Benign prostatic hyperplasia

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

The main goal of therapy for patients with BPH is to improve lower urinary tract symptoms (LUTS), both voiding and storage, in order to improve quality of life.

Counsel patients on options for intervention, which can include behavioural/lifestyle modifications, medical therapy, and/or referral for discussion of procedural options.[17] Use shared decision-making based on understanding the patient’s desires and risks associated with specific therapies to guide treatment strategies.[33]

Advise all patients on self-directed behavioural management programmes such as limitation of fluids (before bedtime or travel), bladder training focused on timed and complete voiding, and treatment of constipation, which may help regulate urinary symptoms.[17][18]

Review the patient's medication to identify opportunities to modify or avoid medications that may impact symptoms of BPH. For patients at risk for BPH progression based on prostate size or prostate-specific antigen levels, make attempts using medical therapy to reduce the risk of acute urinary retention and the need for invasive therapy.

A loose definition of success in treatment of LUTS might include relief of bothersome voiding and storage habits accompanied by a 50% reduction in residual urine at 4 to 6 months following therapy. In general, surgical therapies are associated with greater efficacy in permanent relief of symptoms of lower urinary tract obstruction, while medical management is less invasive.

Conservative treatment

Advise all patients on behavioural and lifestyle modifications as part of first-line management.[17][18] Measures may include:

Education about the condition and reassurance
Advice on reducing fluids at night and before travel, and limiting caffeinated and alcoholic drinks
Avoiding or modifying the timing of diuretics or medications that increase urinary retention
Preventing or treating constipation
Use of techniques to help control bladder symptoms (e.g., bladder training, pelvic floor exercises)

Consider watchful waiting for men with mild to moderate, non-bothersome LUTS or those who wish to delay treatment; few will progress to acute urinary retention and complications, and others may remain stable for years.[18] This entails both self-monitoring of symptom progression by the patient and periodic (yearly) follow-up by the physician to re-assess the condition.

Medical therapy

In general, offer medical therapy as first-line management for patients with bothersome, moderate to severe symptoms of BPH who do not require surgery.[17] A variety of drugs are available and may be selected according to patient characteristics or symptoms.

Alpha-blockers are usually the first-choice medical therapy. A phosphodiesterase-5 (PDE-5) inhibitor may be used for patients who also have erectile dysfunction; anticholinergic therapy is recommended for men with bladder storage symptoms.[17][18]

Evaluate patients 4-12 weeks after starting medical therapy with rapid-onset drugs (providing adverse events have not prompted earlier consultation).[17] Wait longer (3-6 months) before evaluating the effects of longer-onset drugs. Assess patients using a symptom score, such as the International Prostate Symptom Score (IPSS); further evaluation may include a post-void residual (PVR) and uroflowmetry.[17] Consider changing treatment where patients do not show improvement in symptoms and/or experience intolerable adverse effects.[17]

Alpha-blockers

Offer an alpha-blocker as initial therapy for most patients with moderate to severe symptoms of BPH.[17][18]

Effective within a few days and usually well tolerated.[34] Different alpha-blockers (e.g., alfuzosin, doxazosin, silodosin, tamsulosin, or terazosin) have similar efficacy. Base the choice of alpha-blocker on patient age, comorbidities, and adverse event profile.[17][35]
Alpha-blockers work through smooth muscle relaxation in the prostate and bladder neck. The predominant receptor type in the prostate and bladder is the alpha-1A receptor.
Long-acting alpha-1 blockers include terazosin and doxazosin. Terazosin and doxazosin are titrated to avoid first-dose hypotension and syncope (first-dose effect). Alfuzosin is a short-acting alpha-1 blocker that is available as a modified-release formulation. Tamsulosin and silodosin are long-acting sub-type (alpha-1A) selective alpha-blockers, which may result in modest improvements in symptom scores and peak urinary flow rate (Qmax). Silodosin is a more selective alpha-1A blocker than tamsulosin, and has shown superiority over placebo, with significant improvements in symptom scores at 12 weeks.[36]
Use of alpha-blockers is associated with floppy iris syndrome, which can cause technical difficulties during cataract surgery. Risk was found to be highest with tamsulosin. Patients should be asked about any potential eye surgery prior to initiating therapy.[17][18]
Men taking prostate-specific alpha-blockers have been shown to have significantly increased risks of falling and fracture, as well as increased risk of hypotension and head trauma.[37] Ejaculatory dysfunction and an increase in unwanted sexual side effects are frequently reported adverse events with silodosin and may also occur with tamsulosin.[36] [ ] Alfuzosin, doxazosin, and terazosin are associated with a low risk of ejaculatory dysfunction and may, therefore, be preferred in younger or more sexually active men.[17][18] Silodosin may be preferred in individuals taking numerous antihypertensives or those with orthostatic hypertension due to its minimal impact on blood pressure.[18] Men with BPH treated with an alpha-blocker, alone or in combination with a 5-alpha-reductase inhibitor, may be at increased risk for heart failure compared with no medication use; non-selective alpha-blockers appear to be associated with a higher risk of heart failure than selective alpha-blockers.[38]

5-alpha-reductase inhibitors

Consider a 5-alpha-reductase inhibitor (e.g., dutasteride, finasteride) as initial monotherapy for BPH patients with larger prostates (e.g., prostate volume >30 g on imaging, prostate-specific antigen >1.5 ng/dL or palpable prostate enlargement on digital rectal examination).[17][18]

Effective in reducing prostate size in patients with larger prostates, decreasing the short-term risk for acute urinary retention and invasive surgery.[39][40] Finasteride has only been shown to be beneficial in patients with large prostates (>30 g); no benefit was observed over placebo in patients with smaller prostate size.[41]
Counsel patients about the slow onset of action; 5-alpha-reductase inhibitors take several months to improve symptoms and are suitable only for long-term treatment.[18]
Use of 5-alpha-reductase inhibitors may be associated with a delayed diagnosis of prostate cancer and a more advanced histological stage of cancer at the time of diagnosis.[42]
Sexual dysfunction is seen in 5% to 10% of patients, including decreased libido/ejaculate, erectile dysfunction, and gynaecomastia.[7][17][18]
Finasteride is associated with rare psychiatric and sexual adverse effects, including depression, suicidal thoughts, and sexual dysfunction, that may persist after treatment is stopped.[43]

PDE-5 inhibitors

Consider a PDE-5 inhibitor for patients with BPH and erectile dysfunction, or as a second-line option.[17]

May improve LUTS, erectile function, and quality of life. Tadalafil is the only approved PDE-5 inhibitor for patients with comorbid BPH and erectile dysfunction. Tadalafil may be considered for those showing incomplete response and/or those who cannot tolerate an alpha-blocker irrespective of comorbid erectile dysfunction.[17][18][44]
An evaluation of data from eight systematic reviews demonstrated that PDE-5 inhibitors improve LUTS and erectile function with a negligible change in flow rate.[45] PDE-5 inhibitors in combination with alpha-blockers improved flow rate compared with alpha-blockers alone.[46] [ ]
Evidence on disease progression and long-term efficacy and tolerability for PDE-5 inhibitors is lacking.[18][47]

Anticholinergic therapy

An anticholinergic agent may be considered for men with BPH and predominantly bladder storage symptoms.[17][18]

Anticholinergic agents (e.g., tolterodine, fesoterodine, oxybutynin, solifenacin) may improve symptoms of overactive bladder.[48][49][50] [ ]
Anticholinergic-associated adverse events include dry eyes, dry mouth, constipation, micturition difficulties, nasopharyngitis, and dizziness.[18] Previous concerns over risk of worsening bladder retention appear to be unfounded.[17] An increased risk of dementia has been associated with anticholinergics.[51]

Combination therapy

May be considered for patients with moderate or severe symptoms who are at risk of disease progression, and those who have inadequate symptom control or progression on monotherapy.

Options include an alpha-blocker in combination with a 5-alpha-reductase inhibitor, an anticholinergic, a beta-3 adrenergic agonist, or the PDE-5 inhibitor tadalafil. Tadalafil in combination with finasteride may also be an option.[17]

A 5-alpha-reductase inhibitor in combination with an alpha-blocker can be considered for BPH patients with larger prostates who experience symptom progression on monotherapy.[17][18][52][53]

One systematic review found that combination therapy with a 5-alpha-reductase inhibitor plus an alpha-blocker showed a greater than 4 point improvement in International Prostate Symptom Score (IPSS), and was significantly better than monotherapy.[54] Treatment with tamsulosin plus dutasteride for 4 years appears to reduce the risk of clinical progression, acute urinary retention, and the need for BPH-related surgery.[55]
Combination therapy with a 5-alpha-reductase inhibitor and an alpha-blocker may be associated with sexual dysfunction, including erectile and ejaculatory dysfunction.[56]
Men with BPH treated with an alpha-blocker in combination with a 5-alpha-reductase inhibitor may be at increased risk for heart failure compared with no medication use; nonselective alpha-blockers appear to be associated with a higher risk of heart failure than selective alpha-blockers.[38]

Anticholinergic therapy in combination with an alpha-blocker is suitable for men with BHP and predominantly bladder storage symptoms.[17][18][49]

One meta-analysis demonstrated that alpha-blockers in combination with anticholinergic medication may improve symptoms without causing significant deterioration in voiding function.[57]
A subsequent Cochrane review found that combination therapy with anticholinergics and alpha-blockers was associated with little or uncertain effects on urinary symptoms, although it may improve quality of life compared with anticholinergics alone.[58] Combination therapy likely increases adverse effects compared with placebo, but not compared with alpha-blocker or anticholinergic monotherapy.[58]

Beta-3 adrenergic agonists (e.g., mirabegron, vibegron) may be offered in combination with an alpha-blocker to BPH patients with moderate to severe predominantly storage LUTS.[17][18]

One randomised controlled trial showed that combination therapy with tamsulosin and mirabegron improved storage LUTS symptoms in men with BPH who have persistent symptoms despite tamsulosin monotherapy.[59]
Beta-3 adrenergic agonists should be used with caution in older men and those with bladder outlet obstruction (post-void residuals greater than 250 mL).[20]

A PDE-5 inhibitor (e.g., tadalafil) plus an alpha-blocker may be considered for combination therapy, although evidence is limited.[17][18]

Systematic reviews suggest that combination treatment with a PDE-5 inhibitor and an alpha-blocker is more effective than monotherapy for improving symptoms of BPH in men with or without erectile dysfunction, but the rate of adverse effects is higher.[46][60] [ ]
According to one meta-analysis, younger men with lower BMI and severe urinary symptoms may benefit in particular from a PDE-5 inhibitor in combination with an alpha-blocker.[18][61] However, further studies are needed to confirm which patients gain most benefit from this combination.

A combination formulation of the 5-alpha-reductase inhibitor finasteride and the PDE-5 inhibitor tadalafil is available, which may be considered for men with larger prostates.[17]

The Food and Drug Administration (FDA) has approved finasteride/tadalafil for the treatment of the signs and symptoms of BPH in men with an enlarged prostate. Phase 3 studies found that combination treatment with finasteride and tadalafil significantly improved LUTS and erectile and sexual function compared to treatment with finasteride and placebo.[62][63]
Finasteride/tadalafil can be used when considering combination therapies, or if patients have intolerable adverse effects from 5-alpha-reductase inhibitor monotherapy, for a maximum duration of 26 weeks.

Surgical treatment

Refer patients to a urologist for surgery for LUTS/BPH if they:[17]

Have complications attributed to BPH, such as acute and/or chronic renal insufficiency, recurrent bladder stones, gross recurrent haematuria, recurrent urinary tract infections, or refractory urinary retention

Have refractory responses to medication, are unwilling to use medication, or experience intolerable adverse effects with medication.

Prostate imaging is recommended to accurately assess the size and shape of the prostate to inform choice of surgical interventions.[17][18][31] Transrectal or abdominal ultrasound, or cystoscopy may be considered, or pre-existing imaging scans can be used (including magnetic resonance imaging/computed tomography), preferably obtained within the preceding 12 months.[17] Assess PVR before surgical intervention for LUTS attributed to BPH.[17] Some patients may require uroflowmetry to characterise voiding dysfunction and possible surgical outcomes. Urodynamic studies (pressure flow studies) are helpful if there is diagnostic uncertainty.[17] [ ]

A variety of procedures can be performed. The decision to select a specific procedure is shared between the patient and the urologist, with respect to risk/benefit of each procedure, availability of equipment, clinician expertise, and patient comorbidities.[33] Patients on active anticoagulation are at lower risk with procedures associated with less bleeding such as laser enucleation or vaporisation.[17][18]

Surgical treatment options include the following.[18]

Transurethral resection of the prostate (TURP): this is the standard surgical procedure for men with prostate sizes <80 g and bothersome lower urinary symptoms due to BPH.[17][18] TURP is the historical standard against which all other surgical approaches are compared. The procedure can be performed with a spinal or epidural anaesthetic, or with a general anaesthetic. Classic TURP uses monopolar electrocautery; however, bipolar TURP has become a more common procedure, with similar functional outcomes and improved perioperative outcomes compared with monopolar TURP.[64][65] [ ] [Evidence B] Bipolar TURP reduces the risk of dilutional hyponatraemia, clot formation, and blood loss during longer procedures on larger glands. TURP provides excellent resolution of LUTS, but has an increased risk of bleeding compared with other procedures and also has a significant rate of unwanted sexual adverse effects (e.g., ejaculatory dysfunction).[18]
Simple prostatectomy: patients with large to very large glands are usually treated with open, laparoscopic, or robotic-assisted prostatectomy. Open prostatectomy has become less common for LUTS as other techniques have continued to gain acceptance. It is generally only recommended for patients who are good surgical candidates and have significantly enlarged prostates (typically >80 g).[17][18] A practical consideration in recommending open surgery stems from the greater likelihood of hyponatraemia from irrigant absorption during prolonged transurethral surgery of large glands.[66]
Transurethral vaporisation of the prostate (TUVP) traditionally uses a standard monopolar electro-diathermy device as for TURP, but modification with a bipolar current enables use at lower temperatures for vaporisation. It can be considered for patients with small or average prostate size (<80 g).[17][18] Monopolar and bipolar TUVP are equally efficacious, but bipolar TUVP has a more favourable perioperative safety profile.[67] TUVP has reduced blood loss in contrast to TURP.[68] TURP and TUVP are more invasive and entail more risk than minimally invasive therapies, but can improve symptoms to a greater degree. Laser vaporisation may also be used to resect or ablate prostate tissue.
Clinicians should consider laser enucleation (holmium laser enucleation of the prostate [HoLEP] and thulium laser enucleation of the prostate [ThuLEP]), depending on their expertise with either technique, as prostate size-independent suitable options.[17][18][69] HoLEP and ThuLEP both have similar efficacy and re-operation rates compared with TURP.[70][71] Perioperative blood loss is lower in laser-treated patients. Perioperative blood loss is lower in laser-treated patients. HoLEP and ThuLEP should be considered in patients who are at higher risk of bleeding, such as those on anticoagulants.[17]
Photoselective vaporisation of the prostate (PVP) uses a side-firing laser at a wavelength absorbed by haemoglobin. This results in tissue vaporisation and an underlying layer of coagulation providing good haemostasis; therefore, it is preferred in patients at higher risk of bleeding (e.g., patients on anticoagulants). Studies have shown similar outcomes, both beneficial and adverse, compared with TURP.[71] PVP may be more efficacious in glands <60 g as two cohort studies showed conversion to TURP in glands between 60 and 80 g.[72][73] PVP may be considered in patients with prostate size <80 g at higher risk of bleeding, such as those on anticoagulation, because of its haemostatic effect on prostate tissue.[17][18]
The prostatic urethral lift (PUL) is an option when the patient's prostate size is 30 to 80 g and there is verified absence of an obstructive middle lobe.[17] PUL may be offered as an option for eligible patients who want to preserve erectile and ejaculatory function.[17][18] An implantable, spring-loaded, ‘T-shaped’ device is delivered through a cystoscope. The device is placed with the one end outside the prostatic capsule and the other in the prostatic urethral lumen. Once in place, the device opens up the prostatic urethra by compressing the prostate parenchyma.[17] Eligible patients should be informed that long-term effects are uncertain, and efficacy rates are less than those seen with TURP but sexual function is more likely to be preserved and ejaculatory bother rates to improve by 40% at 1 year.[17][18][74]
Water vapor thermal therapy may be considered as an option for men who wish to preserve erectile and ejaculatory function if the prostate volume is 30 to 80 g.[17][75] Little is known regarding efficacy and re-treatment rates compared with TURP.[76] Erectile and ejaculatory function is preserved.[77] One systematic review and network meta-analysis of minimally invasive treatments reported similar improvement in IPSS for water vapor thermal therapy compared with TURP, with a lower impact on sexual function.[78] A further network meta-analysis reported uncertainty about the evidence and the need for retreatment.[79] Water vapor thermal therapy is not recommended in European guidelines due to lack of data.[18]
Transurethral incision of the prostate (TUIP) may be offered to patients with prostate volume ≤30 g for the surgical treatment of LUTS attributed to BPH.[17][18] TUIP is associated with lower rates of retrograde ejaculation and need for blood transfusion compared with TURP.[80]
Aquablation uses a handheld robotic arm with targeted tissue destruction followed by electro-cautery for haemostasis. It may be offered as a treatment option to patients with a prostate volume of 30 to 80 g.[17][18] One randomised controlled trial in men with a 30 to 80 g prostate volume found symptom reduction and uroflow improvement to be durable and consistent at 5-year follow-up.[81] Studies have also been conducted into aquablation for prostates between 80 and 150 g, but long-term follow-up data remain limited. Aquablation is not a minimally invasive surgical procedure as it requires general anaesthesia.
Prostatic artery embolisation (PAE) may be considered for patients with LUTS due to BPH as an alternative to watchful waiting (e.g., for poor surgical candidates and those unable to tolerate more invasive techniques, or for patients who prefer a minimally invasive procedure). Clinicians should explain that PAE may result in poorer outcomes and higher retreatment rates compared with TURP, and discuss the risks and benefits with the patient. PAE is technically demanding and should only be performed by clinicians trained in the procedure.[17][18][82][83] A meta-analysis of 11 randomised controlled trials reported similar patient-reported outcomes, including symptom and quality of life scores, for PAE compared with TURP at 12 months, with fewer complications. However, PAE was less effective than TURP in most functional outcomes (changes in maximum urinary flow, prostate volume, prostate-specific antigen).[84] Systematic reviews show improvement in symptoms.[85][86][87][88][89] However, one Cochrane review found that the evidence was uncertain for major adverse events and that PAE may increase retreatment rates.[89]
Temporary implanted prostatic devices (e.g., the iTIND nitinol device) are mechanical devices that expand to re-model the bladder neck and prostatic urethra to increase urine flow. They may be considered as a minimally invasive treatment option for patients with LUTS attributed to BPH if the prostate volume is between 25 and 75 g and there is absence of an obstructive middle lobe.[17] One systematic review and meta-analysis of minimally invasive techniques suggested that efficacy might be lower for iTIND compared to TURP. However, the evidence is limited.[78] European guidelines do not currently recommend temporary implanted prostatic devices.[18] In the UK, they are only recommended under special arrangements for clinical governance, consent, and data collection.[90]

Procedures no longer recommended

Surgical procedures for BPH have evolved rapidly. As a consequence, several procedures that were previously recommended have been superseded by the adoption of more effective and/or less invasive procedures:[17]

Transurethral needle ablation is no longer recommended as a treatment for LUTS attributed to BPH, due to less reduction in prostate volume than previously anticipated.
Transurethral microwave thermotherapy has largely been replaced by newer procedures. It has higher retreatment rates than other procedures.[91][92][93][94]

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Benign prostatic hyperplasia

Approach

Conservative treatment

Medical therapy

Surgical treatment