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BPH
OVERVIEW / MANAGEMENT
Richard L Haddad
Norwest Private Hospital
17 Oct 2018
Introduction
• Learning outcomes;
• Develop a management plan for BPH patients
• Describe the new medical therapies in BPH and discuss their place in treatment.
• 230,000 GP visits, Australia, per annum
• Autopsy data incidence;
• >50% AGE 50,
• >75% AGE 80
Pathogenesis 1
1. Stromal hyperplasia 2. Glandular hyperplasia 3. Compressed peripheral zone 4. Peri-urethral compression 5. Dynamic smooth muscle hypertonia
Pathogenesis 2
Bladder wall pressure structural dysfunction
Pathogenesis 3
1. Cell proliferation vs. Apoptosis 2. Local androgen environment 3. Pro-inflammatory growth factors 4. Testis derived growth factor 5. Genetic imprinting of prostate cells pre-puberty 6. Inheritable; Odds ratio
4x 1st degree relative / 3x Father / 8x Brother
7. DHT, intracellular conversion from T, by 5AR 8. DHT has a Potent affinity for AR
9. Increased. BCL2 gene = anti-apoptotic 10. Dormant stem cell activation
Clinical Presentations of BPH• Early minor LUTS
• Progressive bothersome LUTS / Failed medical therapy
• PV; 20-25gm / 60gm / >100gm / 200-300gm
• UTI
• Haematospermia
• Haematuria +/- Bladder cancer concomitant
• Elevated PSA / Prostate cancer
• Urinary retention
• ULTRASOUND; bladder stone, bladder diverticulum, High PVR, Middle lobe,
• Chronic prostatitis / pelvic pain syndrome
• Difficult catheterisation; ward or intra-operatively
• Neurological conditions; CVA, DM, pelvic surgery, spinal injury, spinal disc prolapse
• Detrusor Instability vs Detrusor Underactivity
• **Comorbidities & Anaesthetic Risk, Anticoagulants
Differential Diagnoses of LUTS
** DIABETES AUTONOMIC NEUROPATHY
GP Assessment• AJGP VOL. 47, NO. 7, JULY 2018
• History;
• Voiding & storage symptoms
• Urethral stricture
• Haematuria
• UTI / STI
• Prostatitis / pelvic pain
• Urinary retention
• Nocturnal polyuria (Cardiac, OSA)
• DM, Bladder cancer, Spinal dx, Pelvic surgery, Medication (diuretics)
• Focused PE;
• DRE
• Palpable bladder
• Non-circumcised / phimosis
• IDC
GP Investigations
MSU
Pvol. PVR
Bladder tumour Middle lobe
PSA - risk of BPH progression Prostate cancer
Response to 5ARI / TURP MRI / Biopsy
GP Assessment Summary
GP
History; LUTS, PMH, meds, FHx prostate Focused Physical Exam DRE
U/A MSU PSA EUC
Ultrasound
Urologist
IPSS / Bother score IIEF DRE PSA EUC MSU U/S
Urine cytology
Flow study Cystoscopy
Urodynamics MRI
Prostate Biopsy
Principles of Treatment• Based on symptom severity & bother;
• IPSS 60,
• Pvol. >30gm,
• Qmax 1.4
Alpha-blockers
• Uro-selective; Tamsulosin, Alfuzosin, Doxazosin, Terazosin
• DO NOT alter BPH progression
• ie. retention, surgery, Pvol.
• Side Effects;
• RG ejaculation, floppy iris syndrome (cataract), postural hypotension, nasal congestion
5 alpha Reductase Inhibitor
• Dutasteride (type 1&2), Finasteride (type 1)
• Alters BPH progression;
• 30% volume shrinkage
• Reduces PSA by 50%
• Reduces risk surgery and retention
• Inidcations; PSA > 1.5, Haematuria, Large prostate >40cc
• ED, loss libido, gynaecomastia, increased risk HG caP
BJUI, 2018, population based study Confrims; 5-ARI DOES increase risk GS 8-10 cancer Increases risk by 20-25% (low absolute risk 0.5%)
NO increase in prostate cancer mortality Initial 2 RCT NEJM 2003, 2010
Reasons; 1. Easier detection / Artefactual due to glandular cytoreduction
2. Detection bias, men with LUTS are more likely to have CaP investigations
If PSA rises whilst on 5ARI, need cancer investigation
Combination therapy
• Alpha blocker + 5-ARI
• GP can commence Duodart
• Better IPPS/flow outcomes vs. monotherapy alone
• PV >40cc, age >50, PSA >1.5
• Increased sexual dysfn. than monotherapy alone
n=4844 Tamsulosin 400mcgm
Dutasteride 0.5mg Combination
Combination therapy best Reduced RR; AUR, BPH surgery
Most effective PV>40gm Dutasteride-effect
Antimuscarinics & beta-3 agonists
• Urgency, frequency, nocturia
• MECHANISM; detrusor smooth muscle relaxation & increased bladder storage capacity
• Oxybutinin - Ditropan, M1,2,3 cholinergic receptor antagonist
• Solifenacin - Vesicare, M3 cholinergic receptor antagonist
• Tolterodine - Detrusitol, M2,3 cholinergic receptor antagonist (*bladder specific)
• Mirabegron - Betmiga, Beta3 adrenergic agonist, *Better tolerability
• CAUTION; High PVR >200ml, Elderly
• SIDE EFFECTS;
• dry mouth, dry eyes, constipation, confusion, drug interact. (QT)
PDE5I phosphodiesterase inhibitors
• High level evidence for Both BPH + ED
• Tadalafil 5mg, Cialis, longer t(1/2)
• Improves IPPS storage and voiding symptoms
• Mechanisms;
• increased cellular cGMP reduces smooth muscle tone - detrusor urethra prostate
• Increased NO increases blood oxygenation to LUT
Desmopressin
• Synthetic analogue ADH / vasopressin
• Reduces urine production
• Nocturnal polyuria (time/vol. chart) in elderly with Cardiac dx or OSA, can co-exist with BPH
• Reduces nocturnal voids and increases hours of undisturbed sleep
• Hyponatraemia - Na+ monitoring baseline, day 4, day 30
Phytotherapies
• NOT recommended in major guidelines
• Plant based
• Saw palmetto (Serenoa repens)
• African plum bark, (Pygeum africanum)
• Cochrane = placebo effect
• Lack consistent pharmacokinetics
Indications for Surgery
• Moderate to severe LUTS & Bother
• Failed medical therapy
• Urinary retention; recurrent
• Bladder calculi
• Recurrent UTI & High PVR
• Recurrent clots /haematuria
• Renal dysfunction
• Bladder diverticulum
Surgical Options• TURP (Bipolar vs Monopolar)
• Laser prostatectomy
• Greenlight Photoselective Vaporisation PVP 180XPS
• HoLEP holmium laser enucleation
• Diode laser vaporisation
• Thulium laser
• “Plasma button” bipolar plasma kinetic vaporisation
• BNI - Bladder neck incision
• Open enucleative prostatectomy
• MINIMALLY INVASIVE TECHNIQUES (MIT);
• TMUT - transurethral microwave therapy
• TUNA - transurethral needle ablation
• UROLIFT - Prostatic urethral lift
• REZUM - Convective water vapour energy ablation
• PAE - Prostatic artery embolisation
Surgical algorithm
Risks of surgery
• RG ejaculation, 53 - 75%
• ED, 3 - 30%
• incontinence, 2%
• urethral stricture, 2 - 9%
• BN contracture, 3%
• sepsis (MSU)
• bleeding capsular perforation
Surgical issues
• Surgeon vs. Patient preferences
• Established data
• Lasers and anticoagulant
• Aspirin and TURP is ok
• Experimental; Rezum, PAE
• Emerging; Urolift
Urodynamics
• 1990’s
• [1] Uroflow [2] Filling phase [3] Voiding phase
• Meta-analysis evidence
• “Obstructed”
• Detrusor instability / reduced compliance (CVA Parkinson’s MS)
• Underactive bladder (DM spinal cord/disc pelvic surgery)
• Mixed symptoms
• Suture-based implants, retraction of lateral lobes
• No resection or ablation
• >50yr, IPSS>12, Qmax80gm, retention>250ml
• Less RG ejac/ED than TURP
• Outcomes; IPSS 7pts, Qmax 3-4ml/s, QOL 2pts
10 studies n=450
12 month f/up
Convective water vapour + RF current (thermal) ? Reduced risk ejaculatory & ED & MIT / day procedure
Disposable consumable cost to patient $2000 Bias / Company; Rezūm System (NxThera Inc., Maple Grove, MN, USA)
US FDA clearance 2015 0.5ml water vapour injected for 9sec, overlapping zones, circumferentially
Super-selective radiological prostatic arterial embolisation / infarction No Level 1 RCT evidence
ROPE study (2014-2016) n=216 PAE, 89 TURP Claim = reduce IPSS 12 pts
Not as good as TURP Suitable; older patient, >100cc, lateral lobe adenoma, no middle lobe, unfit for GA
Outpatient day procedure Excluded; Heavily calcified internal iliac artery
Re-treatment 20% at 12 months, arterial dissection, sepsis
n=25, mean Pvol. 150gm 77-85% improvements in Qmax, IPSS, PVR
Mean operative time = 214 min. Mean hospital stay 4 days