Committee I

Committee I

Non-Neurogenic Male Lower Urinary Tract Symptoms (Male LUTS)

Prof. Ashraf Shahin, Professor of Urology, Zakazig University

Prof. Hany Mostafa,Professor of Urology, Ain Shams University

Prof. Magdy Sabaa Professor of Urology, Tanta University

Prof. Safwat Abo Hashem,Professor of Urology, Zagazig University

Prof. Ahmed Elbaz, Professor of Urology, Tudor Bilhars Institute

Dr Ahmed Eliwa, Assistant Professor of Urology, Zakazig University

Contents
I.1 List of Abbreviations
  • 5-ARIs - 5α-Reductase Inhibitor
  • AUA - American Urologic Association
  • AUR - Acute Urinary Retention
  • AUS - Artificial Urinary Sphincter
  • B-TURP - Transurethral Bipolar Resection of Prostate
  • BEP - Bipolar Enucleation of the Prostate
  • BOO - Bladder Outlet Obstruction
  • BPH - Benign Prostatic Hyperplasia
  • BPO - Benign Prostatic Obstruction
  • BVP - Bipolar Vaporization of Prostate
  • CAM - Complementary and Alternative Medicines
  • CAU - Canadian Urologic Association
  • CKD - Chronic Kidney Disease
  • CPU - Conformal Planning Unit
  • CT - Computed Tomography
  • DHT - Dihydrotestosterone
  • DO - Detrusor Over activity
  • DRE - Digital Rectal Examination
  • EAU - European Urological Association
  • eGFR - Estimated Glomerular Filtration Rate
  • EjD - Ejaculatory Dysfunction
  • EUG - Egyptian Urological Guidelines
  • FVC - Frequency Volume Charts
  • HoLEP - HoLmium Laser Enucleation of Prostate
  • ICS - International continence society
  • IFIS - Intra-Operative Floppy Iris Syndrome
  • IPP - Intravesical Prostatic Protrusion
  • IPSS - The International Prostate Symptom Score
  • IPSS-Arb - Arabic version of the IPSS
  • KTP - Potassium-Titanyl-Phosphate
  • LBO - Lithium Triborate
  • LUTS - Lower Urinary Tract Symptoms
  • M-TURP - Monopolar Transurethral Resection of Prostate
  • MRI - Magnetic Resonance Imaging
  • NICE - National Institute for Health Care Excellence
  • OP - Open Prostatectomy
  • PAE - Prostatic Artery Embolization
  • PCa - Prediction Of Carcinoma Of The Prostate
  • PDE5Is - Phosphodiesterase 5 Inhibitors
  • PFS - Pressure flow study
  • PMD - Post Micturition Dribble
  • PPI - Post-prostatectomy Urinary Incontinence
  • PSA - Prostate-Specific Antigen
  • PUL - Prostatic Urethral Lift
  • PVP - Photoselective Vaporization of Prostate
  • PVR - Post-Void Residual Urine
  • QoL - Quality of Life
  • ThuLEP - Thulium Laser Enucleation of Prostate
  • TRUS - Transabdominal or Transrectal US
  • TUIP - Transurethral Incision of The Prostate
  • TUMT - Transurethral Microwave Therapy
  • TUNA - Transurethral Needle Ablation
  • TURP - Transurethral Resection of The Prostate
  • UDS - Urodynamic studies
  • UTI - Urinary Tract Infection
  • VGUG - Voiding Cystourethrogram

I.2 Abstract.

I.2.1 Objective
This overview represents the updated recommendations for diagnosis and management of non- neurogenic male lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). It also provides an updated scheme for the management of male urinary incontinence. This document integrates recent international guidelines with local experts’ opinions based on Egyptian healthcare and socioeconomic circumstances.
I.2.2 Method
Databases searched included Medline, Cochrane Libraries, EAU guidelines, ICS recommendations, 6th ICI recommendations, AUA and NICE guidelines, from January 2018 to September 2020. Review of several meta-analyses, leading institutional protocols and relevant Egyptian publications were taken into consideration. All statements were graded according to strength of recommendation. Each statement was given a strength rating (strong or weak).

I.2.3 Result
These guidelines represent the best clinical evidence-based medicine available. These guidelines are not solely based upon the level of evidence of the international publications but also include expertise of the treating doctor and expectations of every patient.

I.2.4 Conclusion
The understanding of the LUT as a functional unit, and the multifactorial aetiology of associated symptoms, means that LUTS now constitute the main focus, rather than the former emphasis on BPH. Guidelines can never replace clinical expertise when making treatment decisions for individual patients, but rather help to focus decisions - also taking personal values and preferences/individual circumstances of patients into account.

I.3 Introduction
• This overview represents the updated recommendations for diagnosis and management of non- neurogenic male lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). It also provides an updated scheme for the management of male urinary incontinence.

• It must be emphasized that the Egyptian guidelines can never replace the clinical expertise when making treatment decisions for individual patients, but rather help to focus decisions, taking in consideration the personal values, expectations, preferences and individual circumstances of patients and the physician’s preferences.

I.3.1 Methodology
• Our recommendations are the outcome of integrating 3 resource categories:
  • Five guidelines (including their latest updates), namely, European Urological Assoliciation (EAU), American Urologic Association (AUA), National Institute for Health Care Excellence (NICE) and Canadian Urologic Association (CAU) and International continence society (ICS) (1-5).
  • Review of several guides, recommendations, position statements, meta-analyses and leading institutional protocols.
  • Relevant Egyptian publications.
  • All statements were graded according to strength of clinical practice recommendations, expressed as strong or weak. While this was guided by other guideline recommendations, it was modified to suit the Egyptian environment dominated by a rich bioecological environment, specific demographics and social constraints and limited financial resources.
I.3.2 EPIDEMIOLOGY
• LUTS in elderly men due to BPH are very common. El‑Gilany et al. (6) in their study found that despite the high prevalence of severe symptoms among the targeted elderly, only 16% of them sought medical advice. Little is known about the quality of life (QoL) of these elderly males with BPH in Egypt, and there is no community‑based studies on the magnitude of the problem of BPH among elderly men in Egypt.

I.4 DIAGNOSTIC EVALUATION (Medical History)

• Full medical history is the cornerstone in the diagnosis of the causes, identifying the complications and comorbidities and knowing patients’ expectations and QoL. During this step, physicians must focus on neurologic symptoms, drugs intake [especially anticoagulants] and previous surgeries. Patient's erectile function and sexual history should be reviewed thoroughly (6,7).

I.4.1 DIAGNOSTIC EVALUATION
• Symptom score questionnaires are important in quantifying patient's symptoms and in detection of the predominant symptoms. They are not disease specific, but they can be used to monitor and follow-up treatment outcomes. These include:

I.4.2 The International Prostate Symptom Score (IPSS)
• It is based on the answers of seven questions concerning urinary symptoms and one question concerning QoL. Each question concerning urinary symptoms allows the patient to choose one out of six answers indicating increased severity of the particular symptom. The answers are assigned points from 0 to 5. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic). The IPSS score is categorized as ‘asymptomatic’ (0 points), ‘mildly symptomatic’ (1-7 points), ‘moderately symptomatic’ (8-19 points), and ‘severely symptomatic’ (20-35 points).

• An Arabic version of the IPSS (IPSS-Arb) was developed through a series of translations and modifications. The validity and reliability were assessed. The IPSS-Arb is shown to be a reliable and valid instrument for patients with BPH. It can be used in patient assessment, follow-up, and in research involving Arabic-speaking patients. (8)

I.5 DIAGNOSTIC EVALUATION (Assessment of erectile function)

• Male erectile function has significant impact on QoL especially in those who are suffering from BPH. There is a strong correlation between the severity of sexual dysfunction and the severity of LUTS. It should be taken into consideration that all treatment options of BPH affect sexual function. Medical, surgical, and minimally invasive treatment options differ in their effect on erectile function, ejaculation, and sexual satisfaction. Choice of treatment modality takes into account baseline sexual function and patient expectations. (1,2)
I.5.1 Diaries
• Urinary diaries include frequency volume charts (FVC) and bladder diary. Frequency volume chart is a simple recording of the voided urine volume and time of the void [day and night]. Bladder diaries include more details such as fluid intake, episodes of incontinence, number of pads and possible associated symptoms. Bladder diary of at least 48 hours seem to be the most defensible policy (9).
I.5.2 Physical examination, digital rectal examination (DRE) and focused neurologic examination.
Examination for BPH includes abdominal, digital rectal and a focused neurological examination. Abdominal examination is done to detect palpable bladder [in cases of urinary retention] and other abdominal masses. The DRE starts with assessment of perianal sensation, anal tone, prostate size and contour. DRE is a good test for identifying enlargement above a threshold value, as occurs in benign and malignant disease; it has not yet proved to be a good quantitative measure of prostate gland enlargement (10)
I.5.3 Urine Analysis
It is a simple, rapid and low-cost test that can detect microscopic hematuria, urinary tract infection (UTI), glycosuria and other pathologic conditions of the urinary tract.
I.5.4 Renal function measurement
Serum creatinine or estimated glomerular filtration rate (eGFR) are the commonly used methods for renal functions’ assessment. Eleven percent of men with LUTS shows renal insufficiency, diabetes mellitus or hypertension which usually lead to elevated renal functions. (11) Hong et al. (12) showed that in hypertensive patients who presented with LUTS, low Qmax was associated with chronic kidney disease (CKD). The risk of post-operative complications is higher in patients with renal impairment (13).
I.5.5 Prostate-specific antigen (PSA)
The role of PSA assessment in male with LUTS due to BPO (benign prostatic obstruction) includes prediction of prostatic volume (14) and Prediction of BPO-related outcomes. Serum PSA is a good predictor of prostate growth (15), changes in symptoms, QoL/bother, and maximum flow-rate (Qmax) (16), clinical progression (17), the risk of acute urinary retention (AUR) and BPE-related surgery risk for treatment [higher in men with a baseline PSA of > 1.4 ng/ml] (18).
I.5.5.1 Prediction of carcinoma of the prostate (PCa)
The potential benefits and harms of screening of serum PSA to diagnose PCa in men with LUTS should be discussed with the patient.
I.5.6 Post-void residual urine [PVR]
Noninvasive method for assessment of PVR is the transabdominal Ultrasound (bladder scan), while catheterization is considered an invasive method. In cases of high PVR volumes, bladder outlet obstruction (BOO) and/or detrusor underactivity should be considered (19). Large PVR may indicate a poor response to medical treatment and changes in PVR over time can detect increased risk for AUR, with elevated chances when prescribing anti-muscarinics for these patients. (20) PVR value represents clinical and medical research challenge, as its value is extremely variable and no known cut-off PVR thresholds have been correlated to various diagnostic or surgical outcomes.
I.5.7 Uroflowmetry
It is an initial non-invasive test to give crude estimate of the voiding phase. It entails measuring the voided volume, Qmax, flow pattern and PVR. Low Qmax means BOO, DUA or an under-filled bladder. Uroflowmetry should be repeated if voided volume is less than 150 ml. (21) Qmax of 10 mL/s has a specificity of 70%, a PPV of 70% and a sensitivity of 47% for diagnosis of BOO. If Qmax is > 15 mL/s, the result is considered equivocal and BOO cannot be excluded. Uroflowmetry can be used for following up of the treatment outcomes and quantifying patient's symptoms. (21)

I.5.8 Imaging

I.5.8.1 Upper urinary tract imaging
Ultrasound allows for assessment of renal masses, hydronephrosis and simultaneous evaluation of the bladder, PVR and prostate size and morphology. It can be used for the evaluation of haematuria, or urolithiasis. Ultrasound is of lower cost, radiation free (22), however it is operator-dependent.
I.5.8.1.1 Imaging of the Prostate
 Prostate imaging is mostly done by transabdominal or Transrectal US [TRUS]. Other imaging modalities include computed tomography (CT), and magnetic resonance imaging (MRI). Prostate volume predicts symptom progression and the risk of complications. (22) It's important to assess prostate size and shape prior to treatment with 5α-reductase inhibitors (5-ARIs) and before choosing the surgical treatment modality [open prostatectomy (OP), enucleation techniques, transurethral resection, transurethral incision of the prostate (TUIP), or minimally invasive therapies]. Transrectal US is superior to transabdominal route for assessment of volume of prostate (23). Median lobe enlargement is considered a contraindication for some minimally invasive treatments.
I.5.8.1.2 Urodynamic (UDS)
 Pressure flow study (PFS) and filling cystometry are performed to assess male LUTS due to BPO. The role of urodynamic testing in male LUTS due to BPO includes identifying the pathophysiologic events in patients with LUTS during voiding, predicting the outcomes of treatment especially when invasive surgical intervention is considered and making causal diagnosis in patients with inconclusive other tests. Urodynamic tests also differentiate between bladder outlet obstructions [BOO], detrusor underactivity and detrusor overactivity. (24)
I.5.8.2 Non-invasive tests in diagnosing BOO in men with LUTS
These tests include prostatic configuration/intravesical prostatic protrusion (IPP) (25), Bladder/ detrusor wall thickness and ultrasound-estimated bladder weight (26). Other non-invasive urodynamic testing includes penile cuff method (external condom), Prostatic urethral angle and Resistive index (27-29) are not validated for use in the assessment of male LUTS.


Table I:1 Recommendations for diagnosis of male non-neurogenic LUTS

Recommendation

strength rating
1. Take a complete medical history from men with LUTS Strong
2. Use IPSS or its validated Arabic form in the primary assessment of male LUTS, monitoring treatment response and for research purposes Strong
3. Consider assessment of patients’ sexual function before starting any modality of active treatment for BPH [medical, surgical or minimally invasive] Strong
4. Advise the BPH patient to record a bladder diary for at least 48 hours Strong
5. Perform physical examination, DRE and focused neurological examination for male patients with LUTS Strong
6. It is crucial to perform urinalysis for male patients with LUTS. Strong
7. Assess renal functions:
  • If there is evidence of Renal impairment (based on history and clinical examination)
  • If there is hydronephrosis
  • Before surgical treatment for male LUTS.
 Strong
8. PSA measurement is important if it helps in the diagnosis or selecting treatment option for LUTS due to BPO. Strong
9. Measure prostate-specific antigen (PSA) if a diagnosis of PCa will change management. The potential benefits and harms of using serum PSA testing to diagnose PCa in men with LUTS should be discussed with the patient. Strong
10. Measure PVR in the initial assessment of male LUTS and before prescribing medical treatment for BPH, using transabdominal ultrasound Strong
11. Perform uroflowmetry in the initial assessment of male LUTS. Weak
12. Perform uroflowmetry before starting medical or invasive treatment and for follow-up to assess the treatment outcomes. Strong
13. Perform ultrasound of the upper urinary tract in men with LUTS if there is elevated renal functions Strong
14. Perform prostate imaging when considering 5-ARIs treatment for male LUTS or considering surgical treatment Strong
15. Voiding cystourethrogram (VGUG) is not recommended in the routine diagnostic work-up of men with BPH Strong
16. Retrograde urethrography may additionally be useful for the evaluation of suspected urethral strictures Strong
17. Urethrocystoscopy should be performed in men with LUTS before invasive or minimally invasive treatment if the endoscopic findings may change the treatment option Strong
18. Patients with history of microscopic or gross heamturia, urethral stricture, or bladder cancer who present with LUTS should undergo urethrocystoscopy during diagnostic evaluation Strong
19. Pressure-flow studies (PFS) should be individualized according to certain indications prior to invasive treatment:
  • In men who have had previous failed invasive treatment for their LUTS
  • In men undergoing invasive treatment for their LUTS and cannot void > 150 mL.
  • In men with bothersome voiding LUTS considering invasive treatment and high Qmax > 10 mL/s or high post void residual > 300 mL
  • In men with bothersome voiding LUTS considering invasive treatment with aged < 50 years or > 80 years.
  • In men with BPH and known or suspected neurological diseases (multiple sclerosis, Parkinsonism, lumbar disc prolapse, diabetes mellitus) considering invasive treatment
 Strong
20. Do not offer non-invasive diagnostic tests as an alternative to pressure-flow studies for diagnosing BOO in men Strong
I.6 Conservative treatment (Watchful waiting, WW)
Minority of the men who are not bothered by their LUTS may occasionally progress to AUR and complications, however hand most of them (about 79 %) usually remain stable for many years (30). Studies comparing WW and transurethral resection of the prostate (TURP) in men with moderate LUTS showed that the surgical group had improved bladder function (flow rates and PVR volumes), especially in those with high levels of bother. 36% of WW patients crossed over to surgery within five years, leaving 64% doing well in the WW group (31). Increasing symptom bother and PVR volumes are the strongest predictors of clinical failure. Men with mild-to-moderate uncomplicated LUTS who are not too troubled by their symptoms are suitable for WW, which is a type of strategy in which the patient is receiving no treatment but on the other hand he is regularly followed- up by his health care provider (32)

Table I:2 Recommendations for conservative treatment of male non-neurogenic LUTS due to BPH

Recommendation

strength rating
1. Patients should share in decisions about their care and treatment with their healthcare providers. Strong
2. Men who are troubled by their symptoms should be assessed prior to treatment to establish symptom severity and detect complications (most patients are uncomplicated and mild to moderate symptoms) Strong
3. Watchful waiting (active surveillance) should be offered as the preferred option in:
  • All patients with mild symptoms of LUTS secondary to BPH (AUA-SI score <8)
  • Patients with moderate or severe symptoms (AUA-SI score ≥8) who are NOT bothered by their LUTS
 Strong
4. Drug treatment can only be offered when conservative therapy has failed or is not appropriate Strong
5. Lifestyle advice, behavioural and dietary modifications are part of WW. This entails education about the natural history of the disease, reassurance (that BPH is not precancerous) and periodic monitoring (first time after 6 months, then yearly as long as there is no deterioration of symptoms and/or appearance of new complaints. Lifestyle advice includes:
  • Restriction of fluid intake at specific times e.g., at night or when going out in public)
  • Avoidance/moderation of intake of caffeine or cola, which may have a diuretic and irritant effect, thereby increasing fluid output and enhancing frequency, urgency and nocturia
  • Use of double-voiding technique
  • Urethral milking to prevent post-micturition dribble
  • Reviewing the medications and optimising the time of administration or substituting drugs for others that have fewer urinary side effects
  • Treatment of constipation
 Strong


I.7 Pharmacological treatment

I.7.1 Alpha Blockers
The prostate and bladder neck have α-adrenergic innervation which is responsible for the “dynamic‟ component of bladder outlet obstruction. The bladder neck and trigone receptors and also the receptors in the prostate capsule are mainly alpha-1A. Alpha blockers are thought to work by relaxing smooth muscles thereby reducing this resistance and improving symptoms and flow rate (33) α1-adrenoceptors in blood vessels, other non-prostatic smooth muscle cells, and the central nervous system may mediate adverse events. (34) Alpha-1-blockers can reduce both storage and voiding LUTS. IPSS reduction and Qmax improvement during α1-blocker treatment appears to be maintained over at least four years (35) Indirect comparisons and limited direct comparisons between α1-blockers demonstrate that all α1-blockers have similar efficacy in appropriate doses (36,37) Selective alpha 1-A blockers (Tamsulosin and Silodosin) are as effective as older non-selective alpha blockers (Alfuzosin, doxazosin, terazosin), however with less likely cardio-vascular events that are common with the non-selective alpha blockers (postural hypotension, dizziness and ECG changes). Neither prostate size nor age correlate with α1-blocker efficacy in short term (less than one year) follow -up studies, however α1-blockers seems to be more effective in patients with smaller prostates (< 40 mL) in longer-term studies (38). Until recently Alpha 1-blockers seemed to have no effect on AUR prevention in long-term studies, however, recent evidence suggests that their use may improve resolution of AUR (39). The first report on intra-operative floppy iris syndrome (IFIS) was in cataract surgery in 2005. Meta-analysis showed that patients using α1-blockers, whatever the type, has IFIS increased risk. However, the risk for IFIS was much higher for tamsulosin. (40). Ejaculatory dysfunction (EjD) seems to be reported more common with α1-blockers than with placebo. Tamsulosin and silodosin reported statistically high incidence of EjD than placebo. On the other hand, both doxazosin and terazosin were associated with less incidence of EjD (41).
I.7.2 5- alpha reductase inhibitors
The androgen that nourishes the prostate gland is dihydrotestosterone (DHT), which results from reduction of testosterone by the enzyme 5α-reductase. 5-alpha reductase has two-types:

  • Type 1: predominant expression and activity in the skin and liver (finastride)
  • Type 2: predominant expression and activity in the prostate (dutasteride)
The main effect of 5α-reductase inhibitors is inducing apoptosis of prostatic epithelial cells (42), thus reducing the prostate volume by about 18-28% after six months. They also cause a decrease in circulating PSA levels of about 50% after six to twelve months of treatment (43). Contrary to alpha blockers, in the PLESS study, finasteride reduced the relative risk of AUR by 57% and need for surgery by 55% (absolute risk reduction 4% and 7%, respectively) at four years, compared with placebo (44). Furthermore, finasteride might reduce blood loss during transurethral prostate surgery, probably due to its effects on prostatic vascularisation. (45)
The most relevant adverse effects of 5-ARIs are related to sexual function, and include reduced libido, erectile dysfunction and less frequently, ejaculation disorders such as retrograde ejaculation, ejaculation failure, or decreased semen volume. They may also cause gynecomastia and breast tenderness.
I.7.3 Muscarinic Receptor Antagonists
Bladder contraction is mediated via the parasympathetic cholinergic nerves. Anticholinergics may also reduce the sensation of urgency during bladder filling and therefore increase the functional bladder capacity. Antimuscarinics (anticholinergics) improve the storage component of male LUTS whether due to BPH or not. Antimuscarinics reduce frequency, urgency, and urgency incontinence episodes (46). They may be used in elderly men and those with significant BOO. There is little evidence of safety in men with high PVRs, however some guidelines prefer cut-off value of 150 ml (1) while others suggest 250 ml (4). Evidence shows that alpha-blockers combination with antimuscarinics can improve men with both voiding and storage symptoms (47).
Adverse events include dry mouth, dizziness, cognitive affection, dry eyes, constipation and theoretical risk of urine retention in males with increased PVR. They should not be used in patients with narrow-angle glaucoma.
I.7.4 Phosphodiesterase 5 inhibitors
The exact mechanism of PDE5Is on LUTS is not completely understood. Many theories have been suggested including reduced smooth muscle tone of the detrusor, prostate and urethra, while others suggest alleged altered reflex pathways in the spinal cord and neurotransmission in the urethra, prostate, or bladder. Increase blood perfusion and oxygenation in the LUT have also been suggested, together with an anti-inflammatory effect on the prostate and bladder (48,49). Clinical trials of several selective oral PDE5Is have been conducted in men with LUTS and all of them showed good efficacy in treatment of LUTS due to BPH, however only tadalafil (5 mg once daily) has been licensed for the treatment of male LUTS due to its longer half-life. The noted reduction in LUTS was not correlated to age, pre-treatment testosterone level or prostate volume (50-52). PDE-5 inhibitors are contraindicated in patients who have had a recent myocardial infarction, unstable angina pectoris or stroke, or those using the non-selective α1-blockers doxazosin and terazosin, nitrates, potassium channel opener nicorandil. Phosphodiesterase 5 inhibitors improve IPSS, QoL and IIEF score, but not Qmax.
I.7.5 Beta-3 agonists
Beta-3 adrenoceptors are the main beta receptors distributed in smooth muscle cells of the detrusor and when stimulated, detrusor relaxation occurs (54). It has been shown that this category of drugs significantly improves all OAB symptom score items and also improves the storage sub- score of the IPSS when studying their add-on effect to alpha blockers (55-56).
I.7.6 Phytotherapy or Complementary and Alternative Medicines (CAM)
Many studies and Cochrane meta-analyses report no statistically significant improvement in IPSS, Q max, PVR, QoL and prostate volume between different phytotherapies compared to placebo (57,58).Many studies and Cochrane meta-analyses report no statistically significant improvement in IPSS , Q max, PVR, QoL and prostate volume between different phytotherapies compared to placebo (57,58).
I.7.7 Combination therapies
Many authors have tested the efficacy of combination therapy of an α1-blocker, 5-ARI or placebo alone and shown that combination therapy was superior to monotherapy in most of the measured parameters, however the frequency of adverse events was more in combination therapy (59-61). Combination treatment with α1-blockers and antimuscarinics or beta-3 agonists is effective for improving LUTS-related QoL impairment. These combinations are more effective for reducing urgency, UUI, frequency, nocturia, or IPSS compared with α1-blockers or placebo alone for up to one year (62-64). A combination of PDE5Is and α-blockers has also been recently studied and showed that the combination is better than α-blockers alone (65). The combination of PDE5Is with 5 alpha reductases have been also studied but to a lesser extent (66).
I.7.8 Desmopressin
As per table 3.
I.7.9 Post micturition dribbling
Post void urethral milking is a technique used to eliminate post micturition dribble (PMD), which is not associated with obstruction but may be caused by the urethra being emptied incompletely by the muscles surrounding it. This technique involves drawing the tips of the fingers behind the scrotum and pushing up and forward to expel the pooled urine (68).

Table I:3 Recommendations for pharmacological treatment of male LUTS due to BPH

Recommendation

strength rating
1. Offer alpha 1-adrenergic blockers (Alpha Blockers available in Egyptian market: alfuzosin, doxazosin, terazosin, tamsulosin and Silodosin) as the first line treatment option for patients with bothersome, moderate to severe LUTS secondary to BPH (AUA-SI score ≥8) Strong
2. Offer alpha 1-adrenergic blockers for those who failed conservative treatment as a first line treatment Strong
3. Give the patient a period of 2 weeks to fully appreciate the clinical effect of the prescribed alpha blocker, however significant efficacy over placebo can occur within hours to days. Strong
4. Offer alpha 1- blockers to improve the two components to LUTS (storage and voiding), which appears in significant improvements in IPSS and Q max, which is mostly maintained for about 4 years. Strong
5. Do not offer alpha 1-blockers with the aim of reduction of prostate size Strong
6. Titrate the dose of Doxazosin and Terazosin and monitor blood pressure when offering these alpha blockers for treatment of BPH Strong
7. Warn the patients of ejaculatory disorders when prescribing selective alpha-1A blockers such as Tamsulosin and Silodosin Strong
8. The choice of the alpha blocker should put into consideration the patient’s comorbidities, side effect profiles, tolerance and economic issues. Weak
9. Offer treatment with any of the two types of 5-ARIs (type 1 and 2) in men with moderate-to-severe LUTS with prostate volume more than (30 - 40 mL) and/or elevated PSA concentration (> 1.4-1.6 ng/mL). Strong
10. Do not offer 5-ARIs for immediate relief of LUTS due to the slow onset of action ranging from 3-6 months. Strong
11. Offer 5-ARIs to decrease the prostate volume on long term use. They can also prevent the risk of AUR and need for surgery. Weak
12. Offer 5-ARIs as treatment alternative for refractory hematuria due to prostatic bleeding, and also preoperatively in BPH cases that present with hematuria Weak
13. Prescribe muscarinic receptor antagonists as a single treatment, however cautiously, in management of male voiding LUTS Weak
14. Offer antimuscarinics only if residual urine volume is estimated to be less than 150 ml Weak
15. Regularly evaluate PVR urine in BPH patients on anitmuscar Strong
16. Advice patient to discontinue medication if worsening voiding LUTS or urinary stream is decreased after initiation of therapy Strong
17. Use long-acting phosphodiesterase 5 inhibitors as a single treatment for patients with bothersome, moderate to severe LUTS secondary to BPH (AUA-SI score ≥ 8) whether they suffer from erectile dysfunction or not Strong
18. Do not prescribe PDE-5 inhibitors in patients using nitrates, potassium channel opener nicorandil, or the α1-blockers doxazosin and terazosin, in patients who have unstable angina pectoris, and those who have had a recent myocardial infarction or stroke Strong
19. Combination therapy using alpha blockers and PDE-5 inhibitors seem better than either alone Weak
20. Offer beta-3 agonists alone in men with moderate-to-severe LUTS who present mainly with storage symptoms (frequency, urgency and urgency incontinence) Weak
21. Prescribe beta-3 agonists only if residual urine volume is estimated to be less than 150 ml Weak
22. Monitor PVR in patients on beta-3 agonists regularly Weak
23. Do not offer beta-3 agonists in patients with severe uncontrolled hypertension Strong
24. Do not offer dietary supplement or combination phytotherapeutic agents as standard therapy for the management of LUTS secondary to BPH Strong
25. Offer combination treatment with an α1-blocker and a 5α-reductase inhibitor to men with moderate-to-severe LUTS and an increased risk of disease progression (e.g. prostate volume > 40 mL). Strong
26. Offer patients successfully treated with combination therapy the option of discontinuing the alpha-blocker after 6 months. If symptoms recur, the alpha-blocker should be restarted (conditional recommendation based on moderate-quality evidence). Weak
27. Offer antimuscarinics or beta-3 agonists to alpha blockers in patients with persistent storage LUTS during α1-blocker mono-therapy treatment Strong
28. Use the combination of PDE5Is and α-blockers for those not responding well to the use of either of the drugs as a monotherapy, especially those with erectile dysfunction Strong
29. Offer Low-dose Desmopressin as a therapeutic option in men with LUTS/BPH with nocturnal polyuria if other medical causes have been excluded as a cause of nocturnal polyuria and if patients did not benefit from other treatments (67) Strong
30. Monitor serum sodium 3 days after the first dose. Re-check again after one month. If serum sodium is reduced to below the normal range, stop desmopressin treatment. Strong


I.8 Surgical treatment
I.8.1 Monopolar Transurethral Resection of Prostate (M-TURP)
M-TURP is the standard surgical treatment for BPH since many decades. It has been proven to be efficacious with durable outcomes in terms of decreased I-PSS score, elevated Qmax, improved QoL and decreased PVR urine levels (69). Intraoperative and short-term postoperative complications include TUR syndrome (0.8-2.5%), blood transfusion (2-4.4%), clot retention (4.9-7.2%) and significant UTI (4-6%). Mid to long term complications include retrograde ejaculation (55-85%), stress urinary incontinence (0.6-1.5%), bladder neck contracture (2-3%) and urethral stricture (3.4-4%). The procedure has overall relatively low incidence of morbidity, which increases with increased prostate size (69-72).
I.8.2 Transurethral Incision of Prostate (TUIP)
Incising bladder neck down to the verumontanum has been used as alternative to conventional TURP with prostate size around 30 g, showing comparable LUTS improvements and increased Qmax (73). An Egyptian RCT comparing TUIP and TURP in prostate size < 30g found no significant differences in terms of I-PSS score, need for blood transfusion and reoperation. TUIP showed favorable results over TURP concerning sexual complications (ED 8% vs. 20%, retrograde ejaculation 30% vs. 70% respectively) (74)
I.8.3 Transurethral Bipolar Resection of Prostate (B-TURP):
With the advent of bipolar trans urethral technology, resection could be carried out in isotonic saline, where the closed circuit of the current is situated locally at the resection site, with no need for returning pole as the grounding pad. Short term results proved to be comparable to M-TURP in terms of efficacy, with more favorable safety criteria and reduced side effects (blood transfusion, clot retention and TUR syndrome) (73). Long term results showed comparable results in terms of efficacy and complications as well (73-75). This technique could be used safely in patients with large prostates and other comorbidities such as cardiac patients and bleeding tendencies.
I.8.4 Transurethral Bipolar Vaporization of Prostate (BVP):
Although short term results show comparable efficacy with TURP and more favorable safety profile, with lower perioperative morbidity, data still is lacking to identify mid to long term efficacy and complications (75)
I.8.5 Transurethral Bipolar Enucleation of the Prostate (BEP):
It has comparable efficacy and safety profile with HoLEP in substantially large prostates more than 80 g (75-77)
I.8.6 Open Simple prostatectomy:
Open prostatectomy could be performed by either trans vesical (Freyer’s) approach or retro pubic (Millin’s) approach. This is the most invasive surgical treatment option for substantially large prostates more than 80gm. Other less invasive endoscopic procedures such as enucleation procedures as HoLEP & BEP proved to have comparable short to mid-term efficacy with open procedures but with superior safety profiles (76,77).

Table I:4 Recommendations for Surgical Treatment of BPH

Recommendation

strength rating
1.Indications of prostatectomy (whatever the technique) include:
  • Recurrent or refractory urinary retention
  • Recurrent urinary tract infections due to BPH
  • Bladder stones or diverticula due to BPH
  • Treatment-resistant recurrent haematuria due to BPH
  • Upper urinary tract dilatation due to BPO, with or without renal insufficiency.
  • Unsatisfied patients with QoL because of LUTS despite conservative or pharmacological treatments
Strong
2.Both monopolar and bipolar TURP can be used for endoscopic removal of prostates in men with BPH and prostate size 30-80 g. Strong
3.Offer bipolar TURP when prostate volume is larger than 80 g, but still, this depends on surgeon’s expertise and resection speed. Offer bipolar TURP in cardiac patients or patients with bleeding tendencies or patients on anticoagulants Weak
4.Junior staff may use cut-off value of prostate size up to 60 g for M-TURP and B-TURP for prostate size 60-80 g until achieving adequate learning curve Weak
5.Offer TUIP to treat properly indicated men with BPH when prostate size < 30 g, and no middle lobe enlargement Strong
6.BVP may be used as alternative to TURP in prostate size 30-80 g, whenever available and by trained urologists Weak
7. In absence of endoscopic enucleation possibility, consider simple open prostatectomy for treating large prostates more than 80 g in properly indicated patients Strong

I.8.7 Laser transurethral prostatectomy

I.8.7.1 HoLmium Laser Enucleation of Prostate (HoLEP)
HoLEP is considered the endoscopic equivalent of open prostatectomy (OP). Its outcome is comparable to OP in terms of IPSS and Qmax improvement in large prostates (77). HoLEP has less incidence of blood transfusion, shorter hospital stay and shorter catheterization time compared to both TURP and OP (77,78). HoLEP has been safely used in patients on anticoagulants and anti-platelet therapy (78,96).
I.8.7.2 Green light Laser (Photoselective) Vaporization of Prostate (PVP)
PVP utilizes one of 3 different forms of laser of the same wavelength (532 nm) with different power and different fibers design: 80W KTP, 120W LBO and 180W XPS Lasers. Mechanism of action: The Potassium-Titanyl-Phosphate (KTP) and the lithium triborate (LBO) lasers work at a wavelength of 532 nm. Laser energy is absorbed by haemoglobin, but not by water. Vaporization leads to immediate removal of prostatic tissue. Three “Greenlight” lasers exist, which differ not only in maximum power output, but more significantly in fibre design and the associated energy tissue interaction of each. The standard Greenlight device is the 180-W XPS laser, but the majority of evidence is published with the former 80-W KTP or 120-W LBO laser systems. Laser vaporization of the prostate using either 80-W KTP, 120- or 180-W LBO lasers is a good option for the treatment of BPH patients who are indicated for surgical intervention with a prostate size of 30-80 g. PVP can be offered as a modality of BPH treatment for those patients on anticoagulants or anti platelet therapy.
  • 1. 80W KTP
    • It has proven equivalent efficacy to TURP at 12 months’ follow-up in terms of Qmax and I-PSS. KTP PVP showed inferior results to TURP concerning incidence of bladder neck contracture, urethral stricture, residual adenoma and need for reoperation (79-81).
  • 2. 120W LBO
    • Short to mid-term objective and subjective outcomes proved to be comparable to TURP with more favorable perioperative complications rate towards PVP concerning blood transfusion, clot retention, duration of catheterization and hospital stay (82).
  • 3. 180W XPS
    • Goliath study showed non-inferiority of 180W PVP to TURP in both functional and subjective outcomes as well as in complications rate (83).
I.8.7.3 Diode laser treatment of the prostate
Diode lasers with a wavelength of 940, 980, 1318 and 1470 nm (depending on the semiconductor used) are used for either vaporization or enucleation of the prostate. A limited number of low-quality RCTs are present in the literature (84). Worth of notice, this modality is still not available in Egypt.
I.8.7.4 Thulium Laser Enucleation of Prostate (ThuLEP)
Long term results of ThuLEP are similar to TURP in terms of PVR, Qmax, I-PSS and QoL. Postoperative results favored ThuLEP over TURP concerning catheter duration, hospital stay and blood loss (85-86)

+

Egyptian Urological Guidelines, First Edition- 2021 27

I.9 Minimally invasive procedures.
I.9.1 Prostatic Urethral Lift (PUL)
This procedure depends on decompressing the prostatic urethra by lateralizing away the prostatic lobes using a cystoscopically-held device, which implants permanent sutures in the lateral lobes. Although PUL showed lower improvements in Qmax and I-PSS when compared to TURP, The QoL score was the same at 2 years’ follow-up as well as need for retreatment due to bothersome symptoms. PUL was superior to TURP in preserving erectile and ejaculatory functions (87). PUL can be offered as an alternative to TURP in patients not fit for this invasive procedure or those willing to preserve their sexual function with prostates less than 70 g and no middle lobe. Worth of notice, this modality is still not available in Egypt.
I.9.2 Transurethral Microwave Therapy (TUMT)
It uses a specialized catheter to emit electromagnetic waves to prostate for thermos-ablative effect. The available data are considered inconsistent with no evidence of long-term efficacy and high retreatment rates (88). Worth of notice, this modality is not available in Egypt.
I.9.3 Transurethral Needle Ablation (TUNA)
It uses an endoscopic catheter through which needles are inserted in the prostate to emit radiofrequency waves to create thermal necrosis. There is no sufficient evidence to support the use of TUNA in the continuum of BPH treatment (89). Worth of notice, this modality is not available in Egypt.
I.9.4 Prostatic stent
No sufficient evidence to support its use in treating BPH attributed LUTS. It has high incidence of adverse events as migration, faulty insertion and worsening irritative symptoms (90).
I.9.5 Intraprostatic injection of Botulinum Toxin A
No evidence to support its use in treating BPH attributed LUTS. All data from the literature has proven that it has no role for treatment of BPH.
I.9.6 Water vapour thermal therapy
Water vapor thermal therapy (also referred to as transurethral destruction of prostate tissue by radiofrequency generated water thermotherapy) (Rezum ®) may be offered to patients with LUTS attributed to BPH provided prostate volume "<"80g. It may be offered to eligible patients who desire preservation of erectile and ejaculatory function. Three-year results showed sustained improvements for the IPSS, IPSS-QoL and Qmax (91). Worth of notice, this modality is recently introduced in Egypt
I.9.7 Aquablation
Aquablation surgery uses a robotic handpiece, console and conformal planning unit (CPU). The resection of the prostate is done via a water jet from a transurethrally placed robotic handpiece. Pre treatment transrectal ultrasound is used to map out the specific region of the prostate to be resected with a particular focus on limiting resection in the area of the verumontanum. After completion of the resection, electro-cautery via a standard resctoscope or traction from a 3-way catheter balloon are used to obtain hemostasis. Aquablation may be offered to patients with LUTS attributed to BPH provided prostate volume 3080g. It has a theoretical advantage in preservation of erectile function or ejaculation as conductive heat (and its potential damage of erectile nerves) is not used to remove prostate tissue (92). Worth of notice, this modality is not available in Egypt
I.9.8 Prostatic Artery Embolization (PAE)
PAE is a newer, largely unproven minimally invasive modality for BPH. High level evidence remains sparse, and the overall quality of the studies is low. Results also differed between the trials regarding improvements in Qmax. Two trials reported lower flow rates with PAE compared with TURP (93-95), and one trial reported similar flow rates between groups (94). Mean prostate volumes were significantly higher in the PAE group compared with the TURP group at all follow-up time points (94,97).

Table I:6 Recommendations for Minimally invasive procedures for BPH

Recommendation

strength rating
1.Consider prostatic stent placement as an alternative to indwelling catheters in patients with BPH attributed refractory urinary retention and not fit for invasive procedures Weak
2.Do not offer intraprostatic Botulinum toxin-A injection as a treatment option for patients with male LUTS due to BPH Strong
3.Do not offer PAE for the treatment of LUTS secondary to BPH. PAE is not recommended outside the context of clinical trials. Strong


I.10 Indwelling catheters.

Indwelling catheters (transurethral or suprnapubic) could be offered for surgically unfit patients who have failed medical management and are unable to perform clean intermittent selfcatheterisation. They could be an option for those surgically unfit patients with skin wounds and pressure ulcers that are being contaminated by urine. Indwelling catheters can be better coated with anti- bacterial materials to prevent biofilm formation and secure maximum stay without infection

I.11 Post-prostatectomy Urinary Incontinence (PPI)

Table I:7 Recommendations for Post Prostatectomy Urinary Incontinence

Recommendation

strength rating
1.Inform patients undergoing radical prostatectomy of all known factors that could affect urinary continence Strong
2.Inform patients undergoing radical prostatectomy that urinary incontinence generally returns to near baseline by one year postoperatively, but may persist and require treatment Strong
3. Instruct patients to perform pelvic floor muscle exercises (pelvic rehabilitation) before radical prostatectomy and six months postoperatively to hasten recovery of urinary continence Weak
4.Exclude the presence of detrusor overactivity (DO) as a cause of PPI Strong
5.Exclude the presence of anastomotic stricture or contractures leading to overflow incontinence. Perform PVR estimation and office cystourethroscopy to confirm the findings Strong
6.Order pressure flow study (PFS) before proceeding to any invasive treatment modality for PPI to exclude other causes of urinary incontinence; at least six months to one year postoperatively Weak
7.Offer duloxetine ONLY to fasten recovery of urinary continence after prostate surgery. It should not be offered as a therapeutic option for PPI due to sphincteric derangement Weak
8.Offer bulking agents to men with mild PPI ONLY with the intent of temporary relief of their urinary incontinence and after meticulous counselling of these patients Weak
9.Offer male slings to men with mild-to-moderate PPI as a treatment option. Patients should be counselled about the possible adverse events of erosion and the possible need for use of CIC Weak
10.Avoid the use of male slings in PPI in the presence of any of the following: severe incontinence, prior pelvic radiotherapy or urethral stricture surgery Weak
11.Offer artificial urinary sphincter (AUS) to men with moderate-to-severe PPI. Patients should be counselled about the possible side effects of infections and malfunctions. AUS implantation should be offered ONLY in expert centers Weak
12.Counsel patients undergoing AUS implantation that AUS will likely lose effectiveness over time, and reoperations are common Strong
13.Offer patients with persistent or recurrent stress urinary incontinence after male slings AUS implantation Weak


I.12 Conclusion

The understanding of the LUT as a functional unit, and the multifactorial aetiology of associated symptoms, means that LUTS now constitute the main focus, rather than the former emphasis on BPH. It must be emphasised that clinical guidelines present the best evidence available to the experts. However, following guideline recommendations will not necessarily result in the best outcome. Guidelines can never replace clinical expertise when making treatment decisions for individual patients, but rather help to focus decisions - also taking personal values and preferences/individual circumstances of patients into account.

I.13 References

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