Evaluation and Nonsurgical Management of Benign Prostatic Hyperplasia

Campbell-Walsh Urology, 11th Edition

PART XIV

Prostate

104 Evaluation and Nonsurgical Management of Benign Prostatic Hyperplasia

Thomas Anthony McNicholas; Mark J. Speakman; Roger S. Kirby

Questions

Where does benign prostatic hyperplasia (BPH) originate? In the:
transition zone.
peripheral zone.
periurethral glands.
transition zone and periurethral zone.
peripheral and periurethral zones.
A strong correlation exists between prostate volume and:
serum prostate-specific antigen (PSA).
American Urological Association (AUA) symptom score.
peak urinary flow rate.
postvoid residual.
all of the above
Medications that may exacerbate lower urinary tract symptoms (LUTS) include:
α-adrenergic antagonists.
α-adrenergic agonists.
β-adrenergic agonists.
muscarinic agonists.
phytotherapy.
What is the primary objective of the digital rectal examination (DRE) in evaluation of men with LUTS? To:
estimate prostate volume.
obtain prostatic secretions.
identify prostate nodules.
determine rectal tone.
assess for prostatic tenderness.
In older men with LUTS, which test should be routinely performed to obtain the differential diagnosis?
Urinalysis
Peak flow rate
Serum creatinine assay
Renal ultrasonography
Flexible cystoscopy
It is advisable in a man with LUTS/BPH and a slightly elevated creatinine level to perform:
transurethral resection of the prostate (TURP).
intravenous pyelogram.
renal ultrasound.
urodynamic study.
flexible cystoscopy.
What percentage of men have histologically proven BPH with a serum PSA value of 4.0 ng/mL or greater?
5%
15%
30%
50%
80%
An AUA symptom score of 20 indicates severe:
LUTS.
BPH.
bladder outlet obstruction.
bladder dysfunction.
overactive bladder (OAB).
An absolute indication for surgery (TURP or open prostatectomy) is:
severe symptoms.
postvoid residual (PVR) urine of 300 mL or more.
single episodes of acute urinary retention.
refractory gross hematuria secondary to BPH.
Lack of response to an alpha blocker.
A low peak flow rate suggests:
severe symptoms.
bladder outlet obstruction.
impaired detrusor contractility.
b or c.
detrusor overactivity.
What is the next step for a man with a PVR of 300 mL?
Repeat the PVR assay
Upper urinary tract imaging
Urodynamic testing
Cystoscopy
TURP
The probability that a urodynamic study helps to decrease the failure rate of TURP in men with a peak flow rate of 15 mL/sec is approximately:
10%.
25%.
50%.
75%.
95%.
What is the percentage of men with LUTS who have uninhibited contraction?
10%
30%
60%
80%
95%
What is the likelihood that uninhibited detrusor contractions (UDCs) in men with BPH will resolve after TURP?
Never
Unlikely
Likely
Always
The finding of bladder trabeculation suggests:
high-grade obstruction.
high successful rate after TURP.
high PVR.
chronic inflammation.
none of the above.
Imaging of the upper tract is indicated for:
prostate glands weighing more than 50 g.
urinalysis demonstrating hematuria.
bladder trabeculation.
severe LUTS.
PSA > 1.5 ng/mL.
An improvement in the AUA symptom score of 5 units correlates with which level of symptoms improved?
Marked
Moderate
Slight
None
Urodynamic testing reliably predicts response after:
TURP.
α-adrenergic blockers.
5α-reductase inhibitors.
antimuscarinic therapy.
none of the above.
There is compelling evidence that PVR is:
related to symptom severity.
associated with the risk for urinary tract infection (UTI).
both a and b.
neither a nor b.
The definition of detrusor overactivity is bladder pressure greater than which level at a bladder volume of 300 mL or less?
5 cm H₂O
15 cm H₂O
40 cm H₂O
60 cm H₂O
The likelihood that a man with acute urinary retention will experience a subsequent episode of urinary retention within 1 week is approximately:
20%.
40%.
60%.
80%.
100%.
The incidence of developing acute urinary retention is related to:
prostate size.
age.
severity of symptoms.
PSA level.
all of the above.
The best way to eliminate bias in a clinical study is to use:
honest investigators.
a placebo-controlled double-blind design.
randomization.
a large sample size.
cohort studies.
The larger the sample size, the:
less treatment effect required to achieve statistical significance.
better the study.
greater the treatment effect required to achieve statistical significance.
none of the above.
all of the above.
Which of the following is the attractive feature of medical therapy relative to TURP?
Fewer side effects
Reversible side effects
Less serious side effects
All of the above
Reduced long-term costs
During the past decade, the incidence of TURP in the United States has decreased by approximately:
10%.
50%.
100%.
200%.
Which of the following percentages of men older than 50 years have moderate or severe LUTS?
2%
5%
30%
50%
The ideal candidate for medical therapy should have which type of symptoms?
Severe
Moderate
Minimal
Bothersome
Smooth muscle accounts for what percentage of the area density of the prostate?
5%
10%
20%
40%
60%
The tension of prostate smooth muscle is mediated by the:
α₁receptor.
α₂receptor.
β₁receptor.
β₂receptor.
muscarinic cholinergic receptor.
What is the advantage of terazosin versus prazosin?
Its longer half-life
Its better absorption
Its greater α1-receptor selectivity
None of the above.
Which α₁receptor subtype mediates prostate smooth muscle tension?
α_1a
α_1b
α_1c
α_1d
None of the above
The improvement in AUA symptom score after terazosin administration depends on baseline:
age.
prostate size.
PVR.
None of the above.
The mean treatment-related improvement in response to terazosin in AUA symptom score units is approximately:
2.
4.
6.
8.
The durability of the improvement in symptom scores and peak flow rates for α₁-adrenergic blockers has been reported to be up to how many months?
12
42
60
92
Which of the following α-adrenergic blockers does not lower blood pressure in men with uncontrolled hypertension?
Terazosin
Doxazosin
Tamsulosin
Prazosin
Retrograde ejaculation is most commonly seen with:
terazosin.
silodosin.
finasteride.
tamsulosin.
alfuzosin.
Approximately what percentage of men have both BPH and hypertension?
5%
15%
30%
50%
70%
What is the likely mechanism for dizziness after α₁-adrenergic blocker therapy?
Vascular
Central nervous system
Carotid baroreceptor
None of the above
The major advantage of tamsulosin 0.4 mg versus terazosin 10 mg is:
greater efficiency.
less retrograde ejaculation.
no dose titration.
greater lowering of blood pressure.
The embryologic development of the prostate is mediated primarily by:
testosterone.
dihydrotestosterone.
androstenedione.
estradiol.
Finasteride significantly decreases the long-term risk of:
acute urinary retention.
surgical intervention.
symptom progression.
all of the above.
none of the above.
Finasteride is most effective at relieving hematuria in men with:
prostatitis.
enlarged prostate.
transurethral prostatectomy.
obstructing prostate.
small prostates
Dutasteride:
is a dual inhibitor of type 1 and type 2 5α-reductase.
is more effective than finasteride.
results in a 95% reduction in PSA after 6 months of therapy.
is less likely than finasteride to result in loss of libido.
is cheaper than finasteride.
The adverse event that limits the use of flutamide as a primary treatment of BPH is:
breast tenderness.
diarrhea.
erectile dysfunction.
loss of libido.
A potential advantage of cetrorelix, a gonadotropin-releasing hormone antagonist, for the treatment of BPH is:
lower cost.
ability to titrate the level of androgen suppression.
ease of administration.
rapid response.
A Veterans Affairs study demonstrated that terazosin is more effective than finasteride at rapidly relieving symptoms in men with:
small prostates.
intermediate-size prostates.
large prostates.
all of the above.
The Medical Therapy of Prostatic Symptoms (MTOPS) study confirmed that:
α-adrenergic blockers and 5α-reductase inhibitors are equivalent in relieving symptoms.
α-adrenergic blockers reduce the risk of acute urinary retention during 7 years of treatment.
finasteride reduces the risk of adenocarcinoma of the prostate.
a combination of an α-adrenergic blocker and a 5α-reductase inhibitor is the most effective way of preventing BPH progression.
combination therapy was more effective than monotherapy after 6 months’ treatment.
The Combination of Avodart and Tamsulosin (CombAT) Study showed that in men with larger prostates:
the combination of dutasteride and tamsulosin was more effective than either agent alone.
with time, the symptomatic response to dutasteride exceeded that to tamsulosin.
both of the above.
none of the above.
tamsulosin did not affect ejaculation.
Combination therapy in LUTS/BPH using dutasteride and tamsulosin:
should be continued long-term in all patients who respond.
may be reduced to dutasteride alone after 6 months in all patients.
may be reduced to dutasteride alone in 80% of patients with a baseline IPSS less than 20, after 6 months’ treatment.
may be reduced to dutasteride alone in all patients with a baseline IPSS less than 20, after 6 months’ treatment.
may be reduced to tamsulosin alone in in 80% of patients with a baseline IPSS less than 20, after 6 months’ treatment.
The CombAT study showed that in men with a pretreatment PSA between 1.5 and 10 ng/mL:
the combination of dutasteride and tamsulosin was more effective than either drug alone in improving symptoms.
in men with larger prostates, although the tamsulosin effect was rapid, with time dutasteride was the more effective agent.
combination therapy was significantly superior to tamsulosin but not dutasteride at reducing the RR of AUR or BPH-related surgery.
none of the above.
all of the above.
Antimuscarinic therapy is contraindicated in men with LUTS/BPH.
Yes, in all such men.
No, only in men with large and persistent residual urine volumes.
No, not if combined with alpha blockers.
Yes, if they have an enlarged prostate.
No, OK in all men with OAB symptoms.
Men with significant obstruction, large residual urine volumes, and OAB who fail first line treatment with alpha blockers should be considered for:
the addition of an antimuscarinic drug.
surgical therapy.
none of the above.
the addition of phosphodiesterase 1 (PDE-1) inhibitors.
psychotherapy.
Overactive bladder (OAB) symptoms in the male are:
always secondary to bladder outflow obstruction (BOO).
occur in all men with proven bladder outflow obstruction.
should always be investigated with a filling/voiding cystometrogram.
always secondary to benign prostatic enlargement (BPE).
none of the above.
Studies of the use of antimuscarinic agents in men with LUTS and a significant storage component have shown that:
the combination of tamsulosin and tolterodine showed a significant benefit over placebo in a patient's perception of benefit question.
the number needed to treat was 5.
trospium XR was safe and effective with significantly reduced frequency and urgency incontinence.
fesoterodine added to an alpha blocker resulted in improvements in urinary frequency and bother.
all of the above.
If a man with LUTs, stabilized on doxazosin, complains of erectile dysfunction, one should NOT give him:
low-dose sildenafil.
low-dose vardenafil.
low-dose tadalafil.
MUSE.
a vacuum pump.
The amount spent on phytotherapy for the treatment of BPH is estimated to be:
$10 million.
$100 million.
$1 billion.
$10 billion.
The definitive mechanism of action for Serenoa repensis:
inhibition of 5α-reductase.
inhibition of cyclooxygenase.
inhibition of lipoxygenase.
inconclusive.
Potential future therapeutic avenues in BPH pharmacotherapy include:
nitric oxide donors.
α-adrenoceptor agonists.
HMG coenzyme A inhibitors.
endothelin antagonists.

Answers

d. Transition zone and periurethral zone.The proliferative process originates in the transition zone and the periurethral glands.
a. Serum prostate-specific antigen (PSA).A strong correlation exists between serum PSA levels and prostate volume.
b. α-adrenergic agonists.Current prescription and over-the-counter medications should be examined to determine whether the patient is taking drugs that impair bladder contractility (anticholinergics) or that increase outflow resistance (α-sympathomimetics).
c. Identify prostate nodules.The DRE and neurologic examination are done to detect prostate or rectal malignancy, to evaluate anal sphincter tone, and to rule out any neurologic problems that may cause the presenting symptoms.
a. Urinalysis.In older men with BPH and a higher prevalence of serious urinary tract disorders, the benefits of an innocuous test such as urinalysis clearly outweigh the harm involved.
c. Renal ultrasound. An elevated serum creatinine level in a patient with BPH is an indication for imaging studies (ultrasonography) to evaluate the upper urinary tract.
c. 30%.Twenty-eight percent of men with histologically proven BPH have a serum PSA level greater than 4.0 ng/mL.
a. LUTS.The International Prostate Symptom Score (I-PSS), which is identical to the AUA Symptom Index, is recommended as the symptom scoring instrument to be used for the baseline assessment of symptom severity in men presenting with LUTS. When the I-PSS system is used, symptoms can be classified as mild (0 to 7), moderate (8 to 19), or severe (20 to 35). The I-PSS cannot be used to establish the diagnosis of BPH.
d. Refractory gross hematuria secondary to BPH. Surgery is recommended if the patient has refractory urinary retention (at least one failed attempt at catheter removal) or any of the following conditions, clearly secondary to BPH: recurrent urinary tract infection, recurrent gross hematuria, bladder stones, renal insufficiency, or large bladder diverticula.
d. b or c.One study found that flow rate recording cannot distinguish between bladder outlet obstruction and impaired detrusor contractility as the cause for a low Qmax.
a. Repeat the PVR assay. Residual urine volume measurement has significant intraindividual variability that limits its clinical usefulness.
a. 10%.One study recommended invasive urodynamic testing for patients with a Qmax higher than 15 mL/sec. For the population in their study, this would have resulted in an additional 9% of patients being excluded from surgery and a decrease in failure rate to 8.3%.
c. 60%. Overactive contractions are present in about 60% of men with LUTS and correlate strongly with irritative voiding symptoms.
c. Likely.UDCs resolve in most patients after surgery.
e. None of the above.Bladder trabeculation may predict a slightly higher failure rate in patients managed by watchful waiting but does not predict the success or failure of surgery.
b. Urinalysis demonstrating hematuria. Upper urinary tract imaging is not recommended for routine evaluation of men with LUTS unless they also have one or more of the following: hematuria; urinary tract infection; renal insufficiency (ultrasonography recommended); history of urolithiasis; and history of urinary tract surgery.
b. Moderate.The group mean changes in AUA Symptom Index for subjects rating their improvement as markedly, moderately, or slightly improved, unchanged, or worse were − 8.8, − 5.1, − 3.0, − .7, and + 2.7, respectively.
e. None of the above.Urodynamic testing does not predict symptom improvement after α-adrenergic blockade, transurethral microwave thermotherapy, or prostatectomy.
d. Neither a nor b.One study reported no correlation between the AUA symptom score and PVR volume. There are also no data documenting that the incidence of UTI is related to PVR volume.
b. 15 cm H₂O. The definition of detrusor instability is the development of a detrusor contraction exceeding 15 cm H₂O at a bladder volume less than or equal to 300 mL.
d. 80%. Of 59 Danish patients presenting to an emergency department with acute retention, 73% had recurrent urinary retention within 1 week after removal of the catheter.
e. All of the above. The incidence of acute urinary retention was related to age, severity of symptoms, and size of the prostate gland.
b. A placebo-controlled double-blind design.The only mechanism to ensure that the potential bias of the subject and the investigator does not influence the outcome is a randomized double-blind placebo-controlled design.
a. Less treatment effect required to achieve statistical significance.The larger the number of subjects enrolled in a study, the smaller the change required to achieve statistical significance.
d. All of the above.The attractive feature of medical therapy relative to prostatectomy is that clinically significant outcomes are obtained with fewer, less serious, and reversible side effects.
b. 50%.A 55% reduction in transurethral prostatectomy has occurred despite the progressively increasing number of men enrolled in the Medicare program.
c. 30%. Approximately 30% of American men older than 50 years of age have moderate to severe symptoms.
d. Bothersome.The ideal candidate for medical therapy should have symptoms that are bothersome and have a negative impact on the quality of life.
d. 40%.Smooth muscle is one of the dominant cellular constituents of BPH, accounting for 40% of the area density of the hyperplastic prostate.
a. α₁receptor. The tension of prostate smooth muscle is mediated by the α₁ adrenergic receptors.
a. Its longer half-life.Terazosin and doxazosin are long-acting α-adrenergic blockers that have been shown to be safe and effective for the treatment of BPH.
a. α_1a. Prostate smooth muscle tension has been shown to be mediated by the α_1aadrenergic receptors.
d. None of the above.The relationships between percent change in total symptom score and peak flow rate versus baseline age, prostate size, peak flow rate, PVR volume, and total symptom score were examined to identify clinical or urodynamic factors that predicted response to terazosin therapy. No significant association was observed between treatment effect and any of these baseline factors.
b. 4.The treatment-related improvement (terazosin minus placebo) in the AUA symptom score and urinary peak flow rate was 1.4 mL/sec and 3.9 symptom units, respectively.
b. 42.The initial improvements in symptom scores and peak flow rate in 450 subjects were maintained for up to 42 months.
c. Tamsulosin.The advantage of not lowering blood pressure in men who are hypertensive at baseline is controversial.
d. Tamsulosin. The treatment-related incidences of asthenia, dizziness, rhinitis, and abnormal ejaculation observed for 0.4 mg of tamsulosin were 2%, 5%, 3%, and 11%, respectively, and for 0.8 mg of tamsulosin were 3%, 8%, 9%, and 18%, respectively.
c. 30%.Approximately 30% of men treated for BPH have coexisting hypertension.
b. Central nervous system.The α₁-mediated dizziness and asthenia are likely due to effects at the level of the central nervous system.
c. No dose titration.The major advantage of 0.4 mg tamsulosin and slow-release alfuzosin is the lack of requirement for dose titration.
b. Dihydrotestosterone. The embryonic development of the prostate is dependent on the androgen dihydrotestosterone.
d. All of the above.The Proscar Long-Term Efficacy and Safety Study (PLESS) represents one of the longest duration multicenter randomized double-blind placebo-controlled studies reported in the literature on medical therapy for BPH. The unique findings of PLESS were related to incidences of both acute urinary retention and surgical intervention for BPH. The risk reduction of acute urinary retention and BPH-related surgery was clinically relevant, especially in men with very large prostates.
c. Transurethral prostatectomy. These preliminary observations have been confirmed by a randomized, double-blind placebo-controlled study demonstrating that finasteride prevents recurrent gross hematuria secondary to BPH after prostatectomy.
a. Is a dual inhibitor of type 1 and type 2 5α-reductase. Unlike finasteride, which only inhibits the type 2 isoenzyme.
a. Breast tenderness.The incidences of breast tenderness and diarrhea in the flutamide group were 53% and 11%, respectively.
b. Ability to titrate the level of androgen suppression.A potential advantage of a gonadotropin-releasing hormone antagonist over the luteinizing hormone-releasing hormone agonists in the treatment of BPH is the ability to titrate the level of androgen suppression.
d. All of the above.In the study, the mean group differences between terazosin versus placebo and terazosin versus finasteride for all of the outcome measures other than prostate volume were highly statistically significant. Terazosin was more effective than finasteride in those subjects with large prostates.
d. A combination of an α-adrenergic blocker and a 5α-reductase inhibitor is the most effective way of preventing BPH progression. This was the key conclusion of the important MTOPS study that looked at finasteride versus doxazosin versus a combination of both and placebo in men with symptomatic BPH.
c. Both of the above.
c. May be reduced to dutasteride alone in 80% of patients with a baseline IPSS less than 20, after 6 months’ treatment.As shown in the study by Barkin and colleagues (2003).*
e. All of the above.
b. No, only in men with large and persistent residual urine volumes.Antimuscarinics are only contraindicated if there is a large residual urine volume, as such men have a higher risk of retention.
b. Surgical therapy.
e. None of the above.
e. All of the above.
c. Low-dose tadalafil.The manufacturers of tadalafil recommend avoiding using it with doxazosin. However, care should be taken with the addition of any PDEI to men already optimized on an α-blocker, as there is an increased risk of symptomatic hypotension in all men being considered for this combination.
c. $1 billion.Use of these agents in the United States and throughout the world has escalated. It has been estimated that more than $1 billion was spent in the United States alone for these products.
d. Inconclusive. Although experimental data have suggested numerous possible mechanisms of actions for the phytotherapeutic agents, it is uncertain which, if any, of these proposed mechanisms is responsible for the clinical responses.
d. Endothelin antagonists.Although currently untested, endothelin antagonists represent a possible therapeutic avenue in BPH.

Chapter review

Patients with severe irritable symptoms and dysuria or microscopic hematuria should have a urine cytology.
Surgery is generally recommended for patients with refractory urinary retention, recurrent urinary tract infections, recurrent gross hematuria, bladder stones, renal insufficiency, and large bladder diverticula.
Flow rates are inaccurate if the voided volume is less than 150 mL. A peak flow rate (PFR) is better than an average flow rate.
Patients with a PFR greater than 15 mL/sec are less likely to have good treatment outcomes after prostatectomy. Patients with a flow rate less than 10 mL/sec have better surgical outcomes.
It takes at least a 3-point change in the IPSS for the patient to perceive a difference.
Conservative therapy to reduce the severity and bother of symptoms involves decreasing fluid intake, especially before bedtime, moderating alcohol and caffeine intake, and maintaining timed voiding schedules.
α-Adrenergic blockers may influence smooth muscle growth in the prostate. They may induce apoptosis.
α-Adrenergic blockers may induce the floppy iris syndrome, and patients should be warned of this if they are to have cataract surgery.
The maximal reduction in prostate volume requires 6 months after initiation of androgen suppressive therapy.
The rationale for aromatase inhibition is that estrogens may be involved in the pathogenesis of BPH.
Finasteride reduces prostate volume by approximately 20%. Maximum reduction in prostate volume following androgen deprivation occurs by 6 months.
Anticholinergic receptor blockers may be safely administered in patients with bladder outlet obstruction to reduce frequent voiding if they have PVR urine volumes less than 200 mL and do not report increasing hesitancy and show signs of increasing PVR urine volume when placed on such therapy.
Phosphodiesterase inhibitors have been known to improve IPSS scores. Phosphodiesterase inhibitors do not improve flow rate.
Concomitant use of α-adrenergic blockers and phosphodiesterase inhibitors may lead to hypotension.
Mortality increases sixfold in patients with renal insufficiency who are treated surgically for BPH.
PSA is of value in predicting the likelihood of response to 5α-reductase inhibitors and the risk of LUTS/BPH progression.
PSA is reduced by one-half in patients on 5α-reductase inhibitors.
The value of pressure flow studies and PVR in predicting the outcome of treatment is uncertain.
There is no convincing evidence in the aging male that an elevated PVR causes recurrent UTIs.
An elevated serum creatinine level in a patient with BPH is an indication for imaging studies (ultrasonography) to evaluate the upper urinary tract.
Overactive contractions are present in approximately 60% of men with LUTS and correlate strongly with irritative voiding symptoms.
Upper urinary tract imaging is not recommended for routine evaluation of men with LUTS unless they also have one or more of the following: hematuria; urinary tract infection; renal insufficiency (ultrasonography recommended); history of urolithiasis; and history of urinary tract surgery.
The definition of detrusor instability is the development of a detrusor contraction exceeding 15 cm H₂O at a bladder volume less than or equal to 300 mL.
Finasteride prevents recurrent gross hematuria secondary to BPH after prostatectomy.
A combination of an α-adrenergic blocker and a 5α-reductase inhibitor is the most effective way of preventing BPH progression.

^* Sources referenced can be found in Campbell-Walsh Urology, 11th Edition, on the Expert Consult website.

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