Benign prostatic enlargement (BPE) is one of the most common conditions in older men, and is caused by the histopathological condition benign prostatic hyperplasia (BPH). Clinical manifestations of BPH include lower urinary tract symptoms (LUTS), as signs and sequelae of bladder outlet obstruction are caused by the enlarged prostate.1 BPH and LUTS represent an important area for basic and clinical research: 800–1,000 manuscripts have been published in this area each year for the past 5 years, with most (55%) investigating new possible options of medical and surgical treatment.

Medical treatment of LUTS due to BPH is aimed at improving quality of life by relieving symptoms and lowering risk of disease progression and complications, such as urinary retention and the need for surgery. Guidelines suggest that patients with mild symptoms and no deterioration of quality of life can be managed by watchful waiting, but that patients with problematic symptoms are best managed with pharmacological treatment.2,3 Six classes of drugs are available: phytotherapeutics, α-blockers, 5α-reductase inhibitors (5-ARIs), antimuscarinics, β3-adrenoreceptor agonists and phosphodiesterase type 5 (PDE5) inhibitors. α-Blocker and 5-ARI monotherapies or combination therapies are the most frequently used drugs for the treatment of LUTS associated with BPH, but the combination of these two drugs with antimuscarinics, β3-adrenoreceptor agonists and PDE5 inhibitors has also been investigated.4 The availability of various different drugs enables medical treatment to be tailored to the needs of the individual patient.4

One 2014 paper from Drake et al.5 evaluated the safety and efficacy of a fixed-dose combination of a modified-release formulation of tamsulosin hydrochloride oral controlled absorption system (TOCAS) and solifenacin succinate in men with LUTS. Patients completing the 12-week NEPTUNE study were invited to continue into the open-label 40-week NEPTUNE II extension study to evaluate the long-term effect of solifenacin in combination with TOCAS in male patients with LUTS.5,6 The study results provide evidence of the safety of this combined treatment over a 1-year period. Symptom improvement was observed as early as 4 weeks, with further improvement up to 16 weeks and maintenance up to 1 year. Mean total International Prostatic Symptom score (IPSS) was reduced by 9.0 points, equivalent to a 48.1% reduction, and the mean total urgency and frequency score was reduced by 10.1 points (a 37.1% reduction). Urinary retention occurred in 13 patients (1.1%) receiving combination treatment. The use of fixed-dose combination treatments is not new in the field of urology, but the option to use a single tablet is more convenient for patients, and would hopefully improve drug adherence (which is usually low in patients treated with antimuscarinics).6

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The PDE5 inhibitor tadalafil has recently been approved for the treatment of LUTS suggestive of BPH, with or without erectile dysfunction, and several reports demonstrated significant improvement with tadalafil versus placebo in the IPSS and quality-of-life scores.4,7 Oelke et al.7 investigated treatment satisfaction with tadalafil or tamsulosin versus placebo in men with LUTS suggestive of BPH. The trial was a multinational, randomized, double-blind, placebo-controlled, parallel-design phase II study designed to compare the efficacy and safety of monotherapy (tadalafil 5 mg or tamsulosin 0.4 mg once daily) with the use of placebo for LUTS suggestive of BPH. The treatment satisfaction scale–BPH, a validated instrument that measures patient satisfaction with treatment, was used as a secondary end point. Overall satisfaction was significantly greater with tadalafil than with placebo (P = 0.005), but was not significantly greater with tamsulosin versus placebo. The subscore for satisfaction in the efficacy domain was significantly greater with tadalafil than with placebo (P = 0.003), but did not reach significance for tamsulosin versus placebo. In the tadalafil group, differences versus placebo were more significant for men aged ≤65 years, men with mild to moderate LUTS, men with a prostate volume ≥40 ml and men who had previously received treatment with α-blockers. Data from this study suggest that a higher proportion of men receiving tadalafil (versus those receiving placebo or tamsulosin) rated their treatment as effective, would recommend it to men with similar symptoms and wanted to continue with their medication. Concomitant improvement in erectile dysfunction has been proposed as a possible explanation of patients' satisfaction with this treatment modality.7 However, the results presented by Oelke et al.7 underline the importance of patient satisfaction when proposing medical treatment to patients with LUTS suggestive of BPH. Considering the different modalities now available, individualised treatment should be considered in patients with LUTS to improve patient satisfaction and to improve drug adherence, a limiting factor in achieving success in the medical treatment of LUTS.8

Although the pharmacological treatment of LUTS associated with BPH is a success story, we have found that different medical needs remain unmet in this area. Patients who do not respond to medical therapy and those with BPH complications are managed surgically. Transurethral prostatic resection (TURP) is still considered the standard surgical treatment for BPE, but as a result of relatively high morbidity, several minimally invasive and less-invasive treatments have been proposed and successfully evaluated in the past 10 years.2,3 Bachmann et al.9 have reported the 1-year results of a prospective, randomized trial (GOLIATH) comparing 180-W GreenLight XPS™ (American Medical Systems, USA) laser vaporization (GL–XPS) with TURP for the treatment of men with LUTS associated with BPH. Patients were randomly assigned to receive either TURP (n = 142) or GL–XPS (n = 139) in a noninferiority trial. Both treatments were effective and no significant differences were observed between treatment arms for IPSS, quality of life, prostate volume and PSA reduction. Treatment-related adverse events occurred in similar proportions of patients in each group, and no significant differences were detected in adverse events, including postoperative storage symptoms, urinary tract infections, urinary incontinence and re-intervention. The 12-month follow-up data of the GOLIATH study provide strong evidence that GL–XPS offers a clinical outcome comparable with that of TURP. GL–XPS treatment is associated with reduced catheterization time and reduced length of hospital stay (about 50% of patients treated with GL–XPS can be discharged within 24 h). Prostate vapourization with GL–XPS is an important therapeutic option to reduce morbidity associated with TURP, to offer surgical treatment to patients with impaired coagulation and to perform BPH surgery as a day case.

Randomized trials of intraprostatic injection of onabotulinumtoxinA did not confirm the efficacy of this therapeutic approach in the management of LUTS associated with BPH, and outcomes of clinical trials using intraprostatic injection of other protoxins are awaited, but new minimally invasive options have appeared on the horizon.2,4 Cantwell et al.10 performed a multicentre crossover study in men with LUTS associated with BPH to evaluate the effects of prostatic urethral lift (PUL) performed 3–6 months after a sham procedure that involved rigid cystoscopy and the mimicking of surgical sounds. The average IPSS after PUL (11.1 points) was significantly higher than after sham operation (5 points). Maximum urinary flow rate increased significantly at 3 months and 12 months after PUL. Most PUL procedures were conducted under local anaesthesia, and no severe adverse events or significant changes in erectile or ejaculatory function were noted. This crossover study showed that PUL is associated with a significant LUTS improvement that is maintained for 12 months. If this finding is confirmed in a long-term follow-up study, PUL could represent a valid option for the minimally invasive management of patients with LUTS associated with BPH. The preservation of erectile and ejaculatory function is complete after treatment, with rapid return to normal daily activities in <1 week. Clinical experience suggests that patients seeking treatments for LUTS are willing to accept a lower degree of efficacy in exchange for a less-invasive treatment.

Most minimally invasive treatments for LUTS suggestive of BPH have failed in the long term over the past decade: trials of new treatments should aim for maximum efficacy and minimal invasiveness. Patient and surgeon expectations sometimes differ widely, and patients should always be offered different therapeutic options, with explanation of the associated pros and cons.

The gold-standard treatments for BPH are about 100 years old, and although urologists have been successful in diagnosing and managing a condition that used to be lethal, it remains troublesome. BPH is a chronic condition that many men have to live with for decades. Proper research is needed in real-life settings to investigate the unmet needs of treatments for LUTS associated with BPH.

Key advances

  • A fixed-dose combination of a modified-release formulation of tamsulosin hydrochloride oral controlled absorption system and solifenacin succinate is safe and effective up to 1 year in men with lower urinary tract symptoms (LUTS)5

  • The PDE5 inhibitor tadalafil (5 mg daily) is associated with significantly greater treatment satisfaction compared with placebo in men with LUTS suggestive of BPH7

  • 180-W Greenlight–XPSâ„¢ is associated with a clinical outcome comparable to use of transurethral prostatic resection after 12 months of follow-up in men with LUTS associated with BPH9

  • Prostatic urethral lift performed 3–6 months after a sham procedure in men with LUTS associated with BPH is associated with a significant improvement in LUTS that is maintained for 12 months10