and adverse events.
We conducted an electronic search of MEDLINE, Embase, CENTRAL, Science
Citation Index, and also searched reference lists of articles and abstracts from
conference proceedings for randomised controlled trials (RCTs) comparing
monopolar and bipolar TURP.
Two reviewers independently undertook data extraction and assessed the risk
of bias in the included trials using the tool recommended by the Cochrane
Collaboration.
The quality of evidence was assessed using the Grading of Recommendations
Assessment, Development and Evaluation (GRADE) approach.
From the 949 abstracts that were identified, 94 full texts were assessed for
eligibility and a total of 24 trials were included in the review.
No statistically significant differences were found in terms of International
Prostate Symptom Score (IPSS) or health-related quality of life (HRQL) score.
Results for maximum urinary flow rate were significant at 3, 6 and 12 months
(all P < 0.001), but no clinically significant differences were found and the
meta-analysis showed evidence of heterogeneity
Bipolar TURP was associated with fewer adverse events including
transurethral resection syndrome (risk ratio [RR] 0.12, 95% confidence
interval [CI] 0.050.31, P < 0.001), clot retention (RR 0.48, 95% CI 0.300.77,
P = 0.002) and blood transfusion (RR 0.53, 95% CI 0.350.82, P = 0.004)
Several major methodological limitations were identified in the included
trials; 22/24 trials had a short follow-up of 1 year, there was no evidence of
a sample size calculation in 20/24 trials and the application of GRADE showed
the evidence for most of the assessed outcomes to be of moderate quality,
including all those in which statistical differences were found.
Whilst there is no overall difference between monopolar and bipolar TURP for
clinical effectiveness, bipolar TURP is associated with fewer adverse events
and therefore has a superior safety profile.
Various methodological limitations were highlighted in the included trials and
as such the results of this review should be interpreted with caution.
 There is a need for further well-conducted, multicenter RCTs with long-term
follow-up data.

Keywords monopolar, bipolar, transurethral resection of the prostate (TURP),

benign prostatic enlargement, systematic review, meta-analysis

Introduction

The prevalence of benign prostatic enlargement (BPE) and associated LUTS

increases with age, with about one in four men estimated to have received
treatment for LUTS by the age of 80 years [1]. TURP has long been the gold
standard of surgical management for LUTS secondary to BPE, achieving long-lasting
functional outcomes [1,2]. However, the procedure may be associated with
considerable morbidity [3] and complications including transurethral resection (TUR)
syndrome, bleeding, and urethral strictures [4].

Traditionally TURP is performed by monopolar diathermy, which involves an

electrical current flowing from an active lectrode to the prostate and through the
body before exiting via a return electrode placed on the skin. The use of hypo-
osmolar irrigation fluids, i.e. glycine, sorbitol or mannitol solutions, which are
molecularly inert, optically clear and non-conductive is required. Such solutions
place the patient at risk of dilutional hyponatraemia and TUR syndrome, which is
characterised by metabolic abnormalities, cardiovascular problems and neurological
irregularities and is associated with a risk of mortality of up to 40% [5]. By contrast,
bipolar TURP (B-TURP) uses a current that travels through the loop and prostatic
tissue but not through the patients body enabling the use of isotonic solutions, i.e.
0.9% normal saline, instead. This is thought to circumvent some of the problems
associated with monopolar TURP (M-TURP), such as TUR syndrome. This systematic
review was undertaken to compare the relative clinical effectiveness and adverse
events of M-TURP and B-TURP.

Methods

The present report is an update of a Health Technology Assessment review on

alternative approaches to endoscopic ablation for BPE [6]. The original systematic
review covered published reports from 1966 to September 2006, whilst this update
extended the literature search period up to March 2012 and focused exclusively on
randomised controlled trials (RCTs) comparing B-TURP with M-TURP. It should be
noted that B-TURP can be performed using resection and/or vaporisation but in this
review we have only included trials using resection. This review was conducted in
accordance with the systematic review guidelines provided by the Cochrane
Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-
Analyses (PRISMA) Checklist.

Electronic databases searched included MEDLINE, Embase, CENTRAL and Science

Citation Index. The search terms used included: benign prostatic enlargement,
prostate hyperplasia, prostate hypertrophy, transurethral resection,
monopolar, bipolar, and randomized controlled trials. Searches were not
restricted by publication year or language and included conference proceedings and
abstracts. The complete search strategy is available on request. Reference lists of
all included trials were further screened to identify additional potentially relevant
trials. Any disagreement about trial eligibility and inclusion were resolved by
discussion or arbitration involving an independent third party. The following
outcomes were selected for clinical effectiveness based upon the advice from
clinical experts:

1. Clinical effectiveness
IPSS
Health-related quality of life (HRQL)
Maximum urinary flow rate (Qmax)
We also reported the adverse events that were identified in the included trials
as listed below:
Incidence of TUR syndrome
Blood transfusion
Clot retention
Incontinence (as defined by trialists)
Erectile dysfunction measured by the International Index of Erectile
Function (IIEF)
Urethral stricture
Need for second procedure
UTI
Incidence of acute retention after removal of catheter
Data Extraction and Risk of Bias Assessment
Two reviewers independently extracted data using a standardised form.
Results were compared and any differences of opinion were discussed and
reconciled amongst review authors. The risk of bias (RoB) in the included
trials was assessed using the tool recommended by the Cochrane
Collaboration [7]. We supplemented the RoB tool with additional domains
including financial support, sample size calculation, approval by medical
ethics committee, and informed consent. We applied the Grading of
Recommendations Assessment, Development and Evaluation (GRADE)
approach to assess the quality of evidence. The GRADE working group
strongly encourages adopting GRADE methodology for a maximum of seven
outcomes in a systematic review [8]. We selected the following seven
outcomes, as recommended by the GRADE Working Group, and which were
considered to be critical in clinical decision-making:
1. IPSS
2. HRQL
3. Incidence of TUR syndrome
4. Need for blood transfusion
5. Incontinence
6. Erectile dysfunction
7. Need for second procedure
Meta-Analysis
The risk ratio (RR) was used in reporting dichotomous outcomes and the
mean difference was used for continuous outcomes. A fixed-effect model was
applied when there was no significant evidence of heterogeneity. The data
were analysed on an intention-to-treat basis as far as possible, meaning that
all participants were analysed in the groups to which they were randomised.
Attempts were made to obtain missing data by contacting the original
trialists. The presence of publication bias was evaluated using funnel plots.
All analyses were undertaken using Review Manager 5.2 software
Results
The Health Technology Assessment systematic review included six trials
comparing M-TURP with B-TURP [6]. The updated search identified 949
abstracts, of which 94 full-text articles were assessed for eligibility and 18
trials met the inclusion criteria. In all, 24 trials were included in this
systematic review (six from the Health Technology Assessment review and 18
from the updated search). The flow of literature through the assessment
process is shown in the PRISMA flowchart (Fig. 1) and the characteristics of
the included trials are described in Table 1. We identified a three-armed trial
in which glycine and glucose irrigation fluid was used in the two M-TURP
arms, and saline in the B-TURP arm [9]. We decided to use only the results
from the glycine arm for M-TURP as it is more commonly used, whereas
glucose solution is rarely used for M-TURP.
The RoB assessment highlighted various methodological limitations in the 24
included trials [942]. It was unclear how random sequence generation had
been carried out in 10/24 trials [10,11,17,18,25,29,33,36,38,41] and
allocation concealment was unclear in 14/24 trials [10,11,13,17,18,
24,25,29,33,36,3841]. Other sources of potential bias within the trials
included incomplete outcome data, lack of blinding of participants,
personnel and outcome assessors. Financial support was unclear in 22/24
trials [911,13,14,17,18,20, 2327,29,30,33,34,36,3841], sample size
calculation was not reported by 20/24 trials [911,14,1618,20,23
25,27,30,33, 34,36,3841], approval by a relevant medical ethics committee
was not reported by 12/24 trials [10, 11,13,17,24,25,27,34,36, 38,39,41] and
8/24 trials did not report if they obtained informed consent from the
participants [10,11,17,25,36,38, 39,41]. Detailed results are summarised in
Fig. 2.
Using the GRADE approach, there was low quality evidence for HRQL (12
months) and erectile dysfunction (IIEF) outcomes. The quality of evidence for
IPSS (12 months), incidence of TUR syndrome, incontinence, blood
transfusion and need for second procedure was moderate. Detailed results
are summarised in Fig. 3.
Clinical Benefits
The mean IPSS was reported at 3, 6, 12 and 48 months. Three trials reporting
IPSS at 3 months [14,29,40], four trials at 6 months [14,25,29,40] and five
trials at 12 months [17,24,33,38,40] were pooled in the meta-analysis. There
were no statistically significant differences in IPSS at 3, 6 and 12 months (P
values 0.47, 0.66 and 0.90, respectively). The mean IPSS at 48 months,
reported by one trial, was 6.9 (B-TURP) and 6.4 (M-TURP) [42].
HRQL, scored from 0 to 6, was reported at 3, 12 and 48 months. Three of the
four trials reporting HRQL at 3 months could not be pooled in the meta-
analysis as they did not report standard deviations (SDs) [20,39,41]. The
remaining trial reported a mean difference of 0.76 (95% CI 1.25, 2.78; P =
0.46) in favour of B-TURP [29]. Two of the five trials reporting HRQL at 12
months could not be pooled in the meta-analysis as they did not report SDs
[16,20]. The remaining three trials reported a mean difference of 0.04 (95%
CI 0.17, 0.24; P = 0.72) in favour of B-TURP [17,24,38]. The HRQL score at
48 months, reported by one trial, was 1.3 (B-TURP) and 1.4 (M-TURP) [16].
The Qmax (mL/s) was reported at 3, 6, 12 and 48 months. Two of five trials
reporting Qmax at 3 months could not be pooled in the meta-analysis as they
did not report SDs [20,39]. The remaining three trials reported a combined
mean difference of 3.04 (95% CI 2.093.99; P < 0.001) in favour of B-TURP
[13,29,40]. Four of five trials reporting Qmax at 6 months were pooled in the
meta-analysis as the remaining trial did not report SDs [20]. The four trials in
the meta-analysis reported a mean difference of 2.14 (95% CI 1.043.25; P <
0.001) in favour of B-TURP [14,25,29,40]. Five of 11 trials reporting Qmax at
12 months could not be pooled in the meta-analysis as they did not report
SDs [16,20,23,26,27]. The remaining six trials reported a mean difference of
1.30 (95% CI 0.771.83; P < 0.001) in favour of B-TURP [13,17,24,33,38,40].
However, there was evidence of statistical heterogeneity at 3, 6 and 12
months (I2 68%, 67% and 72%, respectively). Detailed results are
summarised in Fig. 4.
Adverse Events
In this systematic review it was found that M-TURP was more commonly
associated with adverse events. In all, 22 trials reporting TUR syndrome were
included in the meta-analysis [911,13,14,16,17,20,2326,28
30,33,34,36,3841]. This complication occurred in none of the 1401
participants undergoing B-TURP, and 35of the 1375 undergoing M-TURP. The
difference was statistically significant (P < 0.001). However, it should be
noted that 17 of 35 cases of TUR syndrome were reported in a single study
[9]. Detailed results are summarised in Fig. 5.
In all, 20 trials reporting blood transfusion were included in the meta-analysis
[911,13,14,1618,20,23,24,26,2830, 33,34,3941]. In all, 28 of 1244
participants undergoing B-TURP and 53 of 1226 undergoing M-TURP required
a blood transfusion with a RR of 0.53 (95% CI 0.350.82) and the result was
statistically significant (P = 0.004). Detailed results are summarised in Fig. 6.
In all, 11 trials reporting clot retention were included in the meta-analysis
[9,16,17,20,23,24,27,28,30,34,40]. In all, 24 of 883 participants undergoing
B-TURP and 51of 880 undergoing M-TURP had clot retention with a RR of 0.48
(95% CI 0.300.77; P = 0.002). Detailed results are summarised in Fig. 7.
Results for other adverse effects, i.e. erectile dysfunction, incidence of
incontinence, urethral stricture, need for a second procedure, UTI, acute
retention after removal of catheter are reported in Table 2.
Discussion
This systematic review included 24 RCTs, many of which were new trials not
published at the time of previously conducted systematic reviews. Previous
systematic reviews have included six trials [2,6,43], 10 trials [44] and 16
trials [45]. The major strengths of the present review are that the evidence is
based upon RCTs, the literature search was broad without any restrictions, the
outcomes were pre-defined after consultation with clinical experts, and we
applied GRADE for evaluating the quality of evidence. However, various
methodological limitations were identified in the included trials. In particular,
the RoB assessment showed that the vast majority of the included trials were
potentially underpowered, with only four of the 24 studies reporting that a
sample size calculation had been undertaken. Moreover, only six of the 24
trials reported blinding of outcome assessment, meaning that the results of
the remaining 18 trials may have been influenced by detection bias. Given
that the validity of the conclusions of the present review are closely related to
the quality of the included trials, it is possible that such methodological
limitations may limit the overall quality of evidence obtained from this review.
In addition to this, it is important to consider that whilst the present review
has broadly classified resection techniques into monopolar or bipolar, it does
not account for smaller differences within each of these techniques, or
consider differences in the specific equipment or electrical currents used
across trials.
There were no statistically significant differences between B-TURP and M-
TURP for clinical effectiveness, except for the results for Qmax, where B-TURP
resulted in slightly higher Qmax. Despite this, the greatest observed mean
difference was 3.04 mL/s, seen at 3 months, and this is unlikely to correlate
with a clinically significant improvement in patient symptoms. These results
are consistent with other systematic reviews [2,6,43,45].
TURP has been traditionally associated with significant morbidity and adverse
events [1]. In the present systematic review it was found that M-TURP was
more commonly associated with adverse events. TUR syndrome was reported
in 35/1375 patients undergoing M-TURP and none of the 1401 patients
undergoing B-TURP. However, it should be noted that 17/35 cases of TUR
syndrome were reported by Yousef et al. [9] 2011. Mamoulakis et al. [45] also
reported a higher incidence of TUR syndrome in M-TURP (risk difference 0.02
[95% CI 0.000.03]). The higher incidence of TUR syndrome in some selected
trials may be due to learning curve effects, different hospital setting and
hospital protocol or large size of the prostate. In the trial conducted by Yousef
et al. [9] for example, the average resection weight of the prostate was
significantly larger than that of other included trials, at a mean (SD) of 82.5
(15.5) g (saline) and 89.16 (18.3) g (glycine). This large resection weight
should be considered in the context of more widespread urological practice.
According to European Association of Urology guidelines, the best results for
TURP are obtained if the weight of the prostate gland is below 5060 g [46].
The National Prostatectomy Audit has reported the average resection weight
as 17 g [47]. It is also important to consider that TUR syndrome generally
occurs rarely in urological practice. Sugihara et al. [48] reported that 16/5155
(0.03%) participants developed TUR syndrome in their database study. When
excluding the trial undertaken by Yousef et al. [9], there were only 18 cases of
TUR syndrome in the 24 trials in which this outcome was reported.
Furthermore, it is possible that inconsistencies in the definition or the method
of measuring the presence of TUR syndrome across the different trials could
explain the different rates reported.
Like Lourenco et al. [2,6,43], the present review did not identify any
statistically significant differences in the incidence of incontinence, UTI,
stricture formation, and urinary retention between M-TURP and B-TURP.
However, unlike Lourenco et al. [2,6,43], the present review identified a
statistically significant difference in blood transfusion favouring B-TURP. These
results are consistent with the study conducted by Sugihara et al. [48] who
reported 20/1531 (1.3%) patients undergoing B-TURP and 118/5155 (2.3%)
patients undergoing M-TURP required homologous blood transfusion. Clot
retention was relatively more common in patients undergoing M-TURP. This
was also observed in the review of Mamoulakis et al. [45], where a higher
frequency of clot retention in patients undergoing M-TURP was reported (risk
difference: 5%; 95% CI, 110%; P = 0.03). Such complications can be a
significant cause of morbidity in patients undergoing TURP, as they might
mean the need for re-operation or blood transfusion. The reasons for the
observed haemostatic advantages of B-TURP are not entirely clear, although
some trials have suggested that bipolar energy results in deeper coagulative
effects [49,4951].
The incidence of urethral strictures reported in the present systematic review
are similar to that reported in Mamoulakis et al. [45] with no statistically
significant differences between M-TURP and B-TURP.
The reduced risk of TUR syndrome and reduced bleeding associated with B-
TURP may have important implications for surgical practice. For instance, the
reduced bleeding allows for increased visibility during the procedure, and the
negligible risk of TUR syndrome means that larger prostate glands can be
resected, with more time taken for haemostasis at the end of the procedure.
These issues may be particularly advantageous to trainee urologists as they
learn the procedure. Future studies may wish to further explore these other
potential benefits of B-TURP.
In conclusion, whilst there is no overall difference between M-TURP and B-
TURP in terms of clinical effectiveness. B-TURP is associated with fewer
adverse events, including TUR syndrome, clot retention and need for blood
transfusion. It is important to consider that, despite these apparent benefits
of B-TURP, M-TURP still represents a safe procedure and is rarely associated
with such adverse events in the hands of an experienced surgeon. Various
methodological limitations were highlighted in the included trials and as such
there is a need for larger, well-designed, RCTs which adhere to the
recommendations set out in the Consolidated Standards Of Reporting Trials
(CONSORT) statement, which include clinically important outcome measures.