Benign prostatic hyperplasia

• Aging leads to prostate growth and increase in prostate/bladder neck smooth muscle tone
• Overgrowth of stromal, epithelial, smooth muscle cells occurs in the transition zone (paraurethral region of prostate)
• DHT mediates growth in transition zone - treat with 5α-reductase inhibitors (finasteride/Proscar)
• **hide**5a-reductase enzymes exist in prostate and skin (e.g. finasteride also used for hair loss)
• α-1A receptors mediate prostate smooth muscle contraction - treat with α-1 blockers (tamsulosin/Flomax)
• Results in bladder outlet resistance (BOO) - degree of BOO does not correlate with severity of BPH symptoms
• Similarly, not all enlarged prostates cause symptoms, etc. Goal of BPH treatment is to treat LUTS
• After age 50 - 50% of men will have enlarged prostates, 1/2 of those have symptoms, 1/2 of those require treatment
• Not all patients progress, but risk factors include age > 70, high PSA > 1.4, larger prostate, lower urine flow rate < 8 cc/s, more severe LUTS

Prostate anatomy

Transition zone Lateral to urethra in mid-prostate Most responsible for BPH (5% glandular tissue; 10% of prostate cancer in TZ) Central zone Cone-shaped region extending from bladder base to veru; around ejaculatory ducts (25% of glandular tissue) Peripheral zone Contains majority of glandular tissue (70%) Located at apex, posterolateral prostate. Prostate cancer more common in this zone Blood supply - prostatic artery is branch of anterior trunk of internal iliac artery **hide**located along anterior inferior surface of bladder, directed towards prostate Internal pudendal artery may supply distal 20% of prostate apex and external sphincter

History

• LUTS: decreased stream force, hesitancy, intermittent stream, post void dribbling, nocturia
• Normal nocturia - 1x/night at age 60, 2x/night at age 70 (more urine is proportionally made at night due to ↓ nocturnal ADH secretion, ↑ ANP)
• Classify based on IPSS/AUA symptom score
• 'Quality of life' score may not correlate with patient's objective symptoms
• Progressive BOO can lead to overactive bladder (overworked), retention/overflow incontinence (decompensated)
• Elevated PVR (post-void residual) can lead to UTI, bladder stones
• Can cause hematuria (neovascularity of prostate growth)

Exam

• DRE - BPH prostate should be smooth, non-nodular, with symmetric lobes.
• Each finger-breadth = ~ 10 cc in volume.
• On cysto, each 1 cm of prostatic length = ~ 10 cc in volume
• ~ 30 cc prostate should correlate with PSA ~ 1.5

• Low flow rate on uroflow/urodynamics - normal 20-25 mL/s; < 10-15 mL/s indicates probable obstruction
• Must have adequate voided volume > 125-150 cc for flow rate to be accurate
• High PVR reflects inadequate bladder emptying; correlates with increased risk of LUTS progression/upper tract damage
• Don't treat elevated PVR (100-150cc) in absence of symptoms (LUTS, UTI, kidney dysfunction)
• UA
• PSA is good surrogate of prostate size, response to therapy
• PSA < 4 indicates less likely to respond to 5a-reductase inhibitors (smaller prostate to start off with)
• Indications for formal urodynamics (pressure-flow studies)
• Typically not needed if BPH diagnosis is clear
• Indicated if very large PVR (?neurogenic or noncontractile bladder), hx neurogenic issues (Parkinson's, stroke), predominantly irritative symptoms (eg may be OAB in absence of obstruction), failed previous surgery (confirm diagnosis prior to repeat surgery)

Goal of treatment is to

• Treat symptoms, improve quality of life
• Prevent complications (UTI, bladder stones, upper tract damage, urinary retention)
• Definition of progression = Increase in IPSS of 5 or more points; occurrence of complication (retention), need for surgery

Non-surgical therapy

Lifestyle/other

• Behavioral changes - double voiding or timed voiding
• Avoid worsening urinary symptoms with α-agonists (decongestants), caffeine, alcohol, spicy/acidic food
• Reduce nocturia - avoid diuretics in evening, elevate legs/compression stockings, etc
• Watchful waiting if symptoms not bothersome
• **hide**Saw palmetto may benefit, but data is lacking

Pharmacotherapy

• α-blockers - improve voiding, prevent BPH progression
• α-1A blockade - prostate/bladder neck specific smooth muscle relaxation
• α-1B blockade - hypotension (arterial smooth muscle relaxation)
• α-1D - present in bladder smooth muscle, but action unknown
• Non-selective α-1A/B: terazosin 1-20 mg qhs, doxazosin (Cardura) 1-8 mg qd (more dizziness; require titration)
• **hide**ALLHAT study - doxazosin slightly increased risk for CHF, CAD, stroke
• In between: Alfuzosin (Uroxatrol) 10 mg qd with food - purportedly less ejaculatory dysfunction
• α-1A selective: tamsulosin (Flomax) - 0.4 mg qd
• Flomax - peak effect in first 12 hours; BID dosing has some additional benefit in ~ 10-20% of patients
• Silodosin (Rapaflo) 4-8 mg qd - more 1A selective, but highest rate of ejaculatory dysfunction/anejaculation (30%)
• Dose-dependent improvement in symptom score (symptoms may improve in few days; within 8 hrs if 1A selective)
• Overall - very little difference in overall efficacy; just differences in side effect profile
• Side effects: dizziness, nasal congestion, retrograde ejaculation (α1 blockade weakens ejaculatory response of sphincter contraction; semen flows retrograde into the bladder)
• Intraoperative floppy iris syndrome highest with 1A selectivity. Doesn't affect vision, but makes cataract surgery more difficult. Permanent - stopping therapy doesn't change it
• 5α-reductase inhibitors - reduce prostate volume, improve flow/symptoms, decrease progression
• Inhibits conversion of testosterone to 5-DHT
• Most effect in prostates > 30 cc
• Finasteride (Proscar) (5 mg qd); dutasteride (Avodart) (0.5 mg qd)
• Finasteride - inhibits type 2 5a-reductase; can reduce prostate microvascular density, use to manage gross hematuria 2/2 BPH
• 1 mg finasteride = propecia for hair growth (OTC med)
• Dutasteride - inhibits type 1 and 2 5a-reductase
• Effects manifest earlier than finasteride (2 mo vs 6 mo) but overall efficacy the same
• Decreases total PSA by ≥ 50% after 9-12 mo of treatment
• Prostate volume decreases by 20-30%
• Check baseline PSA and PSA at 6 months
• Symptom improvement in weeks-months (3-6 months, with less significant effect compared to a-blocker; overall one point in symptom improvement)
• Major indication is to reduce incidence of urinary retention in large prostates > 40 cc
• Side effects (<5%): decreased libido, decreased volume of ejaculate, gynecomastia
• Tadalafil (PDE5 inhibitor) (5 mg po qd) - FDA approved for BPH (based on IPSS improvement of 2...)
• Decrease in cGMP increases NO -> smooth muscle relaxation
• Improves ED as well as voiding/flow rate
• Equivalent benefit to α-blockers
• Combination therapy more beneficial for larger prostates
• May add on anticholinergic to treat OAB-LUTS (urgency, frequency). Caution if concern for retention (eg PVR > 100)
• Vasopressin may be considered if nocturia is primary symptom
• Phytotherapies - variable product formulations, variable quality of data
• Saw palmetto effectively = weak form of Proscar; approved in France/Germany

Surgical therapy

• Indications
• Patient preference or failure of medical therapy
• Progression with complications:
• refractory urinary rentention
• UTI
• hematuria, bladder stones
• renal insufficiency
• Brief categorization
• High risk of bleeding - consider HoLEP, PVP
• Size independent - HoLEP/ThuLEP

Minimally invasive

• TUNA (transurethral needle ablation) - RF waves for thermal necrosis (obsolete now, not recommended in AUA guidelines)
• TUMT (transurethral microwave thermotherapy) (becoming obsolete, but works well for chronic prostatitis. Delivered on a Foley catheter)
• PAL (prostatic urethral lift/Urolift) - transurethral placement of implants/sutures that "lift" obstructing tissue away from prostatic urethra. Less effective than TURP but no issues with erectile/ejaculatory function.
• Only for prostate < 80cc, without obstructive middle lobe.
• PAE (prostate artery embolization)
• RPA (water vapor thermal therapy, Aquablation) - for prostate < 80cc, also no issues with ED/ejaculatory issues

Surgical (greatest efficacy)

• Caution if prior prostate cryo/radiation - increased risk of post-op urinary incontinence
• TURP (transurethral resection of the prostate)
• Monopolar - use hypotonic irrigation fluid (water). TUR syndrome = excessive fluid absorption from the prostate vascular bed -> hyponatremia. Increased risk with longer procedure, higher irrigation pressure
• **hide**RBCs will lyse in water so can get better visualization
• Bipolar - use isotonic irrigation (saline) (no TUR syndrome)
• Overall no difference between procedure duration, bleeding, recovery, bladder neck contractures. Only difference is less hyponatremia with bipolar. 
• Laser - similar efficacy as TURP, with fewer complications/bleeding risk. Consider if pt cannot go off anticoagulation. However a/w more irritation/pain after surgery
• Holmium laser (resection/enucleation HoLEP, ablation HoLAP)
• Thulium laser (ThuLEP)
• Green light 532mm (photovaporization/PVP)
• TUIP (incision at 5 and/or 7 o'clock) - similar efficacy as TURP, lower rate of retrograde ejaculation. Use on small prostates < 30 g
• Simple prostatectomy - usually for prostates > 80cc, or cannot tolerate transurethral procedure
• Contraindications - previous prostate cancer, prostatectomy, small fibrous gland
• Robotic vs open - shorter hospital stay and less blood loss, but same in terms of efficacy, complications, etc.
• Complications to ask about on follow up
• 15-20% symptom persistence
• Persistent obstruction, or detrusor hypo/hyperactivity (which may be independent of BPH)
• Detrusor overactivity 2/2 BPH may take a year to resolve after obstruction is relieved
• Urethral stricture from TURP trauma (e.g. weak stream)
• Sphincter damage (incontinence)