A rapid scan of the literature

Transcription

1 A rapid scan of the literature August 2009 Photoselective vaporisation for benign prostatic hyperplasia: a rapid literature scan Gregory Merlo Suzanne Campbell Adele Weston

2 This report should be referenced as follows: Merlo, G., Campbell, S. and Weston, A. Photoselective vaporisation for benign prostatic hyperplasia: a rapid literature scan HSAC Report 2009; 2(11) Health Services Assessment Collaboration (HSAC), University of Canterbury ISBN (online) ISBN (print) ISSN (online) ISSN X (print)

3 i Review Team This review was undertaken by the Health Services Assessment Collaboration (HSAC). HSAC is a collaboration of the Health Sciences Centre of the University of Canterbury, New Zealand and Health Technology Analysts, Sydney, Australia. This report was authored by Gregory Merlo, Dr Suzanne Campbell and Dr Adele Weston. Gregory Merlo developed and undertook the literature search, extracted the data, and prepared the report. Dr Suzanne Campbell and Dr Adele Weston provided guidance and reviewed the report. Acknowledgements Dr Sarah Norris (HSAC Director) reviewed the final draft. Cecilia Tolan (Administrator) provided administrative support. The current review was conducted under the auspices of a contract funded by the New Zealand Ministry of Health. This report was requested by Jane Lyon, Clinical Advisor, The Sector Capability and Innovation Directorate of New Zealand s Ministry of Health. We thank Ricarda Vandervorst, Senior Policy Analyst, for providing background information for the review. The systematic review of the evidence will ultimately be used by The Sector Capability and Innovation Directorate team to inform policy decision making in conjunction with other information. The content of the review alone does not constitute clinical advice or policy recommendations. Copyright Statement & Disclaimer This report is copyright. Apart from any use as permitted under the Copyright Act 1994, no part may be reproduced by any process without written permission from HSAC. Requests and inquiries concerning reproduction and rights should be directed to the Director, Health Services Assessment Collaboration, Health Sciences Centre, University of Canterbury, Private Bag 4800, Christchurch, New Zealand HSAC takes great care to ensure the accuracy of the information in this report, but neither HSAC, the University of Canterbury, Health Technology Analysts Pty Ltd nor the Ministry of Health make any representations or warranties in respect of the accuracy or quality of the information, or accept responsibility for the accuracy, correctness, completeness or use of this report. The reader should always consult the original database from which each abstract is derived along with the original articles before making decisions based on a document or abstract. All responsibility for action based on any information in this report rests with the reader. This report is not intended to be used as personal health advice. People seeking individual medical advice should contact their physician or health professional.

4 ii The views expressed in this report are those of HSAC and do not necessarily represent those of the University of Canterbury New Zealand, Health Technology Analysts Pty Ltd, Australia or the Ministry of Health. Contact Details Health Services Assessment Collaboration (HSAC) Health Sciences Centre University of Canterbury Private Bag 4800 Christchurch 8140 New Zealand Tel: Fax: hsac@canterbury.ac.nz Web Site:

5 iii Executive Summary Introduction This report provides a brief scan of the literature available on the role of photoselective vaporisation of the prostate (PVP) using a high powered potassiumtitanyl-phosphate (KTP) laser (ie, the GreenLight, PVP ) for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). The report was commissioned by the New Zealand Ministry of Health. Methods A systematic method of literature searching and study selection was employed in the preparation of this report. The literature was searched using the bibliographic databases of EMBASE and Medline. The Cochrane library and health technology assessment agencies were also searched to help identify existing reviews or clinical practice guidelines. In addition, the bibliographies of key included papers were examined for relevant studies. It is important to note that this was a brief scan of the evidence, and not a full systematic review. Detailed quality appraisal, data extraction and interpretation of the identified literature were not performed. This review relies heavily upon material reported in each publication s abstract. Key results The search strategy identified a total of 688 citations, of which 113 qualified for inclusion in this review. These included one clinical practice guideline, four health technology assessments, 11 systematic reviews, 11 randomised comparative trials, seven non-randomised comparative studies, and 76 case series. An economic evaluation was included in one of the identified health technology assessments and one of the RCT publications. An additional two publications reported an economic analysis. Note that although 113 studies qualified for inclusion, only 37 have been summarised in this report, five of which were reviewed in more detail. The literature gathered in this report suggests that PVP has similar safety and efficacy outcomes as transurethral resection of the prostate (TURP). However, PVP results in significantly shorter catheterisation time and length of hospitalisation. The literature also provides some evidence that PVP has similar safety and efficacy outcomes as holmium laser ablation of the prostate (HoLAP). Long-term follow-up of PVP in case series demonstrates the durability of effectiveness for up to five years. The economic analyses of PVP provide conflicting results, which reflect the different types of economic evaluations conducted, the different comparators used, and the different settings and perspectives taken in the analyses. Conclusions The body of evidence suggests that PVP is a safe, effective, and durable treatment for LUTS secondary to BPH. The papers retrieved for this Rapid Literature Scan do not provide any evidence that PVP is associated with a decreased rate of adverse events

6 iv compared with TURP (or HoLAP). Although care was taken to retrieve representative papers of high quality and relevance, the large number of included studies means that many relevant papers were only briefly summarised from their abstracts. Therefore, the results of this Rapid Literature Scan should be interpreted with caution.

7 v Table of Contents Review Team... i Acknowledgements... i Copyright Statement & Disclaimer... i Contact Details... ii Executive Summary...iii Introduction...iii Methods...iii Key results...iii Conclusions...iii Table of Contents... v List of Tables... vi List of Abbreviations and Acronyms... vii Introduction... 1 Methods... 3 Literature search... 3 Results... 7 Clinical practice guidelines... 7 Health technology assessments... 7 Lourenco Systematic reviews Stafinski Randomised comparative studies Elzayat Non-randomised comparative studies Case series Hai Economic analyses Armstrong Lourenco Stafinski Summary and Conclusions References Appendix A: HTA Websites Searched Appendix B: Included Citations Appendix C: Excluded Citations... 39

8 vi List of Tables Table 1: Summary of the literature search... 3 Table 2: Criteria for inclusion/exclusion in review... 4 Table 3: Health technology assessments... 8 Table 4: Complications (Lourenco et al., 2008) Table 5: Systematic reviews Table 6: Randomised comparative studies Table 7: Results from Elzayat et al. (2009) Table 8: Non-randomised comparative studies Table 9: Case series Table 10: Results from Hai 2009 PVP clinical outcomes Table 11: Economic analyses... 26

9 vii List of Abbreviations and Acronyms AHRQ Agency for Healthcare Research and Quality ANZHSN Australia and New Zealand Horizon Scanning Network AUA American Urological Association BPH Benign prostatic hyperplasia CADTH Canadian Agency for Drugs and Technology in Health CI Confidence interval CPG Clinical Practice Guideline EAU European Association of Urology HoLAP Holmium laser ablation of the prostate HoLEP Holmium laser enucleation of the prostate HTA Health Technology Assessment ICER Incremental cost effectiveness ratio INAHTA International Network of Agencies for Health Technology Assessment IPSS International Prostate Symptom Score KTP Potassium titanyl phosphate LUTS Lower urinary tract symptoms MSAC Medical Services Advisory Committee Nd:YAG Neodymium: yttrium-aluminium-garnet NICE National Institute for Health and Clinical Excellence NHS National Health Service (United Kingdom) NIHR National Institute for Health Research OP Open prostatectomy PSA Prostate specific antigen PVP Photoselective vaporisation of the prostate PVR Post-void residual urine QALY Quality adjusted life year Qmax Maximum flow rate QoL Quality of life RCT Randomised controlled trial RR Relative risk SD Standard deviation TRUS Transrectal ultrasound TUMT Transurethral microwave therapy TURP Transurethral resection of the prostate TUVP Transurethral electro vaporisation of the prostate

10

11 1 Introduction Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that commonly occurs in men older than 40 years of age. It often results in lower urinary tract symptoms (LUTS), such as frequency, urgency, weak urine flow, straining, recurrent infections and incomplete bladder emptying, which interfere with daily activities and impair quality of life (Sandhu et al., 2004). Severe cases of BPH may lead to bladder stones, bladder decompensation, haematuria and chronic renal failure. Therapy for BPH encompasses pharmaceutical treatment, minimally invasive thermotherapies (eg, microwave therapy), endoscopic transurethral resection/ vaporisation procedures such as transurethral resection of the prostate (TURP), other forms of laser therapy such as holmium laser ablation of the prostate (HoLAP) and holmium laser enucleation of the prostate (HoLEP), photoselective vaporisation of the prostate (PVP), transurethral incision of the prostate, and open prostatectomy. TURP is the current reference standard to which all other BPH therapies are compared. Despite the overall good outcomes with TURP, men who have bleeding disorders, are on anticoagulant therapy or are at high risk of a cardiovascular event are often denied conventional TURP. The complications linked to TURP include bleeding requiring blood transfusion, clot retention, transurethral resection syndrome, urethral stricture and bladder neck contracture (ANZHSN 2007). PVP involves the use of a GreenLight PVP surgical laser system to remove the excess prostate tissue associated with BPH. The system utilises a specially designed, high-powered potassium-titanyl-phosphate (KTP) laser (523 nm) that is selectively absorbed by haemoglobin but is fully transmitted through water. Prostatic tissue, which has a high haemoglobin content, selectively absorbs the laser energy, causing focussed vaporisation (ANZHSN 2007). PVP can be performed with a range of anaesthesia, from a local prostate block with intravenous sedation to general anaesthesia. During the procedure, a small flexible fibre optic is inserted through a cystoscope into the urethra and held within 0.5 mm (or less) of the target tissue to achieve maximum vaporisation efficiency. Light pulses are then sent through this fibre, vaporising and removing the prostatic obstruction (NICE 2005). When first introduced, the KTP laser was used in conjunction with existing lasers. The objective was to combine the coagulation and haemostatic effects of the 1064 nm Neodymium: yttrium-aluminium-garnet (Nd:YAG) laser with the photoselective vaporisation capacity of the 532 nm KTP laser. High powered KTP lasers have since been used alone for the treatment of BHP (NICE 2005). Two reported advantages of the procedure are the reduction in significant bleeding and the fact that it can be performed without the need for a catheter.

12 2

13 3 Methods Literature search A search of EMBASE, Medline and the Cochrane library as well as numerous clinical practice guideline (CPG) and health technology assessment (HTA) websites (Appendix A) was undertaken to identify any published guidelines, systematic reviews or publications pertaining to the use of PVP for BPH. In addition, a general internet search was performed to identify any relevant publications that were not identified by other means. The literature source, search terms, number of citations identified and date of the search is outlined in Table 1. Many of the citations identified through the search of the Cochrane library and HTA websites were duplicates already identified through the EMBASE/Medline search, or were irrelevant to the topic of interest, and were therefore excluded before downloading into the Reference Manager database. Table 1: Summary of the literature search Source a Search terms Citations Date Embase.com (Includes EMBASE and Medline) Cochrane library CADTH ANZHSN NHS evidence NICE (greenlight AND la?er) OR green light laser OR green light lazer OR (photoselective AND vapori?ation) OR photovapori?ation OR KTP laser OR KTP lazer OR potassium titanyl phosphate laser OR potassium titanyl phosphate lazer greenlight laser OR green light laser OR greenlight lazer OR green light lazer OR photoselective vaporisation OR photoselective vaporization OR photovaporisation OR photovaporization OR KTP laser OR KTP lazer OR potassium titanyl phosphate laser OR potassium titanyl phosphate lazer greenlight laser OR green light laser OR greenlight lazer OR green light lazer OR photoselective vaporisation OR photoselective vaporization OR photovaporisation OR photovaporization OR KTP laser OR KTP lazer OR potassium titanyl phosphate laser OR potassium titanyl phosphate lazer greenlight laser OR green light laser OR greenlight lazer OR green light lazer OR photoselective vaporisation OR photoselective vaporization OR photovaporisation OR photovaporization OR KTP laser OR KTP lazer OR potassium titanyl phosphate laser OR potassium titanyl phosphate lazer greenlight laser OR green light laser OR greenlight lazer OR green light lazer OR photoselective vaporisation OR photoselective vaporization OR photovaporisation OR photovaporization OR KTP laser OR KTP lazer OR potassium titanyl phosphate laser OR potassium titanyl phosphate lazer greenlight laser OR green light laser OR greenlight lazer OR green light lazer OR photoselective vaporisation OR photoselective vaporization OR photovaporisation OR photovaporization OR KTP laser OR KTP lazer OR potassium titanyl phosphate laser OR potassium titanyl phosphate lazer /7/ /7/ /8/ /8/ /8/ /8/2009

14 4 Table 1: Summary of the literature search (continued) Source a Search terms Citations Date INAHTA AHRQ Euroscan MSAC National guideline clearinghouse greenlight laser OR green light laser OR greenlight lazer OR green light lazer OR photoselective vaporisation OR photoselective vaporization OR photovaporisation OR photovaporization OR KTP laser OR KTP lazer OR potassium titanyl phosphate laser OR potassium titanyl phosphate lazer greenlight laser OR green light laser OR greenlight lazer OR green light lazer OR photoselective vaporisation OR photoselective vaporization OR photovaporisation OR photovaporization OR KTP laser OR KTP lazer OR potassium titanyl phosphate laser OR potassium titanyl phosphate lazer greenlight laser OR green light laser OR greenlight lazer OR green light lazer OR photoselective vaporisation OR photoselective vaporization OR photovaporisation OR photovaporization OR KTP laser OR KTP lazer OR potassium titanyl phosphate laser OR potassium titanyl phosphate lazer greenlight laser OR green light laser OR greenlight lazer OR green light lazer OR photoselective vaporisation OR photoselective vaporization OR photovaporisation OR photovaporization OR KTP laser OR KTP lazer OR potassium titanyl phosphate laser OR potassium titanyl phosphate lazer greenlight laser OR green light laser OR greenlight lazer OR green light lazer OR photoselective vaporisation OR photoselective vaporization OR photovaporisation OR photovaporization OR KTP laser OR KTP lazer OR potassium titanyl phosphate laser OR potassium titanyl phosphate lazer Total /8/ /8/ /8/ /8/ /8/2009 Remove 688 duplicates b a The HTA websites searched for this project are shown in Appendix A b 44 duplicates were removed by hand Abbreviations: AHRQ = Agency for Healthcare Research and Quality; ANZHSN = Australia and New Zealand Horizon Scanning Network; CADTH = Canadian Agency for Drugs and Technology in Health; INAHTA = International Network of Agencies for Health Technology Assessment; MSAC = Medical Services Advisory Committee; NICE = National Institute for Health and Clinical Excellence; NHS = National Health Service There were 688 citations downloaded into the Reference Manager database from the various sources described in Table 1. These included 618 citations found through the EMBASE/Medline search, 112 citations identified from the Cochrane Library, and two citations identified from online HTA/CPG databases. A total of 44 duplicate citations were removed manually from the Reference Manager database. The titles and abstracts were reviewed using the inclusion and exclusion criteria outlined below in Table 2. Table 2: Criteria for inclusion/exclusion in review Reason for exclusion Number of citations excluded Incorrect study type: opinion piece, letter 147 Incorrect intervention: not PVP 16 Incorrect indication: not BPH 411 Not in English 1 Included 113

15 5 After reviewing the citations and abstracts, there were 113 citations that qualified for inclusion. These included one clinical practice guideline, four health technology assessments (one of which included an economic evaluation), 11 systematic reviews, 11 randomised controlled trials (RCTs, of which one was published together with an economic analysis), seven non-randomised comparative studies, 76 case series, and three economic analyses not identified elsewhere. Included citations are listed in Appendix B while excluded citations are provided in Appendix C.

16 6

17 7 Results Clinical practice guidelines The National Institute of Health and Clinical Excellence (NICE) formulated guidance for the use of PVP for the treatment of benign prostatic obstruction. The guidance, issued in May 2005, states that current evidence on the safety and short-term efficacy of potassium-titanyl-phosphate (KTP) laser vaporisation of the prostate for benign prostatic obstruction appears adequate to support the use of this procedure, provided that the normal arrangements are in place for consent, audit and clinical governance. It was noted by NICE that data on the long-term efficacy of this procedure were limited at that time. In producing the guidance, NICE considered: (i) the results of studies reporting the safety and efficacy of KTP laser vaporisation of the prostate; (ii) opinions from experts; and (iii) consultation with key stakeholders. The guidelines acknowledge the results of two uncontrolled studies with a total of 46 patients followed for 12 months. The studies showed that patients with LUTS secondary to BPH who underwent PVP had improvements in postoperative symptom score, urine flow, and quality of life (QoL). The guidelines stress the importance of specific training in the technique and suggest that efficacy may be related to the experience of the surgeon. The most common complications following PVP are dysuria and haematuria. Other less common problems included retrograde ejaculation, soft bladder-neck contracture, urine infection, and urge incontinence. Specialist Advisors noted that patients were likely to suffer irritative bladder symptoms in the early postoperative period. Health technology assessments Four health technology assessments were identified in the literature search, two of which were brief reports (ANZHSN 2007; and CADTH 2006), and the other two were full health technology assessments (Lourenco et al., 2008; and Ontario Ministry of Health and Long Term Care 2006). Lourenco et al., 2008 was selected for more detailed discussion as it was the most recent health technology assessment.

18 8 Table 3: Citation Health technology assessments Summary Australia and New Zealand Horizon Scanning Network. (2007) Horizon scanning technology prioritising summary: photoselective vaporisation for benign prostatic hyperplasia. Health Policy Advisory Committee on Technology. Canberra. Canadian Agency for Drugs and Technologies in Health. (2006) Photoselective vaporization for benign prostatic hyperplasia (Brief record). Ottawa. Lourenco T, Armstrong N, N'Dow J, Nabi G, Deverill M, Pickard R, Vale L, MacLennan G, Fraser C, McClinton S, Wong S, Coutts A, Mowatt G, and Grant A. (2008) Systematic review and economic modelling of effectiveness and cost utility of surgical treatments for men with benign prostatic enlargement. Health Technology Assessment 12: Australian horizon scan assessing the safety and efficacy of PVP for BPH. ANZHSN concluded that although current evidence suggests that PVP may be as effective as TURP, it is not evident that PVP has significant advantages in terms of safety (eg, reduced bleeding). The PVP procedure takes significantly longer than the TURP treatment. This may limit the clinical applicability of treatment when the prostate is larger than 60 ml. ANZHSN recommended, based on the limited available evidence and the various alternative treatments, that PVP should be archived. Canadian health technology assessment of PVP for BPH. The literature search identified 16 studies, of which 14 addressed safety and efficacy, one addressed volume of prostatic tissue removed, and one compared PVP to TURP. All were observational studies. CADTH concluded that RCTs and long-term follow-up are required to determine the place of PVP in the management of BPH. The potential cost advantage of PVP is limited by the degree to which PVP will replace TURP, and the durability of its effect. If PVP is used alongside TURP, the health system will have to bear the costs of the new capability, including equipment and the maintenance of staff skills in multiple techniques. Systematic review and economic evaluation conducted as part of the UK NIHR Health Technology Assessment Program. Assessed the effectiveness and cost utility of surgical treatments for BPH. Improvements in symptom scores at 12 months non-significantly favoured TURP over PVP. There were fewer complications reported in patients receiving PVP compared with TURP, but this did not reach statistical significance for any individual adverse event. Further details of this paper are provided. Ontario Ministry of Health and Long Term Care. (2006) Energy delivery systems for treatment of benign prostatic hyperplasia: health technology policy assessment. Toronto. Canadian health technology assessment on delivery systems for the treatment of BPH. The literature search found one comparative prospective study on PVP (Bachmann 2005) in which PVP was shown to be clinically as effective as TURP. Time to catheter removal was significantly shorter for PVP patients than TURP patients while operating room time was significantly shorter for the TURP procedure. Abbreviations: ANZHSN = Australia and New Zealand Horizon Scanning Network; BPH = benign prostatic hyperplasia; CADTH = Canadian Agency for Drugs and Technologies in Health; EAU = European Association of Urology; NICE = National Institute for Health and Clinical Excellence; NIHR = National Institute for Health Research; PVP = photoselective vaporisation of the prostate; RCT = randomised controlled trial; TURP = transurethral resection of the prostate.

19 9 Lourenco 2008 The health technology assessment by Lourenco et al. (2008) was aimed at determining the clinical effectiveness and cost utility of alternative procedures to TURP for BPH unresponsive to non-surgical treatments. The authors conducted a systematic review for relevant RCTs using 13 databases. RCTs were eligible for inclusion irrespective of publication language if they assessed interventional treatment options for the treatment of BPH. A total of 156 reports describing 88 RCTs were included in the review. Three of the included RCTs compared PVP with TURP (Carter et al., 1999; Bouchier-Hayes et al., 2006; and Shingleton et al., 2002). Two of these studies used hybrid KTP/ND:YAG lasers (Carter et al., 1999; and Shingleton et al., 2002) while the other study used photoselective vaporisation (ie, KTP) alone (Bouchier-Hayes et al., 2006). For the meta-analysis of outcomes, the results of these three trials were combined with the results of eight RCTs of non-ktp laser vaporisation techniques (including Nd:YAG and holmium:yag lasers). The cost effectiveness analysis will be discussed further in the cost analysis section of this rapid literature scan. Efficacy Efficacy of treatment was assessed in the meta-analysis by combining International Prostate Symptom Score (IPSS) and American Urological Association (AUA) symptom score values. Of the three PVP trials, only Shingleton et al. (2002) reported IPSS/AUA values after three months. Symptom scores in the Shingleton et al. (2002) trial non-significantly favoured TURP over PVP at 12 months (RR 2.20; 95% CI 0.13, 4.53), two years (RR 1.30; 95% CI 1.70, 4.30), and five years (RR 2.20; 95% CI 0.90, 5.30) after treatment. The meta-analysis of all trials of laser vaporisation (including Nd:YAG and holmium:yag lasers) non-significantly favoured TURP over other treatments at 12 months (RR 1.30; 95% CI 0.12, 2.47), two years (RR 1.77; 95% CI 0.16, 3.70), and five years (RR 2.24; 95% CI 0.08, 4.75) after treatment. Safety The complications reported in the meta-analysis of safety outcomes included the need for blood transfusion, urinary retention, urinary tract infection, postoperative strictures and transurethral resection (TUR) syndrome. There were fewer complications reported in patients receiving PVP compared with TURP, but this did not reach statistical significance for any individual adverse event (Table 4).

20 10 Table 4: Complications (Lourenco et al., 2008) Study or subcategory Blood transfusion PVP n/n (%) TURP n/n (%) RR (95% CI) Bouchler-Hayes 2006 (KTP) 0/38 (0) 1/38 (2.6) 0.33 (0.01, 7.93) Carter 1999 (KTP/Nd:YAG) 0/95 (0) 5/96 (5.2) 0.09 (0.01, 1.64) Shingleton 2002 (KTP/Nd:YAG) 0/50 (0) 0/50 ()) Not estimable Urinary retention Carter 1999 (KTP/Nd:YAG) 5/93 (5.4) 2/92 (2.2) 2.47 (0.49, 12.43) Shingleton 2002 (KTP/Nd:YAG) 3/50 (6.0) 1/50 (2.0) 3.00 (0.32, 27.87) Urinary tract infection Carter 1999 (KTP/Nd:YAG) 11/93 (11.8) 6/92 (6.5) 1.81 (0.70, 4.70) Strictures Bouchler-Hayes 2006 (KTP) 5/38 (13.2) 8/38 (21.1) 0.63 (0.22, 1.74) Carter 1999 (KTP/Nd:YAG) 7/84 (8.3) 15/85 (17.6) 0.47 (0.20, 1.10) Shingleton 2002 (KTP/Nd:YAG) 4/50 (8.0) 1/50 (2.0) 4.00 (0.46, 34.54) TUR syndrome Bouchler-Hayes 2006 (KTP) 0/38 (0) 1/38 (2.6) 0.33 (0.01, 7.93) Carter 1999 (KTP/Nd:YAG) 0/93 (0) 0/92 (0) Not estimable Incontinence Carter 1999 (KTP/Nd:YAG) 1/84 (1.2) 0/85 (0) 3.04 (0.13, 73.47) Shingleton 2002 (KTP/Nd:YAG) 1/50 (2.0) 1/50 (2.0) 1.00 (0.06, 15.55) Abbreviations: CI = confidence interval; KTP = potassium titanyl phosphate laser; Nd:YAG = neodymium: yttrium-aluminiumgarnet laser; PVP = photoselective vaporisation of the prostate; RR = relative risk; TUR syndrome = transurethral resection syndrome; TURP = transurethral resection of the prostate. Systematic reviews A total of 11 systematic reviews were identified in the literature search (Table 5). Comparator treatments of interest in the reviews included holmium laser enucleation of the prostate (HoLEP; Aho et al., 2008; Naspro et al., 2009; and Wu et al., 2007) and TURP (Stafinski et al., 2008; and Wu et al., 2007). Based on the body of evidence, it appears that PVP and TURP are comparable in terms of safety and efficacy, although PVP may be associated with a higher rate of reoperation. Stafinski et al. (2008) was selected for more detailed discussion as it was the most recent systematic review comparing PVP with TURP, the gold standard treatment for BPH. Stafinski et al. (2008) compared the safety, efficacy, effectiveness and economics of the two procedures.

21 11 Table 5: Citation Systematic reviews Adlbrecht C, Wild C. (2007) Photoselective vaporisation of the prostate in men with benign prostatic hyperplasia. HTA in hospitals. Wien.: Ludwig.Boltzmann.Institut.fuer.Health Technology Assessment 17. Aho TF, Gilling PJ. (2008) Current techniques for laser prostatectomy-pvp and HoLEP. Arch.Esp.Urol. 61(9): Kuntz RM. (2007) Laser treatment of benign prostatic hyperplasia. World J.Urol. 25(3): Lebed BD, Jaffe WI, Te AE. (2006) Sexual complications of minimally invasive surgical therapy for benign prostatic hyperplasia. Curr.Sex.Health Rep. 3(2): McAllister WJ, Gilling PJ. (2004) Vaporization of the prostate. Curr.Opin.Urol. 14(1):31-4. Naspro R, Bachmann A, Gilling P, Kuntz R, Madersbacher S, Montorsi F et al. (2009) Review of the Recent Evidence ( ) for 532-nm Photoselective Laser Vaporisation and Holmium Laser Enucleation of the Prostate. Eur.Urol. 55(6): Ozden E, Sahin A. (2005) Laser for photoselective vaporization of the prostate in treatment of BPH. Turk Urol.Derg. 31(4): Reich O, Gratzke C, Stief CG. (2006) Techniques and long-term results of surgical procedures for BPH. European Urology 49(6): Summary No abstract available. Systematic review of laser surgery for BPH with a focus on comparing PVP with HoLEP. Indirect comparison was used, as no head-to-head trials were found. More tissue is removed with HoLEP than PVP. HoLEP is reported to be effective for up to 6 years; there was no comparable data for the longevity of PVP. Systematic review of laser prostatectomy techniques. A Medline search was conducted over the previous 6 years. The authors concluded that although the shortterm results of PVP are promising, there is a lack of long-term data and randomised studies. Several RCTs indicate the HoLEP is at least as safe and effective as TURP and open prostatectomy, with significantly lower morbidity. Systematic review of the sexual outcomes of minimally invasive prostate therapies. Outcomes of interest included erectile dysfunction, ejaculatory dysfunction, and the impact of therapy on quality of life. The abstract does not specifically discuss PVP. Systematic review of various techniques for vaporisation of the prostate. Includes both laser vaporisation and electrovaporisation. The abstract does not specifically discuss PVP. The authors conclude that early forms of laser vaporisation of the prostate are not as effective as either TURP or TUVP. These earlier laser treatments also had higher retreatment rates. The authors report that newer, more powerful lasers have been introduced with encouraging initial results. Systematic review comparing the safety, efficacy, and durability of HoLEP with PVP. A Medline search was conducted of clinical studies over the previous two years. Four RCTs for HoLEP were identified; two compared with TURP and two compared with OP. HoLEP shown to be as efficacious and durable as TURP and OP. Two RCTs were identified comparing PVP with TURP (both short follow-up) and one RCT comparing PVP with OP. PVP was associated with low perioperative morbidity. The efficacy of PVP was comparable to TURP, despite a higher reoperation rate. Systematic review of efficacy and safety of PVP. Neither the methods, results, nor the conclusions are reported in the abstract. Systematic review of surgical procedures for BPH. Medline database search between 2000 and Studies with a follow-up of more than 10 years were available for OP and TURP. Studies with a follow-up of at least five years were available for PVP, transurethral incision of the prostate, TUVP, needle ablation and HoLEP. OP and TURP provided the best evidence for long term efficacy of treatment.

22 12 Table 5: Citation Systematic reviews (continued) Summary Seki N, Naito S. (2007) Instrumental treatments for benign prostatic obstruction. Curr.Opin.Urol. 17(1): Stafinski T, Menon D, Harris G, Gray G, Jhangri G. (2008) Photoselective vaporization of the prostate for the treatment of benign prostatic hyperplasia. Canadian Urological Association Journal 2(2): Systematic review of surgical procedures for BPH involving a search of Medline. The authors concluded that PVP appears to be safe and efficient; however, long-term efficacy has not yet been confirmed by RCT. The review found that HoLEP had a favourable safety profile for treating patients with comorbidities. TURP using bipolar electrocautery systems has demonstrated some improved haemostasis and the ability to avoid transurethral resection syndrome; however, more randomised comparisons are needed. Systematic review comparing the safety, efficacy, effectiveness and economics of PVP vs TURP. The authors reported comparable safety and functional outcomes for PVP and TURP. The two treatments did, however, differ significantly with regard to operative outcomes, with PVP having favourable catheterisation time and length of hospitalisation. Further details of this paper are provided. Wu HZ. (2007) Application and development of all solid state green laser and photoselective vaporization of prostate. J.Clin.Rehab.Tissue Eng.Res. 11(1): Systematic review of the safety and efficacy of PVP compared with HoLEP and TURP. No clinical outcomes were discussed in the abstract. Abbreviations: BPH = benign prostatic hyperplasia; HoLEP = holmium laser enucleation of the prostate; OP = open prostatectomy; PVP = photoselective vaporisation of the prostate; RCT = randomised controlled trial; TURP = transurethral resection of the prostate; TUVP = transurethral vaporisation of the prostate.

23 13 Stafinski 2008 The objective of this systematic review was to compare the safety, efficacy, effectiveness and economics of PVP vs TURP. The cost effectiveness analysis is described in the cost analysis section of this rapid literature scan. The literature search identified 14 studies, including 12 case series, one RCT (Bouchier-Hayes et al., 2007), and one multi-centre cohort study (Bachmann et al., 2005). Efficacy Stafinski et al. (2008) evaluated operative outcomes including average operating time, average catheterisation time, length of hospital stay and reoperation rate. The 12 case series reported heterogeneous outcomes for average operation time (20 minutes to 137 minutes), average catheterisation time (7.6 hours to 43 hours), and reoperation rate (0% to 7.5%). In all but one of the 12 case series, the average hospital stay was less than 24 hours. When compared with the published TURP values, the PVP values from the 12 case series were favourable in terms of catheterisation time and length of patient hospitalisation. Reoperation rates were similar between PVP and TURP. The two comparator trials confirmed the results for operative outcomes from the 12 case series. There were no significant differences in operating times and reoperation rates between the two treatment groups. However, the PVP group had a significantly shorter duration of catheterisation and hospital stay compared with the TURP group (no P value provided). Functional outcomes assessed in the comparative studies included postvoiding flow, postvoiding residual volume (PVR), IPSS, quality of life score, erectile dysfunction, and prostate specific antigen (PSA) levels. None of these outcomes differed significantly at the first post-discharge follow-up visit between the PVP and TURP treatment groups. In support of these findings, the 12 case series of PVP reported similar functional outcome values as reported for TURP in the literature. Durability of PVP treatment could not be assessed due to the lack of data beyond two years. Two of the case series included patients on anti-coagulants, where TURP is contraindicated. PVP was performed successfully in these cases, with no transfusions required and no reports of thromboembolic or bleeding events. Functional outcomes were similar to those reported for the patients not taking anti-coagulants. Safety The review assessed the following adverse events: acute renal failure, urinary retention, clot retention, haematuria, dysuria, urinary tract infection, incontinence, urethral stricture, bladder neck contracture, bladder stenosis and sexual dysfunction. The pooled complication rates from the 12 case series of PVP, compared with commonly reported TURP values, were either similar or considerably lower (eg, urinary retention 0.9% vs 4.9%; and clot retention 0.4% vs 6.8%). The review did not report the length of follow-up in the case studies. Pooled analyses of the safety outcomes from the two comparative studies were also reported. With the exception of clot retention rates, which significantly favoured PVP treatment over TURP (RR 0.09; 95% CI 0.01, 0.72), none of the estimates were

24 14 statistically significant, which suggests that the risk of complications is similar between PVP and TURP. Randomised comparative studies Eleven papers describing seven RCTs were identified in the literature search (Table 6). None of the abstracts described the setting of the trials. PVP using a KTP laser was compared with TURP in three studies (Bouchier-Hayes et al., 2006; Bouchier-Hayes et al., 2007; Horasanli et al., 2008), holmium laser ablation of the prostate (HoLAP) in one study (Elzayat et al., 2009), and open prostatectomy in two studies (Alivizatos et al., 2008; Skolarikos et al., 2008). Four of the identified studies evaluated the use of hybrid photoselective KTP and Nd:YAG lasers compared with TURP (Carter et al., 1999a; Carter et al., 1999b; Shingleton et al., 1999; Shingleton et al., 2002). One study compared combined KTP bladder neck incision and Nd:YAG endoscopic ablation of the prostate with Nd:YAG ablation alone (Langsley et al., 1997). The study by Elzayat et al. (2009), which compared PVP with HoLAP, is discussed in more detail below. The studies assessing the hybrid KTP/Nd:YAG procedures were published between 1997 and 2002, while the PVP studies using a KTP laser were published from The body of evidence provides conflicting evidence for the efficacy of the hybrid treatment compared with TURP. The efficacy and safety of PVP using a KTP laser appears to be consistently comparable with TURP, and also comparable with OP and HoLAP.

25 15 Table 6: Randomised comparative studies Citation Alivizatos G, Skolarikos A, Chalikopoulos D, Papachristou C, Sopilidis O, Dellis A, Kastriotis I, and Deliveliotis C. (2008) Transurethral photoselective vaporization versus transvesical open enucleation for prostatic adenomas >80 ml: 12-mo results of a randomized prospective study. European Urology 54: Bouchier-Hayes DM, Anderson P, Van Appledorn S, Bugeja P, and Costello AJ. (2006) KTP laser versus transurethral resection: Early results of a randomized trial. Journal of Endourology 20: Bouchier-Hayes DM. (2007) Photoselective vaporization of the prostate - Towards a new standard. Prostate Cancer and Prostatic Diseases 10:S10-S14. Carter A, Sells H, Speakman M, Ewings P, MacDonagh R, and O'Boyle P. (1999a) A prospective randomized controlled trial of hybrid laser treatment or transurethral resection of the prostate, with a 1-year follow-up. BJU International 83: Carter A, Sells H, Speakman M, Ewings P, O'Boyle P, and MacDonagh R. (1999b) Quality of life changes following KTP/Nd:YAG laser treatment of the prostate and TURP. European Urology 36: Elzayat EA, Al Mandil MS, Khalaf I, and Elhilali MM. (2009) Holmium Laser Ablation of the Prostate Versus Photoselective Vaporization of Prostate 60 cc or Less: Short-Term Results of a Prospective Randomized Trial. Journal of Urology 182: Summary PVP (n=65) vs OP (n=60). All patients had prostate glands >80 ml. Follow-up at 1,3,6, and 12 months after treatment. Compared with OP, PVP had longer mean operation time, shorter time of catheterisation, and shorter hospital stay. Adverse events, IPSS, Qmax, PVR, and erectile function were similar between groups. OP scored better on IPSS-QoL score at 6 and 12 months. The authors concluded that PVP is an acceptable alternative to OP. PVP vs TURP. 120 patients randomised but at time of publication only 76 patients evaluable. Follow-up at 1, 3, 6, and 12 months after treatment. Postoperatively, Qmax increased from 8.5 to 20.6 ml/sec for the PVP group and from 8.7 to 17.9 ml/sec for the TURP group. IPSS improved from 25.7 to 12.0 for PVP and 25.4 to 12.4 for TURP. The PVP group had significantly shorter length of catheterisation (12.2 hours [range: 0-24] vs 44.5 hours [range: 6-192]; P <0.001) and length of stay in hospital (1.08 [range: 1-2] vs 3.4 days [range: 3-9]; P <0.0001). Groups had similar trends for bother and QoL. Sexual function did not decrease in either group. Adverse events were less frequent in the PVP group compared with TURP and the costs were 22% less for PVP than TURP. PVP vs TURP. Update of Bouchier-Hayes et al., patients randomised but at time of publication only 87 evaluable. Follow-up at 1, 3, 6, and 12 months after treatment. Qmax increased from 8.5 to 20.6 ml/s for the PVP group and 8.7 to 17.9 ml/s for the TURP group. Mean IPSS in the PVP group improved from 27.2 to 12.2 compared with the an improvement from 24.4 to 11.1 for TURP. PVP had significantly shorter length of catheterisation (13 hours [range: 0-24] vs 44.7 hours [range: 9-192]; P <0.001) and length of stay in hospital (1.09 days [range: 1-2] vs 3.6 days [range: 3-9]; P <0.001). Groups had similar trends for bother and QoL. Sexual function did not decrease in either group. Adverse events were less frequent in the PVP group and the costs were 22% less for PVP than TURP. KTP/Nd:YAG vs TURP. N = 204. Follow-up at 6 weeks, 6 months, and 1 year. Patients receiving TURP showed significantly favourable results at 6 weeks compared with KTP:Nd:YAG for IPSS (12.4 vs 9.1; P =0.001), and Qmax (20.8 ml/s vs 16.1 ml/s; P <0.001). Differences between KTP/ND:YAG and TURP in IPSS and Qmax disappeared by the 6-month and 1-year follow-up. Similar numbers of patients in each group reported bothersome postoperative urinary symptoms (19% PVP vs 23% TURP). Blood transfusions (0% vs 5%) and urethral strictures (2% vs 9%) were less common for KTP/Nd:YAG than TURP. Early infective complications were more common for KTP/Nd:YAG (24% vs 5%). KTP/Nd:YAG vs TURP. N=204. Results from same trial as Carter 1999a. Follow-up at 6 weeks, 6 months and 1 year. Both groups improved in IPSS and BPHII, but there was a significant difference at week 6 in favour of TURP. KTP/ND:YAG group had significantly worse scores in SF-36 bodily pain, social function and emotional role domains compared with TURP. Differences between KTP/ND:YAG and TURP disappeared by the 6-month and 1-year follow up. PVP (n=52) vs HoLAP (n=57). Follow-up at 1, 3, 6 and 12 months. The two laser treatments were found to have comparable safety and efficacy outcomes for the treatment of LUTS secondary to BPH in patients with a small to moderate size prostate. HoLAP, however, requires a longer operating time. Further details of this paper are provided.

26 16 Table 6: Citation Randomised comparative studies (continued) Horasanli K, Silay MS, Altay B, Tanriverdi O, Sarica K, and Miroglu C. (2008) Photoselective Potassium Titanyl Phosphate (KTP) Laser Vaporization Versus Transurethral Resection of the Prostate for Prostates Larger Than 70 ml: A Short-Term Prospective Randomized Trial. Urology 71: Langley SE, Gallegos CR, and Moisey CU. (1997) A prospective randomized trial evaluating endoscopic Nd:YAG laser prostate ablation with or without potassium titanyl phosphate (KTP) laser bladder neck incision. British Journal of Urology 80: Shingleton WB, Terrell F, Renfroe DL, Kolski JM, and Fowler JE. (1999) A randomized prospective study of laser ablation of the prostate versus transurethral resection of the prostate in men with benign prostatic hyperplasia. Urology 54: Shingleton WB, Farabaugh P, and May W. (2002) Three-year follow-up of laser prostatectomy versus transurethral resection of the prostate in men with benign prostatic hyperplasia. Urology 60: Skolarikos A, Papachristou C, Athanasiadis G, Chalikopoulos D, Deliveliotis C, and Alivizatos G. (2008) Eighteen-month results of a randomized prospective study comparing transurethral photoselective vaporization with transvesical open enucleation for prostatic adenomas greater than 80 cc. Journal of Endourology 22: Summary PVP (n=39) vs TURP (n=37). All patients had prostates >70 ml. Follow-up at 3 and 6 months. Baseline characteristics were similar for treatment groups. Mean preoperative TRUS volume was 88±9.2 ml and 86.1±8.8 ml for TURP and PVP groups respectively. The procedure was significantly shorter for TURP vs PVP (51±17.2 vs 87±18.3 minutes; P <0.05). Compared with TURP, the PVP group had significantly shorter catheter removal time (3.9±1.2 vs 1.7±0.8 days; P <0.05) and length of hospital stay (4.8±1.2 vs 2±0.7 days; P <0.05). Compared with PVP, the TURP group had significantly favourable values for IPSS, Qmax, and PVR. Percentage volume reduction was significantly higher in the TURP group. Reoperation was necessary for 7 patients in the PVP group and no patients in the TURP group. The authors concluded that although PVP has advantages over TURP in terms of intraoperative and perioperative safety, TURP is associated with superior early functional results for patients with prostates >70 ml. KTP BNI + ELAP vs ELAP. N=88. Follow-up at 3 months. Postoperatively, 80% of the KTP BNI + ELAP group were able to void on catheter removal at 18 hours, compared with 57% for the ELAP group (P <0.05). At 1 month, 2 KTP BNI + ELAP and 4 ELAP patients failed to void and required surgery. Both groups improved in PVR, Qmax, symptom and QoL scores at 3 months compared with pretreatment (P <0.005). The KTP BNI + ELAP group showed greater improvement in flow rate and symptom score compared with the ELAP group (P <0.05). KTP/Nd:YAG (n=50) vs TURP (n=50). Follow up at 1, 3, 6, and 12 months and every 12 months thereafter. From pretreatment to the 12-month follow-up, AUA symptom score improved from 22 to 7 for the KTP/Nd:YAG group and from 21 to 3 for the TURP group. Over the same period Qmax increased from 7.6±3.4 to 15.4 ml/s for the KTP/Nd:YAG group and from 6.5±4.0 to 16.7 ml/s for the TURP group. The authors concluded that KTP/Nd:YAG produces similar improvements in Qmax and symptom score as TURP. KTP/Nd:YAG (n=50) vs TURP (n=50). Update of Shingleton et al., Follow up at 1, 3, 6, and 12 months and every 12 months thereafter. At 3 years of follow-up, mean symptom score decreased from 22.0 to 9.9 for the KTP/Nd:YAG group and 21.2 to 7.7 for the TURP group. Qmax increased from 8.2 pretreatment to 12.3 ml/s at 3 years for the KTP/Nd:YAG group and from 7.3 to 12.8 ml/s for TURP. At 3 years the TRUS volume decreased from 33.9 to 32.9 cm 3 for KTP/Nd:YAG and from 29.6 to 26.3 cm 3 for TURP. The authors concluded that at three-years of follow-up, the durability of results for patients treated with KTP/Nd:YAG were similar to that of TURP. PVP (n=65) vs OP (n=60). Update of Alivizatos et al., All patients had prostate glands >80 ml. Follow-up at 1, 3, 6, 12, and 18 months. The PVP group had longer operative time, shorter duration of catheterisation, and shorter hospital stay compared with OP. The OP group had higher rates of transfusion; however, adverse events in general were minor and similar between intervention groups. All functional outcomes improved significantly compared with baseline for both treatment groups. There was no difference in IPSS between PVP and OP at 3, 6, 12, and 18 months of follow-up. The OP group scored better in IPSS-QoL score at 18 months. At 18 month of follow-up there was no significant difference between the two groups in Qmax, PVR, and erectile function. At all follow-up assessments the OP group had significantly lower prostate volume than the PVP group. Abbreviations: AUA = American Urological Association; BNI = bladder neck incision; BPHII = BPH impact index; ELAP = Nd:YAG endoscopic ablation of the prostate; HoLAP = holmium laser ablation of the prostate; IPSS = International Prostate Symptom Score; KTP = potassium titanyl phosphate laser; Nd:YAG = neodymium: yttrium-aluminium-garnet laser; PVP = photoselective vaporisation of the prostate; PVR = postvoid urine residues; Qmax = maximum flow rate; QoL = quality of life; OP = open prostatectomy; TRUS = transrectal ultrasound; TURP = transurethral resection of the prostate.

27 17 Elzayat 2009 The objective of the Elzayat et al. (2009) trial was to compare the safety and efficacy of PVP compared with HoLAP. Patients were eligible for inclusion in this Canadian study if the following criteria were met: presence of lower urinary tract symptoms secondary to BPH with an IPSS of 9 or greater, total prostate volume 60 cc or less as estimated by transrectal ultrasound (TRUS) of the prostate, TRUS biopsy performed when necessary and maximum flow rate (Qmax) less than 15 ml per second. The study included 109 consecutive patients who were randomised to receive either PVP (n=52) or HoLAP (n=57) treatment. Baseline characteristics were similar between treatment groups. The patients were blinded to the laser procedure as were the nurses performing the uroflow studies and bladder scan and the ultrasonagrapher. The study coordinator informed the surgeon of the laser type to be used for each patient after the patient entered the operating room. All of the procedures were performed or supervised by the same surgeon, a recognised expert in holmium laser therapy. The patients in both treatment groups underwent either general or regional anaesthesias. A catheter was inserted after each procedure unless the degree of haematuria required bladder irrigation. The catheter would be removed the morning after surgery, and the patient was discharged from the hospital after voiding. Patients were recatheterised if the patient was unable to void, had significant painful micturition or had a high PVR. Patients were assessed postoperatively and during follow-up at 1, 3, 6 and 12 months. The voiding parameters assessed were IPSS, uroflowmetry and PVR. Other outcomes assessed included degree of dysuria or painful micturition (measured by the dysuria analogue scale), sexual function (IIEF-15), serum PSA, and size of prostate (assessed via TRUS sizing). The operating time was significantly longer for HoLAP treatment compared with PVP (HoLAP vs PVP [mean ± SD]; 69.8 ± 31.6 vs 55.5 ± 21; P = 0.008). HoLAP catheterisation time was non-significantly longer than the time for PVP (2.1 ± 2.7 vs 1.65 ± 1.6). There was no significant difference in hospitalisation between the two treatment groups (PVP vs HoLAP; 0.96 ± 0.27 days vs 0.87 ± 0.3 days). The two groups had similar rates of intraoperative and postoperative complications. For Holap vs PVP, urethral stricture rates were 1.7% (n=1) vs 5.7% (n=3; P = 0.34), bladder neck contractures were 3.5% (n=2) vs 7.7% (n=4; P = 0.42), and reoperation rates were 3.5% (n=2) vs 1.9% (n=1; P = 0.39). Both treatment groups had significant improvements in voiding parameters postoperatively and at subsequent follow-ups (Table 7). There were no significant differences in any of the voiding parameters between the treatment groups either preoperatively or at any of the follow-up assessments. Mean (± SD) IPSS improved from 20 ± 6.8 to 6.2 ± 3.9 for HoLAP, and 18.4 ± 6.6 to 8.2 ± 6.2 for PVP. Qmax increased from 6.7 ± 3.9 to 17.2 ± 8 ml/sec for HoLAP and 6.4 ± 3.9 to 18.4 ± 8.4 ml/sec for PVP. The authors concluded that HoLAP and PVP are comparable with regard to safety and efficacy for the treatment of LUTS secondary to BPH in patients with a small to moderate size prostate. Both procedures are easy to learn but HoLAP requires a longer operating time.