Abstract
Background
Symptomatic benign prostatic obstruction is a common problem for older men. The gold standard treatment, transurethral resection of the prostate (TURP), significantly improves urinary symptoms and urinary flow. However, TURP has up to a 20% morbidity. Currently, there are a number of minimally invasive procedures that may be safe, effective alternatives to TURP. One promising surgical technique is laser prostatectomy.
Objectives
To assess the therapeutic efficacy and safety of laser prostatectomy techniques for treating men with symptomatic benign prostatic obstruction.
Search methods
Randomized controlled trials were identified from the Cochrane Collaboration Library, MEDLINE, EMBASE, bibliographies of retrieved articles and reviews, and contacting expert relevant trialists and laser manufacturers.
Selection criteria
All randomized controlled trials evaluating laser prostatectomy treatment for men with symptomatic BPH. Trials were eligible if they (1) were randomized comparisons of a laser technique with TURP, (2) included at least 10 men with BPO in each treatment arm, (3) provided at least 6‐months follow‐up, and (4) included clinical outcomes such as urologic symptom scales or urodynamic measurements.
Data collection and analysis
Data extraction and assessment of methodologic quality was performed independently by two reviewers. Information on study design, subject and treatment characteristics, adverse events, urinary symptoms, and urinary flow were extracted using a standard form.
Main results
Twenty studies involving 1898 subjects were evaluated, including 4 studies with multiple comparisons. We found eight comparisons of TURP with contact lasers, eight with non‐contact lasers, four with hybrid techniques, and one with interstitial laser coagulation (ILC). Two studies compared transurethral electrovaporization (TUVP) with contact lasers, one study compared interstitial laser coagulation with transurethral microwave thermotherapy (TUMT), and one study compared holmium contact lasers (HoLRP) with open prostatectomy. Among the studies comparing laser prostatectomy with TURP, follow‐up duration ranged from 6 to 36 months. Mean age (67.2 yrs), mean baseline symptom score (20.2), and mean baseline peak urinary flow (9.2 mL/s) did not differ by treatment group. The pooled percentage improvements for mean urinary symptoms ranged from 59% to 68% with lasers and 63% to 77% with TURP. The improvements for mean peak urinary flow ranged from 56% to 119% with lasers and 96% to 127% with TURP. Overall, laser subjects were less likely to receive transfusions or develop strictures and their hospitalizations were shorter. Non‐contact laser subjects were more likely to have dysuria, urinary tract infection, and retention. Re‐operation occurred more often following laser procedures.
Authors' conclusions
Laser techniques are a useful alternative to TURP for treating BPO. Small sample sizes and differences in study design limit any definitive conclusions regarding the preferred type of laser technique. Data were insufficient to compare laser techniques with other minimally invasive procedures.
Plain language summary
Laser prostatectomy for benign prostatic obstruction
Bothersome lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO) is a common problem for older men. LUTS can be both irritative (urgency, frequency, frequent nighttime urinations) and obstructive (weak stream, hesitancy, intermittency, and feeling the bladder is not emptied). Transurethral resection of the prostate (TURP) is considered the gold standard treatment for symptomatic BPO. TURP improves urinary symptoms and urinary flow by surgically removing prostatic tissue through the urethra. However, side effects occurring in approximately 20% of all TURPs include blood loss requiring transfusion, infections, strictures, sexual dysfunction, urinary incontinence, and urinary retention. Laser prostatectomy, which uses a laser to destroy the enlarged prostate tissue that leads to LUTS, is a minimally invasive procedure currently used as an alternative to TURP. This review of 20 studies involving 1898 subjects found laser techniques to be useful and relatively safe alternatives to TURP. The small number of enrolled subjects and differences in study design limit any definitive conclusions regarding which type of laser technique is the most effective. Improvements in LUTS and urine flow slightly favored TURP, though laser procedures had fewer side effects and shorter hospitalization times. The follow‐up durations of these studies ranged from 6 to 36 months and men with extremely large prostates were generally excluded from the trials. The risk of needing a reoperation for recurrent LUTS was higher following laser procedures. Study results were insufficient to adequately compare laser techniques with other minimally invasive procedures. More studies, using randomized treatment assignment, enrolling larger numbers of subjects, and comprehensive measures of treatment effectiveness and side events, are needed to better define the long‐term safety and durability of laser techniques for treating LUTS associated BPO.
Background
Lower urinary tract symptoms (LUTS) consistent with benign prostatic obstruction (BPO) become increasingly prevalent with age. LUTS can be both irritative (urgency, frequency, nocturia) and obstructive (weak stream, hesitancy, intermittency, and incomplete emptying). By age 80, an estimated one in four men will have undergone treatment to relieve LUTS related to BPH (Barry 1990). For many years, the transurethral resection of the prostate (TURP) has been the definitive treatment for BPO. Approximately 400,000 procedures are performed annually at a total cost of $5 billion (Oesterling 1995). Although TURP has been proven to reduce symptoms of BPO and increase urinary flow compared with watchful waiting (Wasson 1995), the procedure has some limitations. The morbidity of TURP is nearly 20%, including blood loss requiring transfusion, infections, strictures, sexual dysfunction, urinary incontinence, urinary retention, and the development of the transurethral resection syndrome (Oesterling 1995; McConnell 1994; AUA 2003). Furthermore, up to 25% of patients undergoing TURP do not have satisfactory results (Lepor, 1990), and the reoperation rates is about 1% to 2% annually (Wasson 1995; Roos 1998).
In recent years a number of minimally invasive surgical techniques have been developed for treating BPH, including transurethral incision of the prostate, prostatic stents, microwave therapy, and laser prostatectomy (Lepor 1996; Jepsen 1998; Tewari 1999; Oesterling 1995). The laser techniques include visual laser ablation of the prostate, contact laser ablation, interstitial laser, transurethral evaporation of the prostate, and transurethral ultrasonic laser incision. There has been considerable interest in laser prostatectomies because preliminary data suggest that they are effective and safe treatments for BPO. Compared to TURP, laser procedures have been reported to have fewer complications, require shorter hospitalizations, and can be performed on outpatients (Oesterling 1995). However, the different laser techniques may not be comparable in efficacy, comparisons with other minimally invasive procedures are limited, and few long‐term follow‐up data are available. Finally, no systematic reviews and quantitative meta‐analyses of these techniques have been published to evaluate safety and efficacy. Primary care physicians are increasingly becoming responsible for managing symptomatic BPO patients with behavioral and drug therapies. However, when patients are considering surgical interventions, primary care physicians should also be able to inform them of the risks and benefits of the various procedures.
Objectives
Our objective was to conduct a systematic review and, where possible, quantitative meta‐analysis, of randomized controlled trials to evaluate the efficacy and safety of laser prostatectomy techniques compared to TURP in treating men with symptomatic BPO.
Methods
Criteria for considering studies for this review
Types of studies
Randomized controlled trials of at least 6 months duration with or without blinding.
Types of participants
Men with symptomatic BPO as determined by urinary symptoms or scale scores with or without documented decreased urinary flow rates.
Types of interventions
Laser prostatectomy techniques reviewed included visual laser ablation of the prostate (VLAP), contact laser ablation, interstitial laser, and transurethral ultrasonic laser incision (TULIP), and transurethral evaporation of the prostate. Control interventions could include transurethral resection of the prostate (TURP), open prostatectomy, transurethral incision of the prostate (TUIP), transurethral electrovaporization of the prostate (TUVP), pharmacologic therapy, watchful waiting, electrovaporization of the prostate, prostate stents, radiofrequency transurethral needle ablation, microwave therapies, or high‐intensity focused ultrasound.
Types of outcome measures
The primary clinical outcome was the efficacy of laser prostatectomy in improving urinary tract symptoms based on changes in urologic symptom scale scores (American Urologic Association (AUA) Symptom Index, International Prostate Symptom Score (IPSS), Madsen‐Iversen, Boyarsky). Secondary outcomes included changes in peak and mean urinary flow. Data were recorded for 6‐ and/or 12‐month follow‐up periods. We also extracted data on operative time, hospital length of stay, catheter duration, the need for re‐hospitalization or re‐operation, adverse events, and perioperative mortality.
Search methods for identification of studies
We searched MEDLINE from 1966 through June 2002 using an optimally sensitive search strategy from the Cochrane Collaboration with the MeSH headings: prostatic hypertrophy, prostatectomy, prostatic hyperplasia/surgery, laser surgery, TULIP, and ELAP (Dickersin 1994). We also searched the Cochrane Library, the Prostatic Diseases and Urologic Cancers Group registry, Science Citation Index, and reference lists of all identified trials and previous reviews. The Journal of Urology and Urology were hand‐searched from 1998 through June 2002. There were no language restrictions.
Data collection and analysis
Titles and abstracts of the electronic search results were evaluated by two independent reviewers. From the results of the electronic searches, bibliography searches, hand searches, and contacts with experts and manufacturers, two reviewers independently selected trials meeting previously defined inclusion criteria. Trials selected by at least one reviewer were retrieved. Two reviewers independently abstracted study characteristics and outcomes, including information on study design, subject characteristics, interventions, follow up, treatment outcomes, and adverse events. Differences were resolved by discussion among the reviewers or using an independent arbitrator. Reasons for study exclusion were documented.
Methodologic quality was assessed based on selection bias (randomization strategies), performance bias (whether those receiving care were blinded), detection bias (whether outcomes assessors were blinded to assigned therapy), attrition bias (systematic differences between groups in losses to follow‐up), clinical description of study subjects, baseline comparison of study groups, duration of follow‐up, discussion of co‐interventions, completeness of efficacy and morbidity data. As a measure of overall methodologic study quality we will assess the quality of concealment of treatment allocation according to a scale developed by Schulz (Schulz 1995) assigning 1 to poorest quality and 3 to best quality: 1= trials in which concealment was inadequate (e.g. such as alternation or reference to case record numbers or to dates of birth); 2 = trials in which the authors either did not report an allocation concealment approach at all or reported an approach that did not fall into one of the other categories; and 3 = trials deemed to have taken adequate measures to conceal allocation (e.g. central randomization; numbered or coded bottles or containers; drugs prepared by the pharmacy; serially numbered, opaque, sealed envelopes etc. that contained elements convincing of concealment).
Statistical methods: We analyzed available efficacy outcomes data on intention‐to‐treat basis using the Cochrane Collaboration Review Manager (RevMan 4.1) software. We calculated weighted mean differences (WMD), the between‐treatment difference in pooled means for outcome variables at follow‐up or the pooled mean change in outcome variables between baseline and follow‐up, and the 95% confidence intervals for continuous variables. A random effects model was used to allow for heterogeneity between the trials (DerSimonian 1986). Continuous variables were also evaluated by comparing differences in pooled mean scores (weighted for sample size) between baseline and follow‐up measurements. We evaluated categorical events by calculating weighted relative risks and their 95% confidence intervals. The Fisher's exact test was used when cell sizes were less than 5.
Results
Description of studies
The combined search strategies identified 46 reports of trials and 20? met our inclusion criteria.
LASER versus TURP (n = 18 trials) Overall, we analyzed 19 comparisons between laser techniques and TURP because two trials each evaluated multiple laser techniques (Suvakovic 1996; Zorn 1999). We found eight comparisons of TURP with non‐contact laser (Anson 1995; Costello 1995; Cowles 1995; Donovan 2000; Gujral 2000; Kabalin 1995; Sengor 1996; Suvakovic 1996), eight comparisons with contact laser (Gilling 1999; Keoghane 2000a; Mottet 1999; Shingleton 1999; Suvakovic 1996; Tuhkanen 1999a; van Melick 2003; Zorn 1999) and four comparisons with hybrid techniques (Carter 1999a; Suvakovic 1996; Tuhkanen 1999b; Zorn 1999). Two studies used holmium laser resection of the prostate (HoLRP) (Gilling 1999; Mottet 1999), the rest used neodymium yttrium‐argon‐garnet (Nd:YAG) lasers.
LASER versus Transurethral Electrovaporization (TUVP) (n = 2 trials) We evaluated two comparisons of contact laser with transurethral electrovaporization (Shingleton 1999; van Melick 2002; van Melick 2003).
LASER versus Open Prostatectomy (n = 1 trial) We evaluated one comparison between HoLRP and open prostatectomy for treatment of prostates > 100 gm (Kuntz 2002).
LASER versus Transurethral Microwave Thermotherapy (TUMT) (n = 1 trial) We evaluated one comparison between interstitial laser coagulation and TUMT prostates > 100 gm (Norby 2002).
We excluded studies that did not present outcomes at 6 or 12 months following treatment or that reported only economic or quality‐of‐life outcomes data (Carter 1999b; Fraundorfer 2001; Gilling 2000; Keoghane 1996; Keoghane 2000b; McAllister 2000; Shingleton 2002; Tuhakanen 2001). We also excluded studies with less than 6 months follow up (Langley 1997), those comparing different laser regimens (high vs. low power) or techniques (coagulation or evaporation) without a sham or active control (TURP) treatment arm (Albert 1997; Beerlage 1998; Boon 1995; Breteau 1997; Bryan 1999; de la Rosette 1995; Narayan 1995; Orihuela 1995), and those providing no indication of randomization or non‐randomized controlled clinical trials (Ichiyanagi 1997; Jung 1996; Kaplan 1995; Kollmorgen 1996; Matsuoka 2000; Schatzl 1997; Wada 2000).
Risk of bias in included studies
Treatment allocation concealment was adequate in seven studies (Anson 1995; Carter 1999a; Cowles 1995; Donovan 2000; Gujral 2000; Keoghane 2000a; van Melick 2003) and outcomes assessors were blinded to treatment allocation in one study (Keoghane 2000a). Nine studies reported excluding subjects in urinary retention (variably defined by a post‐void residual ranging from 250 mL to 300 mL or history of being unable to void) (Carter 1999a; Costello 1995; Cowles 1995; Donovan 2000; Gilling 1999; Mottet 1999; Sengor 1996; Tuhkanen 1999a; Tuhkanen 1999b). Ten studies provided 12 or more months of follow up. The overall proportion of subjects available for follow‐up ranged from 53% to 97% in studies with at 12 months of follow up and 89% to 99% in studies with less than 12 months of follow up.
Effects of interventions
LASER vs. Transurethral Resection of the Prostate (TURP) A total of 1488 participants were randomized in the 16 trials, including 733 to TURP, 374 to non‐contact laser techniques, 244 to contact laser techniques, and 137 to hybrid laser techniques. The mean age, (67.4 years, range 61 to 70.6 years), mean baseline symptom score (20.2, range 15.7 to 24.7), and the mean baseline peak urinary flow (9.5 mL/s, range 6.2 to 12.2 mL/s) did not differ by treatment group.
Operative time, hospital length‐of‐stay, catheter duration, and treatment failure data are shown in Table 1, Table 2, Table 3, and Table 4. Non‐contact laser procedures consistently took less time than TURP, ranging from 13 to 43 minutes compared to 20 to 58 minutes (Cowles 1995; Kabalin 1995; Sengor 1996). Contact and hybrid procedures took similar or longer amounts of time than TURP, ranging from 19 to 88 minutes compared to 20 to 106 minutes for TURP. Hospital length of stay, reported by 10 studies, was significantly less following laser treatment, with differences ranging from 1 to 2 days. No study reported a shorter hospital length of stay with TURP. Duration of urinary catheter placement was significantly shorter following TURP in three non‐contact studies [Anson 1995; Donovan 2000; Gujral 2000], one contact study [Tuhkanen 1999a], and one hybrid study (Tuhkanen 1999b), with differences ranging from 10 hours to 22.5 days. The duration of urinary catheter placement was significantly shorter following laser techniques in one non‐contact study (Suvakovic 1996), four contact studies (Gilling 1999; Keoghane 2000a; Suvakovic 1996; Zorn 1999), and one hybrid study (Zorn 1999). Treatment failure leading to re‐operation was more likely following laser techniques (28/528) than TURP (5/537), relative risk (RR) = 5.7, 95% CI, 2.2 to 14.6.
1. Laser vs. TURP: Operating Time (minutes).
| Study | Laser | TURP | p‐value |
| Anson | NA | NA | |
| Costello | NA | NA | |
| Cowles | 23.4 | 45.2 | < 0.01 |
| Donovan | NA | NA | |
| Gujral | NA | NA | |
| Kabalin | 24.2 | 58.3 | NA |
| Sengor | 43 | 56 | NA |
| Suvakovic (Non‐Contact) | 12.5 | 20.1 | NS |
| Gilling | 26 | 106 | < 0.001 |
| Mottet | 75 | 40 | < 0.04 |
| Keoghane | 36 | 39 | NS |
| Shingleton | NA | NA | |
| Suvakovic (Contact) | 18.9 | 20.1 | NS |
| Tukhanen (Contact) | 51 | 34 | < 0.01 |
| Zorn (Contact) | 70 | 68 | NS |
| Carter | 37.4 | 35.7 | NS |
| Suvakovic (Hybrid) | 13.1 | 20.1 | NS |
| Tukhanen (Hybrid) | 75 | 44 | < 0.001 |
| Zorn (Hybrid) | 88 | 68 | < 0.05 |
2. Laser vs. TURP: Hospital lenght of stay (days).
| Study | Laser | TURP | p‐value |
| Anson | 2.7 | 4.3 | < 0.05 |
| Costello | 6.2 | 5.8 | NA |
| Cowles | 1.8 | 3.1 | < 0.01 |
| Donovan | 2.2 | 3.9 | < 0.0001 |
| Gujral | 2.2 | 4.4 | < 0.0001 |
| Kabalin | NA | NA | |
| Sengor | 1.6 | 5.9 | NA |
| Suvakovic (Non‐contact) | 1.3 | 3.5 | < 0.05 |
| Gilling | 1.1 | 2.0 | < 0.001 |
| Mottet | 1.6 | 3.1 | NA |
| Keoghane | 3 | 4 | < 0.005 |
| Shingleton | NA | NA | |
| Suvakovic (Contact) | 1.3 | 3.5 | < 0.05 |
| Tukhanen (Contact) | 3.4 | 2.9 | NS |
| Zorn (Contact) | 1.2 | 2.5 | < 0.05 |
| Carter | 2.7 | 3.7 | NA |
| Suvakovic (Hybrid) | 1.0 | 5.8 | < 0.05 |
| Tukhanen (Hybrid) | 4 | 3.5 | NS |
| Zorn (Hybrid) | 1.4 | 2.5 | < 0.05 |
3. Laser vs. TURP: Catheter duration (days).
| Study | Laser | TURP | p‐value |
| Anson | 14.7 | 2.7 | < 0.05 |
| Costello | 2.2 | NA | |
| Cowles | NA | NA | |
| Donovan | 11.8 | 2.4 | < 0.0001 |
| Gujral | 25.5 | 3 | < 0.0001 |
| Kabalin | 4.7 | 2.7 | NA |
| Sengor | 4.8 | 3.8 | NA |
| Suvakovic (Non‐contact) | 1.0 | 2.0 | < 0.05 |
| Gilling | 0.8 | 1.6 | < 0.001 |
| Mottet | 2.2 | 2.1 | NA |
| Keoghane | 1 | 2 | < 0.001 |
| Shingleton | NA | NA | |
| Suvakovic (Contact) | 1.0 | 2.0 | < 0.01 |
| Tukhanen (Contact) | 4.3 | 1.7 | <0.01 |
| Zorn (Contact) | 1.1 | 1.7 | <0.05 |
| Carter | 2 | 2 | NS |
| Suvakovic (Hybrid) | 0.8 | 2.0 | < 0.05 |
| Tukhanen (Hybrid) | 10.6 | 2.2 | < 0.01 |
| Zorn (Hybrid) | 1.3 | 1.7 | < 0.05 |
4. Laser vs. TURP: Re‐operations (%).
| Study | Laser | TURP | p‐value |
| Anson | 7.5 | 0 | < 0.02 |
| Costello | 12.5 | 0 | NS |
| Cowles | 10.9 | 0 | < 0.01 |
| Donovan | NA | NA | |
| Gujral | 8.3 | 0 | NS |
| Kabalin | 20.0 | 0 | NS |
| Sengor | NA | NA | |
| Suvakovic (Non‐contact) | NA | NA | |
| Gilling | 1.9 | 8.2 | NS |
| Mottet | 8.3 | 0 | NS |
| Keoghane | 11.3 | 0 | < 0.01 |
| Shingleton | NA | NA | |
| Suvakovic (Contact) | NA | NA | |
| Tukhanen (Contact) | 0 | 0 | NS |
| Zorn | 0 | 0 | NS |
| Carter | 2.4 | 1.2 | NS |
| Suvakovic (Hybrid) | NA | NA | |
| Tukhanen (Hybrid) | 0 | 0 | NS |
| Zorn (Hybrid) | 0 | 0 | NS |
Outcomes: All studies found significant decreases in urinary symptoms and significant increases in peak urinary flow between baseline and follow‐up for both TURP and laser techniques (Table 5; Table 6).
5. Laser vs. TURP Baseline and Follow‐up Urinary Symptom Scores (points).
| Study | Mean baseline score | Mean follow‐up/ 6 mo | Mean follow‐up/ 1 yr |
| Anson Laser TURP | AUA 6 18.1 18.2 | 7.9 5.9 (p = NS) | 7.7 5.1 (p = 0.046) |
| Costello Laser TURP | AUA 7 NA NA | 9.3 4.4 (p = 0.01) | NA NA |
| Cowles Laser TURP | AUA 6 18.7 (6.0) [SD] 20.8 (4.8) | NA NA | 9.7 7.5 (p < 0.04) |
| Donovan Laser TURP | IPSS 19.1 (6.6) 19.2 (6.7 | 7.5 months 8.3 6.9 (p = NS) | NA NA |
| Gujral Laser TURP | IPSS 20.9 (6.4) 19.5 (7.2) | 7.5 months 8.7 5.3 (p = 0.048) | NA NA |
| Kabalin Laser TURP | AUA 7 20.9 (1.9) [SE] 18.8 (1.8) | 4.6 (0.7) 5.7 (1.2) (p = NS) | 4.3 (1.7) 6.3 (1.3) |
| Sengor Laser TURP | AUA 7 15.7 (5.1) 18.8 (4.5) | 8.0 (5.7) 8.5 (3.0) (p = NS) | NA NA |
| Suvakovic (Non‐contact) Laser TURP | AUA 7 15.7 (5.1) 18.8 (4.5) | 8.0 (5.7) 8.5 (3.0) | 10.0 (4.9) 7.2 (6.1) (p = NS) |
| Gilling Laser TURP | AUA 7 21.9 (6.2) 23.0 (5.9) | 3.8 (3.8) 5.0 (4.5) (p=NS) | 4.2 (6.0) 4.3 (4.1) (p=NS) |
| Mottet Laser TURP | IPSS 20.0 23.7 | 6.2 7.7 (p = NS) | 5.9 4.7 (p = NS) |
| Keoghane Laser TURP | AUA 7 19.9 (7.7) 19.4 (6.5) | NA NA | 8.7 (6.5) 5.8 (5.4) (p = 0.006) |
| Shingleton Laser TURP | AUA 7 22.0 (6.0) 21.0 (6.0) | 7 4 (p = 0.01) | 7 3 (p=0.01) |
| Suvakovic (Contact) Laser TURP | AUA 7 18.0 (6.0) 18.8 (4.5) | 8.7 (5.4) 8.5 (3.0) (p = NS) | 8.7 (4.9) 7.2 (6.1) (p = NS) |
| Tukhanen (Contact) Laser TURP | DanPSS‐1 20.0 (11.0) 21.0 (11.0) | 6.0 (9.0) 5.0 (7.0) (p = NS) | NA NA |
| Zorn (Contact) Laser TURP | AUA 7 24.0 24.7 | 9.1 8.3 (p = NS) | 8.4 4.7 (p < 0.05) |
| Carter Laser TURP | IPSS 20.3 19.8 | 6.7 6.4 (p = NS) | 6.6 5.9 (p = NS) |
| Suvakovic (Hybrid) Laser TURP | AUA 7 17.0 (6.0) 19.0 (0.8) | 7.4 (4.3) 8.5 (3.0) (p = NS) | NA NA |
| Tukhanen (Hybrid) Laser TURP | DanPSS‐1 18.6 23.3 | 5.5 4.7 (p = NS) | NA NA |
| Zorn (Hybrid) Laser TURP | AUA 7 24.2 24.7 | 8.3 8.2 | 13.7 4.7 (p < 0.05) |
6. Laser vs. TURP Baseline and Follow‐up Peak Urinary Flow rate (mL/s).
| Study | Mean baseline score | Mean follow‐up/ 6 mo | Mean follow‐up/ 1 yr |
| Anson Laser TURP | 9.5 10.0 | 15.6 19.9 (p = 0.037) | 15.4 21.8 (p = 0.009) |
| Costello Laser TURP | 8.8 9.5 | 15.8 19.1 (p = NS) | NA NA |
| Cowles Laser TURP | 8.9 (3.6) [SD] 9.5 (3.2) | NA NA | 14.2 16.5 (p = NS) |
| Donovan Laser TURP | 10.4 (2.9) 10.3 (2.7) | 7.5 months 16.2 20.0 (p < 0.05) | NA NA |
| Gujral Laser TURP | 11.2 (5.3) 8.5 (3.6) | 7.5 months 16.9 17.0 (p = NS) | NA NA |
| Kabalin Laser TURP | 8.5 (1.1) [SE] 9.0 (1.1) | 20.5 (1.8) 22.9 (2.8) | 21.6 (1.5) 21.6 (2.2) |
| Sengor Laser TURP | 8.7 (2.3) 8.4 (2.8) | 18.2 (2.1) 19.8 (2.5) | NA NA |
| Suvakovic (Non‐contact) Laser TURP | 10.5 (3.7) 11.1 (6.4) | 16.2 (4.2) 19.0 (0.8) (p = NS) | 12.6 (3.7) 15.2 (2.7) (p = NS) |
| Gilling Laser TURP | 8.9 (3.0) 9.1 (3.2) | 23.9 (8.7) 22.4 (9.0) (p = NS) | 25.2 (11.9) 20.4 (8.5) (p = NS) |
| Mottet Laser TURP | 8.5 7.7 | 17.5 16.6 (p = NS) | 19.3 17.6 (p = NS) |
| Keoghane Laser TURP | 11.8 (4.5) 11.4 (5.0) | NA NA | 17.1 (13.2) 21.2 (12.4) (p = NS) |
| Shingleton Laser TURP | 7.6 (3.4) 6.5 (4.0) | 15.8 (6.9) 16.3 (6.4) (p = NS) | 15.4 (4.9) 16.7 (7.6) (p = NS) |
| Suvakovic (Contact) Laser TURP | 12.2 (3.8) 11.1 (6.4) | 18.7 (7.5) 19.0 (8.0 (p = NS) | 25.3 (5.9) 15.2 (2.7) (p = NS) |
| Tukhanen (Contact) Laser TURP | 9.0 (3.8) 8.2 (3.2) | 17.9 (7.1) 21.1 (9.7) (p = NS) | NA NA |
| Zorn (Contact) Laser TURP | 8.7 9.0 | 20.0 23.1 (p = NS) | 20.0 26.9 (p = NS) |
| Carter Laser TURP | 9.5 10.0 | 18.5 19.0 (p = NS) | 18.0 19.5 (p = NS) |
| Suvakovic (Hybrid) Laser TURP | 11.8 (4.1) 11.1 (6.4) | 19.4 (3.4) 19.0 (0.8) | NA NA |
| Tukhanen (Hybrid) Laser TURP | 8.5 7.2 | 14.4 19.6 (p = NS) | NA NA |
| Zorn (Hybrid) Laser TURP | 6.2 9.0 | 28.2 23.1 (p = NS) | 20.5 26.9 |
Non‐contact lasers versus TURP Non‐contact lasers provided similar improvement in LUTS in comparison to TURP. The pooled mean symptom score for men undergoing non‐contact laser techniques decreased 59% by 12 months (19 to 7.7) versus 63% (19.3 to 7.1) in the men undergoing TURP. Weighted mean differences between treatments varied depending upon whether studies reported mean changes or mean values at follow up. The WMD for 3 studies reporting mean changes in urinary symptom scores was ‐ 2.47 points (95% CI, ‐4.24 to ‐0.70) significantly favoring TURP (Cowles 1995; Donovan 2000; Gujral 2000) (figure 01.01). For the 4 studies reporting only the mean urinary symptom scores at follow‐up, and the WMD was 0.21 (95% CI, ‐2.28, 2.70) favoring laser [Anson 1995; Kabalin 1995; Sengor 1996; Suvakovic 1996] (Analysis 1.2). TURP led to greater improvement in urinary flow in three comparisons with non‐contact laser, ranging from 1.6 mL to 6.4 mL/s higher at follow up (Anson 1995; Donovan 2000; Sengor 1996). The pooled mean peak urinary flow for men undergoing non‐contact laser techniques increased 56% (10.1 to 15.8 mL/s) versus 96% (9.8 mL to 19.2 mL/s) in men undergoing TURP. Three studies reported mean changes in peak urinary flow, the WMD was 3.18 mL/s (95% CI, 1.47 to 4.89) significantly favoring TURP (Cowles 1995; Donovan 2000; Gujral 2000) (Analysis 1.3). Four other studies reported mean peak urinary flow data at follow‐up, the WMD was 2.64 (95% CI, 0.53 to 4.75) favoring TURP (Anson 1995; Kabalin 1995; Sengor 1996; Suvakovic 1996) (Analysis 1.4).
1.2. Analysis.
Comparison 1 Non‐contact Laser versus TURP, Outcome 2 AUA Symptom Score:.
1.3. Analysis.
Comparison 1 Non‐contact Laser versus TURP, Outcome 3 Mean Change ‐ Peak Urine Flow (mL/s): > 6 months follow‐up.
1.4. Analysis.
Comparison 1 Non‐contact Laser versus TURP, Outcome 4 Peak Urine Flow (mL/s).
Contact lasers versus TURP We evaluated Nd:YAG and HoLRP separately because of their different tissue effects; NdYAG lasers vaporize tissue while HoLRP lasers vaporize and excise tissue. In three comparisons with Nd:YAG lasers, TURP led to greater improvement in symptoms, ranging from 2.9 to 4.0 points lower at follow up (Keoghane 2000a; Shingleton 1999; Suvakovic 1996; Tuhkanen 1999b; van Melick 2003; Zorn 1999). The pooled mean symptom score for men undergoing Nd:YAG contact laser treatments decreased 66% by 12 months (22.4 to 7.7) versus 78% (20.5 to 4.5) for men undergoing TURP (Keoghane 2000a; Shingleton 1999; Suvakovic 1996; Tuhkanen 1999b; van Melick 2003; Zorn 1999). Three Nd:YAG studies reported mean urinary symptom scores at follow‐up, the weighted mean difference for Nd:YAG contact lasers versus TURP was ‐2.08 points (95% CI, ‐4.51 to 0.36) favoring TURP (Keoghane 2000a; Suvakovic 1996; van Melick 2003) (Analysis 2.1). There were no differences in symptom scores between men treated with HoLRP versus TURP. The pooled mean symptom score for men undergoing HoLRP laser treatments decreased by 79% (21.4 to 4.5) versus 81% (23.1 to 4.4) for men undergoing TURP (Gilling 1999; Mottet 1999). The weighted mean difference for HoLRP versus TURP was 0.10 points (95% CI, ‐1.88 to 2.08), favoring laser (Gilling 1999) (Analysis 2.1).
2.1. Analysis.
Comparison 2 Contact Laser versus TURP, Outcome 1 AUA (IPSS) Symptom Score:.
None of the Nd:YAG laser studies found statistically significant differences between treatments in improving peak urinary flow. The pooled mean peak urinary flow for men undergoing Nd:YAG laser treatments increased by 85% (10.0 mL/s to 18.5 mL/s) versus 125% (9.6 mL/s to 21.6 mL/s) in men undergoing TURP (Keoghane 2000a; Shingleton 1999; Suvakovic 1996; Tuhkanen 1999b; van Melick 2003; Zorn 1999). Five Nd:YAG studies reported peak urinary flow at follow up, the weighted mean difference for lasers versus TURP was 1.72 mL/s (95% CI, ‐0.32 to 3.76) favoring TURP (Keoghane 2000a; Shingleton 1999; Suvakovic 1996; Tuhkanen 1999b; van Melick 2003) (Analysis 2.2). For men undergoing Ho:YAG treatment, peak urinary flow increased by 175% (8.8 mL/s to 24.2 mL/s) versus 128% (8.8 mL/s to 20.1 mL/s) in men undergoing TURP (Gilling 1999; Mottet 1999). One HoLRP study reported peak urinary flow at follow up and the weighted mean difference favored HoLRP (‐4.80 mL/s, 95% CI ‐8.79 to ‐0.81) (Gilling 1999) (Analysis 2.2).
2.2. Analysis.
Comparison 2 Contact Laser versus TURP, Outcome 2 Peak Urine Flow (mL/s).
Hybrid lasers versus TURP The pooled mean symptom score for men undergoing hybrid laser techniques decreased 67% by 12 months (20.5 to 6.8) versus 71% (20.3 to 5.8) in men undergoing TURP. TURP led to significantly better improvement in symptoms than hybrid laser techniques in one study (Zorn 1999). No studies provided data on mean urinary symptom scores at follow up.
The pooled mean peak urinary flow for men undergoing hybrid laser techniques increased 109% by 12 months (9.3 mL/s to 19.1 mL/s) versus 107% (9.9 mL/s to 20.5 mL/s) in men undergoing TURP. Three studies reported mean peak urinary flow at follow up, the weighted mean difference for hybrid lasers versus TURP was 1.53 (95% CI, ‐1.13 to 4.19) favoring TURP (Analysis 3.1) (Carter 1999a; Suvakovic 1996; Tuhkanen 1999b).
3.1. Analysis.
Comparison 3 "Hybrid" Laser versus TURP, Outcome 1 Peak Urine Flow (mL/s).
Adverse events (Analysis 4.1; Analysis 4.2; Analysis 4.3; Analysis 4.4; Analysis 4.5): Most trials did not comprehensively report adverse events. The frequencies of adverse events associated with TURP and laser techniques are shown in Table 4. Overall, subjects undergoing laser techniques had less morbidity and fewer complications. More men undergoing TURP required transfusions (6.7%, 49/735 subjects vs. < 1% 2/720; RR = 24, 95% CI 5.9 to 98) and developed strictures (8.2%, 43/527 vs. 3.8%, 20/520; RR = 2.1, 95% CI 1.3 to 3.6) than men receiving any laser procedure.
4.1. Analysis.
Comparison 4 Adverse Events, Outcome 1 Urinary Tract Infection.
4.2. Analysis.
Comparison 4 Adverse Events, Outcome 2 Urinary Retention.
4.3. Analysis.
Comparison 4 Adverse Events, Outcome 3 Retrograde ejaculation.
4.4. Analysis.
Comparison 4 Adverse Events, Outcome 4 Irritative symptoms/Dysuria.
4.5. Analysis.
Comparison 4 Adverse Events, Outcome 5 Erectile Dysfunction.
We found no differences between TURP and laser groups in erectile dysfunction, retrograde ejaculation, TURP syndrome, epididymitis/orchitis, clot retention, or urinary incontinence. However, urinary retention was more common following laser techniques (RR = 2.4, 95% CI 1.5 to 3.9) and non‐contact laser techniques caused more dysuria than TURP (RR = 3.6, 95% CI, 1.0 to 13.1). No treatment‐related deaths were reported, though one patient died of a myocardial infarction eight days after uncomplicated HoLRP (Gilling 1999).
CONTACT LASER versus Transurethral Electrovaporization (TUVP) (n = 2 trials) A total of 122 subjects were randomized in two trials of Nd:Yag contact lasers (n = 56) versus transurethral electrovaporization (TUVP) (n = 66) (Shingleton 1998; van Melick 2003). Van Melick and colleagues reported similar operative times for the two procedures, 58 minutes for contact laser compared with 50 minutes for electrovaporization, and similar hospital length of stay, 3.8 versus 3.4 days, respectively (van Melick 2003). Neither study reported on catheter duration; Van Melick and colleagues reported one (2%) reoperation during six months follow up after contact laser and 2 (4%) reoperations following electrovaporization.
Both treatments were equally effective for relieving BPO symptoms and improving urinary flow. The contact lasers reduced pooled mean symptom scores by 67% (18.9 to 6.3) at 6‐month follow up while the TUEV reduced symptom scores by 68% (20.8 to 6.6). Pooled mean peak urinary flow increased 106% (10.9 mL/s to 22.5 mL/s) following contact laser and 104% (10.0 to 20.4 mL/s) following TUVP.
Urinary retention developed following 8 (14.3%) contact laser procedures and 1 (1.5%) TUVP procedure. Shingleton and colleagues reported 1 stricture following contact laser and one following TUVP; new erectile dysfunction was reported in 9% and 10% of laser and TUVP subjects, respectively, who had normal function at baseline (Shingleton 1998). Van Melick and colleagues reported 2 (4.3%) cases of clot retention following TUVP; no clot retention developed following contact laser and neither group required transfusions (van Melick 2003). A similar proportion (8% vs. 10%) of subjects developed urinary tract infections following contact laser and TUVP, respectively (van Melick 2003).
INTERSTITIAL LASER COAGULATION versus Transurethral Microwave Thermotherapy (TUMT ) (n = 1 trial) Norby and colleagues (Norby 2002) compared interstitial laser coagulation (n = 48) with transurethral thermotherapy (n = 46). TUMT was performed as an outpatient procedure, the median length of stay for ILC was three days. Median catheter duration was 3 days following ILC, and 7 to 14 days following TUMT, with longer catheterization required after higher energy procedures. During six months of follow up, one TUMT patient underwent reoperation for BPO compared to none in the ILC group.
Both treatments were equally effective for relieving BPO symptoms and improving urinary flow. The ILC reduced mean symptom scores by 56% (21.4 to 9.5) at 6‐month follow‐up while the TUMT reduced mean symptom scores by 54% (20.5 to 9.5). Mean peak urinary flow increased 59% (10.2 mL/s to 16.2 mL/s) following ILC and 45% (9.1 mL/s to 13.2 mL/s) following TURP.
Subjects undergoing ILC were twice as likely (61% vs. 30%) to develop a urinary tract infection. Urinary retention occurred in 4 (9%) subjects following ILC and 3 (7%) subjects following TUMT. One ILC subject developed a stricture, none had clot retention or urinary incontinence. One TUMT subject had clot retention, none developed a stricture or urinary incontinence. Among men with normal sexual function, 29% developed erectile dysfunction and 35% developed retrograde ejaculation following ILC. The corresponding proportions were 9% and 22%, respectively, following TUMT.
CONTACT LASER versus Open Prostatectomy (n = 1 trial) One study (Kuntz 2002) compared HoLRP (n = 60) with open prostatectomy (n = 60) to treat men with large prostates (> 100 gm) with PVR > 50 mL. Operative time was significantly longer with HoLRP (136 vs. 91 minutes, P < 0.0001), while hospital length of stay was significantly longer with open prostatectomy (251 vs. 70 hours, P < 0.0001) as was catheter duration (194 vs. 31 hours, P < 0.0001). During follow up, six laser subjects underwent reoperation, two for BPO, three for bleeding, and one for stricture. Following open prostatectomy, reoperation was required by three subjects for bleeding and by two subjects for strictures.
Both treatments were equally effective for BPO resulting from large prostates. The HoLRP reduced mean symptom scores by 89% (22.1 to 2.4) at 6‐month follow up while the open prostatectomy reduced mean symptom scores by 87% (21.1 to 2.8). Mean peak urinary flow increased from 3.8 mL/s to 29.9 mL/s following HoLRP and 3.6 mL/s to 27.0 mL/s following open prostatectomy. The baseline PUF values for this study were markedly low.
Eight (13%) subjects required transfusion following open prostatectomy compared to none of the HoLRP subjects. Six (10%) subjects developed urinary incontinence following open prostatectomy compared to five (8%) of the HoLRP subjects. Erectile dysfunction developed in 10% of open prostatectomy and 9% of HoLRP subjects with normal baseline erectile function; 79% of open prostatectomy subjects developed retrograde ejaculation compared to 70% of HoLRP subjects. Neither difference was statistically significant.
Discussion
Our systematic review found that laser techniques were effective in reducing lower urinary tract symptoms attributable to BPO and in improving peak urinary flow for up to one year following surgery. Symptom scores were reduced by about 70% and urinary flow usually doubled. Urinary symptom and flow outcomes following laser surgery were generally similar to TURP, though a number of studies found significantly better results following TURP (Anson 1995; Cowles 1995; Donovan 2000; Keoghane 2000a; Shingleton 1999; Zorn 1999). Only one study found a laser technique (non‐contact) more effective than TURP in improving urinary symptoms [Sengor 1996] and only one study found a laser technique (HoLRP) more effective in improving peak urinary flow (Gilling 1999). Hospital lengths of stay were shorter with laser techniques compared to TURP. The operating time for TURP was about the same or shorter than for contact procedures, but TURP took longer than non‐contact procedures. Contact laser procedures had the shortest duration of urinary catheter placement followed by TURP and then non‐contact laser procedures. Adverse events generally occurred less frequently with laser techniques, particularly transfusion, clot retention, strictures, and TUR syndrome. The occurrence of urinary tract infections was similar between laser techniques and TURP, but non‐contact procedures led to a substantially higher occurrence of dysuria than either TURP or contact laser procedures. The re‐operation rate was higher during the 12 months following laser techniques than with TURP.
Baseline characteristics, including age, symptoms, and flow measures, were similar to subjects enrolled in other surgical studies of BPO treatment suggesting that our results are generalizable. The average age of study subjects was 67 years and baseline symptom and urinary flow measures were consistent with moderately severe obstruction. However, men with extremely large prostates or acute retention were generally excluded.
Although we limited our analysis to randomized controlled trials, the majority of the studies had potential methodologic flaws. Just seven studies clearly had adequate concealment of randomization and only one study blinded study personnel. Studies did not consistently report comprehensive information on efficacy outcomes and adverse events, particularly dysuria and erectile dysfunction, and our estimates for these events may be unreliable. Only three studies, which used non‐contact techniques, reported data on the mean changes in urinary symptom scores and peak urinary flow; just 11 studies reported mean values for these outcomes at follow up. Consequently, we were often unable to pool data, limiting our ability to statistically assess the relative efficacy of laser techniques versus TURP, open prostatectomy, and other kinds of minimally invasive techniques. Several studies provided follow up beyond one year, but outcome data were unreliable because sample sizes were small and the rates of attrition were high (Keoghane 1996; Gilling 2000; McAllister 2000; Shingleton 2002; Tuhakanen 2001). There were too few studies to determine whether variations in laser energy source, power setting, laser wavelength, or treatment duration and location affected outcomes. Similarly, there were too few studies to adequately compare laser techniques with other minimally invasive procedures such as TUMT or TUVP.
Authors' conclusions
Implications for practice.
Patients and providers can use the information provided by this systematic review to weigh the relative risks and benefits of TURP and laser procedures. Improvements in urinary symptoms and flow slightly favored TURP, though laser procedures had fewer adverse events and shorter hospitalizations. The risk of re‐operation was higher following laser procedures. Data were insufficient to adequately compare laser techniques with other minimally invasive procedures.
Implications for research.
Despite the widespread use of laser procedures, relatively few subjects have been studied in controlled clinical trials. Further studies, using randomized treatment allocation, larger sample sizes, and comprehensive measures of outcomes and adverse events, are still needed to better define the role of laser techniques for treating BPO.
What's new
| Date | Event | Description |
|---|---|---|
| 2 June 2008 | Amended | Converted to new review format. |
History
Protocol first published: Issue 1, 2000 Review first published: Issue 1, 2004
| Date | Event | Description |
|---|---|---|
| 29 September 1999 | New citation required and conclusions have changed | Substantive amendment |
Acknowledgements
The authors would like to acknowledge Indulis Rutks for his work on literature search and article retrieval and Dr. Claudia Cucino for help with translations.
Data and analyses
Comparison 1. Non‐contact Laser versus TURP.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Mean Change ‐ AUA Symptom Score: > 6 months follow‐up | 3 | 359 | Mean Difference (IV, Random, 95% CI) | ‐2.47 [‐4.24, ‐0.70] |
| 2 AUA Symptom Score: | 4 | 236 | Mean Difference (IV, Random, 95% CI) | 0.21 [‐2.28, 2.70] |
| 2.1 12 months follow‐up | 2 | 157 | Mean Difference (IV, Random, 95% CI) | ‐0.51 [‐5.00, 3.97] |
| 2.2 6 months follow‐up | 2 | 79 | Mean Difference (IV, Random, 95% CI) | 1.35 [‐0.28, 2.97] |
| 3 Mean Change ‐ Peak Urine Flow (mL/s): > 6 months follow‐up | 3 | 385 | Mean Difference (IV, Random, 95% CI) | 3.18 [1.47, 4.89] |
| 4 Peak Urine Flow (mL/s) | 4 | 236 | Mean Difference (IV, Random, 95% CI) | 2.64 [0.53, 4.75] |
| 4.1 12 months follow‐up | 2 | 157 | Mean Difference (IV, Random, 95% CI) | 3.47 [‐2.78, 9.72] |
| 4.2 6 months follow‐up | 2 | 79 | Mean Difference (IV, Random, 95% CI) | 1.78 [0.70, 2.86] |
1.1. Analysis.
Comparison 1 Non‐contact Laser versus TURP, Outcome 1 Mean Change ‐ AUA Symptom Score: > 6 months follow‐up.
Comparison 2. Contact Laser versus TURP.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 AUA (IPSS) Symptom Score: | 4 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 1.1 Nd:YAG or KTP/Nd:YAG Vaporization Technique | 3 | 227 | Mean Difference (IV, Random, 95% CI) | ‐1.78 [‐3.22, ‐0.35] |
| 1.2 Holmium (Ho):YAG Vaporization Technique | 1 | 102 | Mean Difference (IV, Random, 95% CI) | 0.10 [‐1.88, 2.08] |
| 2 Peak Urine Flow (mL/s) | 6 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 2.1 Nd:YAG or KTP/Nd:YAG Vaporization Technique | 5 | 254 | Mean Difference (IV, Random, 95% CI) | 1.72 [‐0.32, 3.76] |
| 2.2 Holmium (Ho):YAG Vaporization Technique | 1 | 102 | Mean Difference (IV, Random, 95% CI) | ‐4.80 [‐8.79, ‐0.81] |
Comparison 3. "Hybrid" Laser versus TURP.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Peak Urine Flow (mL/s) | 3 | 223 | Mean Difference (IV, Random, 95% CI) | 1.53 [‐1.13, 4.19] |
Comparison 4. Adverse Events.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Urinary Tract Infection | 11 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 1.1 Non‐contact Laser versus TURP | 6 | 678 | Risk Ratio (M‐H, Random, 95% CI) | 2.23 [1.02, 4.87] |
| 1.2 Contact Laser versus TURP | 3 | 332 | Risk Ratio (M‐H, Random, 95% CI) | 0.67 [0.28, 1.58] |
| 1.3 "Hybrid" Laser versus TURP | 1 | 205 | Risk Ratio (M‐H, Random, 95% CI) | 3.71 [1.43, 9.61] |
| 1.4 Interstitial Laser versus TURP | 1 | 66 | Risk Ratio (M‐H, Random, 95% CI) | 4.5 [1.53, 13.22] |
| 2 Urinary Retention | 10 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.1 Non‐contact Laser versus TURP | 4 | 311 | Risk Ratio (M‐H, Random, 95% CI) | 3.53 [1.45, 8.58] |
| 2.2 Contact Laser versus TURP | 4 | 344 | Risk Ratio (M‐H, Random, 95% CI) | 1.97 [0.68, 5.72] |
| 2.3 "Hybrid" Laser versus TURP | 1 | 205 | Risk Ratio (M‐H, Random, 95% CI) | 2.57 [0.51, 12.97] |
| 2.4 Interstitial Laser versus TURP | 1 | 66 | Risk Ratio (M‐H, Random, 95% CI) | 2.0 [0.24, 16.84] |
| 3 Retrograde ejaculation | 10 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 3.1 Non‐contact Laser versus TURP | 4 | 160 | Risk Ratio (M‐H, Random, 95% CI) | 4.84 [0.51, 45.93] |
| 3.2 Contact Laser versus TURP | 4 | 213 | Risk Ratio (M‐H, Random, 95% CI) | 1.58 [0.36, 6.94] |
| 3.3 "Hybrid" Laser versus TURP | 1 | 40 | Risk Ratio (M‐H, Random, 95% CI) | 2.67 [0.89, 7.98] |
| 3.4 Interstitial Laser versus TURP | 1 | 40 | Risk Ratio (M‐H, Random, 95% CI) | 0.69 [0.33, 1.46] |
| 4 Irritative symptoms/Dysuria | 5 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 4.1 Non‐contact Laser versus TURP | 4 | 362 | Risk Ratio (M‐H, Random, 95% CI) | 3.62 [1.00, 13.12] |
| 4.2 "Hybrid" Laser versus TURP | 1 | 205 | Risk Ratio (M‐H, Random, 95% CI) | 0.84 [0.48, 1.47] |
| 5 Erectile Dysfunction | 5 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 5.1 Non‐contact Laser versus TURP | 3 | 211 | Risk Ratio (M‐H, Random, 95% CI) | 1.58 [0.27, 9.11] |
| 5.2 Contact Laser versus TURP | 2 | 156 | Risk Ratio (M‐H, Random, 95% CI) | 0.87 [0.27, 2.80] |
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Anson 1995.
| Methods | NON‐ CONTACT LASER. Tissue effect: coagulation. Subjects blinded: No | |
| Participants | N=151 men, >50 yrs old. Country/Region: UK Mean age: 68 yrs (range 52‐84) Race: not stated Not available to follow‐up: 29 (17%). | |
| Interventions | 1. VLAP (n=76): Urolase fiber ‐ Nd‐YAG laser ‐ settings; 60 watts, 60 spd x 4, 4 to 9 minutes per session (mps). 2. TURP (n=75). Catheter protocol: at MD discretion. Routine antibiotics (preop): at MD discretion. Mean average of follow‐up: 12 months | |
| Outcomes | American Urological Association (AUA) symptom score; peak urine flow (PUF); residual volume (RV); total voided volume (TVV); hospital length of stay; rehospitalization/re‐operation; adverse events. | |
| Notes | Inclusion criteria: candidates for surgical treatment of Bladder outflow obstruction (BOO) secondary to Benign prostatic hyperplasia (BPH). | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Low risk | A ‐ Adequate |
Carter 1999a.
| Methods | HYBRID LASER. Tissue effect: coagulation and vaporization. Subjects blinded: Unclear. | |
| Participants | N=204 men. Country: UK Mean age: 67.4 years Race: not stated Not available to follow‐up: 35 (17%) | |
| Interventions | 1. Hybrid laser group (n=101): KTP/Nd:YAG ‐ a. KTP settings; 30 watts. b. Nd:YAG settings; 60 watts. 2. TURP (n=103): Catheter protocol: no Routine antibiotics (preop): yes Mean average of follow‐up: 12 months | |
| Outcomes | IPSS; PUF; prostate size; BPH‐11 (symptom improvement); QoL (SF 36); tissue resected; hospital length of stay; rehospitalization/re‐operation; adverse events. | |
| Notes | Inclusion criteria: "BLUES PROTOCOL" IPSS >12 points; PUF <15 ml/s with a VV >200 ml or PUF <13 (VV 150‐200) or PUF <10 (VV 100‐150); RV <300 ml; BPH "severe enough to warrant an operative intervention." | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Low risk | A ‐ Adequate |
Costello 1995.
| Methods | NON‐CONTACT LASER. Tissue effect: coagulation. Subjects blinded: No | |
| Participants | N=71 "evaluable" men, >50 yrs old. Country/Region: Australia Mean age: 68 yrs (range 50‐88) Race: not stated Not available to follow‐up: "50 patients have completed 6 months of follow‐up." | |
| Interventions | 1. VLAP (n=34): Urolase fiber Nd‐YAG laser ‐ settings; 60 watts, 21.7 kJ, 60 spd x 4 for each lobe, 6.5 mps. 2. TURP (n=37). Catheter protocol: yes Routine antibiotics (preop): yes Mean average of follow‐up: 6 months. | |
| Outcomes | AUA; PUF; Mean urine flow (MUF); RV; PV; hospital length of stay; rehospitalization/re‐operation; adverse events. | |
| Notes | Inclusion criteria: "symptomatic bladder neck obstruction." | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Cowles 1995.
| Methods | NON‐CONTACT LASER. Tissue effect: coagulation Subjects blinded: No. | |
| Participants | N=115 men, >50 yrs old. Country/Region: USA Mean age: 66 yrs (range 50‐84) Race: not stated Not available to follow‐up: 3 (3%) | |
| Interventions | 1. VLAP (n=56): Urolase fiber Nd‐YAG laser settings; 40 watts, 10.2 kJ, 30 spd x 2 for each lobe, 4.2 mps. 2. TURP (n=59). Catheter protocol: unclear Routine antibiotics (preop): unclear Mean average of follow‐up: 12 months | |
| Outcomes | AUA; PUF; RV; PV; QoL; global assessment; hospital length of stay; rehospitalization/re‐operation; adverse events. | |
| Notes | Inclusion criteria: "candidates for surgical treatment." | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Low risk | A ‐ Adequate |
Donovan 2000.
| Methods | NON‐CONTACT LASER. Tissue effect: coagulation Subjects blinded: No | |
| Participants | N=340 men. Country: UK (multicenter) Mean age: 67.0 years Race: white Not available to follow‐up: 8 (2%) | |
| Interventions | 1. Laser group (n=117): Nd‐YAG laser settings; 60 watts. 2. TURP (n=117): 3. CM group (n=106) Catheter protocol: no Routine antibiotics (preop): yes Median follow‐up: 7.5 months | |
| Outcomes | IPSS; PUF; RV; hospital length of stay. | |
| Notes | Inclusion criteria: IPSS >8 points; PUF <15 ml/s | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Low risk | A ‐ Adequate |
Gilling 1998a.
| Methods | HoLRP STUDY. Subjects blinded: unclear Tissue effect: coagulation vs. resection/ vaporization. IRB/Human subjects approval: not reported | |
| Participants | N=44 men, <85 yrs old. Country/Region: USA, New Zealand Mean age: 66 yrs (range 44‐81). Race: not stated Not available to follow‐up: ? | |
| Interventions | 1. HoLRP (n=23): settings; 60 watts, 67 kJ. 2. VLAP (Coagulation group) (n=21): Nd‐YAG laser settings; 60 watts, 53 kJ, 60 spd x 4. Catheter protocol: VLAP 5 days, HoLRP 1 day. Routine antibiotics (preop): unclear Mean average of follow‐up: 12 months | |
| Outcomes | AUA; PUF; RV; PV; tissue resected; rehospitalization/re‐operation; adverse events. | |
| Notes | Inclusion criteria: AUA >8; PUF<15 ml/s; prostate sizes <100 cm."urodynamically proven BOO." | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Gilling 1999.
| Methods | CONTACT LASER. Tissue effect: resection/ vaporization. Subjects blinded: unclear | |
| Participants | N=120 men, <80 yrs old. Country/Region: USA, New Zealand Mean age: 67 yrs (range 36‐80). Race: not stated Not available to follow‐up: 18 (15%) | |
| Interventions | 1. HoLRP (n=61): Nd‐YAG laser settings; 80 watts. 2. TURP (n=59). Catheter protocol: yes Routine antibiotics (preop): unclear Mean average of follow‐up: 12 months | |
| Outcomes | AUA; PUF; RV; PV; QoL; tissue resected; hospital length of stay; rehospitalization/re‐operation; adverse events. | |
| Notes | Inclusion criteria: AUA >/=8**; PUF</=15 ml/s; RV <400 mls; with prostate sizes <100 cm. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Gujral 2000.
| Methods | NON‐CONTACT LASER. Tissue effect: coagulation. Subjects blinded: no | |
| Participants | N=82 men. Country: UK (multicenter) Mean age: 70.2 years Race: white Not available to follow‐up: 2 (2%) | |
| Interventions | 1. VLAP (n=38): Nd‐YAG laser, 2. TURP (n=44) Catheter protocol: no Routine antibiotics (preop): yes Median follow‐up: 7 months | |
| Outcomes | IPSS; PUF; RV; QoL; Hospital length of stay. | |
| Notes | Inclusion criteria: IPSS > 8, PUF <10‐15 ml/s depending on voided volume). Required acute retention or PVR > 300 ml. Prostate size < 120 ml. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Low risk | A ‐ Adequate |
Kabalin 1995.
| Methods | NON‐CONTACT LASER. Tissue effect: coagulation. Subjects blinded: unclear | |
| Participants | N=25 men, >50 yrs old. Country/Region: USA Mean age: 67 yrs Race: not stated Not available to follow‐up: 3 (12%) | |
| Interventions | 1. VLAP (n=13): Urolase Nd‐YAG laser settings; 40 watts, 11.5 kJ, 30‐60 spd >/= 4, >/= 3 mps. 2. TURP (n=12). Catheter protocol: yes Routine antibiotics (preop): yes Mean follow‐up: 6 months | |
| Outcomes | AUA; PUF; RV; PV; global assessment; tissue resected; rehospitalization/re‐operation; adverse events. | |
| Notes | Inclusion criteria: AUA >6, PUF<15 ml/s; "significant voiding symptoms." | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Keoghane 2000a.
| Methods | CONTACT LASER. Tissue effect: coagulation and vaporization Subjects blinded: Yes | |
| Participants | N=152 men. Country: UK Mean age: 70 years Race: not stated Not available to follow‐up: 30 (20%) | |
| Interventions | 1. Contact laser "prototype" (n=76): Nd‐YAG laser settings; 31 kJ. 2. TURP (n=76). Catheter protocol: no Routine antibiotics (preop): yes Mean average of follow‐up: 12 months | |
| Outcomes | AUA‐7; PUF; PV; Short Form‐36 (SF‐36) includes BPH Bother Score and global assessment;rehospitalization/ re‐operation; adverse events. | |
| Notes | Inclusion criteria: "all patients referred for surgical treatment of BPH." | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Low risk | A ‐ Adequate |
Kuntz 2002.
| Methods | CONTACT LASER. Tissue effect: vaporization/resection. Subjects blinded: No. | |
| Participants | N=120 men. Country: Germany. Mean age: 70.2 years. Race: not stated. Not available to follow‐up: 16 (13.3%) | |
| Interventions | 1. HoLRP (n=60) 80‐100W. 2. Open prostatectomy (n=60). Catheter protocol: unclear Pre‐op antibiotics: yes Mean follow‐up: 6 months | |
| Outcomes | AUA, PUF, RV, tissue resected, adverse events, hospital length of stay, reoperations | |
| Notes | Prostate > 100 gm, AUA = 8, PUF = 12 mL/s, RV > 50 ml | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Mottet 1999.
| Methods | CONTACT LASER. Tissue effect: resection/ vaporization.| Subjects blinded: Unclear | |
| Participants | N=36 nondiabetic men, > 45 yrs old. Country/Region: France Mean age: 66 yrs (range 50‐77) Race: not stated Not available to follow‐up: 16 (44%) at 52 weeks. | |
| Interventions | 1. HoLRP (n=23): Nd‐YAG laser settings; 60 watts, 2.4 kJ, 25 spd or 80 watts, 2.6 kJ, 30 spd. Mean energy delivered = 103.6 kJ. 2. TURP (n=13) Catheter protocol: yes Routine antibiotics (preop): not stated. Mean average of follow‐up: | |
| Outcomes | AUA; Madsen score; PUF; PV; catheter time; operation time; adverse events. | |
| Notes | Inclusion criteria: AUA >13; PUF <12 ml/s; RV <250 mls; PV <60 grams. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Norby 2002.
| Methods | INTERSTITIAL LASER COAGULATION. Tissue effect: coagulation Subject blinded: No | |
| Participants | N=118 men. Country: Denmark (multicenter). Mean age: 66 years Race: Not stated. Not available to follow‐up: 8 (6.7%) | |
| Interventions | 1. ILC group (n=48); NdYag: 7‐20W 2. TUMT (n=46): Prostatron 2.0, 2.5. 3. TURP/TUIP (n=24). Catheter protocol: yes Routine antibiotics (pre‐op): yes Mean follow‐up: 6 months | |
| Outcomes | IPSS, PUF, RV, QOL, hospital length‐of‐stay, rehospitalization/reoperation, adverse events. | |
| Notes | Inclusion criteria: PUF < 12 ml/s, IPSS = 7 | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Sengor 1996.
| Methods | NON‐CONTACT LASER. Tissue effect: coagulation Subjects blinded: no | |
| Participants | N=60 men, >50 yrs old. Country/Region: Turkey Mean age: 64 yrs (range 50‐85) Race: not stated Not available to follow‐up: none | |
| Interventions | 1. VLAP (n=30): Ultraline fiber ‐ Nd‐YAG laser settings; 60 watts, 12.5‐110 kJ (mean 46.6 kJ), x 4 positions (1 additional if median lobe enlarged) 2. TURP (n=30) Catheter protocol: yes Routine antibiotics (preop): not stated Mean average of follow‐up: 6 months | |
| Outcomes | AUA; PUF; MUF; PV; Hospital length of stay; Catheter time; Operation time; Adverse events. | |
| Notes | Inclusion criteria: PUF</=15 ml/s; MUF </=10 ml/s; "significant voiding symptoms causing the patient to request therapy." | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Shingleton 1998.
| Methods | CONTACT LASER. Subjects blinded: Tissue effect: vaporization | |
| Participants | N=31 men. N=31 men. Country: USA Mean age: 67 years (range 48‐82) Race: not stated Not available to follow‐up: unclear | |
| Interventions | 1. VLAP + KTP (n=11) Nd‐YAG laser settings; 60 watts, 60 spd. KTP; 40 watts. 2. TVP (n=20): Catheter protocol: yes Routine antibiotics (preop): unclear Mean average of follow‐up: 6 months | |
| Outcomes | AUA; PUF; Adverse events. | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Shingleton 1999.
| Methods | CONTACT STUDY. Subjects blinded: Unclear Tissue effect: vaporization IRB/Human subjects approval: unclear | |
| Participants | N=100 > 45 yrs old. Country/Region: USA Mean age: 68 yrs Race: White 68‐76%, Black 24‐32% Not available to follow‐up: | |
| Interventions | 1. VLAP + KTP BNI (n=50): Nd‐YAG laser settings; 60 watts, 60 spd. KTP; 40 watts. 2. TURP (n=50): Catheter protocol: Routine antibiotics (preop): Mean average of follow‐up: 6 months | |
| Outcomes | AUA; PUF; MUF; Prostate size; Adverse events. | |
| Notes | Inclusion criteria: > 45 yrs of age; PUF</=15 ml/s; failed therapy with alpha‐blockers. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Suvakovic 1996.
| Methods | HYBRID, CONTACT and NON‐CONTACT LASERS Tissue effect: Coagulation and vaporization Subjects blinded: Unclear | |
| Participants | N=40, > 50 yrs old. Country/Region: UK Mean age: 65 yrs Race: White | |
| Interventions | 1. VLAP (non‐contact) side‐fire laser (n=10): Urolase Nd‐YAG laser settings; 60 watts, 60 spd x 4. 2. Contact laser group (n=10): Urolase Nd‐YAG laser settings; 40 watts. 3. VLAP (non‐contact) side‐fire laser + debridement (n=10). 4. TURP (n=10). Catheter protocol: yes Routine antibiotics (preop): yes Mean average of follow‐up: 12 months | |
| Outcomes | AUA; PUF; Prostate size; Adverse events. | |
| Notes | Inclusion criteria: Prostate volume < 40 cc; AUA > 15; PUF</=15 ml/s; PSA < 2.5 ng/ml. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Tuhkanen 1999b.
| Methods | CONTACT LASER. Tissue effect: coagulation and vaporization. Subjects blinded: Unclear | |
| Participants | N=50 Country/Region: Finland Mean age: 67 (range 56‐77) Race: unknown Not available to follow‐up: 2 (4%) | |
| Interventions | 1. Laser group (contact and vaporization) (n=25 ) Nd‐YAG laser settings; 40 watts. 2. TURP (n=25): Catheter protocol: no Routine antibiotics (preop): yes Mean average of follow‐up: 6 months | |
| Outcomes | Danish PSS‐1; PUF; RV; Prostate size; Hospital length of stay; Rehospitalization/re‐operation; Adverse events. | |
| Notes | Inclusion criteria: Prostate volume 40‐100 cc. Urodynamic evidence of obstruction; voiding detrusor pressure >40 cm H2O or slope detrusor pressure/urine flow >2 cm H20 mL/s. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
Tuhkanen 1999a.
| Methods | HYBRID LASER. Tissue effect: coagulation and vaporization. Subjects blinded: Unclear | |
| Participants | N=45 Country/Region: Finland Mean age: 67 (range 46‐78) Race: unknown Not available to follow‐up: 2 (4%) | |
| Interventions | 1. VLAP Hybrid laser group (n= 21): Nd‐YAG laser settings; 40 watts, 56 kj, 90 spd for 75 minutes. 2. TURP (n=24): Catheter protocol: yes Routine antibiotics (preop): yes Mean average of follow‐up: 6 months | |
| Outcomes | Danish PSS‐1; PUF; MUF; RV; Prostate size; Rehospitalization/re‐operation; Adverse events. | |
| Notes | Inclusion criteria: Prostate volume < 40 cc. Urodynamic evidence of obstruction; voiding detrusor pressure >40 cm H2O or slope detrusor pressure/urine flow >2 cm H20 mL/s. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
van Melick 2002.
| Methods | CONTACT LASER. Tissue effect: vaporization. Subjects blinded: No. | |
| Participants | N=141. Country: Netherlands. Mean age: 65.6 years Race: not stated. Not available to follow‐up: 6 (4.3%) | |
| Interventions | 1. Contact laser (n=45); NdYag. 2. Electro‐vaporization (n=46) 3. TURP (n=50). Catheter protocol: no Pre‐op antibiotics: unclear Mean follow‐up: 6 months | |
| Outcomes | IPSS, QOL, PUF, length of stay, re‐operations, adverse events | |
| Notes | LUTS c/w BPH, Schafer obstruction score = 2. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Low risk | A ‐ Adequate |
van Melick 2003.
| Methods | See van Melick 2002 | |
| Participants | ||
| Interventions | ||
| Outcomes | ||
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Low risk | A ‐ Adequate |
Zorn 1999.
| Methods | CONTACT LASER. Tissue effect: vaporization Subjects blinded: | |
| Participants | N=37 men, >50 years old. Country: USA Mean age: 70 years Race: not stated Not available to follow‐up: 10 (27%) | |
| Interventions | 1. Contact laser ablation of the prostate [CLAP] (n=26): Nd‐YAG laser, 2. TURP (n=12): Catheter protocol: no Routine antibiotics (preop): no Mean follow‐up: 12 months | |
| Outcomes | AUA; PUF; RV; hospital length of stay; catheter time; hematocrit changes; adverse events. | |
| Notes | Inclusion criteria: AUA > 12; PUF< 15 mL/s; RV >125 mL/s | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear risk | B ‐ Unclear |
VLAP=Visual Laser Ablation of the Prostate TURP=Transurethral resection of the prostate Nd‐YAG=neodymium:yttrium‐aluminium‐garnet‐laser HoLRP=Holmium laser resection of the prostate spd=second pulse duration
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Albert 1997 | Comparison of 2 laser techniques (coagulation vs, Vaporization) with no active control (i.e. TURP) or sham arm. |
| Beerlage 1998 | Comparison of 2 laser coagulation techniques with no active control (i.e. TURP) or sham arm. Follow‐up of de la Rosette 1995. |
| Boon 1995 | Comparison of 2 laser coagulation techniques with no active control (i.e. TURP) or sham arm. |
| Breteau 1997 | Comparison of 2 laser techniques (coagulation vs, Vaporization) with no active control (i.e. TURP) or sham arm. |
| Bryan 1999 | Pilot study focusing on treatment options for BPH; no outcomes data. |
| Carter 1999b | Quality of life data. Follow‐up of Carter 1999. |
| de la Rosette 1995 | Comparison of 2 laser coagulation techniques with no active control (i.e. TURP) or sham arm. |
| Fraundorfer 2001 | Economic study, follow‐up to Gilling 1999. |
| Gilling 1998b | Comparison of 2 laser techniques (coagulation vs, Vaporization) with no active control (i.e. TURP) or sham arm. |
| Gilling 2000 | Small sample size and/or high rate of attrition. |
| Ichiyanagi 1997 | Non‐randomized study. |
| Jung 1996 | Non‐randomized, controlled clinical trial. |
| Kaplan 1995 | No indication of randomization. |
| Keoghane 1996 | Small sample size and/or high rate of attrition. |
| Keoghane 2000b | Economic study, follow‐up to Keoghane 2000a |
| Kollmorgen 1996 | Non‐randomized, controlled clinical trial. |
| Langley 1997 | Follow‐up < 6 months. |
| Matsuoka 2000 | No indication of randomization, no control group. |
| McAllister 2000 | Small sample size and/or high rate of attrition, follow‐up to Anson. |
| Muschter 1995 | No control group. |
| Narayan 1995 | Comparison of 2 laser techniques (coagulation vs. evaporation) with no active control (i.e TURP) or sham arm. |
| Orihuela 1995 | Comparison of 2 laser coagulation regimens with no active control (i.e TURP) or sham arm. |
| Schatzl 1997 | No indication of randomization |
| Shingleton 2002 | Small sample size and/or high rate of attrition. |
| Tuhakanen 2001 | Small sample size and/or high rate of attrition. |
| Wada 2000 | No indication of randomization. |
Contributions of authors
R Hoffman made contributions to acquisition, analysis and interpretation of data, and drafting of manuscript. R MacDonald made contributions to analysis and interpretation of data, statistical expertise, and administrative, technical and material support. T Wilt contribituted to conception and design of the study, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, statistical expertise, obtaining funding, and overall supervision.
Sources of support
Internal sources
Minneapolis/VISN‐13 Center for Chronic Diseases Outcomes Research (CCDOR), USA.
Dept. of Veterans Affairs Health Services Research and Development Program, USA.
Medicine Department, New Mexico VA Health Care System, Albuquerque, New Mexico, USA.
External sources
No sources of support supplied
Declarations of interest
None
Edited (no change to conclusions)
References
References to studies included in this review
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