Thulium laser transurethral vaporesection versus transurethral resection of the prostate for benign prostatic obstruction: the UNBLOCS RCT.

BACKGROUND: Transurethral resection of the prostate (TURP) is the standard operation for benign prostatic obstruction (BPO). Thulium laser transurethral vaporesection of the prostate (ThuVARP) vaporises and resects the prostate using a technique similar to TURP. The small amount of existing literature suggests that there may be potential advantages of ThuVARP over TURP. OBJECTIVE: To determine whether or not the outcomes from ThuVARP are equivalent to the outcomes from TURP in men with BPO treated in the NHS. DESIGN: A multicentre, pragmatic, randomised controlled parallel-group trial, with an embedded qualitative study and economic evaluation. SETTING: Seven UK centres - four university teaching hospitals and three district general hospitals. PARTICIPANTS: Men aged ≥ 18 years who were suitable to undergo TURP, presenting with bothersome lower urinary tract symptoms (LUTS) or urinary retention secondary to BPO. INTERVENTIONS: Patients were randomised 1 : 1 to receive TURP or ThuVARP and remained blinded. MAIN OUTCOME MEASURES: Two co-primary outcomes - patient-reported International Prostate Symptom Score (IPSS) and clinical measure of maximum urine flow rate (Qmax) at 12 months post surgery. RESULTS: In total, 410 men were randomised, 205 to each arm. The two procedures were equivalent in terms of IPSS [adjusted mean difference 0.28 points higher for ThuVARP (favouring TURP), 95% confidence interval (CI) -0.92 to 1.49 points]. The two procedures were not equivalent in terms of Qmax (adjusted mean difference 3.12 ml/second in favour of TURP, 95% CI 0.45 to 5.79 ml/second), with TURP deemed superior. Surgical outcomes, such as complications and blood transfusion rates, and hospital stay were similar for both procedures. Patient-reported urinary and sexual symptoms were also similar between the arms. Qualitative interviews indicated similar patient experiences with both procedures. However, 25% of participants in the ThuVARP arm did not undergo their randomised allocation, compared with 2% of participants in the TURP arm. Prostate cancer was also detected less frequently from routine histology after ThuVARP (65% lower odds of detection) in an exploratory analysis. The adjusted mean differences between the arms were similar for secondary care NHS costs (£9 higher for ThuVARP, 95% CI -£359 to £376) and quality-adjusted life-years (0.01 favouring TURP, 95% CI -0.04 to 0.01). LIMITATIONS: Complications were recorded in prespecified categories; those not prespecified were excluded owing to variable reporting. Preoperative Qmax and IPSS data could not be collected for participants with indwelling catheters, making adjustment for baseline status difficult. CONCLUSIONS: TURP was superior to ThuVARP in terms of Qmax, although both operations resulted in a Qmax considered clinically successful. ThuVARP also potentially resulted in lower detection rates of prostate cancer as a result of the smaller volume of tissue available for histology. Length of hospital stay after ThuVARP, anticipated to be a key benefit, was equal to that after TURP in this trial. Overall, both ThuVARP and TURP were effective procedures for BPO, with minor benefits in favour of TURP. Therefore, the results suggest that it may be appropriate that new treatment alternatives continue to be compared with TURP. FUTURE WORK: Longer-term follow-up to assess reoperation rates over time, and research into the comparative effectiveness of ThuVARP and TURP in large prostates. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00788389. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 41. See the NIHR Journals Library website for further project information.

An enlarged prostate can make it difficult, or even impossible, for a man to pass urine by blocking the urine flow from the bladder. This can cause significant problems, and 25,000 men in the UK each year are treated with an operation to relieve their symptoms. The standard operation [transurethral resection of the prostate (TURP)], which uses electricity to shave off the enlarged prostate, is successful, but it can have some complications. There is some evidence to suggest that laser surgery can lead to less blood loss and a shorter stay in hospital, but laser operations can be difficult for surgeons to carry out. This trial has looked at a procedure using a new type of laser called thulium, which uses a very similar surgical technique to TURP and has shown promising results so far. A total of 410 men needing a prostate operation received either TURP or a laser operation. Participants were unaware of which operation they received until the end of the study to ensure a fair comparison. Seven hospitals across the UK were involved over 4 years. The trial mainly assessed the benefits of the operations using a urinary symptom questionnaire completed by participants, and by measuring the speed of passing urine after surgery. Overall, both procedures achieved positive results, and participants expressed high levels of satisfaction with the outcomes. Participants who had either operation reported a similar improvement in urinary symptoms in their questionnaires. However, although both operations did a good job of improving the speed of passing urine, TURP was better. Participants experienced few complications, and the complications that did occur were similar after both operations, including levels of bleeding and time spent in hospital. The cost of the two operations to the NHS was also similar. Overall, we concluded that both operations are suitable for patients with prostate enlargement, with TURP showing some minor additional benefits.

Thulium laser transurethral vaporesection of the prostate versus transurethral resection of the prostate for men with lower urinary tract symptoms or urinary retention (UNBLOCS): a randomised controlled trial.

BACKGROUND: Transurethral resection of the prostate (TURP) is the standard operation for benign prostatic obstruction. Thulium laser transurethral vaporesection of the prostate (ThuVARP) is a technique with suggested advantages over TURP, including reduced complications and hospital stay. We aimed to investigate TURP versus ThuVARP in men with lower urinary tract symptoms or urinary retention secondary to benign prostatic obstruction. METHODS: In this randomised, blinded, parallel-group, pragmatic equivalence trial, men in seven UK hospitals with bothersome lower urinary tract symptoms or urinary retention secondary to benign prostatic obstruction were randomly assigned (1:1) at the point of surgery to receive ThuVARP or TURP. Patients were masked until follow-up completion. Centres used their usual TURP procedure (monopolar or bipolar). All trial surgeons underwent training on the ThuVARP technique. Co-primary outcomes were maximum urinary flow rate (Qmax) and International Prostate Symptom Score (IPSS) at 12-months post-surgery. Equivalence was defined as a difference of 2·5 points or less for IPSS and 4 mL per s or less for Qmax. Analysis was done according to the intention-to-treat principle. The trial is registered with the ISRCTN Registry, ISRCTN00788389. FINDINGS: Between July 23, 2014, and Dec 30, 2016, 410 men were randomly assigned to ThuVARP or TURP, 205 per study group. TURP was superior for Qmax (mean 23·2 mL per s for TURP and 20·2 mL per s for ThuVARP; adjusted difference in means -3·12, 95% CI -5·79 to -0·45). Equivalence was shown for IPSS (mean 6·3 for TURP and 6·4 for ThuVARP; adjusted difference in means 0·28, -0·92 to 1·49). Mean hospital stay was 48 h in both study groups. 91 (45%) of 204 patients in the TURP group and 96 (47%) of 203 patients in the ThuVARP group had at least one complication. INTERPRETATION: TURP and ThuVARP were equivalent for urinary symptom improvement (IPSS) 12-months post-surgery, and TURP was superior for Qmax. Anticipated laser benefits for ThuVARP of reduced hospital stay and complications were not observed. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Clinical and Patient-reported Outcome Measures in Men Referred for Consideration of Surgery to Treat Lower Urinary Tract Symptoms: Baseline Results and Diagnostic Findings of the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM).

BACKGROUND: Clinical evaluation of male lower urinary tract symptoms (MLUTS) in secondary care uses a range of assessments. It is unknown how MLUTS evaluation influences outcome of therapy recommendations and choice, notably urodynamics (UDS; filling cystometry and pressure flow studies). OBJECTIVE: To report participants' sociodemographic and clinical characteristics, and initial diagnostic findings of the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM). UPSTREAM is a randomised controlled trial evaluating whether symptoms are noninferior and surgery rates are lower if UDS is included. DESIGN, SETTING, AND PARTICIPANTS: A total of 820 men (≥18 yr of age) seeking treatment for bothersome LUTS were recruited from 26 National Health Service hospital urology departments. INTERVENTION: Care pathway based on routine, noninvasive tests (control) or routine care plus UDS (intervention arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome is International Prostate Symptom Score (IPSS) and the key secondary outcome is surgery rates 18 mo after randomisation. International Consultation on Incontinence Questionnaires were captured for MLUTS, sexual function, and UDS satisfaction. Baseline clinical and patient-reported outcome measures (PROMs), and UDS findings were informally compared between arms. Trends across age groups for urinary and sexual PROMs were evaluated with a Cuzick's test, and questionnaire items were compared using Pearson's correlation coefficient. RESULTS AND LIMITATIONS: Storage LUTS, notably nocturia, and impaired sexual function are prominent in men being assessed for surgery. Sociodemographic and clinical evaluations were similar between arms. Overall mean IPSS and quality of life scores were 18.94 and 4.13, respectively. Trends were found across age groups, with older men suffering from higher rates of incontinence, nocturia, and erectile dysfunction, and younger men suffering from increased daytime frequency and voiding symptoms. Men undergoing UDS testing expressed high satisfaction with the procedure. CONCLUSIONS: Men being considered for surgery have additional clinical features that may affect treatment decision making and outcomes, notably storage LUTS and impaired sexual function. PATIENT SUMMARY: We describe initial assessment findings from a large clinical study of the treatment pathway for men suffering with bothersome urinary symptoms who were referred to hospital for further treatment, potentially including surgery. We report the patient characteristics and diagnostic test results, including symptom questionnaires, bladder diaries, flow rate tests, and urodynamics.

Urethral injection therapy for urinary incontinence in women.

BACKGROUND: Urinary incontinence imposes a significant health and economic burden to society. Periurethral or transurethral injection of bulking agents is a minimally invasive surgical procedure used as one the surgical treatments of stress urinary incontinence (SUI) in adult women. OBJECTIVES: To assess the effects of periurethral or transurethral injection therapy on the cure or improvement of urinary incontinence in women. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 8 November 2010) and the reference lists of relevant articles. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials of treatment for urinary incontinence in which at least one management arm involved periurethral or transurethral injection therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed methodological quality of each study using explicit criteria. Data extraction was undertaken independently and clarification concerning possible unreported data sought directly from the investigators. MAIN RESULTS: Excluding duplicate reports, we identified 14 trials (excluding one that was subsequently withdrawn from publication and not included in this analysis) including 2004 women that met the inclusion criteria. The limited data available were not suitable for meta-analysis because they all came from separate trials. Trials were small and generally of moderate quality.One trial of 45 women that compared injection therapy with conservative treatment showed early benefit for the injectable therapy with respect to continence grade (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.52 to 0.94) and quality of life (mean difference (MD) 0.54, 95% CI 0.16 to 0.92). Another trial, comparing Injection of autologous fat with placebo, terminated early because of safety concerns. Two trials that compared injection with surgical management found significantly better objective cure in the surgical group (RR 4.77, 95% CI 1.96 to 11.64; and RR 1.69, 95% CI 1.02 to 2.79), although the latter trial data did not reach statistical significance if an intention-to-treat analysis was used.Eight trials compared different agents and all results had wide confidence intervals. Silicone particles, calcium hydroxylapatite, ethylene vinyl alcohol, carbon spheres and dextranomer hyaluronic acid combination gave improvements which were not shown to be more or less efficacious than collagen. Dextranomer hyaluronic acid compound treated patients appeared to have significantly higher rates of injection site complications (16% with the hyaluronic acid compound versus none with collagen; RR 37.78, 95% CI 2.34 to 610.12) and this product has now been withdrawn from the market.A comparison of periurethral and transurethral methods of injection found similar outcomes but a higher (though not statistically significant) rate of early complications in the periurethral group. One trial of 30 women showed a weak (but not clinically significant) advantage for patient satisfaction (data not suitable for analysis in RevMan) after mid-urethral injection in comparison to bladder neck injection but with no demonstrable difference in continence levels. AUTHORS' CONCLUSIONS: The available evidence base remains insufficient to guide practice. In addition, the finding that placebo saline injection was followed by a similar symptomatic improvement to bulking agent injection raises questions about the mechanism of any beneficial effects. One small trial comparing silicone particles with pelvic floor muscle training was suggestive of benefit at three months but it is not known if this was sustained, and the treatment was associated with high levels of postoperative retention and dysuria. Greater symptomatic improvement was observed with surgical treatments, though the advantages need to be set against likely higher risks. No clear-cut conclusions could be drawn from trials comparing alternative agents, although dextranomer hyaluronic acid was associated with more local side effects and is no longer commercially available for this indication. There is insufficient evidence to show superiority of mid-urethral or bladder neck injection. The single trial of autologous fat provides a reminder that periurethral injections can occasionally cause serious side effects. Also, a Brief Economic Commentary (BEC) identified three studies suggesting that urethral bulking agent might be more cost-effective compared with retropubic mid-urethral slings, transobturator or traditional sling procedure when used as an initial treatment in women without hypermobility or as a follow-up to surgery failure provided injection is kept minimal. However, urethral bulking agent might not be cost-effective when compared with traditional sling as an initial treatment of SUI when a patient is followed up for a longer period (15 months post-surgery).

A randomised controlled trial to determine the clinical and cost effectiveness of thulium laser transurethral vaporesection of the prostate (ThuVARP) versus transurethral resection of the prostate (TURP) in the National Health Service (NHS) - the UNBLOCS trial: a study protocol for a randomised controlled trial.

BACKGROUND: Transurethral resection of the prostate (TURP) has been the standard operation for benign prostatic obstruction (BPO) for 40 years, with approximately 25,000 procedures performed annually, and has remained largely unchanged. It is generally a successful operation, but has well-documented risks for the patient. Thulium laser transurethral vaporesection of the prostate (ThuVARP) vaporises and resects the prostate using a surgical technique similar to TURP. The small amount of study data currently available suggests that ThuVARP may have certain advantages over TURP, including reduced blood loss and shorter hospital stay, earlier return to normal activities, and shorter duration of catheterisation. DESIGN: A multicentre, pragmatic, randomised, controlled, parallel-group trial of ThuVARP versus standard TURP in men with BPO. Four hundred and ten men suitable for prostate surgery were randomised to receive either ThuVARP or TURP at four university teaching hospitals, and three district general hospitals. The key aim of the trial is to determine whether ThuVARP is equivalent to TURP judged on both the patient-reported International Prostate Symptom Score (IPSS) and the maximum urine flow rate (Qmax) at 12 months post-surgery. DISCUSSION: The general population has an increased life expectancy. As men get older their prostates enlarge, potentially causing BPO, which often requires surgery. Therefore, as the population ages, more prostate operations are needed to relieve obstruction. There is hence sustained interest in the condition and increasing need to find safer techniques than TURP. Various laser techniques have become available but none are widely used in the NHS because of lengthy training required for surgeons or inferior performance on clinical outcomes. Promising initial evidence from one RCT shows that ThuVARP has equivalent clinical effectiveness when compared to TURP, as well as other potential advantages. As ThuVARP uses a technique similar to that used in TURP, the learning curve is short, potentially making it also very quickly generalisable. This randomised study is designed to provide the high-quality evidence, in an NHS setting, with a range of patient-reported, clinical and cost-effectiveness outcomes, which will underpin and inform future NICE guidance. TRIAL REGISTRATION: ISRCTN registry, ISRCTN00788389 . Registered on 20 September 2013.

Urethral injection therapy for urinary incontinence in women.

BACKGROUND: Periurethral or transurethral injection of bulking agents is a minimally invasive surgical procedure used for the treatment of stress urinary incontinence in adult women. OBJECTIVES: To assess the effects of periurethral or transurethral injection therapy on the cure or improvement of urinary incontinence in women. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 8 November 2010) and the reference lists of relevant articles. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials of treatment for urinary incontinence in which at least one management arm involved periurethral or transurethral injection therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed methodological quality of each study using explicit criteria. Data extraction was undertaken independently and clarification concerning possible unreported data sought directly from the investigators. MAIN RESULTS: Excluding duplicate reports, we identified 14 trials (excluding one that was subsequently withdrawn from publication and not included in this analysis) including 2004 women that met the inclusion criteria. The limited data available were not suitable for meta-analysis because they all came from separate trials. Trials were small and generally of moderate quality.One trial of 45 women that compared injection therapy with conservative treatment showed early benefit for the injectable with respect to continence grade (risk ratio (RR) 0.7, 95% confidence interval (CI) 0.52 to 0.94) and quality of life (RR 0.54, 95% CI 0.16 to 0.92). Another, comparing Injection of autologous fat with placebo, terminated early because of safety concerns. Two trials that compared injection with surgical management found significantly better objective cure in the surgical group (RR 4.77, 95% CI 1.96 to 11.64; and RR 1.69, 95% CI 1.02 to 2.79), although the latter trial data did not reach statistical significance if an intention-to-treat analysis was used.Eight trials compared different agents and all results had wide confidence intervals. Silicone particles, calcium hydroxylapatite, ethylene vinyl alcohol, carbon spheres and dextranomer hyaluronic acid combination gave improvements which were not shown to be more or less efficacious than collagen. Dextranomer hyaluronic acid compound treated patients appeared to have significantly higher rates of injection site complications (16% with the hyaluronic acid compound versus none with collagen; RR 37.78, 95% CI 2.34 to 610) and this product has now been withdrawn from the market.A comparison of periurethral and transurethral methods of injection found similar outcomes but a higher (though not statistically significant) rate of early complications in the periurethral group. One trial of 30 women showed a weak (but not clinically significant) advantage for patient satisfaction (data not suitable for analysis in Revman) after mid-urethral injection in comparison to bladder neck injection but with no demonstrable difference in continence levels. AUTHORS' CONCLUSIONS: The available evidence base remains insufficient to guide practice. In addition, the finding that placebo saline injection was followed by a similar symptomatic improvement to bulking agent injection raises questions about the mechanism of any beneficial effects. One small trial comparing silicone particles with pelvic floor muscle training was suggestive of benefit at three months but it is not known if this was sustained, and the treatment was associated with high levels of postoperative retention and dysuria. Greater symptomatic improvement was observed with surgical treatments, though the advantages need to be set against likely higher risks. No clear-cut conclusions could be drawn from trials comparing alternative agents, although dextranomer hyaluronic acid was associated with more local side effects and is no longer commercially available for this indication. There is insufficient evidence to show superiority of mid-urethral or bladder neck injection. The single trial of autologous fat provides a reminder that periurethral injections can occasionally cause serious side effects.

Glucose transporter polymorphisms are associated with clear-cell renal carcinoma.

Clear-cell renal cell carcinoma (CCRCC) is identified by abundant glycogen-rich cytoplasm, due to the aberrant influx and storage of glucose. The objective was to investigate the frequency of polymorphisms of the facilitative glucose transporter (GLUT1). GLUT1 is a downstream target of Hypoxia-inducible factor (HIF-1alpha), a mediator of hypoxia-controlled angiogenesis. In this study, we examine the allelic frequency of polymorphisms in the promoter and the second intron of the GLUT1 gene. Genomic DNA was extracted from normal tissue of 92 patients undergoing nephrectomy for CCRCC, and 99 normal cord blood DNA samples were used to provide control frequencies. The regions of DNA encompassing the polymorphisms were amplified and digested with appropriate endonuclases. The products were separated and viewed by gel electrophoresis. There was a highly significant decrease in the A-2841 genotype (P=0.0004) in the promoter region of those patients with CCRCC compared to the control population. There was also a significant decrease in the T+22999 allele in the intron 2 of those patents with CCRCC (P=0.004) compared to the same control population. This study suggests that GLUT1 is one of a number of genes that may increase susceptibility to developing CCRCC.