3. THE GUIDELINE
3A EPIDEMIOLOGY, AETIOLOGY AND
PATHOPHYSIOLOGY
LUTS can be divided into storage, voiding and post-micturition symptoms [2]
LUTS progress dynamically: for some individuals
LUTS persist and progress over long time periods, and for others they remit [6].
Recent studies have shown, however, that LUTS are often unrelated to prostate [3, 6]. Bladder
dysfunction may also cause LUTS, including detrusor overactivity/OAB, detrusor underactivity/underactive
bladder, as well as other structural or functional abnormalities of the urinary tract [3]. In addition, many nonurological
conditions also contribute to LUTS, especially nocturia [6].
3B DIAGNOSTIC EVALUATION
The clinical assessment of patients with LUTS has two main
objectives:
To consider the differential diagnoses, since the origin of male LUTS are multifactorial
ascertain treatment options and identify men at risk of disease progression
3B.1 Medical History
medical
and neurological diseases
current medication, lifestyle habits, emotional
and psychological factors are reviewed
reassuring the patient that there is no definite relation
between LUTS and prostate cancer (PCa)
a self-completed validated symptom questionnaire should be assessed to objectify and quantify LUTS. Voiding diaries are particularly beneficial
when assessing patients with nocturia and/or other storage LUTS
When relevant, sexual function should be investigated, preferably with validated symptom questionnaires such
as the International Index for Erectile Function (IIEF).
3B.2 Symptom score questionnaires
3B.2.1 The International Prostate Symptom Score (IPSS)
The IPSS is an 8-item questionnaire, consisting of seven symptom questions and one QoL question.
The IPSS score is categorised as ‘asymptomatic’ (0 points), ‘mildly symptomatic’ (1-7 points), ‘moderately
symptomatic’ (8-19 points), and ‘severely symptomatic’ (20-35 points).
Limitations include lack of assessment
of incontinence, post-micturition symptoms, and bother caused by each separate symptom.
3B.2.2 The International Consultation on Incontinence Questionnaire (ICIQ-MLUTS)
It contains 13 items, with subscales for nocturia and OAB, and is available in 17
languages.
3B.3 Frequency volume charts and bladder diaries
The recording of volume and time of each void by the patient is referred to as a frequency volume chart (FVC).
Inclusion of additional information such as fluid intake, use of pads, activities during recording, or symptom
scores is termed a bladder diary [2].
Parameters that can be derived from the FVC bladder diary include: daytime
and night-time voiding frequency, total voided volume, the fraction of urine production during the night
(nocturnal polyuria index [NPi]), and volume of individual voids.
The FVC diary is particularly relevant in nocturia, where it underpins the categorisation of
underlying mechanism(s)
FVC should
continue for 3 or more days
3B.4 Physical examination and digital-rectal examination
particularly focussing on the suprapubic area, the
external genitalia, the perineum and lower limbs. Urethral discharge, meatal stenosis, phimosis and penile
cancer must be identified if present.
3B.4.1 Digital-rectal examination and prostate size evaluation
the simplest way to assess prostate volume
Transrectal ultrasound (TRUS)
is more accurate in determining prostate volume than DRE
One study concluded
that DRE was sufficient to discriminate between prostate volumes > or < than 50 mL
3B.5 Urinalysis
to determine conditions, such as UTI, microhaematuria and diabetes mellitus
If abnormal findings are detected
further tests are recommended (Cancer and infection guidelines)
3B.6 Prostate-specific antigen (PSA)
3B.6.1 PSA and the prediction of prostatic volume
Several reports have demonstrated the reliability of measuring the PSA concentration for predicting prostate
volume
To achieve a specificity of 70%, whilst maintaining a sensitivity between 65-70%,
approximate age-specific criteria for detecting men with prostate glands exceeding 40 mL are PSA > 1.6 ng/
mL, > 2.0 ng/mL, and > 2.3 ng/mL, for men with BPH in their 50s, 60s, and 70s, respectively [41].
A strong association between PSA and prostate volume was found in a large community-based
study in the Netherlands [42].(Krimpen study)
A PSA threshold value of 1.5 ng/mL could best predict a prostate volume of > 30
mL, with a positive predictive value (PPV) of 78%.
The prediction of prostate volume can also be based on total
and free PSA. Both PSA forms predict the TRUS prostate volume (± 20%) in > 90% of the cases [43, 44].
3B.6.2 PSA and the probability of PCa
3B.6.3 PSA and the prediction of BPO-related outcomes
Serum PSA is a stronger predictor of prostate growth than prostate volume [46].
the PLESS study
showed that PSA also predicted the changes in symptoms, QoL/bother, and maximum flow rate (Qmax) [47].
In the placebo arms of large double-blind studies, baseline serum PSA predicted the risk of acute
urinary retention (AUR) and BPE-related surgery [49, 50]. An equivalent link was also confirmed by the Olmsted
County Study. The risk for treatment was higher in men with a baseline PSA of >1.4 ng/mL [51]. Patients with
BPO seem to have a higher PSA level and larger prostate volumes. The positive predictive values of PSA for
the detection of BPO was recently shown to be 68% [52
3B.7 Renal function measurement
diabetes mellitus or hypertension were the
most likely causes of the elevated creatinine concentration
pts with elevated creatinine level require investigational ultrasound of the kidney.
Patients with renal insufficiency are at an increased risk of
developing post-operative complications [61].
3B.8 Post-void residual urine
In both the MTOPS and ALTESS studies, a high baseline PVR
was associated with an increased risk of symptom deterioration [49, 50].
A large PVR measurement is
not a contraindication to watchful waiting (WW) or medical therapy
baseline PVR has little prognostic value for the risk of BPE-related invasive therapy in patients on α1-blocker
or WW [65
no PVR threshold for
treatment decision has yet been established
3B.9 Uroflowmetry
Uroflowmetry parameters should preferably be evaluated
with voided volume > 150 mL. Qmax is prone to within-subject variation [66, 67]; it is therefore useful to repeat
uroflowmetry measurements, especially if the voided volume is < 150 mL, or Qmax or flow pattern is abnormal.
A threshold value of Qmax of 10 mL/s has a PPV of
70% for BOO. The PPV using a threshold Qmax of 15 mL/s was
67% [68]. If Qmax is > 15 mL/s, physiological compensatory processes mean that
BOO cannot be excluded.
Low Qmax can arise as a consequence of BOO [69], detrusor underactivity or an
underfilled bladder
it is limited as a diagnostic test because it is unable to discriminate between the
underlying mechanisms.
3B.10 Imaging
3B.10.1 Upper urinary tract
Routine imaging of the upper urinary tract in men with LUTS is not recommended
3B.10.2 Prostate
3B.10.2.1 Prostate size and shape
Assessment of prostate size is important for the selection of interventional treatment either surgical or prior to treatment with 5-ARIs
TRUS is superior to suprapubic (transabdominal) volume measurement
3B.10.3 Prostatic configuration/intravesical prostatic protrusion (IPP)
the presumed circle area ratio
(PCAR)
PCAR evaluates how closely the transverse US image of the prostate approaches a circular shape.
The ratio tends toward 1 as the prostate becomes more circular. PCAR sensitivity was 77% for diagnosing BPO
when PCAR was > 0.8
Ultrasound measurement of intravesical prostatic protrusion (IPP) assesses the distance between
the tip of the prostate median lobe and bladder neck in the midsagittal plane, using a suprapubically positioned
US scanner, with the bladder volume at 150-250 mL;
grade I protrusion is 0-4.9 mm,
grade II is 5-10 mm and
grade III is >10 mm.
IPP correlates well with BPO (presence and severity) on urodynamic testing, with a PPV of 94%
IPP may be
a feasible option to infer BPO in men with LUTS
3B.10.4 Bladder/detrusor wall thickness and ultrasound-estimated bladder weight
A significant correlation between bladder wall thickness (BWT) and pressure flow studies (PFS) parameters has been
reported. A threshold value of 5 mm at the anterior bladder wall with a bladder filling of 150 mL was best at
differentiating between patients with or without BOO
Threshold values of 2.0, 2.5, or 2.9 mm for detrusor wall thickness (DWT) in patients with LUTS is able to
identify 81%, 89%, and 100% of patients with BOO, respectively
Disadvantages of the method include the lack of standardisation, and lack of evidence to indicate which
measurement (BWT/DWT) is preferable [86]. Measurement of BWT/DWT is therefore not recommended for the
diagnostic work-up of men with LUTS.
Ultrasound-estimated bladder weight (UEBW) may identify BOO with a diagnostic accuracy of 86%
at a cut-off value of 35 g [87, 88].
The role of BWT, DWT and UEBW as a non-invasive alternative to PFS in the
assessment of male LUTS or BOO is under evaluation.
3B.10.5 Voiding cysto-urethrogram
Voiding cysto-urethrogram (VCUG) is not recommended in the routine diagnostic work-up of men with LUTS,
but it may be useful for the detection of vesico-ureteral reflux, bladder diverticula, or urethral pathologies in
selected patients. Retrograde urethrography may additionally be useful for the evaluation of urethral strictures
where suspected.
3B.11 Urethrocystoscopy
Patients with a history of microscopic or gross haematuria, urethral stricture, associated risk factors, or bladder
cancer, who present with LUTS, should undergo urethrocystoscopy during diagnostic evaluation.
3B.12 Urodynamics
3B.12.1 Diagnosing bladder outlet obstruction
Due to the invasive nature of the test, a urodynamic investigation is generally only offered if
conservative treatment has failed.
3B.12.2 Videourodynamics
if there is
uncertainty regarding mechanisms of LUTS.
3B.12.3 Non-invasive pressure-flow testing
The penile cuff method, in which flow is interrupted to estimate isovolumetric bladder pressure), shows
promising data
Figure 2: Assessment algorithm of LUTS in men aged 40 years or older
Readers are strongly recommended to read the full text that highlights the current position of each test in detail.
3C DISEASE MANAGEMENT
3C.1 Conservative treatment
3C.1.1 Watchful waiting
Watchful waiting (WW) is a viable option for many men with non-bothersome LUTS as few will progress to acute urinary retention and complications (e.g. renal insufficiency or stones)
36% of WW patients crossed over to surgery within five years, leaving 64% doing well in the WW group
Men with mild-to-moderate uncomplicated LUTS who are not too troubled by their symptoms are suitable for WW.
lifestyle advice [110, 111, 114, 115] such as:
reduction of fluid intake at specific times aimed at reducing urinary frequency when most inconvenient (e.g. at night or when going out in public);
avoidance/moderation of intake of caffeine or 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;
urethral milking to prevent post-micturition dribble;
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 storage symptoms
bladder retraining that encourages men to hold on when they have sensory urgency to
increase their bladder capacity and the time between voids;
reviewing the medication and optimising the time of administration or substituting drugs for
others that have fewer urinary effects (these recommendations apply especially to diuretics);
providing necessary assistance when there is impairment of dexterity, mobility, or mental
state;
treatment of constipation.
3C.2 Pharmacological management
3C.2.1 α1-Adrenoceptor antagonists (α1-blockers)
treatment-associated improvement of LUTS is correlated only poorly with obstruction [119]. Thus, other mechanisms of action may be relevant.
Efficacy: Indirect comparisons between α1-blockers and limited direct comparisons demonstrate that all α1-blockers have a similar efficacy in appropriate doses [120]. Effects take a few weeks to develop fully, but significant efficacy over placebo can occur within hours to days [121].
Controlled studies show that α1-blockers typically reduce IPSS by approximately 30-40% and increase Qmax by approximately 20-25%
Prostate size does not affect α1-blocker efficacy in studies with follow-up periods of < 1 year, but α1-blockers do seem to be more efficacious in patients with smaller prostates (< 40 mL) in longer-term studies
α1-blockers neither reduce prostate size nor prevent acute urinary retention in long-term studies
Nevertheless, IPSS reduction and Qmax improvement during α1-blocker treatment appears to be maintained over at least four years.
Tolerability and safety
The most frequent adverse events of α1-blockers are asthenia, dizziness and (orthostatic) hypotension. Vasodilating effects are most pronounced with doxazosin and terazosin, and are less common for alfuzosin and tamsulosin
Patients with cardiovascular comorbidity and/or vaso-active co-medication may be susceptible to α1-blocker-induced vasodilatation [142]. In contrast, the frequency of hypotension with the α1A- selective blocker silodosin is comparable with placebo
A systematic review concluded that α1-blockers do not adversely affect libido, but sometimes cause abnormal ejaculation
Originally, abnormal ejaculation was thought to be retrograde, but more recent data demonstrate that it is due to a decrease or absence of seminal fluid during ejaculation, with young age being an apparent risk factor.
Abnormal ejaculation
has been observed more frequently with tamsulosin and silodosin than with other α1-blockers
Silodosin has the highest incidence of abnormal ejaculation; however, efficacy seems to be increased in patients experiencing abnormal ejaculation
Practical considerations: Alpha1-blockers are often considered the first-line drug treatment of male LUTS because of their rapid onset of action, good efficacy, and low rate and severity of adverse events. Ophthalmologists should be informed about α1-blocker use prior to cataract surgery.
3C.2.2 5α-Reductase inhibitors
Mechanism of action: Androgen effects on the prostate are mediated by dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase, a nuclear-bound steroid enzyme [148]. Two isoforms of this enzyme exist: • 5α-reductase type 1, with minor expression and activity in the prostate but predominant activity in
extraprostatic tissues, such as skin and liver. • 5α-reductase type 2, with predominant expression and activity in the prostate.
Finasteride inhibits only 5α-reductase type 2, whereas dutasteride inhibits 5α-reductase types 1 and 2 with similar potency
5-ARIs act by inducing apoptosis of prostate epithelial cells [149] leading to prostate size reduction of about 18-28% and circulating PSA levels of about 50% after 6-12 months of treatment
Continuous treatment reduces the serum DHT concentration by approximately 70% with finasteride and 95% with dutasteride. However, prostate DHT concentration is reduced to a similar level (85-90%) by both 5-ARIs.
After two to four years of treatment, 5-ARIs improve IPSS by approximately 15-30%, decrease prostate volume by approximately 18-28%, and increase Qmax by approximately 1.5-2.0 mL/s in patients with LUTS due to prostate enlargement
dutasteride and finasteride are equally effective in the treatment of LUTS
5-ARIs reduce LUTS slower and that finasteride is less effective than either doxazosin or terazosin, but equally effective compared with tamsulosin
The greater the baseline prostate volume (or serum PSA concentration), the faster and more pronounced the symptomatic benefit of dutasteride
5α-reductase inhibitors, but not α1-blockers, reduce the long-term (>1 year) risk of acute urinary retention (AUR) or need for surgery
In the (MTOPS) study, a significant reduction in the risk of AUR and surgery in the finasteride arm compared with placebo was reported (68% and 64%, respectively)
Tolerability and safety: 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 [49, 125, 150]. The incidence of sexual dysfunction and other adverse events is low. Gynaecomastia (with breast or nipple tenderness) develops in 1-2% of patients.
Data from two trials on prostate cancer chemoprevention (the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events trial) found a higher incidence of high-grade cancers in the 5-ARIs arms
men taking a 5-ARI should be followed-up regularly using serial PSA testing and any confirmed PSA increase should be evaluated accordingly
Practical considerations: Treatment with 5-ARIs should be considered in men with moderate-to-severe LUTS and an enlarged prostate (> 40 mL) and/or elevated PSA concentration (> 1.4-1.6 ng/mL). Due to the slow onset of action, they are suitable only for long-term treatment (years). Their effect on the serum PSA concentration needs to be considered for prostate cancer screening. 5α-reductase inhibitors (finasteride) might reduce blood loss during transurethral prostate surgery, probably due to their effects on prostatic vascularisation
3C.2.3 Muscarinic receptor antagonists
Tolerability and safety: Antimuscarinic drug trials generally show approximately 3-10% withdrawals, which is similar to placebo. Drug-related adverse events include dry mouth (up to 16%), constipation (up to 4%), micturition difficulties (up to 2%), nasopharyngitis (up to 3%), and dizziness (up to 5%).
Increased PVR in men without BOO is minimal and similar to placebo
short-term treatment with antimuscarinics in men with BOO is safe
Mechanism of action: PDE type 5 inhibitors (PDE5Is) increase intracellular cyclic guanosine monophosphate, thus reducing smooth muscle tone of the detrusor, prostate and urethra.
only tadalafil (5 mg once daily) has been licensed for the treatment of male LUTS.
Efficacy: Several RCTs have demonstrated that PDE5Is reduce IPSS, storage and voiding LUTS, and QoL
In a meta-analysis, PDE5Is were found to improve IPSS and International Index of Erectile Function (IIEF) score, but not Qmax
combination therapy significantly improved IPSS score (-1.8), IIEF score (+3.6) and Qmax (+1.5 mL/s) compared with α-blockers alone
Tolerability and safety:
flushing, gastroesophageal reflux, headache, dyspepsia, back pain and nasal congestion
3C.2.4 Phosphodiesterase 5 inhibitors
PDE5Is are contraindicated in patients using nitrates, the potassium channel opener, nicorandil, or α1-blockers doxazosin or terazosin.
unstable angina pectoris, have had a recent myocardial infarction (<3 mo) or stroke (<6 mo), myocardial insufficiency (New York Heart Association stage >2), hypotension, poorly controlled blood pressure, significant hepatic or renal insufficiency, or if anterior ischaemic optic neuropathy with sudden loss of vision is known or was reported after previous use of PDE5Is.
Practical considerations: To date, only tadalafil 5 mg once daily has been officially licensed for the treatment of male LUTS with or without erectile dysfunction. The meta-analysis of PDE5Is suggested that younger men with low body mass index and more severe LUTS profit the most from treatment with PDE5Is
3C.2.5 Plant extracts - phytotherapy
Recommendations: The Guidelines Panel have not made any specific recommendations on phytotherapy for the treatment of male LUTS because of product heterogeneity, limited regulatory framework, and methodological limitations of the published trials and meta-analyses.
3C.2.6 Vasopressin analogue - desmopressin
Desmopressin is a synthetic analogue of AVP with high V2 receptor affinity and antidiuretic properties, but has no relevant V1 receptor affinity or hypertensive effects. Desmopressin may be used by intravenous infusion, nasal spray, tablet or ‘melt’ formulation. Nasally or orally administered desmopressin is rapidly absorbed, and excreted 55% unchanged by the kidneys [222]. Desmopressin has been used for more than 30 years for diabetes insipidus or primary nocturnal enuresis, and it is approved in most European countries for the treatment of nocturia secondary to nocturnal polyuria in adults
Hyponatraemia, not necessarily associated with symptoms, occurs in 5.0-7.6% of patients soon after treatment initiation [235, 236]. The risk of developing hyponatraemia significantly increases with age (odds ratio 1.16 per year of age), lower serum sodium concentration at baseline (odds ratio 0.76), and higher basal 24-hour urine volume per bodyweight (odds ratio 1.09) [235]. The risk of hyponatraemia in patients < 65 years is < 1%; for older patients with normal sodium concentration it is 8%, but it is up to 75% in old patients with low sodium concentration at baseline [235]. A recent subanalysis suggests that oral doses of 50-100μg desmopressin (melt) are safe in men [237].
At the time of treatment initiation or dose change, older men with normal values of serum sodium should be monitored by Na+ measurement at day three and day seven of treatment, and one month later. If serum sodium concentration has remained normal and no dose adjustment is intended, Na+ should be monitored every three to six months thereafter [238]. Patients should be informed about the symptoms of hyponatraemia, (headache, nausea or insomnia).
Practical considerations
Desmopressin is taken once daily before sleeping. Because the optimal dose differs between patients, desmopressin treatment should be initiated at a low dose (0.1 mg/day) and may be gradually increased up to a dosage of 0.4 mg/day every week until maximum efficacy is reached. Patients should avoid drinking fluids at least one hour before and for eight hours after dosing. In men aged 65 years or older, desmopressin should not be used if the serum sodium concentration is below normal.
Mechanism of action: Beta-3 adrenoceptors are the predominant beta receptors expressed in the smooth
muscle cells of the detrusor and their stimulation is thought to induce detrusor relaxation.
Mirabegron has undergone extensive evaluation in three 12-week, RCTs conducted in Europe,
Australia, and North America
Tolerability and safety: The most common treatment-related adverse events in the mirabegron groups were
hypertension, urinary tract infection, headache and nasopharyngitis
dry mouth and constipation in the mirabegron groups was notably lower than reported in RCTs of other OAB
agents or of the active control tolterodine
3C.2.8 Combination therapies
3C.2.8.1 α1-blockers + 5α-reductase inhibitors
The α1-blocker exhibits clinical effects within hours or days, whereas the 5-ARI needs several
months to develop significant clinical efficacy
Long-term data (4 years) from MTOPS, and Combination of Avodart and Tamsulosin (CombAT)
trials showed that combination treatment is superior to monotherapy for symptoms and Qmax, and superior to
α-blocker in reducing the risk of acute urinary retention or need for surgery
The CombAT study demonstrated that combination treatment is superior to either monotherapy for
symptoms and flow rate starting from month nine, and superior to α1-blocker for acute urinary retention and
the need for surgery after month eight
In both the MTOPS and CombAT trials, combination therapy was superior to monotherapy in
preventing clinical progression as defined by an IPSS increase of at least four points, acute urinary retention,
urinary tract infection, incontinence, or an increase in creatinine >50%. The MTOPS study found that the risk of
long-term clinical progression (primarily due to increasing IPSS) was reduced by 66% with combined therapy
(vs placebo) and to a greater extent than with either finasteride or doxazosin monotherapy (34% and 39%,
respectively) [49]. In addition, finasteride (alone or in combination), but not doxazosin, significantly reduced
both the risks of AUR and the need for BPH-related surgery over the four-year study. In the CombAT study,
combination therapy reduced the relative risks of AUR by 68%, BPH-related surgery by 71%, and symptom
deterioration by 41% compared with tamsulosin, after four years [246].
Practical considerations: Compared with α1-blockers or 5-ARI monotherapy, combination therapy results in
a greater improvement in LUTS and increase in Qmax, and is superior in prevention of disease progression.
However, combination therapy is also associated with more adverse events. Combination therapy should
therefore be prescribed primarily in men who have moderate-to-severe LUTS and are at risk of disease
progression (higher prostate volume, higher PSA concentration, advanced age, etc.). Combination therapy
should only be used when long-term treatment (more than 12 months) is intended; this issue should be
discussed with the patient before treatment. Discontinuation of the α1-blocker after six months might be
considered in men with moderate LUTS.
3C.2.8.2 α1-blockers + muscarinic receptor antagonists
Combination treatment is more efficacious in reducing urgency, UUI, voiding frequency, nocturia, or
IPSS compared with α1-blockers or placebo alone, and improves QoL [182]. Symptom improvement is higher
regardless of PSA concentration, whereas tolterodine alone improved symptoms mainly in men with a serum
PSA of < 1.3 ng/mL
Persistent LUTS during α1-blocker treatment can be reduced by the additional use of an
antimuscarinic, especially when detrusor overactivity is demonstrated
The commonest side-effect is xerostomia. Some side-effects (e.g. xerostomia
or ejaculation failure) may show increased incidence which cannot simply be explained by summing the
incidence with the drugs used separately. Increased PVR may be seen, but is usually not clinically significant,
and risk of AUR is low
3C.3 Surgical treatment
3C.3.1 Transurethral resection of the prostate and transurethral incision of the prostate
Mechanism of action: Transurethral resection of the prostate (TURP) removes tissue from the transition zone
of the gland. Transurethral incision of the prostate (TUIP) involves incising the bladder outlet without tissue
removal. This technique may replace TURP in selected cases, especially in prostate sizes < 30 mL without a
middle lobe.
In a recent analysis of 20 contemporary RCTs with a maximum follow-up of 5 years, TURP resulted
in a substantial mean Qmax improvement (+162%), a significant reduction in IPSS (-70%), QoL score (-69%),
and PVR (-77%) [258]
Failures were associated with detrusor underactivity rather than re-development of
BPO [98].
A review analysing 29 RCTs found a re-treatment rate of 2.6% after a mean follow-up of
16 months
Tolerability and safety
Data from 20,671 TURPs and 2,452 open
prostatectomies (OP) showed that short- and long-term procedural mortality was similar (0.7% vs. 0.9% at
90 days, 2.8% vs. 2.7% at 1 year, 12.7% vs. 11.8% at 5 years, 20% vs. 20.9% at 8 years)
The risk of TUR-syndrome decreased to < 1.1%
Data from 10,654 TURPs reported bleeding requiring transfusion in 2.9%
Similar results for TURP complications were reported by an analysis of contemporary RCTs
using TURP as a comparator: bleeding requiring transfusion 2% (0-9%), TUR-syndrome 0.8% (0-5%), AUR
4.5% (0-13.3%), clot retention 4.9% (0-39%), and urinary tract infection (UTI) 4.1% (0-22%)
Long-term
complications comprise urinary incontinence (1.8% after TUIP vs. 2.2% after TURP), urinary retention and UTIs,
bladder neck contracture (BNC) (4.7% after TURP), urethral stricture (3.8% after TURP vs. 4.1% after TUIP),
retrograde ejaculation (65.4% after TURP vs. 18.2% after TUIP), and erectile dysfunction (6.5% after TURP)
Practical considerations: TURP and TUIP are effective treatments for moderate-to-severe LUTS secondary
to BPO. The choice should be based primarily on prostate volume (< 30 mL and 30-80 mL suitable for TUIP
and TURP, respectively).
The upper limit for TURP is mostly suggested as 80 mL
3C.3.1.1 Modifications of TURP: bipolar TURP
Mechanism of action: Bipolar TURP (B-TURP) addresses a major limitation of monopolar TURP (M-TURP) by
allowing performance in normal saline. Contrary to M-TURP, in B-TURP systems, the energy does not travel
through the body to reach a skin pad. Bipolar circuitry is completed locally; energy is confined between an
active (resection loop) and a passive pole situated on the resectosope tip (“true” bipolar systems) or the sheath
(“quasi-” bipolar systems). Prostatic tissue removal is identical to M-TURP. However, B-TURP requires less
energy/voltage because there is a smaller amount of interpolated tissue. Energy from the loop is transmitted to
the saline solution, resulting in excitation of sodium ions to form a plasma; molecules are then easily cleaved
under relatively low voltage enabling resection. During coagulation, heat dissipates within vessel walls, creating
a sealing coagulum and collagen shrinkage.
Early pooled results concluded that no clinically relevant differences exist in short-term (up to
12 months) efficacy (IPSS, QoL score and Qmax)
Tolerability and safety: Early pooled results concluded that no differences exist in short-term (up to 12 months)
US/BNC rates, but B-TURP is preferable due to a more favourable perioperative safety profile (elimination of
TUR-syndrome; lower clot retention/blood transfusion rates; shorter irrigation, catheterisation, and possibly
hospitalisation times)
A comparative evaluation of the effects on the overall sexual function,
quantified with IIEF-15 showed no differences between B-TURP and M-TURP at 12 months of follow-up
Practical considerations: B-TURP offers an attractive alternative to M-TURP in patients with moderate-tosevere
LUTS secondary to BPO, with similar efficacy but lower peri-operative morbidity [280]
The choice of
B-TURP should be based on equipment availability, surgeon’s experience, and patient’s preference.
3C.3.2 Open prostatectomy
Mechanism of action: OP is the oldest surgical treatment for moderate-to-severe LUTS secondary to BPO.
Obstructive adenomas are enucleated using the index finger, approaching from within the bladder (Freyer
procedure) or through the anterior prostatic capsule (Millin procedure).
Efficacy: OP is the treatment of choice for large glands (> 80-100 mL). Three RCTs showed that Holmium
laser enucleation of the prostate (HoLEP) and photoselective vaporisation of the prostate (PVP) lead to similar
outcomes compared to OP in men with large glands (> 70 mL) at a significantly lower complication rate
OP reduces LUTS by 63-86% (12.5-23.3 IPSS
points), improves QoL score by 60-87%, increases mean Qmax by 375% (+16.5-20.2 mL/s), and reduces PVR
by 86-98% [291-295]. Efficacy is maintained for > 5 years
Tolerability and safety: Mortality has decreased significantly during the past two decades (< 0.25%) [294].
The estimated transfusion rate is about 7-14% [291, 294, 295]. Long-term complications include urinary
incontinence (up to 10%), BNC and US (about 6%)
Practical considerations: OP is the most invasive but also the most effective and durable procedure for the
treatment of LUTS/BPO. In the absence of an endourological armamentarium and a holmium laser, OP is the
surgical treatment of choice for men with prostates > 80 mL.
3C.3.3 Transurethral microwave therapy
Mechanism of action: Microwave thermotherapy works by emitting microwave radiation through an intraurethral
antenna to deliver heat into the prostate. Tissue is destroyed by being heated at temperatures above
cytotoxic thresholds (> 45°C) (coagulation necrosis). The heat may also cause apoptosis and denervation of
α-receptors, thereby decreasing the smooth muscle tone of the prostatic urethra.
effective than TURP in reducing LUTS. Symptom score after TUMT decreased by 65% in 12 months, compared
to 77% after TURP. TURP achieved a greater Qmax improvement (119% vs. 70%)
Previously, urinary retention was considered a contraindication for TUMT. Nowadays, LE:2b studies
have reported an 80-93% success rate for TUMT, defined as the percentage of patients who regained their
ability to void spontaneously [303-305]. However, these studies had a short follow-up (< 12 months), which
makes it difficult to estimate the durability of TUMT outcome in patients with retention. In a study with a longer
follow-up, treatment failure was 38% in the retention group, with a cumulative risk of 59% at 5 years
Tolerability and safety: Treatment is well tolerated, although most patients experience perineal discomfort and
urinary urgency, and require pain medication for therapy.
In the Cochrane RCT-based systematic review, catheterisation time,
dysuria/urgency and urinary retention rates were significantly less with TURP. Hospitalisation time, haematuria,
clot retention, transfusion, TUR syndrome, and urethral stricture rates were significantly less for TUMT [299].
Sexual dysfunction and re-treatment rates for urethral stricture/BNC were higher after TURP.
Due to the low peri- and post-operative morbidity and lack
of need for anaesthesia, TUMT is a true outpatient procedure, and an option for older patients, and those with
comorbidities or anaesthesia risk
3C.3.4 Transurethral needle ablation of the prostate
Mechanism of action: The transurethral needle ablation (TUNA™) device delivers low-level radiofrequency
energy to the prostate via needles inserted transurethrally into the parenchyma under direct vision using an
attachment to the standard cystoscope. The energy induces coagulation necroses in the transition zone
resulting in prostate volume reduction and BPO reduction.
TUNA™ achieved a 50% decrease in IPSS and a 70% improvement in Qmax at 1 year
TURP vs. TUNA™ differences in means were - 4.72 and 5.9 mL/sec for IPSS and Qmax respectively
A study with 5 years’ follow-up demonstrated symptomatic improvement in 58% and improved flow in
41%. However, 21% required additional treatment [319]. TUNA™ has a significantly higher re-treatment rate
compared with TURP. The overall re-treatment rate after TUNA™ was 19% based on an analysis of 17 noncomparative
studies
Tolerability and safety: Post-operative urinary retention with a mean duration of 1-3 days is seen in 13-42% of
patients; within 1 week, 90-95% of patients are catheter-free [320]. Storage LUTS are common for the first 4-6
weeks after intervention [321]. TUNA™ is associated with fewer adverse events compared to TURP, including
mild haematuria, urinary infections, strictures, incontinence, ED, and ejaculation disorders
Practical considerations: TUNA™ can be performed as a day-case procedure under local anaesthesia or
sedation [320]. TUNA™ is unsuitable for prostates > 75 mL or isolated bladder neck obstruction. TUNA™
cannot effectively treat prostatic middle lobes. There is anecdotal evidence for TUNA™ in men receiving aspirin
and anti-coagulants. TUNA™ can be performed as a day-case procedure and is associated with fewer sideeffects
than TURP (e.g. bleeding, ED, urinary incontinence). However, there are concerns about the durability of
the effects achieved by TUNA™.
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