Lower urinary tract symptoms include irritative (storage), obstructive (voiding) and post-micturition symptoms.  There are many possible causes of LUTS, including abnormal function of the prostate, urethra, bladder or sphincter. In men, the most common cause is benign prostate enlargement (BPE), which obstructs the bladder outlet. Voiding symptoms include weak or intermittent urinary stream, straining, hesitancy, terminal dribbling and incomplete emptying. Storage symptoms include urgency, frequency, urgency incontinence and nocturia. The major post-micturition symptom is post-micturition dribbling, which is common and bothersome.

There are up-to-date European, British and US guidelines on the assessment and management of LUTS available online and thinking about terminology has changed in recent years.^1,2,3 The acronym for lower urinary tract symptoms (LUTS) has replaced the term ‘prostatism’, which indicated bladder outlet obstruction as a result of benign enlargement of the prostate. LUTS refers to a set of symptoms, while BPH is a condition, but LUTS includes symptoms of BPH as well as due to other causes.²

Although LUTS do not usually cause severe illness, they can considerably reduce men’s quality of life, and may point to serious pathology of the urogenital tract. Bothersome LUTS can occur in up to 30% of men older than 65 years.^1,2 Men with LUTS should have the opportunity to make informed decisions about their care and treatment in partnership with their healthcare professionals. Care decisions should be supported by evidence-based written information tailored to the man’s needs. 

Assessment in primary care

Initial assessment can be carried out in primary care. A prospective, multicentre study in three European countries, the Diagnosis Improvement in Primary Care Trial (D-IMPACT) found that in men aged ≥ 50 years who spontaneously reported LUTS to their GP, where an in-office diagnostic algorithm was used, patients were accurately diagnosed for BPH by their GP in 75% of cases.⁴ The algorithm included only the objective variables of age, IPSS (International Prostate Symptom Score), and PSA. 

Apart from a detailed history of presenting symptoms, assessment of patients’ general medical history is carried out to identify possible causes of LUTS, and associated comorbidities. A review of current medication, including herbal and over-the-counter medicines, should identify drugs that may be contributing to the problem. Physical examination is guided by urological symptoms and other medical conditions. Particular attention should be paid to evidence of abdominal mass, distended bladder, phimosis and abnormal digital rectal examination (DRE). Urinalysis should be carried out in all patients as it may show evidence of infection (nitrites/leucocytes positive), haematuria (≥ 1), glycosuria (diabetes) or proteinuria (renal damage) which may be contributing to symptoms. 

Men with LUTS should be offered information, advice and time to decide if they wish to have prostate specific antigen (PSA) testing. PSA should be considered if LUTS are suggestive of bladder outlet obstruction secondary to benign prostatic enlargement, abnormal feeling prostate on DRE or if the patient is concerned about prostate cancer. Serum creatinine test (plus estimated glomerular filtration rate [eGFR] calculation) is carried out only if renal impairment is suspected (for example, the man has a palpable bladder, nocturnal enuresis, recurrent urinary tract infections or a history of renal calculi).

Patients should be referred for specialist assessment if they have LUTS complicated by recurrent or persistent urinary tract infection, retention, renal impairment that is suspected to be caused by lower urinary tract dysfunction, or suspected urological cancer. 

International Prostate Symptom Score (IPSS)

LUTS can be objectively measured by an International Prostate Symptom Score (IPSS) which comprises seven questions (four regarding storage and three regarding voiding) with a maximum possible score of 35. In this guidance, ‘mild’ refers to an IPSS of 0-7, ‘moderate’ refers to an IPSS of 8-19 and ‘severe’ refers to an IPSS of 20-35. An adjunctive ‘bother score’ which is a simple quality of life score is also helpful, as often the symptoms can be quite severe but the patient has little bother. Men with bothersome LUTS should complete a urinary frequency volume chart which gives an indication of fluid intake, functional bladder capacity, polyuria and nocturnal polyuria. 

Nocturnal polyuria can be the most troublesome for the patient and the most difficult to treat effectively. Medical conditions that can cause nocturnal polyuria symptoms include diabetes mellitus, diabetes insipidus, adrenal insufficiency, hypercalcaemia, liver failure, polyuric renal failure, chronic heart failure, obstructive apnoea, dependent oedema, pyelonephritis, chronic venous stasis and sickle cell anaemia. Medications that can cause nocturnal polyuria symptoms include calcium channel blockers, diuretics and selective serotonin reuptake inhibitors (SSRIs). 

Additional tests may be performed upon specialist referral, including flow rate and post-void residual, cystoscopy, upper tract imaging or full urodynamics. Maximum flow rates (Qmax) ≤ 10ml/s generally indicate the patient is obstructed. A large post-void residual indicates bladder outlet obstruction or a hypotonic bladder. Cystoscopy is clinically indicated if there is a suggestion of an underlying bladder malignancy. Imaging of the upper urinary tracts with ultrasound or computerised tomography (CT) is not indicated in routine work-up of uncomplicated LUTS. It should be performed if there is a history of chronic retention, haematuria, recurrent infection, sterile pyuria or pain. 

Cystometric urodynamics involves measuring the pressures in the bladder (intravesical) and rectum (abdominal) by placing small-calibre pressure transducers in the bladder and rectum respectively. Detrusor pressures can then be measured by subtracting abdominal from intravesical pressures. A high detrusor pressure on voiding indicates bladder outlet obstruction. This test is helpful in deciding if a patient is urodynamically obstructed and would benefit from transurethral resection of the prostate (TURP).

Conservative management approach

Conservative management should be implemented if LUTS are not bothersome and there is no evidence of haematuria or recurrent UTIs. This ‘watchful waiting’ (WW) approach has been shown to be successful, especially in men with mild to moderate uncomplicated LUTS. In one large study, Flanigan et al compared WW and TURP in men with moderate symptoms. Thirty-six per cent of patients crossed over to surgery in five years, leaving 64% doing well in the WW group.⁵ Approximately 85% of men will be stable on WW at one year, deteriorating progressively to 65% at five years.^6,7 The reason why some men deteriorate with WW and others do not is not well understood; increasing symptom bother and PVR volumes appeared to be the strongest predictors of failure.

Lifestyle advice

Most experts agree that the key elements of conservative management should involve reassurance, offering advice on lifestyle interventions and information on their condition, along with periodic monitoring of the patient’s symptoms. Lifestyle advice should comprise the following: 

• Reduction of fluid intake at specific times aimed at reducing urinary frequency when most inconvenient, eg. at night or going out in public. The recommended total daily fluid intake of 1,500ml should not be reduced
• Avoidance or moderation of caffeine and alcohol which may have a diuretic and irritant effect, thereby increasing fluid output and enhancing frequency, urgency and nocturia 
• Use of relaxed and double-voiding techniques 
• If post-micturition dribble is the predominant symptom, explain to the patient how to perform urethral milking
• Distraction techniques, such as penile squeeze, breathing exercises, perineal pressure and mental ‘tricks’ to take the mind off the bladder and toilet, to help control irritative symptoms
• Bladder retraining, by which men are encouraged to ‘hold on’ when they have sensory urgency to increase their bladder capacity (to around 400ml) and the time between voids
• Reviewing a man’s medication and optimising the time of administration or substituting drugs for others that have fewer urinary effects
• Treatment of constipation
• Providing necessary assistance when there is impairment of mobility, dexterity or mental state
• Clinical guidelines do not advocate homeopathy or phytotherapy for treating LUTS. 

Drug therapy

Drug treatment is appropriate for men with bothersome LUTS, when conservative management options have been unsuccessful or are not appropriate.² Take into account comorbidities (especially cardiovascular) and current treatments when offering drug treatment for LUTS. 

Alpha-blockers

An alpha blocker (alfuzosin, tamsulosin, silodosin, terazosin, doxazosin) is appropriate for men with moderate to severe LUTS. The different alpha-blockers have similar efficacy, as expressed by a per cent improvement in IPSS (35-50%).⁸ Their efficacy appears to be maintained over at least a four-year period. However, alpha-blockers do not reduce prostate size and do not prevent acute urinary retention in long-term studies,⁹ so eventually some patients will have to be surgically treated. Review men taking alpha blockers at four to six weeks and then every six to 12 months. The most frequent side-effects of alpha-blockers are asthenia, dizziness and orthostatic hypotension. Vasodilating effects are most pronounced with doxazosin and terazosin, and are much less common for alfuzosin, tamsulosin and silodosin.¹⁰

Anticholinergics

Offer an anticholinergic to men to manage the symptoms of OAB. The main side-effects to warn patients of are dry mouth (up to 16% higher frequency when compared to placebo), dizziness (up to 5%) and constipation (up to 4%). Review men taking anticholinergics every four to six weeks until symptoms are stable, and then every six to 12 months. 

5-alpha-reductase inhibitors

Offer a 5-alpha-reductase inhibitor (finasteride, dutasteride) to men with LUTS who have prostates estimated to be larger than 30g (rough estimate > three finger breadths) or a PSA level greater than 3.3ng/ml. Clinical effects relative to placebo are seen after minimum treatment duration of at least six to 12 months. After two to four years of treatment, 5α-reductase inhibitors reduce LUTS (IPSS) by approximately 15-30%, decrease prostate volume by approximately 18-28% and increase maximum flow rate (Qmax) of free uroflowmetry by approximately 1.5-2.0ml/s in patients with LUTS due to prostate enlargement (prostate volume ≥ 30g).^11,12

5-alpha-reductase inhibitors, but not alpha-blockers, reduce the long-term (> one  year) risk of acute urinary retention or need for surgery.^9,11,12 Review men taking 5-alpha reductase inhibitors at three to six months and then every six to 12 months. It is important to note that 5-alpha-reductase inhibitors cause a decrease in mean serum PSA levels by approximately 50% after six months of treatment. 

Finasteride 

When using finasteride, it is recommended that PSA values should be doubled for comparison with normal ranges in untreated men. This adjustment preserves the sensitivity and specificity of the PSA assay and maintains its ability to detect prostate cancer.¹³

Dutasteride

Patients receiving dutasteride should have a new PSA baseline established after six months of treatment with dutasteride. It is recommended to monitor PSA values regularly thereafter. New product labelling states: “any confirmed increase from lowest PSA level while on dutasteride may indicate the presence of prostate cancer (particularly high-grade cancer) or non-compliance to therapy with dutasteride and should be carefully evaluated, even if those values are still within the normal range for men not taking a 5-alpha-reductase inhibitor.” 

This new recommendation follows the REDUCE trial results, where men at increased risk of prostate cancer were randomised to four years of dutasteride versus placebo. There was an increased incidence of Gleason Score 8-10 or more aggressive prostate cancers with dutasteride versus placebo (1% versus 0.5%, respectively).¹⁴ The relationship between dutasteride and high-grade prostate cancer is unclear.

Combination therapy

Combination therapy aims to combine the differential effects of two drug classes to improve efficacy in symptom control and prevention of disease progression.¹ A combination of an alpha blocker and a 5α-reductase inhibitor is beneficial in men with moderate to severe LUTS and prostates estimated to be larger than 30g or a PSA level greater than 3.3ng/ml.^2,15 The alpha blocker shows clinical effects within hours or days. The 5-alpha-reductase inhibitor achieves clinical efficacy over several months.¹ 

Consider offering an anticholinergic as well as an alpha-blocker to men who still have storage symptoms after treatment with an alpha-blocker alone. Combination alpha-blocker and anticholinergic use is most effective in bladder outlet obstruction for men with smaller prostates or PSA < 1.3ng/ml, with recorded reductions in daytime frequency, 24-hour voiding frequency and IPSS storage symptoms.¹⁶

A late afternoon loop diuretic can be considered in rare circumstances for men with nocturnal polyuria. Oral desmopressin can also be used in the treatment of nocturnal polyuria if other medical causes have been excluded and they have not benefited from other treatments. In these circumstances, serum sodium must be measured three days after the first dose. If serum sodium is reduced to below the normal range, stop desmopressin.

Surgery for voiding symptoms 

Surgery is only offered if drug treatment and conservative management options have been unsuccessful or patients present with a strong indication for surgery (refractory urinary retention, renal insufficiency due to BPH, bladder stones, and recurrent urinary tract infection). 

The most commonly performed surgical treatment for BPH is transurethral resection of the prostate which remains the ‘gold standard’. Open prostatectomy can be considered in men with prostates estimated to be larger than 80g. 

Transurethral vaporisation of the prostate (TUVP) is an alternative to TURP, especially for high-risk patients with small prostates. Laser treatments include GreenLight HPS 120-W (photoselective vapourisation of the prostate (PVP)) and Holmium. Holmium laser enucleation of the prostate (HoLEP) is another alternative to TURP and open prostatectomy in high-risk patients, irrespective of any anatomical configuration. 

Surgery for storage symptoms 

Surgery should only be offered for severe storage symptoms and only to men whose storage symptoms have not responded to conservative management and drug treatment. Surgery to manage severe voiding symptoms would include cystoscopy and intravesical botulinum toxin injection, augmentation cystoplasty or urinary diversion with ileal conduit. Alternatives would include a long-term catheter. 

References

1. European Association of Urology (EAU): Guidelines on the Treatment of Non-neurogenic Male LUTS http://www.uroweb.org/gls/pdf/12_Male_LUTS.pdf

2. NICE Guidelines Lower urinary tract symptoms – The management of lower urinary tract symptoms in men. http://guidance.nice.org.uk/CG97

3. McVary KT, et al. Update on AUA Guideline on the Management of Benign Prostatic Hyperplasia. J Urol. Mar 17 2011 

4. Carballido J, et al. Can benign prostatic hyperplasia be identified in the primary care setting using only simple tests? Results of the Diagnosis Improvement in Primary Care Trial. Int J Clin Pract. 2011; 65(9): 989-996

5. Flanigan RC, et al. 5-year outcome of surgical resection and watchful waiting

6. for men with moderately symptomatic BPH: a department of Veterans Affairs cooperative study. J Urol 1998; 160(1): 12-6 

7. Wasson JH, et al. A comparison of transurethral surgery with watchful waiting for moderate symptoms of benign prostatic hyperplasia. The Veterans Affairs Cooperative Study Group on Transurethral Resection of the Prostate. New Engl J Med 1995; 332(2): 75-9

8. Netto NR, et al. Evaluation of patients with bladder outlet obstruction and mild international prostate symptom score followed up by watchful waiting. Urol 1999; 53(2): 314-6 

9. Djavan B, et al. State of the art on the efficacy and tolerability of alpha1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Urology 2004; 64(6): 1081-8

10. McConnell JD, 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): 2387-98

11. Nickel JC, Sander S, Moon TD. A meta-analysis of the vascular-related safety profile and efficacy of a-adrenergic blockers for symptoms related to benign prostatic hyperplasia. Int J Clin Pract 2008; 62(10): 1547-59

12. Marberger MJ, on behalf of the PROWESS Study Group. Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind, placebo-controlled, multicenter study. Urology 1998; 51(5): 677-86

13. Roehrborn CG, et al; CombAT Study Group. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombATstudy. Eur Urol 2010; 57(1): 123-31 

14. Thompson IM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003; 349: 215-224

15. Andriole GL, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med 2010; 362: 1192-1202

16. Roehrborn CG. BPH progression: concept and key learning from MTOPS, ALTESS, COMBAT, and ALF-ONE. BJU Int 2008; 101(S3): S17-S21

17. Roehrborn CG, et al. Effects of serum PSA on efficacy of tolterodine extended release with or without tamsulosin in men with LUTS, including OAB. Urology 2008; 72(5): 1061-7 

18. Capitán C, et al. GreenLight HPS 120-W Laser Vaporization versus Transurethral Resection of the Prostate for the Treatment of Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia: A Randomized Clinical Trial with 2-year Follow-up. Eur Urol. 2011; 60(4): 734-739