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