'Pain-free TRUS B': a phase 3 double-blind placebo-controlled randomized trial of methoxyflurane with periprostatic local anaesthesia to reduce the discomfort of transrectal ultrasonography-guided prostate biopsy (ANZUP 1501).

OBJECTIVE: To determine whether the addition of inhaled methoxyflurane to periprostatic infiltration of local anaesthetic (PILA) during transrectal ultrasonography-guided prostate biopsies (TRUSBs) improved pain and other aspects of the experience. PATIENTS AND METHODS: We conducted a multicentre, placebo-controlled, double-blind, randomized phase 3 trial, involving 420 men undergoing their first TRUSB. The intervention was PILA plus a patient-controlled device containing either 3 mL methoxyflurane, or 3 mL 0.9% saline plus one drop of methoxyflurane to preserve blinding. The primary outcome was the pain score (0-10) reported by the participant after 15 min. Secondary outcomes included ratings of other aspects of the biopsy experience, willingness to undergo future biopsies, urologists' ratings, biopsy completion, and adverse events. RESULTS: The mean (SE) pain scores 15 min after TRUSB were 2.51 (0.22) in those assigned methoxyflurane vs 2.82 (0.22) for placebo (difference 0.31, 95% confidence interval [CI] -0.75 to 0.14; P = 0.18). Methoxyflurane was associated with better scores for discomfort (difference -0.48, 95% CI -0.92 to -0.03; P = 0.035, adjusted [adj.] P = 0.076), whole experience (difference -0.50, 95% CI -0.92 to -0.08; P = 0.021, adj. P = 0.053), and willingness to undergo repeat biopsies (odds ratio 1.67, 95% CI 1.12-2.49; P = 0.01) than placebo. Methoxyflurane resulted in higher scores for drowsiness (difference +1.64, 95% CI 1.21-2.07; P < 0.001, adj. P < 0.001) and dizziness (difference +1.78, 95% CI 1.31-2.24; P < 0.001, adj. P < 0.001) than placebo. There was no significant difference in the number of ≥ grade 3 adverse events. CONCLUSIONS: We found no evidence that methoxyflurane improved pain scores at 15 min, however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

Mini-Review: What Is New in Urolift?

CONTEXT: Lower urinary tract symptoms (LUTS) are one of the most common benign conditions affecting aging men. Among surgical procedures, minimally invasive treatment options have emerged with the main objective to be at least equally effective as current standard techniques, but with a more favourable safety profile. OBJECTIVE: To present the technical principle for prostatic urethral lift (PUL) and review clinical outcomes. EVIDENCE ACQUISITION: Medline, PubMed, the Cochrane database, and Embase were screened for randomised controlled trials, clinical trials, and reviews on PUL. EVIDENCE SYNTHESIS: Data from the L.I.F.T study proved that PUL can provide rapid and durable relief of LUTS without compromising sexual function. The BPH6 trial compared PUL with transurethral resection of the prostate (TURP), and its outcomes indicated that improvement of LUTS was more pronounced after TURP, whereas PUL was superior in terms of quality of recovery, ejaculatory function, and quality of sleep. CONCLUSIONS: PUL is an attractive option for selected patients who seek rapid and durable relief of LUTS with complete preservation of sexual function and fast recovery after intervention. PATIENT SUMMARY: Prostatic urethral lift is an efficient and safe minimally invasive procedure that offers rapid and durable relief of lower urinary tract symptoms without compromising sexual function.

Perioperative antithrombotic therapy in patients undergoing endoscopic urologic surgery: where do we stand with current literature?

The number of patients on chronic anticoagulant or antiplatelet therapy requiring endoscopic urological surgery is increasing worldwide. Therefore, there is a strong demand to standardize the perioperative treatment of this cohort of patients, both from a surgical and cardiological point of view, balancing the risks of bleeding versus thrombosis, and the important possible clinical and medical legal repercussions therein. Although literature is scarce and the quality of evidence quite low, in line with other surgical specialties, guidelines and recommendations for the management of urological patients have begun to emerge. The aim of this review is to analyze current available literature and evidence on the most common endoscopic procedures performed in this high-risk group of patients, focusing on the perioperative management. In particular, to analyze the most frequently performed endoscopic procedures for the treatment of benign prostate enlargement (transurethral resection of the prostate, Thulium, Holmium and greenlight laser prostatectomy), bladder cancer (transurethral resection of the bladder), upper urinary tract urothelial cancer, and nephrolithiasis. Despite the lack of randomized studies, regardless of individual patient considerations, studies would support continuation of acetylsalicylic acid, which is recommended by cardiologists, in patients with intermediate/high risk of coronary thrombosis. In contrast, multiple studies found that bridging with light weight molecular weight heparin can potentially lead to more bleeding than continuation of the anticoagulant(s) and antiplatelet therapy, and caution with bridging is advised. All urologists should familiarize themselves with emerging guidelines and recommendations, and always be prepared to discuss specific cases or scenarios in a dedicated multidisciplinary team.

Evaluation of the changing landscape of prostate cancer diagnosis and management from 2005 to 2016.

BACKGROUND: Approaches to prostate cancer (PCa) diagnosis and treatment have evolved significantly over past decades. There has been an increasing focus on minimizing overdiagnosis and overtreatment of clinically insignificant PCa. The objective of this study was to evaluate the changes in the diagnostic approach and initial treatment strategy that has evolved over time in an Australian urological private practice. MATERIALS AND METHODS: Men with newly diagnosed PCa were identified from the private practice electronic and paper medical records from 2005 to 2016 and data was consolidated into six groups of 2-year intervals. Diagnostic strategy was analyzed with particular reference to the use of multiparametric magnetic resonance imaging (mpMRI) scan and 68Ga-prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) scans. National Comprehensive Cancer Network risk group stratification was correlated with initial treatment strategy and compared over time. RESULTS: Chart review identified 839 men who had a mean age of 65.8 years. In 2011-2012, prebiopsy mpMRI scan was introduced. Its uptake correlated with a decrease in numbers of men diagnosed with low risk cancer (r = -0.80, P = 0.04) and an increase in numbers of men diagnosed with high-risk cancer (r = 0.90, P = 0.01). The use of 68Ga-PSMA PET/CT was associated with decreasing use of CT and bone scans performed. Open radical prostatectomy had a declining trend particularly when robotic surgery (robotic assisted radical prostatectomy (RARP)) was introduced. Pelvic lymph node dissections performed progressively decreased. An increased use of luteinizing hormone receptor hormone (LHRH) antagonists was seen in favor of LHRH agonists. Whilst use of high dose rate brachytherapy declined, there was an increased use of low dose rate brachytherapy. CONCLUSION: Prebiopsy mpMRI has been associated with an increased proportion of newly diagnosed men having clinically significant PCa. Over time, 68Ga-PSMA PET/CT scans, robotic assisted radical prostatectomy (RARP) and LHRH antagonists have increased in use, whilst CT and bone scans, and pelvic lymph node dissections have decreased.

Perioperative adverse events in patients on continued anticoagulation undergoing photoselective vaporisation of the prostate with the 180-W Greenlight lithium triborate laser.

OBJECTIVES: To compare perioperative factors and adverse events (AEs) in men undergoing photoselective vaporisation of the prostate (PVP) with or without continued anticoagulation therapy. PATIENTS AND METHODS: Retrospective review of a PVP database of men treated with the 180-W lithium triborate (LBO) laser from 2010 to 2016. Of 373 men, 59 underwent PVP with continued anticoagulant therapy, which was defined as treatment with heparin, warfarin, clopidogrel, dipyridamol or new oral anticoagulant drugs. Perioperative factors and AEs occurring within 90 days of surgery were analysed. RESULTS: There was no statistically significant difference in the overall incidence of perioperative AEs between those receiving and not receiving anticoagulation therapy (30.5% vs 19.9%, P = 0.07). However, there was a statistically significant difference in the incidence of high-grade Clavien-Dindo events in men who continued anticoagulation during PVP (P = 0.01). No men required blood transfusion. There was no difference in operative times and energy utilisation between the groups. In all, 53 of the 59 men in the anticoagulation group had a high-grade American Society of Anesthesiologists score, compared to 27 of the 272 men in the control group. The anticoagulation group were also significantly older. The anticoagulation group had a significantly longer length of hospital stay and duration of catheterisation compared to the controls. CONCLUSIONS: While continued anticoagulation therapy is not associated with an overall increase in perioperative AEs, it is associated with an increased rate of high-grade Clavien-Dindo events. The findings of this study suggest that there should be caution in extrapolating results about the safety profile of earlier generation lasers to the current 180-W LBO laser for patients on anticoagulation.

Current methods of analgesia for transrectal ultrasonography (TRUS)-guided prostate biopsy -- a systematic review.

Transrectal ultrasonography (TRUS)-guided prostate biopsy is the most commonly used method of sampling prostate tissue for the diagnosis of prostate cancer. The technique is well recognised to potentially cause severe pain and discomfort for patients and this has led to numerous attempts to devise ways to minimise these problems. This systematic review summarises the techniques that have been described to date, with special reference to studies using either a visual analogue or numerical analogue scale to report outcomes. Commonly used approaches that are effective to minimise pain or discomfort include intravenous sedoanalgesia, inhalational agents and periprostatic infiltration of local anaesthetic. Whilst diclofenac suppositories are more effective than placebo, intra-rectal local anaesthetic gels appear to be of no benefit. Performing TRUS-guided prostate biopsy without any form analgesia is not appropriate.

Minimally invasive prostatic urethral lift: surgical technique and multinational experience.

BACKGROUND: Many men with benign prostatic hyperplasia (BPH) are dissatisfied with current treatment options. Although transurethral resection of the prostate (TURP) remains the gold standard, many patients seek a less invasive alternative. OBJECTIVE: We describe the surgical technique and results of a novel minimally invasive implant procedure that offers symptom relief and improved voiding flow in an international series of patients. DESIGN, SETTING, AND PARTICIPANTS: A total of 102 men with symptomatic BPH were consecutively treated at seven centers across five countries. Patients were evaluated up to a median follow-up of 1 yr postprocedure. Average age, prostate size, and International Prostate Symptom Score (IPSS) were 68 yr, 48 cm(3), and 23, respectively. SURGICAL PROCEDURE: The prostatic urethral lift mechanically opens the prostatic urethra with UroLift implants that are placed transurethrally under cystoscopic visualization, thereby separating the encroaching prostatic lobes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were evaluated pre- and postoperatively by the IPSS, Quality-of-Life (QOL) scale, Benign Prostatic Hyperplasia Impact Index, maximum flow rate (Qmax), and adverse event reports including sexual function. RESULTS AND LIMITATIONS: All procedures were completed successfully with a mean of 4.5 implants without serious adverse effects. Patients experienced symptom relief by 2 wk that was sustained to 12 mo. Mean IPSS, QOL, and Qmax improved 36%, 39%, and 38% by 2 wk, and 52%, 53%, and 51% at 12 mo (p<0.001), respectively. Adverse events were mild and transient. There were no reports of loss of antegrade ejaculation. A total of 6.5% of patients progressed to TURP without complication. Study limitations include the retrospective single-arm nature and the modest patient number. CONCLUSIONS: Prostatic urethral lift has promise for BPH. It is minimally invasive, can be done under local anesthesia, does not appear to cause retrograde ejaculation, and improves symptoms and voiding flow. This study corroborates prior published results. Larger series with randomisation, comparator treatments, and longer follow-up are underway.

Photoselective vaporisation of the prostate using 80-W and 120-W laser versus transurethral resection of the prostate for benign prostatic hyperplasia: a systematic review with meta-analysis from 2002 to 2012.

CONTEXT: Photoselective vaporisation (PVP) of the prostate is being used increasingly to treat symptomatic benign prostatic hyperplasia, due to the associated lower morbidity. Holmium laser enucleation of the prostate was considered to be the treatment with the highest evidence; however, evidence for PVP has dramatically increased recently. OBJECTIVE: To conduct a systematic review and meta-analysis of level 1 evidence studies to determine the effectiveness of PVP versus transurethral resection of the prostate (TURP) for surgical treatment of benign prostatic hyperplasia. Outcomes reviewed included perioperative data, complications, and functional outcomes. EVIDENCE ACQUISITION: Biomedical databases from 2002 to 2012 and American Urological Association and European Association of Urology conference proceedings from 2007 to 2011 were searched. Trials were included if they were randomised controlled trials, had PVP as the intervention, and TURP as control. Meta-analysis was performed using a random effects model. EVIDENCE SYNTHESIS: Nine trials were identified with 448 patients undergoing PVP (80 W in five trials and 120 W in four trials) and 441 undergoing TURP. Catheterisation time and length of stay were shorter in the PVP group by 1.91 d (95% confidence interval [CI], 1.47-2.35; p<0.00001) and 2.13 d (95% CI, 1.78-2.48; p<0.00001), respectively. Operation time was shorter in the TURP group by 19.64 min (95% CI, 9.05-30.23; p=0.0003). Blood transfusion was significantly less likely in the PVP group (risk ratio: 0.16; 95% CI, 0.05-0.53; p=0.003). There were no significant differences between PVP and TURP when comparing other complications. Regarding functional outcomes, six studies found no difference between PVP and TURP, two favoured TURP, and one favoured PVP. CONCLUSIONS: Perioperative outcomes of catheterisation time and length of hospital stay were shorter with PVP, whereas operative time was longer with PVP. Postoperative complications of blood transfusion and clot retention were significantly less likely with PVP; no difference was noted in other complications. Overall, no difference was noted in intermediate-term functional outcomes.

Laser prostatectomy of lower urinary tract symptoms due to benign prostate enlargement: a critical review of evidence.

PURPOSE OF REVIEW: Different transurethral prostatic laser systems are available. In 2011, new Oxford evidence levels (LoEs) were published with significant changes compared with the former version. They are easier to use and incorporate more clinical aspects. Randomized trials of laser systems used before 2002, except Holmium laser, were not included in this critical evidence analysis, as these techniques are not in clinical use any more. RECENT FINDINGS: Twenty-five [18 Holmium enucleation of the prostate (HoLEP) and seven photoselective vaporization of the prostate (PVP)] randomized trials covering transurethral electroresection of the prostate or HoLEP, PVP or Thulium laser enucleation were identified. According to evidence levels, there is a large gap in terms of long-term follow-up. The majority of randomised controlled trials are of low quality. Typically with HoLEP, many articles were published covering the same patient population (LoE II). Only one randomised controlled trial was published with Tm:YAG prostatectomy (LoE II) and none with diode lasers (980-1340 nm, LoE IV-V). Large cohort studies (LoE III-IV) provide additional evidence for PVP and HoLEP, typically for subgroups. SUMMARY: In 2011, higher evidence on HoLEP and PVP has been published. Evidence levels for HoLEP and PVP are comparable with meta-analysis (LoE II). However, evidence that laser prostatectomy is better than transurethral electroresection of the prostate in terms of efficacy is lacking (LoE II). All lasers are safer in terms of perioperative bleeding (LoE II).

Acceptance of repeat transrectal ultrasonography guided prostate biopsies with local anaesthesia.

OBJECTIVE: • To measure patient discomfort associated with transrectal ultrasonography guided prostate biopsy (TRUSPB) performed with periprostatic local anaesthetic (LA) infiltration and to document agreement to possible repeat biopsy, as a recent audit showed that 86% of Australian urologists performed prostate biopsies using sedation or general anaesthesia (GA), which implies many urologists think patients are unwilling to tolerate the procedure under LA block and/or may refuse a repeat procedure. PATIENTS AND METHODS: • This was a prospective cohort study following all men undergoing TRUSPB in 2008. • Immediately after the procedure the men were asked to complete a visual analogue pain score. • They were then asked whether, if it was necessary to have a repeat biopsy, they would agree to LA again or request GA/sedation. RESULTS: • In all, 476 men participated in the study with a mean age of 64 years. • Of these, 464 men (97.5%) tolerated the procedure well and would, if required, agree to repeat biopsy with LA. • Only 12 men (2.5%) indicated they would request GA/sedation if a repeat biopsy was necessary. CONCLUSION: • The vast majority of men accepted having prostate biopsy with LA infiltration and therefore this should be the first method offered. • It may be possible to screen for men who would not tolerate biopsy under LA. • Resource saving by performing most biopsies under LA can be estimated to be >A$10 million annually.

A comparison of techniques for eliciting patient preferences in patients with benign prostatic hyperplasia.

PURPOSE: We compared the Health Utility Index (HUI), EuroQol (EQ-5D) and time trade-off methods to identify the most suitable technique for collecting preference data in a clinical trial of patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 29 men with symptomatic BPH were interviewed by a single trained interviewer who collected demographic data and administered EQ-5D and time trade-off questionnaires. Participants self-administered the HUI and a symptom severity index, the International Prostate Symptom Score (I-PSS) questionnaire. Utility values for current patient health states obtained from the HUI, EQ-5D and time trade-off questionnaires were compared and their relationship with I-PSS data was examined using Spearman's correlation coefficients. Administration time and patient assessments of the relevance of the questions were also compared for the 3 methods. RESULTS: Although mean utility values for HUI, EQ-5D and 1-year time trade-off were similar, only utility values elicited using time trade-off with a 1-year time frame significantly correlated with symptom scores. The 1 and 10-year time trade-off derived values were reasonable predictors of the I-PSS with multiple correlation coefficient values of 0.379 and 0.265, respectively. All participants indicated that the HUI and EQ-5D were appropriate for assessing BPH, while approximately 10% considered time trade-off questions irrelevant. Average completion time for the HUI, time trade-off and EQ-5D questionnaires was 31, 25 and 10 minutes, respectively. CONCLUSIONS: Because only time trade-off resulted in utility values that significantly correlated with symptom scores, we recommend its use for estimating utility in clinical trials of BPH.