Mark Speakman

Meta-analysis of Functional Outcomes and Complications Following Transurethral Procedures for Lower Urinary Tract Symptoms Resulting from Benign Prostatic Enlargement

CONTEXT There is a continuous decline in the number of transurethral resections of the prostate (TURP) and an increase use of minimally invasive surgical therapy (MIST) for lower urinary tract symptoms resulting from benign prostatic enlargement. Current results from randomised controlled trials (RCT) and methodologically sound prospective studies suggest that some of the proposed procedures have the potential to replace TURP. OBJECTIVE To determine the contemporary status of TURP and of the currently most commonly applied transurethral MISTs: (1) bipolar TURP, (2) bipolar transurethral vaporisation of the prostate (bipolar TUVP), (3) holmium laser enucleation of the prostate (HoLEP), and (4) potassium-titanyl-phosphate (KTP) laser vaporisation of the prostate. EVIDENCE ACQUISITION This meta-analysis was based on a systematic Medline search assessing the period 1997-2009. All RCTs comparing TURP and the most commonly discussed ablative treatments were included. The end points of our analyses were functional outcomes and treatment-related adverse events. EVIDENCE SYNTHESIS Twenty-seven publications involving 23 different RCTs with a total of 2245 patients provided the highest level of evidence available (level 1b) and were fully assessed. Meta-analysis was conducted with SAS v.9.1.3 (SAS Institute, Cary, NC, USA). Forest plots were produced using the R software. Pooled odds ratios and 95% confidence intervals were calculated between various operative techniques versus TURP. Functional results between the specific transurethral procedures versus TURP were summarised as differences in means. CONCLUSIONS This meta-analysis demonstrates statistically comparable efficacy and overall morbidity for MISTs versus contemporary TURP. Type, category (minor vs major), and the number of complications (safety profile) vary specifically for each of the different transurethral techniques. We feel that the individual patients clinical profile should be carefully assessed to identify the most appropriate transurethral technique.

Tamsulosin 0,4 mg once daily : effect on sexual function in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction.

Objective: To evaluate the effect of tamsulosin, 0.4 mg once daily, on sexual function in comparison with placebo and alfuzosin, 2.5 mg three times daily, in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). Methods: Data from 830 patients randomized into three European multicenter studies with similar protocols were analyzed. In two studies, patients were randomized to receive either tamsulosin, 0.4 mg once daily, or placebo, and in the third, patients were randomized to receive either a fixed dose of tamsulosin, 0.4 mg once daily, or alfuzosin, titrated to 2.5 mg three times daily. The studies employed a 2-week placebo run-in period, followed by a 12-week study period. Sexual function was assessed by related adverse events and by a sexual function score determined from a life-style questionnaire. Results: Abnormal ejaculation occurred significantly more frequently in patients treated with tamsulosin than in those receiving placebo (p = 0.045); however, the incidence of abnormal ejaculation was similar in patients receiving tamsulosin or alfuzosin in the comparative study. Abnormal ejaculation was not perceived as a major problem by the patients since it resulted in few treatment discontinuations (n = 3). It was also reversible on drug withdrawal. There was no difference between tamsulosin and placebo or alfuzosin with regard to the occurrence of decreased libido or impotence. In addition, there was no significant difference in the change in sexual function score between patients treated with tamsulosin and those treated with alfuzosin. Compared with patients receiving placebo, there was, however, a significant improvement in total sexual function score in patients receiving tamsulosin (p = 0.042). Conclusions: Tamsulosin, 0.4 mg once daily, is well tolerated and has no overall negative impact on sexual function compared with placebo or alfuzosin. Compared with placebo, tamsulosin may even improve sexual function.

Guideline for the primary care management of male lower urinary tract symptoms

As my Comment in the first section of the journal suggested, the MTOPS results have offered the possibility to general practitioners of reducing the risk of side‐effects of BPH, particularly urinary retention, by giving patients dual therapy with 5α‐reductase inhibitor and alpha‐adrenergic blocker. Authors from the UK present guidelines for the primary case management of male LUTS, which significantly fills this gap in the literature.

Tamsulosin: 3-year long-term efficacy and safety in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction: Analysis of a European, multinational, multicenter, open-label study

Objective: This open-label extension study evaluated the efficacy and safety of tamsulosin (0.4 mg as a modified release formulation) once daily in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) treated for up to 3 years. Methods: Patients were enrolled from two European, 12-week, placebo-controlled trials. This analysis reports on 355 patients randomized originally to tamsulosin (n = 244) or placebo (n = 111) in the two placebo-controlled trials with follow-up data for up to 3 years. Results: The significant improvements in the primary efficacy parameters, maximum urinary flow rate (Qmax) and total Boyarsky symptom score that were observed during the placebo-controlled trials were sustained throughout the long-term extension study for up to 3 years in patients who remained on therapy. Mean Qmax increased from baseline (range 0.7–1.8 ml/s; p < 0.05 vs. baseline) and remained between 11.5 and 12 ml/s during the entire follow-up period. Total Boyarsky symptom score also improved from baseline (range –3.7 to –4.1 (or –39 to –44%); p < 0.001 vs. baseline). Similarly, the percentage of treatment responders, defined as an increase in Qmax of ≥30% or a decrease in total symptom score of ≥25%, remained constant throughout the 3-year period. The number of patients who had a clinically significant total Boyarsky symptom score response ranged between 69 and 80%. During the 3-year study period, 95 patients (27%) experienced an adverse event considered to be possibly or probably related to study medication, the most common of which (occurring in ≤6% of patients) were dizziness and abnormal ejaculation. There were no clinically significant changes in blood pressure or pulse rate during the study. Conclusion: Long-term tamsulosin therapy is safe, well-tolerated and improvements in urinary flow and symptoms are maintained in patients with LUTS suggestive of BPO who remain on treatment for up to 3 years.

Prospective, Randomized, Multinational Study of Prostatic Urethral Lift Versus Transurethral Resection of the Prostate: 12-month Results from the BPH6 Study

BACKGROUND Transurethral resection of the prostate (TURP) is considered the gold standard for male lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). However, TURP may lead to sexual dysfunction and incontinence, and has a long recovery period. Prostatic urethral lift (PUL) is a treatment option that may overcome these limitations. OBJECTIVE To compare PUL to TURP with regard to LUTS improvement, recovery, worsening of erectile and ejaculatory function, continence and safety (BPH6). DESIGN, SETTING, AND PARTICIPANTS Prospective, randomized, controlled trial at 10 European centers involving 80 men with BPH LUTS. INTERVENTION PUL or TURP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The BPH6 responder endpoint assesses symptom relief, quality of recovery, erectile function preservation, ejaculatory function preservation, continence preservation, and safety. Noninferiority was evaluated using a one-sided lower 95% confidence limit for the difference between PUL and TURP performance. RESULTS AND LIMITATIONS Preservation of ejaculation and quality of recovery were superior with PUL (p<0.01). Significant symptom relief was achieved in both treatment arms. The study demonstrated not only noninferiority but also superiority of PUL over TURP on the BPH6 endpoint. Study limitations were the small sample size and the inability to blind participants to enrollment arm. CONCLUSIONS Assessment of individual BPH6 elements revealed that PUL was superior to TURP with respect to quality of recovery and preservation of ejaculatory function. PUL was superior to TURP according to the novel BPH6 responder endpoint, which needs to be validated in future studies. PATIENT SUMMARY In this study, participants who underwent prostatic urethral lift responded significantly better than those who underwent transurethral resection of the prostate as therapy for benign prostatic hyperplasia with regard to important aspects of quality of life. TRIAL REGISTRATION ClinicalTrials.gov NCT01533038.

Combination Therapy with Solifenacin and Tamsulosin Oral Controlled Absorption System in a Single Tablet for Lower Urinary Tract Symptoms in Men: Efficacy and Safety Results from the Randomised Controlled NEPTUNE Trial

BACKGROUND Storage symptoms are particularly bothersome in men with lower urinary tract symptoms (LUTS) but may not be adequately treated by α-blocker monotherapy. OBJECTIVE To assess the efficacy and safety of a fixed-dose combination (FDC) of solifenacin and an oral controlled absorption system (OCAS) formulation of tamsulosin compared with placebo and compared with tamsulosin OCAS (TOCAS) monotherapy in men with moderate to severe storage symptoms and voiding symptoms. DESIGN, SETTING, AND PARTICIPANTS A double-blind 12-wk phase 3 study in 1334 men with storage and voiding LUTS: total International Prostate Symptom Score (IPSS) ≥ 13, maximum urinary flow rate (Qmax) 4.0-12.0 ml/s, two or more urgency episodes per 24 h of Patient Perception of Intensity of Urgency Scale grade 3 or 4, and eight or more micturitions per 24h. INTERVENTION Patients were randomised to placebo, TOCAS 0.4 mg, FDC solifenacin 6 mg plus TOCAS 0.4 mg, or FDC solifenacin 9 mg plus TOCAS 0.4 mg. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary efficacy end points were (1) total IPSS and (2) Total Urgency and Frequency Score (TUFS). An FDC met the success criteria if it demonstrated superiority compared with placebo and noninferiority compared with TOCAS for total IPSS, as well as superiority compared with TOCAS for TUFS. RESULTS AND LIMITATIONS Reductions in total IPSS and TUFS were observed with both solifenacin 6 mg plus TOCAS (-7.0 and -8.1, respectively) and solifenacin 9 mg plus TOCAS (-6.5 and -7.6, respectively) compared with TOCAS (-6.2 and -6.7, respectively) and placebo (-5.4 and -4.4, respectively). Solifenacin 6 mg plus TOCAS met all prespecified success criteria for both primary end points, while solifenacin 9 mg plus TOCAS met success criteria compared with placebo but not compared with TOCAS. Both FDCs improved quality of life (QoL) measures and were well tolerated, with low incidences of acute urinary retention. CONCLUSIONS The FDC of solifenacin 6 mg plus TOCAS significantly improved storage and voiding symptoms, as well as QoL parameters, compared with placebo. This FDC also improved storage symptoms and QoL compared with TOCAS alone in men with moderate to severe storage symptoms and voiding symptoms, and it was well tolerated.

Burden of male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) – focus on the UK

Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) can be bothersome and negatively impact on a patients quality of life (QoL). As the prevalence of LUTS/BPH increases with age, the burden on the healthcare system and society may increase due to the ageing population. This review unifies literature on the burden of LUTS/BPH on patients and society, particularly in the UK. LUTS/BPH is associated with high personal and societal costs, both in direct medical costs and indirect losses in daily functioning, and through its negative impact on QoL for patients and partners. LUTS/BPH is often underdiagnosed and undertreated. Men should be encouraged to seek medical advice for this condition and should not accept it as part of ageing, while clinicians should be more active in the identification and treatment of LUTS/BPH.

Erectile dysfunction and lower urinary tract symptoms: a consensus on the importance of co-diagnosis

Despite differences in design, many large epidemiological studies using well‐powered multivariate analyses consistently provide overwhelming evidence of a link between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS). Preclinical evidence suggests that several common pathophysiological mechanisms are involved in the development of both ED and LUTS. We recommend that patients seeking consultation for one condition should always be screened for the other condition. We propose that co‐diagnosis would ensure that patient management accounts for all possible co‐morbid and associated conditions. Medical, socio‐demographic and lifestyle risk factors can help to inform diagnoses and should be taken into consideration during the initial consultation. Awareness of risk factors may alert physicians to patients at risk of ED or LUTS and so allow them to manage patients accordingly; early diagnosis of ED in patients with LUTS, for example, could help reduce the risk of subsequent cardiovascular disease. Prescribing physicians should be aware of the sexual adverse effects of many treatments currently recommended for LUTS; sexual function should be evaluated prior to commencement of treatment, and monitored throughout treatment to ensure that the choice of drug is appropriate.

Who Should Be Treated and How? Evidence-Based Medicine in Symptomatic BPH

The management of benign prostatic hyperplasia (BPH), although based on the best available evidence, should be individualised to patients’ circumstances and personal choices. Subjective symptoms (LUTS), bothersomeness and negative impact on the quality of life are the main reasons for the patient to seek treatment for BPH. Therefore, the improvement of this subjective discomfort ought to be an important treatment goal and criterion of appraisal. Although transurethral resection of the prostate (TURP) remains the most effective and definite way of treatment, it is less attractive from the patients’ perspective, especially after medical treatments with better tolerability have become available. For this reason, the indication for surgery is nowadays set on more stringent criteria of ‘appropriateness’. Several new, less-invasive surgical techniques have been introduced, but their ultimate position is difficult to appraise because of the lack of appropriate long-term data from prospective, properly designed, controlled trials, also in terms of lack of data on cost-efficiency. Therefore, medical therapy with either finasteride or α1-blockers remains an attractive therapeutic alternative: both approaches are effective, reasonably well tolerated and in the ‘shorter’ term more cost-efficient than TURP. Available evidence suggests that finasteride is mainly effective on a long-term basis in patients with substantially enlarged prostates. In the shorter term, α1-blockers have consistently been shown to be more effective than finasteride, irrespective of prostate size. In addition, α1-blockers have the important advantage of a rapid alleviation of subjective discomfort. To date, the combination of an α1-blocker and finasteride seems to offer no more than an α1-blocker alone. Among the α1-blockers, tamsulosin is particularly suited because of its clinical selectivity (i.e. its low risk of safety relevant cardiovascular effects) and its ease of use (once daily administration without the need for stepwise dose increments on treatment initiation).

A cost-utility analysis of once daily solifenacin compared to tolterodine in the treatment of overactive bladder syndrome

ABSTRACT Objective: To evaluate the cost-utility of solifenacin, a new generation antimuscarinic, compared with tolterodine in the treatment of overactive bladder syndrome (OAB), from the perspective of the UK National Health Service (NHS). Research design and methods: A 1-year Markov model was constructed using data from a 12-week, randomised, double-blind study that compared flexible dosing with solifenacin (5 mg and 10 mg) with tolterodine (IR 2 mg bd/ER 4 mg) in adults with OAB. The model incorporated five discrete health states that were based on disease severity (micturitions/day and incontinence episodes/day). A ‘drop out’ state was also used in the model to account for patients that discontinued treatment in the first year. UK-specific costs for drug treatment and pad use as well as utilities were assigned to each health state. Results: Solifenacin was a less costly and more effective treatment strategy compared with tolterodine. During the course of 1 year, the estimated cost per patient was £509 for patients treated with solifenacin and £526 for those given tolterodine, a cost saving of £17 per patient. Treatment with solifenacin was also associated with a small incremental gain of 0.004 quality-adjusted-life-years (QALYs) over tolterodine. Sensitivity analysis suggests that the incremental cost effectiveness of solifenacin relative to tolterodine does not appear to exceed £30 000/QALY with even large variations in key model parameters. Conclusion: Flexible dosing with solifenacin is likely to be cost-effective versus tolterodine in the treatment of OAB. Further studies are needed to confirm these results.