As men age, the incidence of benign prostatic hyperplasia (BPH) increases; with up to 40% of men in their 40s and almost 90% of men over 80 years of age having the condition. BPH is characterised by smooth muscle proliferation within the prostate; often accompanied by an increase in smooth muscle tone and this can result in bladder outlet obstruction (BOO). BPH is a histological diagnosis, whereas BOO is most frequently made clinically.

Bladder outlet obstruction in turn can lead to a variety of complications including urinary retention, recurrent urinary tract infections, renal impairment and bladder calculi.

Clinical assessment includes:

• History
• Physical examination
• Further investigations.

History

Generally speaking, men will present initially complaining of voiding symptoms and storage symptoms. Voiding symptoms include: slow stream, interrupted stream, terminal dribbling, hesitancy and haematuria. Storage symptoms include: frequency, urgency and nocturia. 

Indeed men may also present with symptoms related to complications of BPH and BOO, such as presenting with suprapubic pain from retention or dysuria from a urinary tract infection (UTI). 

Other essential details to ascertain from a patient history include a sexual history (as lower urinary tract symptoms [LUTS] have been identified as an independent risk factor for erectile dysfunction) as well as a family history of prostate and breast cancer.

Also it is important to note that some men remain asymptomatic despite having chronic retention. In such cases it is particularly important to determine the amount of daily fluid intake and note  all medications – prescription or otherwise.

Physical examination

Evaluation of BPH in men should include an abdominal examination, especially for an enlarged bladder, along with examining the penis, testes and a digital rectal examination (DRE) to assess the prostate. The size of the prostate should be assessed, its consistency (firm/rubbery/boggy/soft) and its contour (smooth, irregular, nodules, craggy). A useful guide to estimating prostate size is that each index-finger breadth that can be swept across the rectal surface of the prostate on digital rectal examination (DRE) roughly equates to 15-20g of prostate tissue. 

Further assessments

Post-void residual volume (PVR) and urine flow rates should ideally be assessed as a baseline assessment. In the case of BPH these may reveal an obstructed picture, ie. an elevated residual volume and reduced flow rate. 

Urinalysis should be routinely performed to out-rule infection as a source of the LUTS, or indeed UTI secondary to BOO. 

Routine bloods can be sent to check the renal function for comparison with baseline and, if appropriate after patient counselling, the prostate specific antigen (PSA) level. 

PSA should be interpreted with caution in the context of recent infection, recent prostate biopsy or urogenital surgery, where the patient is or has recently been catheterised, following prolonged exercise, or indeed following ejaculation (which may result in elevated PSA for up to 48-72 hours). 

PSA levels can be elevated for a variety of conditions: prostate cancer, BPH, inflammation, infection and retention. PSA levels should only be checked with the consent of the patient as an elevated PSA can result in invasive investigations which some patients find distressing. If a patient has a high PSA or an abnormal DRE then the option to refer to a urologist should be discussed. 

A urology specialist may offer a patient the option of having a transrectal ultrasound-guided (TRUS) biopsy of the prostate to outrule a malignancy in men who have an elevated PSA for age, an abnormal DRE or a positive family history for prostate cancer. A TRUS biopsy has a small risk of complications, including haematuria, retention, UTI and urosepsis.

The International Prostate Symptom Score (IPSS) is a short, validated questionnaire that assesses the storage (frequency, urgency and nocturia) and voiding (weak stream, intermittency, straining and the feeling of incomplete emptying) symptoms and their effect on quality of life. The patient grades the severity of each of these seven symptoms from 0-5. The maximum score is 35, scores between 0-7 are mildly symptomatic, 8-19 are moderately symptomatic and scores over 20 are severely symptomatic. IPSS is also a valuable tool for assessing a patient’s response to treatments over time. 

Treatment options include:

• Conservative
• Medical
• Surgical.

Conservative management options

There are a variety of treatment options available for men with LUTS. Where complications are absent and when men who do not feel that their LUTS are affecting their quality of life, a conservative approach can be taken. 

Conservative treatment options include lifestyle modifications accompanied by regular medical assessments with interval IPSS scores to ensure that the LUTS are not progressing. Such lifestyle modifications include engaging in regular moderate-intensity exercise, reducing alcohol and caffeine intake, reducing fluid intake before going to bed and using a double-voiding technique when micturating.

Two main groups of medications 

The two main medication groups used in the management for BPH are:

• Alpha-blockers and
• 5-alpha reductase inhibitors. 

The alpha-blockers are alpha-adrenergic receptor antagonists. The bladder neck and proximal urethra have high concentrations of alpha-1 adrenergic receptors. 

Overstimulation of the post-synaptic alpha-1 adrenergic receptors causes the smooth muscle of the prostate to contract, along with contractions of the bladder neck and proximal urethra, thus, reducing the lumen and causing LUTS. The use of alpha-blockers inhibit this contraction. Common alpha-blockers include alfuzosin, tamsulosin and the newer silodosin, which is highly selective in its alpha-1 adrenoceptor antagonism.

Alpha-blockers can reduce the IPSS score by up to 30% and increase the urinary flow rate by up to 25%, although they will not reduce the size of a prostate.¹ Side-effects of these medications vary but include orthostatic hypotension, retrograde ejaculation and also intraoperative floppy iris syndrome in patients undergoing cataract operations. As such, it is not advised to start an alpha-blocker for patients awaiting cataract surgery. Alpha-blockers result in an improvement in symptoms within four weeks.

5-alpha reductase inhibitors such as dutasteride and finasteride inhibit the conversion of testosterone to its active metabolite, dihydrotestosterone.  Unlike alpha-blockers, the 5-alpha reductase inhibitors take much longer to take effect as they have apoptotic effects on prostate tissue and therefore reduce the size of the prostate. It can take at least three months until there is an improvement in symptoms. 

These medications can reduce the IPSS by up to 30%, reduce the size of the prostate by 25% and increase the flow rate.² 5-alpha reductase inhibitors can also reduce the prostate-specific antigen (PSA) level by up to 50%. 

In the case of dutasteride/tamsulosin hydrochloride, the SPC states that patients receiving this should have a new PSA baseline established after six months of treatment. It is recommended to monitor PSA values regularly thereafter. It also states that any confirmed increase from the lowest PSA level may signal the presence of prostate cancer (particularly high-grade cancer) or non-compliance to therapy. This should be carefully evaluated, even if those values are still within the normal range for men not taking a 5a-reductase inhibitor. In the interpretation of a patient taking dutasteride, previous PSA values should be sought for comparison.

5-alpha reductase inhibitors, but not alpha-blockers, can reduce the risk of acute urinary retention over time, and also reduce the risk of progression of BPH warranting surgical intervention.

The Medical Therapy of Prostatic Symptoms (MTOPS) trial found that combination therapy with an alpha-blocker and a 5-alpha reductase inhibitor  is more effective than using either drug alone to relieve symptoms and prevent BPH progression. The two-drug regimen reduced the risk of BPH progression by 67%, compared with 39% for the alpha-blocker alone and 34% for the 5-alpha reductase inhibitor alone.³

More recently, the CombAT study in 2010 also supported combination therapy.⁴

In the case of more significant BOO/BPH, surgical intervention may be considered.

Surgical options for the treatment of BPH 

• Transurethral resection of the prostate (TURP) 
• Laser photoselective vaporisation of the prostate (PVP) 
• Open prostatectomy. 

TURP

The transitional zone tissue of the prostate is endoscopically resected and sent for histological analysis. Coagulation is then attained with the use of a diathermy. TURP has the ability to improve LUTS by up to 70%.⁵

Generally, men are admitted for up to three days and anticoagulants such as clopidogrel, warfarin and direct thrombin inhibitors must be stopped prior to surgery. 

Complications of this procedure include: haematuria, failed trial without catheter, UTIs, bladder neck stenosis, urethral stricture, retrograde ejaculation, TURP syndrome (hyponatraemia) and incontinence. 

Laser PVP

The laser PVP can be perfomed as a day-case procedure with most patients having a successful trial without catheter on the day of surgery. The PVP is performed endoscopically with the use of a fibre-optic delivery device. The laser quickly vaporises the prostatic tissue, removing the obstruction. It has similar complications to TURP; however, an advantage is that oral anticoagulants do not need to be stopped pre-operatively.⁶

Another advantage is the cost; this procedure can be performed as a day case and can also reduce inpatient stay, potentially saving the health service considerable costs. A disadvantage of this mode of treatment is that there is no tissue for histological analysis, thus PSA and DRE should be performed and a TRUS biopsy may need to be performed if indicated prior to this procedure.

Open prostatectomy

For men with very large prostates, an open prostatectomy is perhaps more appropriate. The development of the open prostatectomy procedure was pioneered by two Irish urologists, Sir Peter Freyer (1851-1921) and Mr Terence Millin (1903-1980). Freyer removed the prostate through an incision in the bladder, while Millin incised the prostate capsule and removed the prostate via blunt dissection with his fingers, a procedure still in clinical use 60 years later.

Summary

LUTS can have a significant negative effect on a man’s quality of life. A careful history and physical examination can suggest BOO and BPH as a possible cause. Further investigation and use of the IPSS questionnaire are valuable tools for monitoring a patient’s response to conservative, medical or surgical treatments over time. 

Referral to a urologist should be made for those men who fail initial management. Prompt referral to a rapid access prostate assessment clinic should be made for those men with features suggestive of prostate carcinoma.  

References

1. van Kerrebroeck P, Jardin A, Laval KU, van Cangh P. Efficacy and safety of a new prolonged release formulation of alfuzosin 10mg once daily versus alfuzosin 2.5mg thrice daily and placebo in patients with symptomatic benign prostatic hyperplasia. ALFORTI Study Group. Eur Urol 2000; 37(3): 306-313
2. Roehrborn CG, Boyle P, Nickel JC et al. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002; 60(3): 434-441
3. McConnell JD, Roehrborn CG, Bautista OM et al. The long-term effect of doxazosin, finasteride and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003; 349(25): 2387-2398
4. Roehrborn CG, Siami P, Barkin J et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol 2010; 57(1): 123-131. doi: 10.1016/j.eururo.2009.09.035. Epub 2009 Sep 19
5. Madersbacher S, Marberger M. Is transurethral resection of the prostate still justified? BJU Int 1999; 83(3): 227-237
6. Sohn JH, Choi YS, Kim SJ et al. Effectiveness and safety of photoselective vaporization of the prostate with the 120 W HPS Greenlight laser in benign prostatic hyperplasia patients taking oral anticoagulants. Korean J Urol 2011; 52(3): 178-183