Bipolar versus monopolar transurethral resection of the prostate for lower urinary tract symptoms secondary to benign prostatic obstruction

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the efficacy and safety of bipolar transurethral resection of the prostate compared to monopolar transurethral resection of the prostate for treating patients with lower urinary tract symptoms secondary to benign prostatic obstruction.

Background

There is evidence from randomised controlled trials (RCTs) (Mamoulakis 2009a) and RCT-based meta-analyses (Mamoulakis 2009b) that bipolar transurethral resection of the prostate (B-TURP) carries some advantages over its ancestor, the conventional monopolar TURP (M-TURP) in the management of male lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO).

Description of the condition

Male LUTS include urinary storage symptoms (daytime frequency, nocturia, urgency, incontinence), voiding symptoms (slow stream, splitting or spraying, intermittency, hesitancy, straining, terminal dribble), and post micturition symptoms (sensation of incomplete emptying, post micturition dribble). Benign prostatic hyperplasia (BPH) is histologically characterised by cellular proliferation of the epithelial and stromal tissues of the prostate. It is a non-malignant condition that inevitably affects almost every aging male and there is a general agreement on its progressive nature (Djavan 2002). Benign prostatic enlargement (BPE) refers to an increase in size of the prostate due to BPH. About 50% of men with BPH will develop BPE, 25% to 50% will present LUTS and approximately 50% of men with LUTS have bladder outlet obstruction (CG97 LUTS: NICE guideline, 2010). BPH-related obstruction, namely BPO (obstruction that has been proven by pressure flow studies, or is highly suspected from flow rates and if the gland is enlarged (Abrams 2009) without any suspicion for prostate cancer), can be associated with bothersome LUTS that reduce the quality of life (QoL). The incidence rate of LUTS/BPH is high and increases linearly with age, as shown by a large retrospective cohort study in the Netherlands (Verhamme 2002). It has been estimated to be 15 per 1000 man-years overall, increasing from 3 cases per 1000 man-years at the age of 45 to 49 years to 38 cases per 1000 man-years at the age of 75 to 79 years, and remaining constant thereafter. Around 4.5 million visits were recorded to physician offices for a primary diagnosis of BPH and almost 8 million visits were made with a primary or secondary diagnosis of BPH during the year 2000 in the United States. Within this year, the estimated direct treatment cost was $1.1 billion (USD) exclusive of outpatient pharmaceuticals (Wei 2008). Surgery for LUTS secondary to BPO is the tenth most common operation in the National Health Service UK (Kirby 2010). Consequently, the tremendous impact of the disease on the QoL and health care cost justifies additional research into therapeutic resource use, effectiveness and cost benefit of treatment strategies.

Description of the intervention

TURP has been considered the gold standard for the surgical management of LUTS secondary to BPO mainly due to its well-documented long-term efficacy (Reich 2006). Traditionally, it is carried out with a monopolar electrosurgical unit (ESU) using a non-conductive hypo-osmolar irrigation medium such as mannitol, sorbitol, or glycine solutions, which may place the patient at risk of dilutional hyponatraemia and transurethral resection (TUR) syndrome. In M-TURP an active electrode (loop) transmits energy into the prostate, and a return one completes the circuit at the skin level (skin pad). Since the system works in a non-conductive solution, the body serves as the conduit between electrodes. The longer the distance between electrodes (more body tissue must be traversed), the higher the voltage needed to drive current to the return electrode. Consequently, in M-TURP systems, excessive voltage is required to push energy through the body. Thus, M-TURP is usually performed using high energy setting, the loop is often over-energised, and energy travelling/cutting is too fast through tissue with minimal coagulation effect (Issa 2008).

Despite a decreasing trend over time, M-TURP complications may still occur (Rassweiler 2006). Procedural negative outcomes have been reduced due to significant technological improvements achieved during the recent years but complications such as TUR syndrome, bleeding and urethral strictures remain a concern (Hawary 2009; Rassweiler 2006). In a large scale, multicenter, observational study on patients with LUTS secondary to BPO submitted to TURP, it was shown that mortality rate has decreased (0.1%) but morbidity, although reduced, is still considered high (11.1%) (Reich 2008). Nevertheless, in the absence of strong, high quality evidence favouring newer surgical methods, including minimally invasive techniques (Ahyai 2010; Burke 2010), M-TURP remains clinically effective (Lourenco 2008a; Lourenco 2008b; Lourenco 2008c).

Incorporation of bipolar technology represents a recent technical modification of TURP. In B-TURP systems, the active and return poles are incorporated into the electrode design. The circuit is completed between the poles at the site of surgery. Therefore, the energy remains confined at the resection site instead of travelling through the body. Consequently, B-TURP systems require less energy/voltage compared to M-TURP systems to complete the circuit because of the relatively less tissue (resistance) encountered. B-TURP addresses the fundamental flaw of M-TURP by allowing performance in a conductive fluid medium (normal saline). Consequently, the risks of dilutional hyponatraemia and TUR syndrome are expected to be eliminated, allowing for longer and safer resection (Issa 2008).

How the intervention might work

During M-TURP, most of the energy is converted to heat at the prostate level, rather than being dissipated through the non-conductive irrigation medium, and the effect of cutting and/or coagulation is achieved.

During B-TURP, energy is transmitted from the active electrode to the surrounding conductive solution. As a result, the water evaporates, creating an interface gas layer that surrounds the loop, and poses resistance to the energy flow. By adding voltage to the gas layer, sodium ions get excited, orange radiation is emitted, and a highly energised state of matter (the plasma) is formed around the active electrode that gives a characteristic glowing appearance to the loop. The plasma consists of charged particles that move freely. They can be easily cleaved to cause initial tissue disruption at a molecular level, allowing subsequent relatively low voltage to separate tissue. Plasma formation needs therefore high current initially. Subsequently, plasma maintenance requires minimal voltage and energy. Thus, B-TURP systems can utilise plasma formation on the surface of the electrode to minimise the voltage needed to enable tissue resection. The coagulation mechanism is different. Initial heating effect occurs, but plasma formation is prevented because voltage is kept at a low level and the current cannot overcome the high gas layer resistance. The energy dissipates as heat within the vessel walls resulting in coagulum formation by tissue and blood that seals the bleeders. Instead of the orange glow of energised plasma associated with cutting, white tissue blanching is observed, which indicates the coagulum formation and collagen shrinkage (Issa 2008).

Why it is important to do this review

Despite the fact that B-TURP has been introduced since years, it seems that its true merits over M-TURP still remain obscured (Reich 2009). We recently conducted a comparative effectiveness meta-analysis (Mamoulakis 2009b), the largest one published to date (Ahyai 2010; Burke 2010; Lourenco 2008c; Lourenco 2008b; Mamoulakis 2010), focusing on the comparison of efficacy and safety of the two techniques. Best available evidence was provided thus, for the first time, showing that no clinically relevant differences exist in short-term efficacy (at 12 months of follow up), and complication rates (acute urine retention (AUR) after catheter removal, blood transfusions or urethral strictures). Nevertheless, it was concluded that B-TURP is preferable due to a more favourable safety profile (elimination of TUR syndrome, less bleeding: lower clot retention and blood transfusion rates with the use of Gyrus device (ACMI Southborough, MA, USA)), shorter irrigation and catheterization duration. In addition, the lack of well-designed international/multicentre RCTs and the generally low methodological quality of the existing trials was underlined. To the best of our knowledge, at least nine new RCT-based papers have been recently published (Acuña-López 2010; Chen 2009; Chen 2010; Fagerstrom 2010; Kong 2009; Michielsen 2010a; Michielsen 2010b; Singhania 2010), including results from the first international multicentre trial (Mamoulakis 2012). This flurry of trials has resulted in an increase of around 50% of the existing RCT-based publications (> 90% increase in the total number of patients evaluated). We aim at providing updated information by including the data from all published RCTs after our previous systematic literature search end (19 February 2009) and at rating the quality of the existing evidence by adopting the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach (Balshem 2011; Guyatt 2008; Guyatt 2011a; Guyatt 2011b; Guyatt 2011c; Guyatt 2011d; Guyatt 2011e; Guyatt 2011f; Guyatt 2011g; Guyatt 2011h).

Objectives

To assess the efficacy and safety of bipolar transurethral resection of the prostate compared to monopolar transurethral resection of the prostate for treating patients with lower urinary tract symptoms secondary to benign prostatic obstruction.

Methods

Criteria for considering studies for this review

Types of studies

RCTs comparing B-TURP with M-TURP for the treatment of patients with LUTS secondary to BPO.

Types of participants

Patients with LUTS secondary to BPO as defined above (Abrams 2009), having an indication for TURP.

Types of interventions

B-TURP or M-TURP as defined above.

Types of outcome measures

Primary outcomes

The main outcome measures for efficacy will include:

  • International Prostate Symptom Score (IPSS) questionnaire results (including QoL score) measured at three- to six-month intervals postoperatively until the maximum follow up point recorded;

  • re-TURP.

The main outcome measures for safety will include postoperative occurrence of:

  • drop in serum sodium level;

  • TUR syndrome;

  • drop in haemoglobin level;

  • need for blood transfusion;

  • clot retention;

  • AUR after catheter removal;

  • urinary tract infections;

  • meatal stenosis;

  • bladder neck contracture;

  • urethral strictures;

  • urinary incontinence;

  • erectile dysfunction;

  • retrograde ejaculation;

  • death (mortality) from all causes.

Secondary outcomes
  • Operation time

  • Duration of bladder irrigation

  • Catheterization time

  • Hospitalisation time

  • Postoperative maximum flow rate (Qmax)

Primary and secondary outcomes, as defined above, have been classified by the review authors as critical, important or not-important from patient’s perspective for making decision. GRADE working group strongly recommends including up to seven critical outcomes in a systematic review to be assessed via GRADE approach. Thus, the final decision on the selection of the seven outcomes to be rated has been based on a consensus among the review authors.

In this systematic review, GRADE methodology will be applied for assessing the quality of evidence of the following outcomes:

  • postoperative IPSS questionnaire results;

  • TUR syndrome;

  • blood transfusion;

  • clot retention;

  • AUR after catheter removal;

  • urethral strictures;

  • catheterization time.

Search methods for identification of studies

The literature will be systematically searched with the assistance of a clinical librarian to detect all RCTs comparing B-TURP with M-TURP in patients with LUTS secondary to BPO. No temporal, regional, publication status, or language restrictions will be set. If necessary, official translations into English or Dutch will be obtained through the independent Dutch Interpretation and Translation Center (http://www.tvcn.nl/en/).

Electronic searches

The following electronic databases will be used up to the present: MEDLINE (from 1950 onwards), EMBASE (from 1980 onwards), Science Citation Index (form 1975 onwards), and The Cochrane Library (from 1950 onwards). The search strategy that will be followed is summarised in 'Appendix 1'. Searches of other electronic sources (www.google.com) will also be performed using the general terms "bipolar" AND "prostate".

Searching other resources

The official websites of the manufacturers of all currently commercially available B-TURP systems will be also checked. The reference lists of all selected papers will be handsearched for potentially relevant trials.

Data collection and analysis

Selection of studies

Two review authors (CM & DTU) will independently screen the titles and abstracts of the articles identified from the search for relevance and design. Any disagreement will be resolved by discussion, and final decision will be based on a consensus. Of the trials that seem to meet the inclusion criteria, or are impossible to reject with certainty based on title and abstract, a full text copy of the article will be obtained. Any published RCT in the form of full paper comparing B-TURP with M-TURP for the treatment of patients with LUTS secondary to BPO that reports on any primary or secondary outcome of interest defined, will be eligible for inclusion. Citations in abstract form, trials that studied different interventions (e.g., transurethral vaporization of the prostate or laser technology), and non-RCTs will be excluded.

Data extraction and management

Two review authors (CM & DTU) will independently extract and summarise study characteristics and outcomes of the selected trials, including information on study design, subject characteristics, interventions, follow-up, treatment outcomes, and adverse events using a predefined data extraction sheet. One review author will enter quantitative data into The Cochrane Collaboration Review Manager software, and the other review author will check it. Unreported complications will be considered to be not recorded unless specifically stated as not occurring. Disagreements will be resolved by discussion, and final decision will be based on a consensus.

Assessment of risk of bias in included studies

The methodological quality assessment of the selected RCTs will be based on the Dutch Cochrane Collaboration checklist, which is in accordance with Table 8.5.a of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2009). This tool addresses six specific domains, namely sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting and other issues (e.g. baseline imbalance, source of funding). Blinding and completeness of outcome data will be assessed for each outcome separately. We will complete a risk of bias table for each eligible study. It will also be done by the two investigators independently. We will present our assessment of the risk of bias using a "risk of bias summary figure", which presents all judgments in a cross-tabulation of study by entry. This display of internal validity indicates the weight the reader may give to the results of each study.

Measures of treatment effect

When appropriate, the mean differences (MD) or standardised mean differences (SMD) will be presented for continuous outcomes. The absolute risk reduction, i.e. risk difference (RD), will be presented for dichotomous outcomes, which is an absolute effect measure that expresses the difference between the experimental and the control event rates. This will allow calculation of the number needed to treat (NNT) or number needed to harm (NNH). If data can be pooled, depending on heterogeneity (Higgins 2003), summary estimates of treatment effect with 95% confidence intervals (CIs) will be calculated for every comparison and the P value for the overall treatment effect will be added.

Unit of analysis issues

Trials to be included should randomise individual patients with LUTS secondary to BPO into either M-TURP or B-TURP arm (parallel group design). Quasi-randomised trials will not be used.

Dealing with missing data

Missing data (e.g. mean values or standard deviations) or additional information required will be sought and retrieved from authors/sponsors of trials, who will be contacted if necessary, whenever possible.

Assessment of heterogeneity

Statistical heterogeneity will be assessed using the I2 statistic. In the absence of heterogeneity (I2 < 30%), a fixed-effect model will be used. A random-effects model will be used for mild heterogeneity (I2 30% to 60%). For I2 > 60% we will refrain from performing a meta-analysis.

Assessment of reporting biases

The presence of publication bias, if any, will be evaluated using funnel plots (Egger 1997).

Data synthesis

Available efficacy and safety RCT data will be meta-analysed, if applicable, in Review Manager software. Quality of evidence will be rated using the GRADE Working Group GRADEprofiler (GRADEpro 3.6) software.

Subgroup analysis and investigation of heterogeneity

The various bipolar systems (Vista Coblation/controlled tissue resection (CTR) system (ACMI, Southborough, MA, USA); Gyrus (ACMI Southborough, MA, USA); TURis® (Olympus, Tokyo, Japan); S(a)line Resectoscope (Richard Wolf GmbH, Knittlingen, Germany); Tekno Tom (Tekno-Medical, Tuttlingen, Germany); AUTOCON® II 400 ESU (Karl Storz Endoscope, Tuttlingen, Germany)) share a common feature, namely the ability to perform in normal saline (Issa 2008; Rassweiler 2007). However, some of them are considered "quasi-" rather than "true" bipolar systems because they do not meet the definition that requires both electrodes be attached to a single port (International Electrotechnical Commission 1998; www.iec.ch). Therefore, each one follows distinct electrophysiological principles regarding current flow due to the different configuration-arrangement of the active and neutral electrode (mainly the position and shape of the latter) at the resectoscope, which may result in significant clinical effects (Faul 2008). Consequently, efficacy, and principally safety should be cautiously and separately evaluated for each system (Faul 2008). For this reason, subgroup analysis of the different bipolar systems used in RCTs will be performed to check for potential differences.

Furthermore, subgroup analysis of the different hypo-osmolar solutions used for M-TURP in RCTs will be performed to check for potential differences. Finally, subgroup analyses will be optionally (if possible) carried out, considering patient or disease factors reported to influence TURP outcomes (preoperative prostate volume or prostate resection weight: > 60 g, 30 to 60 g and < 30 g; preoperative catheterization state: patients on catheterization versus patients not on catheterization) (Reich 2008).

Sensitivity analysis

Sensitivity analysis will be conducted based on the methodological quality of the studies and pending results of clinical/statistical assessment of heterogeneity. In the case of clinical or statistical heterogeneity, sensitivity analyses will be attempted to facilitate the meta-analysis by omitting trials with an apparent reason for heterogeneity.

Acknowledgements

We thank James Tacklind, former Coordinator of the Cochrane Prostatic Diseases and Urologic Cancers Group.

Appendices

Appendix 1. Search strategy protocols used for each electronic database

MEDLINE®

((bipolar AND prostate) OR ((ablative OR minimally invasive[tw] OR plasmakinetic* OR plasmasect* OR PKRP OR turis OR vista OR gyrus OR wolf[tiab] OR storz[tiab] OR bipolar) AND (TURP[tw] OR Transurethral prostatectom*[tw] OR Transurethral prostate resection*[tw] OR "Transurethral Resection of Prostate"[Mesh] OR transurethral resection of the prostate[tw]) AND (((((((((((((((((((volunteer*[tw]) OR ((prospectiv*[tw]))) OR ((control*[tw]))) OR ((prospective studies[mh]))) OR ((follow-up studies[mh]))) OR ((evaluation studies[pt]))) OR ((comparative study[pt]))) OR ((research design[mh:noexp]))) OR ((random*[tw]))) OR (((singl* OR doubl* OR trebl* OR tripl*) AND (blind* OR mask*)))) OR ((clinical trial[tw]))) OR ((clinical trials[mh]))) OR ((clinical trial[pt]))) OR ((single-blind method[mh]))) OR ((double blind method[mh]))) OR ((random allocation[mh]))) OR ((randomized clinical trials[mh]))) OR ((controlled clinical trial[pt]))) OR ((randomized controlled trial[pt])))))

EMBASE

(bipolar and prostate).mp. or (((ablative or minimally invasive or plasmakinetic$ or plasmasect$ or pkrp or turis or vista or gyrus).mp. or wolf.ti. or wolf.ab. or storz.ti. or storz.ab. or bipolar.mp.) and (transurethral resection/ or transurethral resection of the prostate.mp. or transurethral prostate resection.mp. or TURP.mp. or transurethral prostatectom$.mp.) and (Clinical Trial/ or exp controlled clinical trial/ or random$.mp. or trial*.mp.))

Science Citation Index

Topic=(bipolar AND prostate) OR Topic=((ablative OR minimally invasive OR plasmakinetic* OR plasmasect* OR PKRP OR turis OR vista OR gyrus OR wolf OR storz OR bipolar) AND (TURP OR Transurethral prostatectom* OR Transurethral prostate resection) AND (Trial or trials))

Cochrane CENTRAL

(bipolar AND prostate):ti,ab,kw OR ((ablative OR minimally invasive OR plasmakinetic* OR plasmasect* OR PKRP OR turis OR vista OR gyrus OR wolf OR storz OR bipolar):ti,ab,kw AND (TURP OR Transurethral prostatectom* OR Transurethral prostate resection* OR "Transurethral Resection of Prostate"[Mesh] OR transurethral resection of the prostate):ti,ab,kw)

What's new

DateEventDescription
20 January 2014New citation required and minor changesAuthors are actively working on the review. Updated contact person e-mail address. Corrected typos.

Contributions of authors

Conceiving the review: C. Mamoulakis
Designing the review: C. Mamoulakis, D.T. Ubbink
Coordinating the review: D.T. Ubbink
Data collection for the review: C. Mamoulakis, D.T. Ubbink
Designing search strategies: C. Mamoulakis, D.T. Ubbink
Undertaking searches: C. Mamoulakis, D.T. Ubbink
Screening search results: C. Mamoulakis, D.T. Ubbink
Screening retrieved papers against inclusion criteria: C. Mamoulakis, D.T. Ubbink
Appraising quality of papers: C. Mamoulakis, D.T. Ubbink
Extracting data from papers: C. Mamoulakis, D.T. Ubbink
Writing to authors of papers for additional information: F. Sofras, J. de la Rosette, J. N'Dow
Data management for the review: C. Mamoulakis
Entering data into RevMan: C. Mamoulakis, D.T. Ubbink
Analysis of data: C. Mamoulakis, F. Sofras, J. de la Rosette, M.I. Omar, T. Lam, J. N'Dow, D.T. Ubbink
Interpretation of data: C. Mamoulakis, F. Sofras, J. de la Rosette, M.I. Omar, T. Lam, J. N'Dow, D.T. Ubbink

Drafting the protocol: C. Mamoulakis
Drafting the review: C. Mamoulakis

Critical revision of the protocol/review for important intellectual content: F. Sofras, J. de la Rosette, M.I. Omar, T. Lam, J. N'Dow, D.T. Ubbink
Providing general advice on the review: F. Sofras, J. de la Rosette, J. N'Dow, D.T. Ubbink

Performing previous work that was the foundation of the current study: C. Mamoulakis, D.T. Ubbink, J. de la Rosette

Declarations of interest

JR has received payment for consultancy unrelated to the review from Boston Scientific and AngioDynamics, his institution has received grants/grants pending unrelated to the review from Lilly, and he has received payment for lectures unrelated to the review including service on speakers bureaus from Olympus, Coloplast and Storz. JR was also principal investigator for a randomised study sponsored by the Storz company, and is collaborating with the Olympus company in the field of endourology. TBLL is a member of the European Association of Urology Renal Cell Carcinoma Guideline panel, and has received payment unrelated to the review as a speaker in educational meetings for Pfizer, Astellas and GSK regarding medical treatment of benign prostatic hyperplasia, overactive bladder syndrome, prostate cancer, renal cancer and catheter-associated urinary tract infections. All other co-authors have no known declarations of interest.

Sources of support

Internal sources

  • None, Not specified.

External sources

  • None, Not specified.

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