AUA: Management of LUTS Attributed to BPH (2021)

See Original Guidelines Part 1 and Part 2

See Pharmacological Management of LUTS Chapter Notes

Background

• Definition of benign prostatic hyperplasia (BPH): a histologic diagnosis that refers to the proliferation of glandular epithelial tissue, smooth muscle, and connective tissue within the prostatic transition zone.
• BPH can lead to benign prostatic enlargement (BPE)
  • Not all men with BPH will develop any evidence of BPE.
• BPE can cause obstruction at the level of the bladder neck, termed benign prostatic obstruction (BPO)
  • Not all men with BPE will develop obstruction or BPO.
• Long standing bladder outlet obstruction from BPO can progress to incomplete bladder emptying, bilateral hydroureteronephrosis, and, ultimately, acute and/or chronic renal insufficiency.

Etiology of BPH

• Multifactorial process, exact etiology unknown
• Requires testosterone
  • 5-alpha reductase converts testosterone to its active metabolite, dihydrotestosterone (DHT).
  • DHT, which has a higher affinity for the androgen receptor and is considered the more potent androgenic steroid hormone, forms a complex with androgen receptors that is then transported to the nucleus.
  • Within the nucleus, this complex exerts its effects on transcription of DNA and translation, with subsequent normal development, growth, and hyperplasia of the prostate.
  • BPH develops due to an imbalance between growth and apoptosis (cellular death) in favor of growth, subsequently causing an increase in cellular mass.

Lower Urinary Tract Symptoms

• Classification: storage vs. voiding/emptying
• Male LUTS may be caused by a variety of conditions, including BPE and BPO.
  • BPE contributes to LUTS via at least two routes:
    1. Direct BOO/BPO from enlarged tissue (static component)
    2. Increased smooth muscle tone and resistance within the enlarged gland (dynamic component).
• In men, overactive bladder (OAB) storage symptoms may be the result of primary detrusor overactivity (DO), underactivity, or from obstruction induced by BPE and BPO.

Epidemiology of BPH/LUTS

• Prevalence of BPH increases with age
  • Prevalence by age 60 is 60%, by age 80 is 80%
• Prevalence and severity of lower urinary tract symptoms increases with age

Diagnosis and Evaluation of Patients Presenting with Bothersome LUTS Possibly Attributed to BPH

Initial Evaluation

• Recommended (3)

1. History and Physical Exam
2. Urinalysis
3. International Prostate Symptom Score (IPSS)

• Optional (3)

1. Post-void residual (PVR)
2. Uroflowmetry
3. Urodynamics

Recommended (3)

History and Physical Exam

• History
  • Signs and Symptoms
    • Presence and severity of symptoms
    • Degree of bother associated with symptoms
      • Most important motivation for seeking treatment; while LUTS/BPH is rarely life-threatening, the impact on QoL is significant and should not be underestimated.
  • Sexual history
  • Use of medications
  • Overall fitness and health
• Physical Exam

Urinalysis

• Can help rule out other causes of LUTS not associated with BPH through the detection of bacteria, blood, white cells, glucose, or protein in the urine.
  • When interpreting the results of the urinalysis, focus on the presence or absence of glucosuria, proteinuria, hematuria, and infection.

International Prostate Symptom Score (IPSS)

• Also known as AUA-Symptom Index (AUA-SI)
• A validated self-administered questionnaire
• Can provide information regarding the symptom burden patients are experiencing
• 7 Symptoms + Quality of Life
  • Each symptom is scored on a scale from 0-5
  • Quality of Life is scored 0-6
• Total score classified as:
  • 0 - 7 = mildly symptomatic
  • 8 - 19 = moderately symptomatic
  • 20 - 35 = severely symptomatic
• (English link)(Spanish link)

Optional (3)

Post-void residual (PVR)

• Can help determine a baseline ability of the bladder to empty, identify severe urinary retention that may not be amenable to medical therapy, and/or indicate detrusor dysfunction
• Correlation between residual volume and degree of obstruction is weak
  • Not a strong predictor of acute urinary retention
• No universally accepted definition of a clinically significant residual urine volume; following a trend over time is suggested
  • A “large” PVR (>300 mL) is worth monitoring, at the very least
  • A patient with an incidentally discovered elevated PVR who does not have any safety issues related to retention or does not report any bothersome urinary symptoms can be followed with longitudinal safety and QoL assessments

Uroflowmetry

• The generally accepted minimum threshold voided volume for adequate interpretation is 150cc
• Patients should be instructed not to Valsalva void.
• Flow rates of <10 mL/s have shown a specificity of 70%, a positive predictive value of 70%, and a sensitivity of 47% for BOO
• In addition to the flow rate, the shape of the curve and duration of voiding provide useful information to characterize the voiding dysfunction.

Urodynamics

• Most complete means to determine the presence of BOO
  • Pressure flow studies can help differentiate urinary retention related to detrusor underactivity, detrusor sphincter dyssynergia, or obstruction due to prostatic enlargement.
    • Only pressure flow studies can document detrusor contractility, or lack thereof
• Most men with BOO will void with low urinary flow (Qmax < 10 cc/s) at peak voiding pressures and a pressure flow study will confirm BOO if high voiding pressures accompany the low urinary flow
• Should be considered for more complex voiding scenarios with clinical uncertainty
  • Most patients can be managed and treated surgically without pressure flow studies
  • In patients with catheter-dependent urinary retention who may have underactive detrusor function, a pressure flow study is advised
• There are patients (e.g., those with bladder diverticulum) in whom urodynamics inaccurately indicate a lack of detrusor contractility.

Management

First-line: Lifestyle and Behavioral Interventions

• Limiting intake of the following (3):
  1. Fluids prior to bedtime or travel
  2. Mild diuretics, such as caffeine and alcohol
  3. Bladder irritants, such as highly seasoned or irritative foods
• Other interventions include (6):
  1. Avoiding constipation
  2. Increasing physical activity
  3. Weight loss
  4. Kegel exercises at time of urinary urgency
  5. Timed voiding regimens
  6. Double-voiding techniques
• Pelvic floor muscle training, including biofeedback, may be helpful for patients with urgency and storage symptoms.
• For those patients with bothersome LUTS in whom additional therapy is warranted, it is appropriate to discuss medical therapy.
  • The potential benefits and harms of proceeding to a procedural intervention without trialing medications may also be discussed as part of the informed decision-making process.
    • As primary care providers may not feel comfortable discussing procedural interventions, offering referral to a specialist without a trial of medication is reasonable.

Second-line: Medical Therapy

• Pharmacologic classes of medications used to treat LUTS/BPH, which may be utilized alone or in combination to take advantage of their different mechanisms of action, include
  1. Alpha-adrenergic antagonists (alpha blockers)
  2. 5-ARIs
  3. PDE5
  4. Anticholinergics
  5. Beta-3 agonists (in combination with alpha blockers)

Monotherapy

Alpha blockers

• Recommended alpha blockers for patients with bothersome, moderate to severe LUTS/BPH (5):
  1. Alfuzosin
  2. Doxazosin
  3. Silodosin
  4. Tamsulosin
  5. Terazosin
     • All relatively equally effective in terms of IPSS improvement ranging from 4-7 points as compared to placebo
       • Attempts to identify subgroups of patients who may respond better to one alpha blocker or another have not shown differences in efficacy.
     • Changing from one alpha blocker to another on the basis of
       • Side effects is worthwhile
       • Insufficient response is not recommended, given that medication type and patient characteristics do not impact effectiveness
• Choice of alpha blocker should be based on patient age, comorbidities, and different adverse event profiles (eg, ejaculatory dysfunction, changes in blood pressure).
  • Ejaculatory Dysfunction
    • Previously referred to as retrograde ejaculation.
      • A study evaluating patients on alpha blockers found a significant difference in ejaculate volume but no significant difference in the sperm concentrations of post-ejaculate urine.[1]
      • True retrograde ejaculation is commonly found after TURP and surgeries affecting the anatomy of the bladder neck and prostate
    • Preferred alpha blockers in patients concerned with ejaculatory dysfunction (3):
      1. Alfuzosin
      2. Doxazosin
      3. Terazosin
    • More common with silodosin and tamsulosin
      • Most common with silodosin
      • No significant difference between doxazosin, terazosin, and alfuzosin compared to placebo
        • Clinical implication: Avoid silodosin and tamsulosin in younger sexually active men are more likely to discontinue due to ejaculatory dysfunction.
  • Changes in Blood Pressure
    • Preferred alpha blockers in patients at risk for orthostatic hypotension and syncope (3):
      1. Alfuzosin
      2. Tamsulosin
      3. Silodosin
    • Terazosin and doxazosin are non-specific alpha-1 receptor blockers approved for hypertension, as well as BPH.
      • Note that alfuzosin is also considered non-specific[2]
    • When treating patients on several antihypertensives, or with orthostatic hypotension, it is best to select an alpha blocker that exhibits minimal impact on blood pressure (eg, the highly selective alpha 1a blocker silodosin)
  • Concomitant use of a PDE5
    • The hypotensive effects of terazosin and doxazosin can be potentiated by concomitant use of a PDE5, such as sildenafil or vardenafil.
    • Tamsulosin at a dose of 0.4 mg/day, however, does not appear to significantly potentiate the hypotensive effects of sildenafil.
    • Regardless, patients utilizing both these medications should be counselled appropriately regarding the risk for drops in blood pressure and symptoms associated with this.
• When initiating alpha blocker therapy, patients with planned cataract surgery should be informed of the associated risks and be advised to discuss these risks with their ophthalmologists.
  • Urologists initiating alpha blocker therapy should inquire about plans for future cataract surgery and inform them of Intraoperative Floppy Iris Syndrome risk, with delay of medication initiation until after planned procedures
    • Tamsulosin has the highest risk for IFIS (40x that of alfusozin), but all alpha blockers increase the risk of IFIS to some degree.
    • For every 255 men receiving tamsulosin in the immediate preoperative cataract surgical period, one serious complication (e.g., retinal detachment, lost lens or lens fragment, endophthalmitis) would result.
    • Discontinuation of tamsulosin 4 to 7 days prior to cataract surgery is routine practice, but it does not completely eliminate IFIS risk.
• Alpha blockers for Acute Urinary Retention
  • An oral alpha blocker should be prescribed prior to a voiding trial to treat patients with AUR related to BPH. The patient should complete at least 3 days of medical therapy prior to attempting a voiding trial.
  • Clinicians should inform patients who pass a successful voiding trial for AUR from BPH that they remain at increased risk for recurrent urinary retention.
    • Given the lack of standardized follow-up, long-term efficacy of alpha blocker therapy in treating AUR is unclear. All trials report a significant number of patients with subsequent urinary retention and LUTS after treatment occurring days to months later, necessitating catheterization or surgical procedures.
  • Consider delayed a voiding trial in patients with an active UTI until the infection has resolved.

5-Alpha Reductase Inhibitors

• Finasteride selectively inhibits the 5-AR type II isoenzyme, while dutasteride inhibits both types I and II.
  • This difference in activity reduces serum levels of DHT by approximately 70% with finasteride, compared to 95% with dutasteride. However, in BPH tissue, type II 5AR is far more common than type I. Therefore, the reduction of DHT in prostate tissues has been measured at approximately 80% (finasteride) and 94% (dutasteride).
  • The serum half-life of finasteride ranges from six to eight hours, whereas that of dutasteride is five weeks. This pharmacokinetic difference may have implications in terms of treatment compliance, as well as persistence of side effects
• Use of 5-ARI reduces prostate size by 15-25% at 6 months
  • Atrophy is most pronounced in the glandular epithelial component of the prostate, the source of production and release of serum PSA, reducing levels by approximately 50% (and a concomitant decrease in free PSA by 50%, which means that the ratio of free/total PSA remains constant).
  • After 1 year of 5-ARI therapy, the measured serum PSA value should be doubled to accurately gauge disease progression
• Efficacy
  • Finasteride showed an improvement of 3-4 points in standardized symptom scores (eg, IPSS) superior to placebo that was maintained for 6 to 10 years of follow-up.
  • Only one study has directly compared the outcomes of men randomized to either finasteride or dutasteride. Amongst men randomized to either medication over 12 months, no differences were noted with regards to prostate volume, AUA-SI and Qmax
• Indications (3):
  1. Improve LUTS
     • For the purpose of symptom improvement, 5-ARI monotherapy should be used as a treatment option in patients with LUTS/BPH with prostatic enlargement as judged by (3):
       1. Prostate volume >30cc on imaging
       2. Prostate specific antigen (PSA) > 1.5ng/dL
       3. Palpable prostate enlargement on digital rectal exam (DRE)
          • A minimum prostate volume of >30cc or PSA >1.5ng/dL is necessary for a reliable 5-ARI response, but the larger the gland, the more pronounced the effects.
  2. Prevent progression of LUTS/BPH and/or reduce the risks of urinary retention and need for future prostate-related surgery.
     • In the PLESS study, a lower risk of AUR and BPH related surgery was seen amongst men randomized to 5-ARI instead of alpha blocker alone or placebo groups
  3. Prostatic bleeding
     • One of the early intraprostatic effects of finasteride has been the suppression of vascular endothelial growth factor (VEGF).
     • Consider 5-ARIs as a treatment option to reduce intraoperative bleeding and peri- or postoperative need for blood transfusion after transurethral resection of the prostate (TURP) or other surgical intervention for BPH.
       • Conflicting evidence on the role of 5-ARI on blood loss during surgery, excessive or severe bleeding, or clot retention.
     • After exclusion of other causes of hematuria, 5-ARIs may be an appropriate and effective treatment alternative in men with refractory hematuria presumably due to prostatic bleeding.
       • If gross hematuria persists, surgical removal/ablation of the offending adenomatous tissue should be the next step unless precluded for other reasons.
       • The potential role of PAE in the management of refractory hematuria is evolving
• Before starting a 5-ARI, clinicians should inform patients of the risks of sexual side effects, certain uncommon physical side effects, and the association with prostate cancer incidence and grade.
  • Gynecomastia and sexual side effects (erectile and ejaculatory function, as well as libido) can occur with 5-ARI therapy
    • Amongst men who do experience bothersome ED as an effect of 5-ARI therapy, cessation of drug may allow them to return to the baseline rates of ED
  • Conflicting evidence on the association between 5-ARIs and the risk of incident prostate cancer and risk of higher grade prostate cancer
  • Observational studies suggest that 5-ARI use may be associated with dementia and depression.
  • Post-finasteride syndrome (PFS), a controversial and poorly-defined constellation of sexual, physical, and psychological symptoms that putatively persist after discontinuation of the drug. However, the robustness of the data justifying this change, which is based on anecdotal patient-reported outcomes rather than prospective trials, remains unclear
• Due to the slow onset of action of these medications as compared to alpha blockers, patients should be counseled on a slower symptom improvement if treated with 5-ARI alone
• PSA screening should be undertaken in age-appropriate males as part of shared medical decision-making for prostate cancer screening.

Phosphodiesterase-5 Inhibitor (PDE5)

• For patients with LUTS/BPH irrespective of comorbid erectile dysfunction (ED), 5mg daily tadalafil should be discussed as a treatment option.
  • The majority of studies that address the impact of PDE5s on LUTS/BPH used tadalafil.
    • Although tadalafil is the only PDE5 approved by the FDA for treatment of LUTS, there are limited data suggesting sildenafil may also be useful.
  • The mechanism of action of this PDE5 effect is only partially understood
  • Mean decrease in IPSS for tadalafil was 1.7 points from baseline, across 10 RCTs
  • Impact of low-dose daily tadalafil on LUTS appears similar to that seen with tamsulosin.
    • In a trial comparing tadalafil 5 mg vs. tamsulosin 0.4 mg, no significant difference in change in IPSS at 3 months
  • Does not improve urodynamic profiles
  • Adverse events: headache, nasopharyngitis, and back pain
  • Tadalafil is a reasonable option to trial in selected men, ideally those with concomitant erectile dysfunction.

Combination Therapy

• Combination therapy is a common approach to symptomatic LUTS, working on the premise that each medication targets a different site in the lower urinary tract. Together, they presumably maximize symptom control.
• Standard combinations include (3):
  • Alpha blockers + 5-ARI
  • Alpha-blocker + anticholinergic/antimuscarinic therapy
  • Alpha blockers + beta-3-agonists.

Alpha blockers + 5-ARI

• Should be offered as a treatment option only to patients with LUTS associated with demonstrable prostatic enlargement as judged by a prostate volume of >30cc on imaging, a PSA >1.5ng/dL, or palpable prostate enlargement on DRE.
• Two large studies evaluated alpha blocker and 5ARI combinations: Medical Therapy of Prostatic Symptoms (MTOPS) and Combination of Avodart and Tamsulosin (CombAT). Both studies showed statistically significant reductions in parameters of clinical progression with combination approaches over monotherapy.
• Providers may start combination therapy with the intention of later discontinuing the alpha blocker (sometimes called “Withdrawal Therapy”).
  • The rationale for this treatment is for men to initially gain the benefit of the alpha blocker and once the efficacy of the 5-ARI is fully developed at a later time, the alpha blocker may be removed.
  • While this is a reasonable strategy, the concept has not been studied rigorously, and there are insufficient data to gauge the utility of this approach or the duration at which combination therapy should be continued before cessation of the alpha blocker.

Anticholinergic agents, alone or in combination with an alpha blocker

• Anticholinergics have been approved and used for OAB symptoms in males and females
• May be offered as a treatment option to patients with moderate to severe predominant storage LUTS.
• Monotherapy with anticholinergics has been shown to lead to significant differences in LUTS secondary to BPH
  • There has been some reluctance on the part of clinicians to use them alone in patients with LUTS/BPH due to the potential risk of worsening bladder residuals or retention. However, studies show the risk of urinary retention to be low in appropriately selected patients.
  • Since there are increased adverse events, it may make sense to initially start with alpha blocker alone and add anticholinergics in selected cases
• PVR should be obtained pre-treatment and monitored at follow-up.
  • A safety trial was conducted in patients with urodynamically-proven obstruction and overactivity, comparing tolterodine 2 mg to placebo. The results showed mild increase in PVR (25 mL versus 0 mL) and mild decrease in bladder contractility index, with no urinary retention in the treatment group. Other studies have confirmed similar findings and as such, use in appropriately selected patients is reasonable.

Alpha blockers + beta-3-agonists

• May be offered as a treatment option to patients with moderate to severe predominate storage LUTS.
  • Combination therapy with a beta-3-agonist appears to be reasonably safe and tolerated and can lead to improvement in symptoms similar to those seen with anticholinergics. Therefore, in older patients where anticholinergic therapy is not recommended, a beta-3- agonist can be utilized.
• Monotherapy with a beta-3-agonist has, thus far, not been shown to lead to significant differences in LUTS secondary to BPH

Low-dose daily 5mg tadalafil with alpha blockers

• Should not be offered for the treatment of LUTS/BPH as it offers no advantages in symptom improvement over either agent alone.

Supplements and nutraceuticals

• Many supplements and nutraceuticals containing ingredients such as saw palmetto, Pygeum africanum, stinging nettle, zinc, selenium, and others are popular and have been marketed and studied. Overall the results have been variable, as have study methods and quality, thus positive recommendations regarding their use are not warranted

Follow-up after initiating treatment

• Patients should be evaluated 4-12 weeks after initiating treatment (provided adverse events do not require earlier consultation) to assess response to therapy.
  • For faster onset drugs (alpha blockers, beta-3 agonists, PDE5s and anticholinergics), the first follow-up visit can be as early as 4 weeks.
  • For longer onset drugs (5-ARIs), waiting 3-6 months is advised.
• Revaluation should include (2):
  1. Evaluation of adverse medication effects
  2. IPSS
     • The administration of the IPSS is recommended at each time point of follow-up as it enables a conversation about expectations and satisfaction and may lead to changes in treatment.
• Further evaluation may include a post-void residual (PVR) and uroflowmetry.
  • Qmax changes after nonsurgical therapies may be subtle and not necessarily correlate with IPSS, but trends over time may encourage a change in treatment strategy.
  • Increasing PVR may require additional investigations and/or a change in therapy.
  • There are no published thresholds for monitoring changes in PVR, Imax or IPSS/QOL to help guide therapy.
• Patients with bothersome LUTS/BPH who elect initial medical management and do not have symptom improvement and/or experience intolerable side effects should undergo further evaluation and consideration of change in medical management or surgical intervention.
  • An initial trial of medical management over 4 weeks with an alpha blocker or PDE5, and over 6-12 months with a 5-ARI is reasonable in men with bothersome LUTS.
  • Potential reasons for medication failure
    • Contribution of detrusor underactivity; urodynamics can help clarify
    • Lack of medication efficacy
    • Complicated LUTS (potentially not just related to BPH) with a combination of storage and voiding symptoms. Additional medication classes should be considered along with procedural options.

Surgical Therapy

Indications (6)

• Desire to avoid, symptoms refractory to, or intolerable pharmaceutical side effects related to, medical therapy
• Conditions resulting from BPH and for which medical therapy is insufficient:
  1. Acute and/or chronic renal insufficiency (defined as GFR <60 for at least 3 months)
  2. Refractory urinary retention
  3. Recurrent urinary tract infections (UTIs)
  4. Recurrent bladder stones
  5. Recalcitrant gross hematuria.
  6. Progressive bladder dysfunction (i.e. loss of low-pressure bladder storage function due to poor compliance)
• Asymptomatic bladder diverticulum
  • Should not be used as the only indication for bladder outlet surgery; however, evaluation for the presence of bladder outlet obstruction (BOO) should be considered.
    • Prior to surgery for diverticulum, clinicians should perform assessment for BOO and treat as clinically indicated
• Elevated PVR should not be used as the only indication for bladder outlet surgery
• Cystolithalopaxy can be performed concomitantly with the surgical procedure used to remove the obstructing prostate tissue and depending on the size and number of stones present, can influence the choice of surgical approach (e.g., transurethral, open, or laparoscopic).

Prior to Surgical Intervention for LUTS/BPH

• Preoperative Testing
  • Recommended (1)
    1. Post void residual (PVR) assessment
       • Valuable for post-operative management and determining success of surgical interventions.
       • Baseline assessments with post-operative comparisons can provide objective outcome measurements, determine the impact of therapy on improving obstruction, and demonstrate to both surgeon and patient that the intervention led to improvement. Lack of change with continued symptoms can indicate another process that may warrant further investigation or treatment.
  • Consider (4)
    1. Assessment of prostate size and shape via (if such studies are available)
       • Cystoscopy
       • Imaging (2):
         • Transrectal or abdominal ultrasound
         • Cross-sectional imaging (ie, magnetic resonance imaging [MRI]/ computed tomography [CT])
       • Prostate size may direct the clinician as to which interventions to consider.
       • Since the specific gravity of the prostate is 1.05 g/mL, the units gram and milliliter and cc can be used interchangeably to denote size or volume.
       • Imaging obtained within 12 months is preferred
         • When existing imaging is “older,” considering prostate growth rates of 1.6% per year on average can give a reasonably accurate estimate of current size.
       • Digital rectal exam is unreliable in estimating prostate size and cannot assess for a middle lobe
       • Serum Prostate Specific Antigen (PSA) is only a rough indicator of prostate size.
    2. Uroflowmetry
    3. Pressure flow studies, when diagnostic uncertainty exists.
       • Pressure flow studies are the most complete means to determine the presence of BOO, but most patients can be managed and treated surgically without them.
       • Urodynamics can help differentiate urinary retention related to detrusor underactivity, detrusor sphincter dyssynergia, overactivity unrelated to obstruction, and categorize LUTS related to DO or low bladder compliance.
       • In patients with catheter-dependent urinary retention who may have underactive detrusor function, a pressure flow study is advised; however, clinicians should be aware that there are patients (e.g., those with bladder diverticulum) in whom studies inaccurately indicate a lack of detrusor contractility.
    4. PSA for prostate cancer screening
       • Not discussed in AUA guidelines
       • 2023 EAU Guidelines 4.6.3: Measure prostate-specific antigen (PSA) if a diagnosis of prostate cancer will change management.
• Counsel patients of the possibility of
  1. Treatment failure and the need for additional or secondary treatments
  2. Sexual side effects (ejaculatory dysfunction and may contribute to or worsen erectile dysfunction (ED))
     • Libido, however, does not appear to be affected significantly by surgical therapy
     • Some studies have even shown an improvement in erectile function (EF) after surgical treatment (this improvement is controversial as other studies show a worsening of EF).
     • Sexual side effects from surgical treatments are more likely to be permanent than those from medical treatments, which can often be reversed by stopping medical treatment or switching to an alternative option.

Options

• Should be offered
  1. Transurethral Resection of the Prostate (TURP)
  2. Transurethral Incision of the Prostate (TUIP)
  3. Photoselective Vaporization of the Prostate (PVP)
• Should be considered
  1. Simple Prostatectomy (open, laparoscopic, or robotic assisted)
  2. Prostatic Urethral Lift (PUL)
  3. Water Vapor Thermal Therapy (WVTT)
  4. Laser enucleation (Holmium laser enucleation of the prostate (HoLEP) or thulium laser enucleation of the prostate (ThuLEP))
• May be offered
  1. Transurethral Vaporization of the Prostate (TUVP)
  2. Transurethral Microwave Therapy (TUMT)
  3. Robotic Waterjet Treatment (RWT)
• Not recommended
  1. Transurethral Needle Ablation (TUNA)
  2. Prostate Artery Embolization (PAE)

Transurethral Resection of the Prostate (TURP)

• Transurethral surgery involves removal of obstructing adenomatous tissue via an endoscopic transurethral route
  • Classically performed with monopolar electroconductive transurethral resection of the prostate (TURP).
• TURP remains the historical standard by which all other subsequent surgical approaches to treatment of BPH are compared
• Efficacy
  • Helps to reduce urinary symptoms associated with BPH, including frequent/urgent need to urinate, difficulty initiating urination, prolonged urination, nocturia, non-continuous urination, a feeling of incomplete bladder emptying, and UTIs.
  • Successful TURP can relieve symptoms quickly with most men experiencing significantly stronger urine flow within days of the procedure.
• Alternatives to standard monopolar TURP have been developed, including bipolar TURP and various laser-based therapies, to achieve similar clinical efficacy while reducing the risks of perioperative bleeding and short- and long-term complications.
  • Differences between bipolar and monopolar TURP
    • Contrary to monopolar TURP, bipolar energy does not travel through the body to reach a skin pad as the energy is confined between an active (resection loop) and a passive pole situated on the resectoscope tip.
    • While monopolar TURP requires the use of either isoosmolar solutions of sorbitol, mannitol, or glycine, bipolar TURP is performed in 0.9% NaCl solution. This reduces (if not eliminates) the risk for acute dilutional hyponatremia during prolonged resection, which may lead to the so-called TUR syndrome.
      • The reduced risk of hyponatremia and TUR syndrome allows for longer resection times; therefore, bipolar TURP may be used in larger glands compared to monopolar TURP.
        • The experience and skill of the surgeon determines how large of a prostate can be addressed with this technology, and for many this includes glands up to 100cc, or even larger.
• Clinicians may use a monopolar or bipolar approach to TURP as a treatment option, depending on their expertise with these techniques.

Transurethral Incision of the Prostate (TUIP)

• TUIP should be offered as an option for patients with prostates ≤30cc for the surgical treatment of LUTS/BPH.
• Preserves ejaculatory function, compared to TURP
• Need for repeat procedure more common with TUIP, compared to TURP.

Photoselective Vaporization of the Prostate (PVP)

• PVP (includes Greenlight) is a transurethral form of treatment that utilizes a 600-micron side firing laser fiber in a noncontact mode. The laser wavelength is 532nm, which is preferentially absorbed by hemoglobin, resulting primarily in tissue ablation/vaporization with a thin layer of underlying coagulation that provides hemostasis. The depth of penetration with PVP is 0.8 mm.
• The goal of the procedure is to vaporize the prostate adenoma sequentially outwards until the surgical capsule is exposed and a defect is created within the prostate parenchyma through which the patient may void.
• The procedure is generally performed with saline irrigation, eliminating the possibility of TUR syndrome that can occur with non -ionic irrigation.
• PVP should be offered as an option using 120W or 180W platforms for the treatment of LUTS/BPH.
  • 80W platform had higher retreatment rates compared to TURP

Simple Prostatectomy

• Approaches: open, laparoscopic, or robotic assisted simple prostatectomy (ie, adenoma enucleation)
• Indications
  • Should be considered only in patients with large to very large prostates, depending on surgeon expertise with these techniques

Prostatic Urethral Lift (PUL)

• Mechanism of Action: alters prostate anatomy without ablating tissue via the placement of transprostatic suture implants.
  • The implants pull the lumen of the prostatic urethra towards the capsule and widen the prostatic urethral lumen. The urethral side of the implant epithelializes within 12 months. Histopathologic analysis of tissue obtained after PUL demonstrates a benign response to the implant.
• No significant changes have been noted in PSA after implantation
• Indications
  • Should be considered as a treatment option for patients with LUTS/BPH provided (2):
    1. Prostate volume 30–80cc
    2. Verified absence of an obstructive middle lobe
  • May be offered as a treatment option to eligible patients who desire preservation of erectile and ejaculatory function
• Efficacy
  • Similar retreatment rates compared to TURP

Water Vapor Thermal Therapy (WVTT)

• Also known as Rezum
• Mechanism of Action: Utilizes convective radiofrequency to create stored thermal energy in the form of steam, which is delivered transurethrally via a specialized device into the transition zone. The steam travels through the transition zone, denaturing tissue and thereby ablating the adenoma to create an opening
• Indications
  • Should be considered as a treatment option for patients with LUTS/BPH provided (2):
    1. Prostate volume 30–80cc
  • May be offered as a treatment option to eligible patients who desire preservation of erectile and ejaculatory function

Laser Enucleation

• MOA: Due to the chromophore of water and minimal tissue depth penetration with both holmium and thulium (0.4mm for holmium, 0.2 mm for thulium), these two lasers achieve rapid vaporization and coagulation of tissue without the disadvantage of deep tissue penetration. They have better coagulative properties in tissue than either monopolar or bipolar TURP, and combined with their superficial penetration, both thulium and holmium are appropriate for endoscopic enucleation.
• Holmium laser enucleation of the prostate (HoLEP) or thulium laser enucleation of the prostate (ThuLEP) should be considered as an option, depending on the clinician’s expertise with these techniques, as prostate size-independent options for the treatment of LUTS/BPH.
• HoLEP and ThuLEP have similar outcomes when compared to TURP for the treatment of symptomatic BPH as measured by IPSS and IPSS-QoL outcomes.

Transurethral Vaporization of the Prostate (TUVP)

• TUVP of the prostate is a technical electrosurgical modification of the standard TURP.
• TUVP can utilize a variety of energy delivery surfaces including:
  1. Spherical rolling electrode (rollerball)
  2. Grooved roller electrode (vaportrode) (see Figure)
  3. Loop electrode
  4. Hemi-spherical/oval mushroom electrode (button)
  5. Others
• TUVP typically uses saline and is powered with a bipolar energy source. Compared to traditional resection loops, the various TUVP designs aspire to improve upon tissue visualization, blood loss, resection speed and patient morbidity.
• Bipolar TUVP may be offered as an option to patients for the treatment of LUTS/BPH.

Transurethral Microwave Therapy (TUMT)

• TUMT was one of the earliest office-based MISTs available and several iterations have been modified since it was first described over 25 years ago.
• MOA: TUMT is a process whereby coagulation necrosis of the prostatic tissue is achieved by transferring energy into the tissue and creates heat. A specialized catheter with a cooling component is placed transurethrally into the prostatic fossa, as well as a rectal catheter that measures temperature, and a microwave antenna heats the prostatic tissue to a minimum 45°C. As the prostate shrinks over the ensuing weeks, the channel opens up.
• TUMT may be offered as a treatment option to patients with LUTS/BPH.
• Higher retreatreatment rate compared to TURP.
• Newer minimally-invasive technologies will likely displace TUMT within the next several years.

Robotic Waterjet Treatment (RWT)

• Also known as Aquablation
• Mechanism of Action: Utilizes a robotic handpiece, console, and conformal planning unit (CPU). The resection of the prostate is performed using 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 vermontanum. It is also used to monitor tissue resection in real time during the procedure. After completion of the resection, electro-cautery/thermal energy via a standard cystoscope/resectoscope, use of a tamponade balloon catheter, or traction from a 3-way catheter balloon is used to obtain hemostasis.
  • The technique is not in the MIST category as patients must undergo general anesthesia.
• May be offered as a treatment option to patients with LUTS/BPH provided prostate volume 30–80cc.

Prostate Artery Embolization (PAE)

• Not recommended outside the context of clinical trials
  • Not supported by current data for the routine treatment of LUTS/BPH, and benefit over risk remains unclear
• The potential role of PAE in the management of refractory hematuria is evolving and makes intuitive sense. While many of the studies include a small number of patients with various etiologies of hematuria, the ability to both decrease prostate volume and vascular inflow makes PAE a potential adjunct in management of BPH related refractory hematuria.

Factors Influencing Choice of Surgical Procedure

Prostate Size

• See Algorithm
• Small (<30 g) (6):
  1. Transurethral Incision of the Prostate (TUIP)
  2. Transurethral Resection of the Prostate (TURP)
  3. Photoselective Vaporization of the Prostate (PVP)
  4. Transurethral Vaporization of the Prostate (TUVP)
  5. Transurethral Microwave Therapy (TUMT)
  6. Laser enucleation (Holmium laser enucleation of the prostate (HoLEP) or thulium laser enucleation of the prostate (ThuLEP))
• Average (30–80 g) (7):
  1. Transurethral Resection of the Prostate (TURP)
  2. Photoselective Vaporization of the Prostate (PVP)
  3. Transurethral Vaporization of the Prostate (TUVP)
  4. Transurethral Microwave Therapy (TUMT)
  5. Laser enucleation (Holmium laser enucleation of the prostate (HoLEP) or thulium laser enucleation of the prostate (ThuLEP))
  6. Water Vapor Thermal Therapy (WVTT)
  7. Robotic Waterjet Treatment (RWT)
  8. Prostatic Urethral Lift (PUL)
• Large (>80 to 150 g) or Very large (>150 g) (2):
  1. Simple Prostatectomy (open, laparoscopic, or robotic assisted)
  2. Laser enucleation (Holmium laser enucleation of the prostate (HoLEP) or thulium laser enucleation of the prostate (ThuLEP))
• These category suggestions assume surgical expertise with BPH and reflect Panel opinion, but do not necessarily imply lack of efficacy in prostates outside the recommended ranges.
  • The Panel hopes that surgeons will choose the surgical technique with the best benefit-to-risk ratio for a specific size range and, in cases where that technique is not readily available or where no expertise exists, the patient is referred to another surgeon with such access and expertise.
  • Randomized trials for some devices enrolled men with prostates within specific size ranges. As such, statements for those treatments contain the size ranges most commonly referenced in the currently available and reviewed RCT’s included in these Guidelines, and/or as used for FDA approval. However, the Panel recognizes that these devices do not necessarily lack efficacy in prostates below or above the size ranges stipulated in the Statements.

Preservation of erectile and ejaculatory function

• Given the strong observed relationship between ED and LUTS/BPH, this group of men is at high risk for sexual dysfunction.
• Preferred treatment options in patients concerned with preservation of erectile and ejaculatory function (2):
  1. Prostatic Urethral Lift (PUL)
  2. Water Vapor Thermal Therapy (WVTT)

Medically Complicated Patients

• Preferred treatments options in patients who are at higher risk of bleeding (2):
  • Photoselective Vaporization of the Prostate (PVP)
  • Laser enucleation (Holmium laser enucleation of the prostate (HoLEP) or thulium laser enucleation of the prostate (ThuLEP))
• For patients who take anticoagulants and must proceed to operative intervention without cessation of their medication, laser surgery leads as the preferred choice given the coagulative power of these energy sources, including reduced post-operative bleeding.

Questions

1. What are the recommended investigations in the diagnosis and evaluation of LUTS attributed to BPH?
2. Which alpha blocker(s) are preferred to reduce the risk of ejaculatory dysfunction?
3. Which alpha blocker(s) can be used to treat concomitant hypertension?
4. Which alpha blocker(s) should be avoided in a patient on sildenafil for erectile dysfunction?
5. What are the recommended options for surgical intervention in a prostate estimated to be 50g?
6. Which options for surgical intervention are more likely to preserve erectile and ejaculatory function?

Answers

1. What are the recommended investigations in the diagnosis and evaluation of LUTS attributed to BPH?
2. Which alpha blocker(s) are preferred to reduce the risk of ejaculatory dysfunction?
3. Which alpha blockers can be used to treat concomitant hypertension?
4. Which alpha blocker(s) should be avoided in a patient on sildenafil for erectile dysfunction?
5. What are the recommended options for surgical intervention in a prostate estimated to be 50g?
   1. Transurethral Resection of the Prostate (TURP)
   2. Photoselective Vaporization of the Prostate (PVP)
   3. Transurethral Vaporization of the Prostate (TUVP)
   4. Transurethral Microwave Therapy (TUMT)
   5. Laser enucleation (Holmium laser enucleation of the prostate (HoLEP) or thulium laser enucleation of the prostate (ThuLEP))
   6. Water Vapor Thermal Therapy (WVTT)
   7. Robotic Waterjet Treatment (RWT)
   8. Prostatic Urethral Lift (PUL)
6. Which options for surgical intervention are more likely to preserve erectile and ejaculatory function?
   1. Prostatic Urethral Lift (PUL)
   2. Water Vapor Thermal Therapy (WVTT)

Mock Oral Exams

• BPH and Male LUTS (Master the Medicine)

References

• Lerner, Lori B., et al. "Management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA guideline part I—initial work-up and medical management." The Journal of urology 206.4 (2021): 806-817.
• Lerner, Lori B., et al. "Management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA guideline part II—surgical evaluation and treatment." The Journal of urology 206.4 (2021): 818-826.