June R Tooher, P Swindle, H Woo, J Miller, G Maddern. Australian Safety & Efficacy Register of New Interventional Procedures Surgical

Transcription

1 ASERNIP S Australian Safety and Efficacy Register of New Interventional ProceduresSurgical Laparoscopic Radical Prostatectomy Accelerated Systematic Review June 2005 R Tooher, P Swindle, H Woo, J Miller, G Maddern Australian Safety & Efficacy Register of New Interventional Procedures Surgical The Royal Australasian College of Surgeons

2 Laparoscopic radical prostatectomy: an accelerated systematic review. R Tooher, P Swindle, H Woo, J Miller, G Maddern. ISBN Published June 2005 The ASERNIPS Programme Under the auspices of the Royal Australasian College of Surgeons, ASERNIPS (Australian Safety and Efficacy Register of New Interventional Procedures Surgical) conducts systematic reviews of new and emerging surgical techniques and technologies. ASERNIPS is supported by the Commonwealth of Australia Department of Health and Ageing. Accelerated Systematic Reviews Accelerated systematic reviews are produced in response to a pressing need for a systematic summary and appraisal of the available literature for a new or emerging surgical procedure. This need may arise if the uptake of the new technique or technology appears to be inappropriate given the evidence available at the time (it may be diffusing too quickly or too slowly). Alternatively there may be uncertainty or controversy regarding the clinical or cost effectiveness of the new procedure, or there may be significant concerns regarding its safety or indications for use in particular populations. Accelerated systematic reviews use the same methodology as full systematic reviews, but may restrict the types of studies considered (for example, by only including comparative studies and not case series) in order to produce the review in a shorter time period than a full systematic review. This report should be cited in the following manner: Tooher R, et al. Laparoscopic radical prostatectomy: An accelerated systematic review. ASERNIPS Report No. 48. Adelaide, South Australia: ASERNIPS, June Copies of these reports can be obtained from: ASERNIPS The Royal Australasian College of Surgeons PO Box 553, Stepney, SA 5069 AUSTRALIA Ph: Fax: College.asernip@surgeons.org

3 The accelerated systematic review of laparoscopic radical prostatectomy was ratified by: The ASERNIPS Management Committee on May 6, 2005 The Executive of the Council of the Royal Australasian College of Surgeons in June 2005

4 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 Members of the review group Professor Guy Maddern (Chair) Surgical Director ASERNIPS, Adelaide, SA Dr Rebecca Tooher Senior Researcher ASERNIPS, Adelaide, SA Dr Henry Woo Urologist Department of Surgery, University of Sydney, NSW Department of Urology, Westmead Hospital, NSW Dr Peter Swindle Urologist Mater Prostate Cancer Research Centre, Mater Medical Research Institute, South Brisbane, QLD Dr John Miller Urologist University of Adelaide Department of Surgery, The Queen Elizabeth Hospital, Woodville, SA Conflict of interest statement None of the authors declared a conflict of interest, other than as detailed below: Dr John Miller recently purchased equipment for the purposes of performing open radical retropubic prostatectomy. MEMBERS OF THE REVIEW GROUP

5 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 Executive Summary Background Prostate cancer is the most common form of cancer for men (excluding nonmelanoma skin cancer) in Australia and around the world, and increases with age in men over 50 years. The Urological Society of Australia nominated laparoscopic radical prostatectomy for review by ASERNIPS due to the need for a timely assessment of the literature for this procedure, in particular complication rates and surgical margin rates for this difficult to learn procedure. Objectives To compare the safety, efficacy and costs associated with laparoscopic radical prostatectomy compared with open radical prostatectomy through a systematic assessment of the literature. A secondary objective was to assess the contribution of learning curve to efficacy outcomes. Methods A systematic search of online databases (from 1996 to December 2004) and the internet was undertaken, without language restriction. Comparative studies that reported safety or efficacy outcomes of transperitoneal laparoscopic radical prostatectomy (TLRP) or extraperitoneal endscopic radical prostatectomy (EERP) or roboticassisted radical prostatectomy (RALRP) compared to open radical retropubic prostatectomy (RRP) or radical perineal prostatectomy (RPP) were included. Comparisons between different laparoscopic approaches were also included. Results There were 21 studies comparing open and laparoscopic approaches; 13 compared transperitoneal (TLRP) to open (RRP) radical prostatectomy, three compared extraperitoneal (EERP) to open prostatectomy, and five compared roboticassisted (RALRP) to open prostatectomy. There were nine studies comparing different laparoscopic approaches; six compared EERP and TLRP and three compared RALRP with TLRP. There were no randomised controlled trials, ten concurrently controlled comparisons (level III2), 17 historically controlled comparisons (level III 3) and three comparisons using concurrent and historical controls (level III2/3). In terms of safety, there did not appear to be any important differences in the complication rate between laparoscopic and open approaches, however, blood loss and transfusions were lower for the laparoscopic approaches. In terms of efficacy, EXECUTIVE SUMMARY

6 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 operative times were longer for laparoscopic than open prostatectomy but length of stay and duration of catheterisation were shorter. There was no consistent pattern of analgesia use across the included studies. Positive margin rates were similar and there did not appear to be any important differences between laparoscopic and open prostatectomy when tumour stage or margin location were taken into consideration. Recurrencefree survival was poorly reported but did not appear to differ between the two approaches.continence and potency were not well reported but appeared similar between the two approaches, though continence may have recovered more quickly after laparoscopic than open prostatectomy and potency may have recovered more quickly after roboticassisted prostatectomy compared with open. Quality of life did not differ between TLRP and RRP in two studies. There were no important differences between laparoscopic approaches. Cost and resource use issues Cost and resource use issues were not well reported in any of the included studies, however, in three economic models open radical prostatectomy was found to be less expensive than laparoscopic prostatectomy, and costs would only become equivalent if operative times and/or length of stay for the lapaproscoic approaches were to fall. However, none of the models used a patientrelevant effectiveness outcome such as potency, continence or survival and therefore do not provide a great deal of guidance for decisionmakers with regard to cost effectiveness. Learning curve Six studies reported outcomes in such a way that the effect of increasing experience with the laparoscopic approaches could be tracked. As experience with the laparoscopic approaches increased most clinical outcomes improved, including conversions to open, complications, blood loss, transfusions and operative time, but not length of hospital stay and duration of catheterization. There were no clear effects of increasing experience for positive margins rate or continence and potency outcomes. Conclusions Laparoscopic radical prostatectomy is emerging as an alternative to open radical prostatectomy for treating localised prostate cancer. However at the present time there is insufficient comparative data regarding continence, potency and survival. There did not appear to be any clear differences between the laparoscopic approaches. Roboticassisted prostatectomy offers the promise of shorter operative times than standard laparoscopic approaches and may produce a quicker recovery of continence and potency than open prostatectomy. EXECUTIVE SUMMARY

7 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 A clear learning curve for laparoscopic prostatectomy was documented which affected many clinical outcomes. Although it was not possible to determine from the included studies how many laparoscopic procedures must be completed to negotiate this learning curve, the introduction of LRP should be closely monitored. Previous experience in laparoscopy and/or open radical prostatectomy is required and outcomes during the initial phase of the learning curve should be carefully documented. Recommendations 1. a national audit of laparoscopic radical prostatectomy, including roboticassisted LRP, should be instituted to monitor the introduction of the technique into the Australian healthcare system. The audit could be carried out under the auspices of ASERNIPS and arranged in conjunction with the Urological Society of Australia and the Royal Australasian College of Surgeons. 2. hospital credentialling committees should monitor the progress of surgeons introducing LRP into their practice at regular intervals, paying particular regard to rates of complications and surgical margins during the learning phase. 3. Economic evaluations taking into consideration the Australian healthcare context should be conducted. EXECUTIVE SUMMARY

8 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 Table of contents 1. Introduction...12 Objective...12 Context...12 Background...12 Prostate cancer...12 Diagnosis of prostate cancer...13 Staging prostate cancer...13 Treatment options...15 Surgical treatments...15 Open versus laparoscopic radical prostatectomy Methodology Search Strategy...20 Inclusion Criteria...20 Types of studies included...21 Search results...21 Data Extraction and Synthesis Results Included studies and critical appraisal...23 Laparoscopic vs open radical prostatectomy...23 Comparisons between laparoscopic approaches...25 Multiple publications from the same centre/group...26 Safety...28 Conversions to open...28 Complications...29 Types of complications...30 Blood loss...36 Transfusions...37 Efficacy...39 Operative time...39 Analgesia use (perioperative)...41 Length of stay...42 Catheterization...43 Cancer control...45 Positive margin rate all tumours...45 Positive margin rate pt2 tumours...46 Positive margin rate pt3 tumours...48 Positive margin rate by margin location...49 Survival...50 Patientreported outcomes...51 Continence...51 Potency...54 Quality of life...57 Patientreported pain...57 Cost considerations...58 Learning curve issues Discussion Limitations of the review...67 Safety...67 TABLE OF CONTENTS

9 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 Efficacy Cancer control Patientreported outcomes Cost and resource use issues Learning curve Conclusions...71 References Appendix A: Excluded studies Appendix B: Study profiles and results laparoscopic versus open radical prostatectomy...81 Appendix C: Study profiles and results comparisons between laparoscopic approaches TABLE OF CONTENTS

10 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 Tables and Figures Table 1: TNM Classifications (AJCC 2002)...14 Table 2: Inclusion and exclusion criteria...20 Figure 1: Flow chart of search results...21 Table 3: NHMRC Hierarchy of Evidence (NHMRC 2000)...22 Table 4: Included studies comparing laparoscopic to open radical prostaectomy...24 Table 5: Included studies comparing different laparoscopic approaches...26 Table 6: Multiple publications from the same centre/group...27 Table 7: Conversions to open: laparoscopic vs open radical prostatectomy...28 Table 8: Complications...29 Table 9: Ureteral complications...31 Table 10: Rectal complications...31 Table 11: Bladder complications...32 Table 12: Infections/inflammations...33 Table 13: Neurological complications...33 Table 14: PE/DVT...34 Table 15: Anastomotic leak...35 Table 16: Urinary retention...35 Table 17: Ileus...36 Table 18: Estimated blood loss (ml)...37 Table 19: Transfusions...38 Table 20: Operative time (mins)...39 Table 21: Analgesia use (mean morphine equivalent, mg)...41 Table 22: Length of stay (days)...43 Table 23: Catheterization (days)...44 Table 24: Positive margin rate all tumour pt stages...45 Table 25: Positive margin rate T2 tumours...47 Table 26: Positive margin rate T3 tumours...48 Table 27: Positive margin rate at apex...49 Table 28: Positive margin rate bladder neck/base...50 Table 29: Positive margin rate lateral/posterolateral...50 Table 30: Biochemical recurrencefree survival...51 Table 31: Continence postoperatively...52 Table 32: Recovery of continence...54 Table 33: Potency postoperatively...55 Table 34: Recovery of potency...56 Table 35: Cost breakdown of TLRP and RRP from Link et al Table 36: Predicted costs of TLRP, RRP and RALRP from Lotan et al Table 37: Percentage difference in cost between RALRP and RRP from Guru et al Table 38: Included studies addressing the learning curve...61 Table 39: Learning curve for conversions to open...62 Table 40: Learning curve for complications...62 Table 41: Learning curve for estimate blood loss...63 Table 42: Learning curve for transfusions...63 Table 43: Learning curve for operative time...64 Table 44: Learning curve for length of stay...64 Table 45: Learning curve for duration of catheterization...65 Table 46: Learning curve for positive margin rates...65 Table 47: Learning curve for continence...66 Table 48: Learning curve for potency...66 TABLE OF CONTENTS

11 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 Abbreviations AIHW BMI BN DRE DVT EERP LRP NHMRC PSA PE QoL RALRP RPP RRP TLRP TRUS TURP Australian Institute of Health and Welfare body mass index bladder neck digital rectal examination deep vein thrombosis extraperitoneal endoscopic radical prostatectomy laparoscopic radical prostatectomy National Health and Medical Research Council prostate specific antigen pulmonary embolism quality of life roboticassisted laparoscopic radical prostatectomy radical perineal prostatectomy radical retropubic prostatectomy transurethral laparoscopic radical prostatectomy transrectal ultrasound guided biopsy transurethral resection of the prostate Measures and symbols [ ] standard deviation ( ) range { } measure of variance not stated µg/l ml min n ct pt microgram per litre (for serum PSA) millilitre minutes number of patients clinical tumour stage pathological tumour stage ABBREVIATIONS, MEASURES AND SYMBOLS

12 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE Introduction Objective To compare the safety, efficacy and costs associated with laparoscopic radical prostatectomy compared with open radical prostatectomy through a systematic assessment of the literature. A secondary objective is to assess the contribution of learning curve to efficacy outcomes, in particular cancer control, continence and potency. Context Laparoscopic radical prostatectomy has recently been introduced to the Australian healthcare system, and has attracted some attention from the media and consumer groups because of its purported benefits as a minimally invasive surgical procedure. However, there are concerns that the learning curve for laparoscopic prostatectomy may be too high for surgical teams in Australia to overcome it, given that only around 2500 prostatectomy operations are performed each year, and that as a result poor outcomes in terms of complications and positive margin rates may occur. The Urological Society of Australia nominated laparoscopic radical prostatectomy for review by ASERNIPS in July 2004 and it was accepted as an accelerated systematic review in October 2004, due to the need for a timely assessment of the literature for this procedure. Background Prostate cancer Prostate cancer is the abnormal growth of cells in the prostate, typically the glandular cells responsible for secretion of seminal fluid (prostate adenocarcinoma) (American Cancer Society, 2004). Prostate cancer is usually a slow growing form of cancer which can persist for years without any symptoms. Symptoms usually arise when the prostate gland enlarges as a result of tumour growth and blocks the urethra causing urinary symptoms such as hesitancy, frequency, nocturia, dribbling of urine before and after urination and, rarely, haematuria. Prostate cancer is the most common form of cancer for men (excluding nonmelanoma skin cancer) in Australia and around the world, and increases with age in men over 50 years (AIHW 2000, Narain et al. 2002, Hummel et al. 2003). In Australia, in 2000, there were cases of prostate cancer and 2665 deaths and Australian men have a lifetime risk of 1 in 11 of having prostate cancer. In Australia, prostate cancer incidence rates were relatively stable up to 1989 but increased dramatically 12 SECTION 1 INTRODUCTION

13 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 from 1990 to 1994, due to a sharp increase in detection rates when PSA blood testing was introduced, before declining by 30% from 1994 to 1997 and then stabilising since Over the same period ( ) the mortality rate from prostate cancer declined slightly (1.3%) (AIHW 2000). Although prostate cancer is the most common form of cancer for males, it is the second most common cause of death from cancer, and because of its increasing incidence in older men, many men will die with cancerous prostates without any treatment for the cancer, and sometime without a diagnosis ever being made. For example, in Australia in 2000, although 2665 men died from prostate cancer, a further 1067 diagnosed with prostate cancer died from another cause (AIHW 2000). Diagnosis of prostate cancer As many men are symptom free, early prostate cancer is often detected through screening, using a combination of digital rectal examination (DRE) and prostate specific antigen (PSA) blood tests. Hard or unusual nodules detected on DRE or an elevated PSA blood count of at least 4.0µg/L for men up to 70 (Ooesterling et al. 1993) can lead to a provisional diagnosis of prostate cancer, which is confirmed through transrectal ultrasound guided (TRUS) biopsy (Keika & Freydenberg, 2004). At the present time the impact of screening for prostate cancer on mortality rates is unclear and as a result recommendations regarding routine screening vary (National Cancer Institute 2004, Narain et al. 2002); however, there are a number of ongoing randomised trials specifically focussed on this question which should help to clarify this issue in the future. Staging prostate cancer Staging prostate cancer is important for determining prognosis and planning treatment and can be achieved through clinical examination, results of diagnostic tests (in particular PSA blood tests) and imaging with computed tomography or magnetic resonance imaging. Radionuclide bone scans can also indicate if cancer has spread beyond the prostate to the bones. (Australian Cancer Network Working Party on Management of Localised Prostate Cancer, 2002). The TNM system is used to stage prostate cancer according to the American Joint Committee on Cancer Stages (American Joint Committee on Cancer, 2002) (See Table 1). SECTION 1 INTRODUCTION 13

14 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 Table 1: TNM Classifications (AJCC 2002) T TX T0 T1 T2 T3 T4 N NX N0 N1 M MX M0 M1 Status of primary tumour Primary tumour cannot be assessed No evidence of primary tumour Clinically important tumour not palpable or visible by imaging T1a: Tumour incidental histologic finding in 5% or less of tissue resected T1b: Tumour incidental histologic finding in more than 5% of tissue resected T1c: Tumour identified by needle biopsy (because of elevated PSA) Tumour confined within the prostate* T2a: Tumour involves one half of one lobe or less T2b: Tumour involves more than one half of one lobe but not both lobes T2c: Tumour involves both lobes Tumour extends through prostate capsule** T3a: Extracapsular extension (unilateral or bilateral) T3b: Tumour invades seminal vesicle(s) Tumour is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscle, and/or pelvic wall Status of regional lymph nodes Regional lymph nodes were not assessed No regional lymph node metastasis Metastasis in regional lymph node(s) Status of distant metastasis Distant metastasis cannot be assessed (not evaluated by any modality) No distant metastasis Distant metastasis M1a: Nonregional lymph node(s) M1b: Bone(s) M1c: Other site(s) with or without bone disease NOTE: * A tumour found in one or both lobes by needle biopsy but not palpable or reliably visible by imaging is classified T1c; ** Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is T2 not T3. In addition to TNM classifications, a Gleason score can also be assigned which indicates the degree of tumour differentiation and abnormality of histological growth patterns. Well differentiated tumours with slight anaplasia have a Gleason score of 2 to 4, moderately differentiated specimens with moderate anaplasia have a Gleason score of 5 to 6, and poorly differentiated or undifferentiated specimens with marked anaplasia have a Gleason score of 7 to 10. TNM classification, preoperative PSA level and Gleason score are related to diseasefree survival. High PSA level (over 15µg/L) has been shown to influence survival more than tumour classification in patients with localised tumours (Zietman et al. 1994). Similarly, higher Gleason scores are associated with a greater chance of dying from prostate cancer within 15 years (if treated conservatively) but are at least partly age dependent (Albertsen et al. 1998). 14 SECTION 1 INTRODUCTION

15 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 Treatment options Treatment options for prostate cancer depend on whether the cancer is localised or advanced, the Gleason score, the PSA level, and the patient s age, general health and preference with regard to the side effects of various treatment options (Keika & Freydenberg, 2004). There are generally three options for treatment: surgery, radiation therapy, and watchful waiting. A Gleason score of seven or more is indicative of more aggressive cancers which may be likely to spread rapidly and therefore require radical treatment either with surgery or radiation therapy. Surgery is generally indicated for younger men with localised cancer, radiation therapy for patients in which surgery is contraindicated, and watchful waiting for older men (>75 years) or those with poor health where life expectancy may be shorter than expected survival from treatment (Pirtskhalaishvili et al. 2001). Surgical treatments Surgical treatments are offered as a cure for localised prostate cancer and are not usually offered to patients with advanced cancer which has spread to the lymph nodes or to other organs of the body (Richie 1997). The general principle of prostate surgery is to remove the prostate gland and the seminal vesicles and sometimes the pelvic lymph nodes (depending on the PSA and Gleason score), with the aim of curing the cancer while at the same time preserving continence and sexual function (Hasan & Gill, 2004). All the available surgical treatments for prostate cancer share this common goal, differing primarily in the extent to which the approach used is more or less invasive. Of the two open surgical approaches, radical retropubic prostatectomy and radical perineal prostatectomy, the perineal approach is considered to be less invasive than the retropubic approach, though it is less widely used (Salomon et al. 2004a). Since 1997 a minimally invasive approach has been available in the form of laparoscopic radical prostatectomy, and more recently surgical robotic systems have been used as an additional tool for laparoscopic radical prostatectomy. Open Radical Prostatectomy The standard surgical treatment is radical retropubic prostatectomy, developed and refined by Walsh (Walsh et al. 1983). An alternative to the retropubic approach is the perineal approach (Weldon & Tavel 1988). If clinically appropriate, both techniques can incorporate a nervesparing technique in which the neurovascular bundles located posterolaterally to the prostate are spared in order to preserve sexual function. Nervesparing is possible if the tumour is intracapsular and does not extend into the neurovascular bundles. SECTION 1 INTRODUCTION 15

16 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 Radical retropubic prostatectomy (RRP) Under general or spinal/epidural anaesthetic, a 68cm lower midline abdominal incision is made and the prostate exposed by excising the endopelvic fascia lateral to the puboprostatic ligaments. The dorsal vein complex is suture ligated to allow access to the urethra and minimise bleeding. If nervesparing is being used the neurovascular bundles are separated from the prostatic capsule prior to urethral incision. Frozensection pathological analysis may be used to determine the surgical margin status and to ensure it is safe to spare the neurovascular bundle. The urethra is cut and the prostatic and rectal arteries ligated, and Denonvilliers fascia is dissected over the seminal vesicles and ampullae of the vas deferens. The ampullae are then clipped or tied and the seminal vesicles exposed. The prostate is separated from the bladder neck circumferentially and removed, and the bladder neck anastomosed to the urethra. A closed drainage system is placed and the wound closed. If indicated, pelvic lymphadenectomy can be carried out through the same retropubic incision, prior to the radical prostatectomy (Downs et al. 2002). Radical perineal prostatectomy (RPP) In the perineal approach the patient is placed in an exaggerated dorsal lithotomy position. Access is via a semicircular perineal incision positioned to avoid damage to the nerves supplying the external anal sphincter. The rectum is mobilized and the neurovascular bundles exposed. If nervesparing surgery is indicated the rectal fascia and enclosed neurovascular bundle are carefully separated from the prostatic capsule and the neural pedicles sharply divided and clipped to avoid bleeding. The vascular pedicles are divided and the urethra dissected. The puboprostatic ligaments are divided and the bladder neck circumcised from the prostate. The seminal vesicles and vasal ampullae are then completed dissected freeing the prostate for removal. The bladder neck is anastomosed to the urethra, the rectum closed and a drain placed. The perineal wound is closed with two layers of continuous subcutaneous and subdermal absorbable sutures to ensure sitting is possible without damage to the wound (Weldon 2002). Laparoscopic Radical Prostatectomy (LRP) Since 1997 laparoscopic radical prostatectomy has been offered as a minimally invasive alternative to open prostatectomy, with the aim of providing improved visualisation of the anatomy during surgery, reduced patient blood loss, better preservation of anatomical structures and reduced postoperative recovery time (Fromont et al. 2002). The standard laparoscopic approach often called the Montsouris technique is transperitoneal and was developed by Guilloneau and Vallancien (2000) in France, although first described by Schuessler et al. (1997). Modifications of the Montsouris technique include the Heilbronn technique (Rassweiler et al. 2001) and roboticassisted LRP (Tewari et al. 2002). An alternative 16 SECTION 1 INTRODUCTION

17 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 to transperitoneal LRP is the use of extraperitoneal access meaning that the procedure is strictly an endoscopic procedure using laparoscopic instruments as the peritoneal cavity is not entered (Stolzenburg & Truss 2003). As with the open approaches it is also possible, when indicated, to use a nervesparing technique with each of these laparoscopic/endoscopic approaches. Transperitoneal LRP (TLRP) In the Montsouris technique, the patient is placed in the dorsal supine position with lower limbs in abduction to provide perineal access. Five trocars are inserted: a 10mm trocar in the umbilicus, three 5mm trocars sequentially inserted into the left iliac fossa midway between the umbilicus and pubis and into the right pararectal fossa, and a 10mm trocar in the right iliac fossa above McBurney s point. Pneumoperitoneum is established through the umbilical trocar with a Veress needle. If required lymphadenectomy can be carried out prior to removal of the prostate. The vasa deferentia and seminal vesicles are mobilized, and then Denonvilliers fascia is divided and the dorsal venous plexus ligated to avoid bleeding. Dissection of the bladder neck is followed by complete dissection of Denonvilliers fascia and the prostatic pedicles. The neurovascular bundles can be spared at this point if required. The prostate is completely mobilized and Santorini s plexus divided. The urethra is incised and then the prostate and seminal vesicles dissected completely. The urethra is anastomosed to the bladder neck and the specimen removed through the umbilical incision (enlarged to 10 12mm) or McBurney s incision into an Endocatch bag (Stolzenburg & Truss 2003). Roboticassisted LRP (RALRP) Roboticassisted LRP uses the same basic technique as standard transperitoneal LRP, however, modifications are required to accommodate the robotic surgical system, generally the da Vinci surgical robotics system (Menon et al. 2003). 1 The da Vinci system consists of a surgeon console remotely located from the patient and a surgical robotic arm cart position by the patient which has robotic arms with specialised jointed laparoscopic instruments and a laparoscopic camera. The surgeon controls the movement of the arms with master handles and observes the operation via the 3D console. Patientside assistants control the docking of the instrumentation and the placement of the surgical arms. The patient is placed in a supine position with adequate room between the legs for the surgical arm cart (either a lithotomy or frogleg position depending on the patient s height). Pneumoperitoneum is established with Veress needle via a left abdominal or umbilical puncture. Six ports are placed: one 12mm umbilical port for the 1 the AESOP robotic arm has also been used to assist in laparoscopic radical prostatectomy (e.g. Antiphon et al. 2003), but this is much less common than the use of the da Vinci system. The robotic arm may be used for bladder and prostate retraction and for maintaining tension on the running suture during vesicourethral anastomosis. SECTION 1 INTRODUCTION 17

18 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 laparoscope, two 8mm ports for the surgical instruments 10cm from the midline between the anterosuperior iliac spine and umbilicus, two ports (10mm and 5mm) on the right side for retraction and insertion of sutures, and a sixth 5mm port for the surgical assistant in the left flank. Lymphadenectomy is performed first if required, then the vasa deferentia and seminal vesicles are dissected, and the bladder and prostate mobilized. The dorsal venous complex is controlled with sutures and the bladder neck transected. The prostatic pedicles are clipped and the neurovascular bundle dissected away from the prostate if nervesparing is indicated. The dorsal venous complex and urethra are incised and the prostate freed for removal. Anastomosis of the urethra and bladder neck is followed by removal of the prostatic specimen through the (enlarged) umbilical port and placement of a suction drain (Tewari et al. 2002). Extraperitoneal endoscopic radical prostatectomy (EERP) The extraperitoneal approach has been developed to avoid some of the complications known to occur from intraperitoneal laparoscopic approaches (Stolzenburg & Truss, 2003). The technique replicates radical retropubic prostatectomy using laparoscopic instruments. A balloon trocar is placed via a 15mm incision in the infraumbilical crease laterally to the midline. Following insertion of the optical system and visualisation of landmarks the balloon trocar is deflated and removed. The preperitoneal space is insufflated with CO2 and four trocars are placed. Lymphadenectomy is carried out if indicated. The prostate and bladder neck are exposed by dissection of the endopelvic fascia and puboprostatic ligaments. Santorini s plexus is ligated and the bladder neck transversed. The urethra is incised and the vasa deferentia and seminal vesicles mobilized. Care is taken to avoid damage to the neurovascular bundles (if nervesparing is possible). Denonvilliers fascia is dissected and the prostatic pedicles coagulated and divided. Santorini s plexus is sectioned, the urethra dissected and the prostate and seminal vesicles are then completely mobilized. Anastomosis of the urethra and bladder neck is made, a drain is placed through the 5mm right iliac fossa port and the specimen removed via the left iliac fossa port enlarged to 34cm (Stolzenberg et al. 2002). The Heilbronn technique The Heilbronn technique is a modification of laparoscopic radical prostatectomy which has been performed using both transperitoneal access and extraperitoneal access. It aims to replicate radical retropubic prostatectomy enabling the surgeon to transfer skills acquired in open radical prostatectomy to the laparoscopic procedure. It also utilises a voicecontrolled robotic arm to reduce the number of assistants required by the surgeon (Rassweiler et al. 2001). The patient is placed in a deflected supine position with 30 Trendelenburg decline and a rectal balloon catheter is inserted and inflated to improve identification of the rectum. Six 18 SECTION 1 INTRODUCTION

19 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 trocars are placed: a 13mm umbilical trocar for the scope (controlled by the AESOP voicecontrolled robotic arm), three 5mm trocars (right and left lateral and right suprapubic), and two 10mm trocars (right and left medial). After pneumoperitoneum is established via the umbilical trocar, the endopelvic fascia is incised on both sides and deep dorsal vein complex controlled, the prostatic apex and neurovascular bundles are dissected, and the urethra is divided and prostate dissected posteriorly. The bladder neck is incised and the seminal vesicles and vas deferentia dissected. The prostatic pedicles are divided and the freed prostate is placed in an endocatch bag. After the urethra is anastomosed to the bladder neck the prostatic specimen is removed via the periumbilical incision (Erdogru et al. 2004). Open versus laparoscopic radical prostatectomy Survival after open radical prostatectomy techniques is up to 95% after 5 years (Salomon et al. 2004b), with positive surgical margin rates of 823%, depending on patient selection criteria (Salomon et al. 2004b). However, radical prostatectomy is also associated with significant levels of urinary incontinence (between 5% and 42%) and sexual dysfunction (between 22 and 77% depending on whether unilateral or bilateral nervesparing is possible) (Salomon et al. 2004b). Furthermore, up to 30% of open radical prostatectomy patients in the US between 1991 and 1994, experienced at least one complication (LuYao et al. 1999). Complications included cardiorespiratory failure, rectal and ureteral injury, urinary retention, infection, haemorrhage, haematoma and leaking anastomosis (Salomon et al. 2004a). Significant blood loss (up to 1500mL for radical retropubic prostatectomy) has also been reported (Catalona et al. 1999). Typical length of stay in the United States is 2 to 3 days, whereas in Europe it is 57 days, primarily due to differences in hospital protocols (Salomon et al. 2004a). Minimally invasive approaches, such as laparoscopic and endoscopic radical prostatectomy, like all minimally invasive approaches, are expected to reduce patient blood loss and postoperative recovery time. Laparoscopic approaches, in theory, should provide improved visualisation of the pelvic anatomy with possibly better preservation of anatomic structures, which could lead to improvements in continence and potency. However, at the present time it is unclear whether these theoretical benefits are realised in practice, without compromising cancer control, in particular surgical margin rates, cancer recurrence and survival (Downs et al. 2002). It is also accepted that laparoscopic radical prostatectomy is a technically difficult operation with a significant learning curve and uncertainty exists regarding the number of procedures required to achieve acceptable competence in the procedure (Salomon et al. 2004b, Hasan & Gill 2004, Stolzenberg & Truss 2003, Link et al. 2004, Rassweiler et al. 2001). SECTION 1 INTRODUCTION 19

20 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE Methodology Search Strategy We searched MEDLINE, EMBASE, Current Contents, PubMed and The Cochrane Library from 1996 to December The York (UK) Centre for Reviews and Dissemination databases, Clinicaltrials.gov, National Research Register, relevant online journals and the Internet were also searched. Searches were conducted without language restriction. The search terms were: ((laparoscopic radical prostatectomy or LRP or (prostat* and laparosc*)) or ((LAPAROSCOPY/or ENDOSCOPY/) and PROSTATIC NEOPLASM)) or (robot* and PROSTATIC NEOPLASM/). Articles were retrieved if they were judged to possibly meet the inclusion criteria. Two reviewers independently applied the inclusion criteria and any differences were resolved by discussion. Excluded studies are listed in Appendix A with reasons for exclusion. The bibliographies of all retrieved publications were hand searched for any relevant references missed in the database search (pearling). Inclusion Criteria The inclusion and exclusion criteria are shown in Table 2. Table 2: Inclusion and exclusion criteria Participants New intervention Comparative intervention Outcomes Inclusion criteria human studies of patients with localised prostate cancer diagnosed by any method laparoscopic radical prostatectomy or endoscopic extraperitoneal radical prostatectomy, with or without roboticassistance, and with or without nervesparing irrespective of concomitant lymphadenectomy or pre or postoperative adjuvant therapy studies comparing laparoscopic and endoscopic approaches radical prostatectomy, using either the retropubic or perineal approach, with or without nervesparing irrespective of concomitant lymphadenectomy or pre or postoperative adjuvant therapy peri and postoperative morbidity and mortality intraoperative and early postoperative factors including: operative time, blood loss, blood transfusion, conversion to open procedure, analgesic requirement, length of hospital stay, resumption of oral intake, catheterisation incontinence, sexual function and quality of life cancer control measures including: surgical margins, postoperative PSA levels, cancer recurrence and survival costs and resource use Exclusion criteria advanced or recurrent prostate cancer LRP combined with any other procedure 20 SECTION 2 METHODOLOGY

21 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 Types of studies included Randomised controlled trials (RCTs), and other controlled or comparative studies were included. Conference abstracts and manufacturer s information were included if they contained relevant safety and efficacy data. The English abstracts from foreign language articles were included if they met the study inclusion criteria and contained safety and efficacy data. In the case of duplicate publications, the latest and most complete study was included. Search results The results of the search are shown in the flow chart in Figure 1. Figure 1: Flow chart of search results potentially relevant articles n = 250 economic models: 3 full text retrieved n = 76 excluded abstracts: 174 not comparative n = 64 background n = 110 included studies n = 30 (39 papers) excluded full text: 34 not laparoscopic n = 16 not comparative n = 6 no relevant outcomes n = 6 lap + other procedure n = 3 internal comparison n = 2 not localised cancer n = 1 laparoscopic versus open n = 21 comparisons of different laparoscopic approaches n = 9 TLRP vs RRP n = 13 EERP vs RRP n = 3 RALRP vs RRP n = 5 EERP vs TLRP n = 6 RALRP vs TLRP n = 3 Data Extraction and Synthesis Data were extracted by one researcher and checked by a second using standardised data extraction tables developed a priori. Included studies were assigned a Level of Evidence according the NHMRC Hierarchy of Evidence (Table 3) and critically appraised for study quality according to the guidelines in Chapter 6 of the Cochrane Reviewer s Handbook (Alderson et al. 2004). Included RCTs were to be examined with respect to the adequacy of allocation concealment and blinding (if possible), handling of losses to followup, and any other aspect of the study design or execution that may have introduced bias. Nonrandomised comparative studies were evaluated for the method of patient selection, comparability of the patient groups, SECTION 2 METHODOLOGY 21

22 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 completeness of followup, and any other feature of the study design or execution that may have introduced bias. Two reviewers critically appraised each of the included studies, and any differences in interpretation were resolved through discussion. A quality score was not assigned, instead the quality of the included studies is described in a narrative fashion, and any important quality issues are highlighted in the discussion of outcomes. We judged that the data were not suitable for statistical pooling and no metaanalysis was undertaken. Table 3: NHMRC Hierarchy of Evidence (NHMRC 2000) Level of evidence I II III1 III2 III3 IV Study design Evidence obtained from a systematic review of all relevant randomised controlled trials Evidence obtained from at least one properlydesigned randomised controlled trial Evidence obtained from welldesigned pseudorandomised controlled trials (alternate allocation or some other method) Evidence obtained from comparative studies (including systematic reviews of such studies) with concurrent controls and allocation not randomised, cohort studies, casecontrol studies, or interrupted time series with a control group Evidence obtained from comparative studies with historical control, two or more single arm studies, or interrupted time series without a parallel control group Evidence obtained from case series, either posttest or pretest/posttest 22 SECTION 2 METHODOLOGY

23 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE Results Included studies and critical appraisal Altogether there were 30 included comparative studies: 21 comparing laparoscopic to open radical prostatectomy (thirteen transperitoneal, three extraperitoneal, five roboticassisted); and nine comparing different approaches to laparoscopic radical prostatectomy (three with robotic assistance). No randomised controlled studies were located, and no ongoing randomised trials were identified. Median followup for laparoscopic approaches in the included studies was 8.1 months (range 1 to 33.8 months) and for open was 11 months (1 to 67 months). Nine of the included studies were identified from hand searches of conference proceedings, one from a letter to the editor, and two were editorials reporting results from a conference presentation. Laparoscopic vs open radical prostatectomy We included 21 studies comparing laparoscopic to open radical prostatecomy (Table 4 and Appendix B). Of the 13 studies comparing the transperitoneal approach to the open approach, four were concurrently controlled studies (Level III2), two were concurrently and historically controlled (Level III2/3) and seven were historically controlled (III3). Two of the three studies comparing the extraperitoneal to the open approach were concurrently controlled (Level III2) and one used historical controls (Level III3). Of the five studies comparing roboticassisted radical prostatectomy to open prostatectomy, three were concurrently controlled (Level III 2), one was historically controlled (Level III3) and one used both concurrent and historical controls (Level III2/3). All of these studies were weakened by the use of designs with nonrandomised controls increasing the chance that the groups being compared would differ in systematic ways which might influence postoperative outcomes, for example age, preoperative PSA levels or tumour stage/grade. However, most of the studies found little difference in preoperative parameters between the two groups being compared. One study using concurrent and historical controls (Salomon 2003) compared transperitoneal laparoscopic radical prostatectomy (TLRP) to radical retropubic (RRP) and radical perineal prostatectomy (RPP). The RRP patients had a higher mean PSA level preoperatively than either the TLRP or RPP patients (p<0.05). In one historically controlled study (Egawa 2003) PSA level was significantly lower for TLRP than RRP (p=0.01) and in another historically controlled study (Fromont 2002) significantly more RRP patients than TLRP patients had clinical stage T2 tumours (p<0.01), although patients were matched on preoperative PSA level. In one historically controlled study comparing extraperitoneal endoscopic radical SECTION 3 RESULTS 23

24 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 prostatectomy (EERP) to RRP (Artibani 2003) more EERP patients had clinical stage T2a tumours than RRP patients. Table 4: Included studies comparing laparoscopic to open radical prostaectomy Study Level of Evidence Dates N Followup Transperitoneal laparoscopic vs open Bhayani 2003 USA Hara 2003 JAPAN Khedis 2004 a FRANCE (conference abstract) Martorana 2004 ITALY Brown 2004 USA Salomon 2003 b FRANCE Atallah 2004 a FRANCE (letter to the editor) Bickert 2002 USA Egawa 2003 c JAPAN Fromont 2002 FRANCE Mitka/Dahl 2001 USA (conference abstract) Namiki 2004 c JAPAN (conference abstract) Rassweiler 2003 d GERMANY Extraperitoneal endoscopic vs open Kimura 2004 JAPAN (conference abstract) Roumeguere 2003 BELGIUM Artibani 2003 ITALY Roboticassisted laparoscopic vs open Binder 2002 GERMANY (conference abstract) Sokoloff 2004 USA (conference abstract) Webster 2004 USA (conference abstract) Tewari 2003 e USA III2 Jul 01 Jun 02 TLRP: 33 RRP: 24 III TLRP: 52 RRP: 54 III2 Aug 99 Mar 2002 TLRP: 140 RRP: 162 III2 Mar 02 Nov 03 TLRP: 50 RRP: 50 III2/3 TLRP: Mar 00 Mar 02 RRP: Jun 01 Mar 02 III2/3 TLRP: RRP: RPP: TLRP: 60 RRP matched: 60 RRP consecutive: 60 TLRP: 235 RRP: 184 RPP: 119 III3 Period of 3.5 years TLRP: 59 RRP: 115 III3 Dates not stated. TLRP: 40 RRP: 14 III3 Jan 98 Sep 01 TLRP: 34 RRP: 49 III3 TLRP: 2000 RRP: III3 TLRP: More than 18 months prior to 2001 TLRP: 139 RRP: 139 TLRP: 37 RRP: 37 III3 Dates not stated. TLRP: 34 RRP: 78 III3 TLRP: Mar 99 Sep 02 RRP: Dec 94 Nov 99 TLRP: 438 RRP: 219 III2 Jan 01 Feb 04 EERP: 93 RRP: 114 III2 Sep 99 Sep 01 EERP: 85 RRP: 77 III3 Jan 01 Dec 01 EERP: 71 RRP: 50 III2 Dates not stated. RALRP: 50 RRP: 50 III2 Feb 03 Feb 04 RALRP: 51 RRP: 50 III2 Dates not stated. RALRP: 99 RRP: 71 III2/3 Oct 99 Dec 02 RALRP: 200 RRP: days 8.1 months 7.9 months 2 months immediate postoperative 30 days 1.3 years 4.5 years 3.9 years immediate postoperative up to 2 months 14 months 34 months immediate postoperative immediate postoperative 12 months 8 30 months 67 months 12 months 12 months 10.3 months 10.1 months immediate postoperative 12 months immediate postoperative 7.7 months 18.3 months Ahlering 2004 USA III RALRP: 60 RRP: 60 immediate postoperative NOTE: a there is likely patient crossover in these two studies; b there is likely patient crossover with Ruiz 2004 (see Table 5); c LRP patients may be the same in these two studies; d there is likely patient crossover with Erdogru 2004 (see Table 5); e there is likely patient crossover with Menon 2002 (see Table 5). 24 SECTION 3 RESULTS

25 ASERNIPS REVIEW OF LAPAROSCOPIC RADICAL PROSTATECTOMY JUNE 2005 Few studies reported exclusion criteria, however, those that did used criteria generally consistent with indications for RRP, that is patients with resectable localised prostate cancer. Four studies excluded patients who received neoadjuvant therapy (Brown 2004, Egawa 2004, Fromont 2002, Artibani 2003), and one did not use any exclusion criteria (Roumeguere 2003). While selection bias could not be properly controlled without random allocation to treatment, all but two of the studies which reported it (12/18) allocated patients to treatments consecutively which should have minimised bias. One study with concurrent and historical controls (Tewari 2003) reported that patients were able to choose whether they received laparoscopic or open prostatectomy after attempts to conduct a randomised trial failed when patients refused to be randomised. Another concurrently controlled study (Roumeguere 2003) used either patient or surgeon preference to allocate patients to treatment. One study using concurrent and historical controls (Brown 2004) addressed the influence of preoperative factors and possible surgeon selection bias by using two controls groups of RRP patients; one with concurrent consecutively selected patients, and the other with patients matched for age and tumour grade preoperatively. In this review results from the matched group have been reported unless otherwise stated. Comparisons between laparoscopic approaches We included nine studies comparing different laparoscopic approaches (Table 5 and Appendix C). There were six studies comparing the transperitoneal to the extraperitoneal approach; one used concurrent controls (Level III2), and five used historical controls (Level III3). There were three historically controlled studies comparing roboticassisted radical prostatectomy to TLRP (Level III3). Since eight of the nine studies used historical controls it is likely that biases introduced by changes over time in hospital protocols and patient selection criteria may have affected the outcomes of these studies. For example, Erdogru 2004 preferred to use EERP in patients with obesity, simultaneous hernia repair and previous abdominal surgery. It should be noted that in this review we have excluded studies in which other procedures were conducted at the same time as laparoscopic radical prostatectomy, however, in the case of Erdogru 2004, concommitant surgery was not the focus of the study and only six of the 53 patients received both EERP and hernia repair. As a result the study has been included. The majority of studies reported no exclusion criteria or used the standard indications for radical prostatectomy (i.e. localised resectable tumours in patients medically fit for surgery). In five of the ten studies no significant differences were found between the two groups on preoperative parameters such as age, PSA, Gleason score or clinical T stage. In one historically controlled study (Cathelineau 2004) EERP patients were significantly younger than TLRP patients (p=0.03), in a second study (Eden 2004) SECTION 3 RESULTS 25