3 Clinical evidence

3 Clinical evidence

Summary of clinical evidence

3.1 The key clinical outcomes for the GreenLight XPS system presented in the decision problem were:

  • symptoms of benign prostatic hyperplasia (BPH; using the International Prostate Symptom Score [IPSS] and International Prostate Symptom Score Quality of Life [IPSS-QOL], change in prostate volume, maximum flow rate [Qmax], post-void residual volume [PVR])

  • duration of catheterisation

  • rate of dysuria (pain)

  • quality of life

  • length of hospital stay

  • frequency of completion as a day-case

  • rate of re-admission

  • procedural blood loss and blood transfusion need

  • rate of transurethral resection of the prostate (TURP) syndrome

  • rate of capsular perforation

  • device-related adverse events.

Non-high-risk patients with GreenLight XPS

3.2 The company submission of clinical evidence for non-high-risk patients was based on a single trial that compared GreenLight
XPS with TURP (the GOLIATH study: Bachmann et al. 2014, Bachmann et al. 2015, Thomas et al. 2015).

3.3 The external assessment centre carried out an independent literature search and identified 1 additional trial that compared GreenLight XPS with TURP (Jovanovic et al. 2014).

3.4 The GOLIATH study was a European multicentre randomised controlled trial including 281 patients with BPH who were not considered to be at high risk (not on anticoagulant therapy, with prostates smaller than 100 ml and without urinary retention). Patients were randomised to either GreenLight XPS or TURP (monopolar or bipolar) and followed up for 2 years. The comparator was either monopolar or bipolar to reflect standard practice at participating centres, but results from the monopolar and bipolar subgroups were not reported separately.

3.5 Results were reported at 6 months (Bachmann et al. 2014), 1 year (Bachmann et al. 2015) and 2 years (Thomas et al. 2015). When compared with TURP, GreenLight XPS resulted in a significantly shorter duration of catheterisation (40.8 hours compared with 59.5 hours, p<0.001) and shorter lengths of hospital stay (65.5 hours compared with 96.9 hours, p<0.001). However, procedures with GreenLight XPS were longer than with TURP (49.6 minutes compared with 39.3 minutes, p<0.001). There was no statistically significant difference between groups in regard to symptoms of BPH as measured by IPSS or Qmax. Rates of adverse events and the percentages of patients who were complication-free after 180 days were similar between groups.

3.6 Jovanovic et al. (2014) studied 62 patients with lower urinary tract symptoms secondary to BPH in a single-centre study in Serbia. Patients in this study were not taking anticoagulants and had prostates smaller than 100 ml, but 11 patients had indwelling catheters. Patients were randomised to either GreenLight XPS or TURP (monopolar or bipolar not specified). GreenLight XPS was associated with a significantly shorter hospital stay (1.9 days compared with 4.4 days, p<0.0001) and duration of catheterisation (1.1 days compared with 2.9 days, p<0.0001), but longer operating times (92 minutes compared with 82 minutes, p<0.01) when compared with TURP. There were statistically significantly fewer adverse events with GreenLight XPS than with TURP, including blood transfusions, capsule perforations and TURP syndrome. In both groups, IPSS and Qmax improved from baseline but no statistically significant differences between GreenLight XPS and TURP were reported.

High-risk patients with GreenLight XPS or GreenLight HPS

3.7 The company identified 3 studies of GreenLight XPS or GreenLight HPS in the high-risk subgroup populations of interest (Woo et al. 2008, Woo and Hossack 2011, Chung et al. 2012). These included patients with a higher risk of bleeding (such as those on anticoagulants), patients with larger prostates and patients with urinary retention.

3.8 The external assessment centre considered 1 study in the submission not to be relevant (Chung et al. 2012), because results were not stratified by high-risk subgroup. The external assessment centre identified 10 further studies, 5 of which had comparative clinical data (Chen et al. 2013, Sohn et al. 2011, Tao et al. 2013, Hueber et al. 2015, West and Woo 2015).

3.9 Woo et al. (2008) was a case series of 305 patients with BPH who had GreenLight HPS at 8 centres across 6 countries. Patients considered to be at high risk (prostates larger than 80 ml, taking anticoagulants or in urinary retention) were compared with those without high-risk factors, with a mean follow-up of 4.2 months. For all patients, clinical outcomes improved significantly from baseline (p<0.001). For patients with large prostates, the only difference when compared with those with smaller prostates was in regard to prostate volume reduction (p<0.001). There were no differences in outcomes for patients taking anticoagulants compared with those not taking them. For patients with or without urinary retention, the only significant difference between groups was in Qmax (16 ml/sec compared with 22.7 ml/sec, p<0.001).

3.10 Woo and Hossack (2011) reported a retrospective case series of 43 high-risk patients with BPH taking anticoagulants who had the GreenLight HPS procedure at a single centre in Australia. For the whole cohort, the mean hospital stay was 32 hours. Outcomes were reported at 3 months, including a subgroup of patients with urinary retention at baseline. There were no significant differences in outcomes between these groups except for IPSS score, which was significantly worse in patients with urinary retention than those without (6.7 compared with 12.6, p<0.01).

3.11 Chen et al (2013) reported a retrospective case series studying 132 patients having GreenLight HPS in Taiwan, who were divided into 4 high-risk subgroups (aged >80 years, prostate size >80 ml, high anaesthetic risk [American Society of Anesthesiologists score of 3], taking anticoagulants). Patients taking anticoagulants (n=21) and with larger prostates (n=32) were compared with patients without high-risk factors (n=72). There were no significant differences reported in IPSS, quality of life score, Qmax or PVR for the anticoagulant group or larger prostrate group compared with the group without risk factors. For the anticoagulant group, hospital stay and duration of catheterisation were significantly longer than for the group without risk factors (2.3 days compared with 1.7 days, p=0.033 and 28.8 hours compared with 19.1 hours, p=0.045). The larger prostate group had significantly longer operation times (35.5 minutes compared with 29.7 minutes, p=0.022), hospital stays (2.5 days compared with 1.7 days, p=0.01) and duration of catheterisation (30.8 hours compared with 19.1 hours, p=0.021) than the group without risk factors. No patients were given blood transfusions in any group and there were no significant differences in postoperative complications between groups, except for more urinary tract infections in patients taking anticoagulants (3 compared with 1, p=0.035).

3.12 Sohn et al. (2011) described a retrospective study of 60 patients having GreenLight HPS in Korea, which compared 30 patients who stopped anticoagulants before surgery with 30 patients who continued them. Operating time in the 2 groups was not significantly different (24.9 minutes compared with 16.9 minutes; p=0.628). There were no statistically significant differences between groups in IPSS, quality of life score or PVR at 3-month follow-up and no patients in either group developed complications.

3.13 Tao et al. (2013) described a prospective study of 188 high-risk patients having GreenLight HPS treatment in China. A subgroup taking anticoagulants (n=45) were compared with the entire high-risk cohort (n=188), but statistical analysis was not done. Perioperative outcomes were similar between the anticoagulant group and the entire cohort, with comparable operation times (49.5 minutes compared to 50.8 minutes), admission times (4.5 days for both) and lengths of catheterisation (1.8 days compared to 1.9 days). Follow-up results were not reported for the anticoagulant group.

3.14 Hueber et al. (2015) described a large retrospective study of 1196 patients having GreenLight XPS treatment in 6 centres in Canada, the US, France and England. Subgroups of patients with larger prostates (>80 ml, n=741) were compared with those with smaller prostates (<80 ml, n=387) with a 2-year follow-up. The population included some patients on anticoagulants and in urinary retention. Perioperative results in groups with larger versus smaller prostates showed that operation times and length of catheterisation increased with prostate size (80 minutes compared with 45 minutes, p<0.01; 34 hours compared with 26 hours, p<0.01), but mean hospital stay was 24 hours in both groups. There were no significant differences in adverse events, apart from a greater conversion to TURP in the larger prostate group (8.4% compared with 0.6%, p<0.01). Improvements in IPSS, quality of life score, Qmax and PVR from baseline were not significantly different between groups.

3.15 West and Woo (2015) described a retrospective study of 137 patients having GreenLight XPS treatment at a single centre in Australia, who were divided into subgroups according to prostate size: <40 ml (n=27), 40–79 ml (n=56), 80–119 ml (n=38), >120 ml (n=22). Operating time increased with prostate size (p<0.01 between groups) and there were no statistically significant differences across groups in other reported outcomes, including duration of catheterisation, length of hospital stay, incidence of adverse events and proportion discharged home catheter-free within 24 hours.

Additional work by the external assessment centre

3.16 The external assessment centre identified 1 trial that compared GreenLight XPS and holmium laser enucleation of the prostate (HoLEP) using GreenLight XPS for vapo-enucleation instead of standard vaporisation techniques (Elshal et al. 2015). The external assessment centre also identified a randomised controlled trial which compared GreenLight HPS with HoLEP (Elmansy et al. 2012).

3.17 Elshal et al. (2015) described a randomised controlled trial of 103 patients with LUTS secondary to BPH, randomised to either vapo-enucleation with GreenLight XPS or HoLEP done by a single surgeon in Canada. The population included high-risk subgroups, including patients taking anticoagulants, and those with urinary retention and larger prostates. Peri- and postoperative outcomes at 12 months did not differ significantly between GreenLight XPS and HoLEP, apart from Qmax (18.5 ml compared with 31.1 ml, p=0.01) and the percentage of patients with a hospital stay of more than 1 night (23.5% compared with 6.4%, p=0.02). GreenLight XPS vapo-enucleation is a different technique to photoselective vaporisation and is described as 'off-label' use by the company, so this study was not included in the submission. The external assessment centre included this study in its assessment as the only direct evidence available comparing GreenLight XPS with HoLEP. Expert opinion stated that using GreenLight XPS for vapo-enucleation is a valid but novel technique that does not represent standard care in the NHS.

3.18 Elmansy et al. (2012) studied 80 patients with LUTS secondary to BPH with prostates larger than 60 ml, who were randomised to GreenLight HPS or HoLEP treatment in a single centre in Canada. The population included high-risk patients taking anticoagulants, those in urinary retention and those with large prostates (62–160 ml). Results showed no difference in operative time or duration of catheterisation between groups. Functional outcomes at 12 months were similar for GreenLight HPS and HoLEP, apart from Qmax (24.1 ml compared with 30.5 ml, p=0.02) and PVR (64.8 ml compared 29.4 ml, p=0.02). Adverse event rates were similar between groups, except for 8 cases with GreenLight HPS that required conversion to TURP or HoLEP because of bleeding or inadequate tissue removal. No blood transfusions were needed in either group.

3.19 The external assessment centre undertook a comparative review of studies that compared GreenLight XPS and GreenLight HPS treatment. The review concluded that operating times and mean hospital stays tend to be shorter with GreenLight XPS. The external assessment centre concluded that fewer laser fibres tend to be used with GreenLight XPS, but it also carries a slightly greater risk of capsular perforation. At follow-up, there were few consistent differences in terms of readmissions and complications with the 2 devices, but the numbers of events were low for both treatments.

3.20 The external assessment centre appraised a systematic review of HoLEP compared with TURP (Li et al. 2014). This meta-analysis of 8 randomised controlled trials showed that HoLEP operations take longer than TURP, but the average length of hospital stay is shorter. There were few statistically significant differences in postoperative complications, but HoLEP had statistically significantly better curative outcomes at 12-month follow-up as compared with TURP.

Committee considerations

3.21 The committee concluded from the evidence that GreenLight XPS and TURP are equally effective in treating BPH in non-high-risk patients. The committee also noted evidence of fewer complications and readmissions with GreenLight XPS when compared with TURP.

3.22 The committee noted that published evidence to support the use of GreenLight XPS in high-risk patients was limited in quantity and quality. The committee was advised by experts that in high-risk patients, TURP would often not be considered and that GreenLight XPS offers a safe alternative to TURP. The committee was advised that, because TURP is not normally used in high-risk patients, randomised studies compared with TURP in this group of patients are not considered ethical. The committee therefore concluded that multicentre prospective studies with GreenLight XPS were needed in this population.

3.23 The committee heard expert advice that a 10-minute longer procedure time with GreenLight XPS compared with TURP would be unlikely to have a negative effect on operating theatre lists.

3.24 The committee discussed the lack of long-term outcomes data with GreenLight XPS when compared with TURP for both non-high-risk and high-risk groups. The committee was advised that in the absence of long-term clinical data, other outcomes that were measured and reported in the GOLIATH trial serve as valid surrogates of the durability of symptomatic relief. In this regard, the volume of prostatic tissue resected, reduction in prostate serum antigen (PSA) and 1-year re-operation rates were similar between GreenLight XPS and TURP. Experts highlighted that the 10-year re-operation rate with TURP is approximately 16% and that this may be lower with HoLEP.

3.25 The committee noted that long-term catheterisation is associated with considerable patient morbidity and NHS resource use. The committee also noted comments received during consultation regarding the risk of urinary incontinence after treatment for lower urinary tract symptoms. It accepted expert advice that in the GOLIATH study, urinary incontinence rates at 1-year follow-up were similar for GreenLight XPS and TURP and that all cases of incontinence reported in the study were mild.

3.26 The committee considered its recommendations regarding the use of GreenLight XPS in high-risk patients, having noted that this cohort includes people with comorbidities who may be considered as having a disability under the Equalities Act 2010. Expert advisers stated that GreenLight XPS may provide a safe alternative to TURP in this cohort of patients. However, the committee decided that the current evidence was not sufficiently robust to support a recommendation for the device's routine use for high-risk patients. Instead, the committee recommended collaborative data collection on the effectiveness of GreenLight XPS to supplement the currently limited published evidence for high-risk patients.

  • National Institute for Health and Care Excellence (NICE)