BPH OVERVIEW / MANAGEMENT. Richard L Haddad Norwest Private Hospital 17 Oct 2018

Transcription

1 BPH OVERVIEW / MANAGEMENT Richard L Haddad Norwest Private Hospital 17 Oct 2018

2 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

3 Pathogenesis 1 1. Stromal hyperplasia 2. Glandular hyperplasia 3. Compressed peripheral zone 4. Peri-urethral compression 5. Dynamic smooth muscle hypertonia

4 Pathogenesis 2 Bladder wall pressure structural dysfunction

5 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

6 Clinical Presentations of BPH Early minor LUTS Progressive bothersome LUTS / Failed medical therapy PV; 20-25gm / 60gm / >100gm / gm 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

7 Differential Diagnoses of LUTS ** DIABETES AUTONOMIC NEUROPATHY

8 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

9 GP Investigations MSU PSA - risk of BPH progression Prostate cancer Response to 5ARI / TURP MRI / Biopsy Pvol. PVR Bladder tumour Middle lobe

10 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

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14 Principles of Treatment Based on symptom severity & bother; IPSS <7, IPSS 8-18, IPSS Treatment is NOT recommended in minor LUTS or low bother (AUA) At risk of BPH progression; Age >60, Pvol. >30gm, Qmax <12ml/s, Identifiable LUTS, PSA >1.4

15 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

16 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

17 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

18 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

19 n=4844 Tamsulosin 400mcgm Dutasteride 0.5mg Combination Combination therapy best Reduced RR; AUR, BPH surgery Most effective PV>40gm Dutasteride-effect

20 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)

21 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

22 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

23 Phytotherapies NOT recommended in major guidelines Plant based Saw palmetto (Serenoa repens) African plum bark, (Pygeum africanum) Cochrane = placebo effect Lack consistent pharmacokinetics

24 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

25 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

26 Surgical algorithm

27 Risks of surgery RG ejaculation, 53-75% ED, 3-30% incontinence, 2% urethral stricture, 2-9% BN contracture, 3% sepsis (MSU) bleeding capsular perforation

28 Surgical issues Surgeon vs. Patient preferences Established data Lasers and anticoagulant Aspirin and TURP is ok Experimental; Rezum, PAE Emerging; Urolift

29 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

30 10 studies n= month f/up Suture-based implants, retraction of lateral lobes No resection or ablation >50yr, IPSS>12, Qmax<12ml/s, Pvol.20-80gm Exclusion; median lobe, pvol.>80gm, retention>250ml Less RG ejac/ed than TURP Outcomes; IPSS 7pts, Qmax 3-4ml/s, QOL 2pts

31 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 ml water vapour injected for 9sec, overlapping zones, circumferentially <24 month clinical data 2 weeks for symptom improvement Majority need IDC 3 days and still irritation post procedure Suitability;? Unclear suitable Pvol.? median lobe Claimed benefits; IPSS & Qmax Re-treatment rate, Treatment failures? True rates DURABILITY is unknown

32 Super-selective radiological prostatic arterial embolisation / infarction No Level 1 RCT evidence ROPE study ( ) 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

33 n=25, mean Pvol. 150gm 77-85% improvements in Qmax, IPSS, PVR Mean operative time = 214 min. Mean hospital stay 4 days