BPH / LUTS Dr Jonny Coxon MA MD MRCS MRCGP DRCOG Beaconsfield Medical Practice, Brighton As man draws near the common goal Can anything be sadder Than he who, master of his soul Is servant to his bladder Plan of attack Prevalence including under-reporting Presentation What are lower urinary tract symptoms (LUTS)? Distinction between storage / voiding etc LUTS 1 LUTS 2 LUTS 3 Plan of attack Prevalence of BPH Prevalence Initial assessment in primary care Medical management Who to refer What happens in secondary care It is abnormal NOT to have benign growth of the prostate with increasing age LUTS 4 LUTS 5 LUTS 6 Prevalence Prevalence Prevalence 2007 US study: enlarged prostate = 4th most common diagnosis in men over 50. TZ PZ Approximately 1/3 of men over 50 have moderate to severe LUTS i.e. ~ 3 million men in UK LUTS 7 LUTS 8 LUTS 9 1
Reporting specific relationship concerns 14/07/2015 what do patients say? Huge issue = men reporting symptoms at all Some can be rather stoical: just part of growing old what do patients say? I don t understand it doc, I keep feeling like I need a pee, but hardly any comes out. My sleeping s getting terrible. You know, the public toilets round here are awful I have to plan my day around toilet breaks what do patients say? I might be fine for ages then suddenly, whoosh, I ve got to go. I keep having to make excuses in meetings. I can t make it round the golf course these days. LUTS 10 LUTS 11 LUTS 12 what do patients say? I m worried about me prostrate Presentation Men with mild symptoms (n=216) Men with moderate-to-severe symptoms (n=203) what do patients say? I m worried about me prostrate Spouses of men with enlarged prostate (n=77) While I m here doc While I m here doc I m here because the wife sent me in. Lack of physical intimacy Anger or conflict Avoidance or withdrawal A feeling of Lack of distance or communication isolation LUTS 13 Roehrborn CG et al. Prostate Cancer Prostatic Dis 2006;9:30 34. LUTS 15 what do we say? GPs worry about missing prostate cancer only 11% confident distinguishing between BPH & PCa ~ ½ refer before maximising medical therapy GPs seek specialist advice in 1/3 men with LUTS what do we say? Urologists feel ~40% of BPH referrals could be managed in primary care ~ 2/3 of urologists agree that interpreting PSA is difficult for GPs What are LUTS? What happened to prostatism? Or at least BPH? LUTS 16 LUTS 17 LUTS 18 2
BPH = Benign Prostatic Hyperplasia BOO = Bladder Outlet Obstruction BPE = Benign Prostatic Enlargement LUTS = Lower Urinary Tract Symptoms Renal BOO What are LUTS? BPH CNS BPE LUTS: Storage symptoms Urgency +/- Urge Incontinence Frequency Nocturia (Nocturnal enuresis) (OAB) Pituitary Cardiac LUTS 19 LUTS 20 LUTS 21 LUTS: Voiding symptoms Poor flow Intermittency Hesitancy Straining Terminal dribble 1) Post micturition dribble 2) Incomplete emptying LUTS: Post-micturition LUTS: Assessment June 2015 LUTS 22 LUTS 23 LUTS 24 LUTS: Assessment 4 pages of interest: Initial assessment Referral Conservative management Drug treatment LUTS: Assessment Consider as minimum 2-part consultation: Part 1 Initial Hx & Ex Provide info Tests & forms to fill in Part 2 Review & discuss management LUTS Assessment: History Storage symptoms Voiding symptoms How much bother from symptoms? What is the patient s worry? LUTS 25 LUTS 26 LUTS 27 3
LUTS Assessment: History Other elements of PMH, e.g. Diabetes Heart failure Kidney failure Liver failure OSA Oedema, chronic venous stasis Neurological conditions LUTS Assessment: History Medications, e.g.: α-blockers Diuretics Ca channel blockers SSRIs Bronchodilators (anti-cholinergics) Antihistamines LUTS Assessment: History Medications, e.g.: Lithium Benzodiazepines NSAIDs Pioglitazone Gabapentin Pregabalin LUTS 28 LUTS 29 LUTS 30 LUTS Assessment: Examination Abdomen LUTS Assessment: Examination PR / DRE: LUTS Assessment: Examination External genitalia PR / DRE Is it smooth? Is it big? LUTS 31 LUTS 32 LUTS 33 LUTS Assessment: Examination LUTS Assessment: Investigations Urine dipstick test Bloods: Offer a serum creatinine test only if you suspect renal impairment PSA? LUTS Assessment: PSA? Offer men information, advice and time to decide if they wish to have PSA testing if: LUTS are suggestive of bladder outlet obstruction secondary to BPE or their prostate feels abnormal on DRE or they are concerned about prostate cancer LUTS 34 LUTS 35 LUTS 36 4
Incidence, % 14/07/2015 LUTS Assessment: Investigations Ask men with bothersome LUTS to complete a urinary frequency volume chart. Offer men considering treatment an assessment of baseline symptoms with a validated symptom score (e.g. IPSS). LUTS Assessment: Investigations What s normal? Void: ~250ml Fluid in: ~1.5-2L / 24 hrs Urine out: ~1.5-2L / 24 hrs 30ml/kg / 24hrs Frequency: > 8 voids/ 24hrs Nocturia: as > 1 void at night (Nocturnal polyuria: >⅓ volume at night) LUTS 37 LUTS 38 LUTS 39 LUTS Assessment: Investigations Small volume voids with variation in voided volume characteristic of OAB Small volume voids without significant variation in voided volume: LUTS 40 LUTS 41 LUTS 42 LUTS Assessment: Not NICE LUTS & Erectile Dysfunction LUTS & ED Ask re ED Measure BP Might add to bloods: Lipids Glucose 70 No, I cannot get an erection 64 Net reduction in stiffness 60 53 53 50 45 43 40 33 30 25 19 20 17 12 12 10 7 5 6 2 2 0 LUTS Severity LUTS Severity 52 50 44 45 41 31 20 16 LUTS Severity Interest in sex declines with worsening LUTS Many studies shown association of LUTS with ED Prostate disease 2nd only to DM as ED risk factor: more than PVD, hyperlipidaemia, HT, depression, IHD. Age 50 59 years Age 60 69 years Age 70 79 years LUTS 43 LUTS 45 Rosen et al. Eur Urol 2003;44(6):637-49. 5
LUTS & ED Treatment itself can worsen or even improve sexual function Unclear how much association is physiological, or related to sleep disturbance/anxiety LUTS & Metabolic Syndrome Link with Metabolic Syndrome LUTS 46 Gacci et al, Eur Urol 2011; 60: 809-825 LUTS 47 LUTS 48 N=409, men presenting with moderate/severe LUTS Lee et al BJUI 2012; 110:540-5 Link with Metabolic Syndrome LUTS & Metabolic Syndrome LUTS & Metabolic Syndrome LUTS 49 N=409, men presenting with moderate/severe LUTS Lee et al BJUI 2012; 110:540-5 Kellogg Parsons J et al Eur Urol 2011 LUTS 50 St Sauver JL et al BJU Int 2010 LUTS 51 LUTS & Metabolic Syndrome LUTS & Metabolic Syndrome LUTS Management Primary Care = ideal setting for holistic management of male LUTS The prostate as the gateway to men s health Uncomplicated LUTS Gradual onset Impalpable bladder Normal external genitalia Benign feeling prostate Normal PSA No infection / haematuria Complicated LUTS Raised PSA / Abnormal DRE Pelvic / Urogenital pain UTI / Dysuria Palpable bladder Incontinence Haematuria Severe symptoms Bladder stones! LUTS 52 LUTS 53 LUTS 54 6
LUTS Management If LUTS not bothersome or complicated, reassure Cancer worry: Actually for majority of cases, NO strong link between LUTS & onset of prostate cancer LUTS Management Think possible causes (PMH/Meds) Offer: advice on lifestyle interventions (e.g. fluid intake, caffeine, time of diuretics) information on the condition LUTS 55 LUTS 56 LUTS 57 LUTS Management For men with mild-moderate bothersome LUTS, discuss: Active surveillance: reassurance & lifestyle advice without immediate treatment, or Active intervention: conservative management drug treatment surgery LUTS Management - Conservative If you suspect OAB, offer: supervised bladder training lifestyle advice, fluid intake if needed, containment products. LUTS Management - Conservative If you suspect OAB, offer: supervised bladder training lifestyle advice, fluid intake if needed, containment products. Do not offer penile clamps LUTS 58 LUTS 59 LUTS 60 LUTS Management - Conservative For men with storage LUTS (particularly urge incontinence): Offer temporary containment products (e.g. pads or collecting devices) Achieve social continence until diagnosis & management plan discussed LUTS Management - Conservative Explain to men with post-micturition dribble how to perform urethral milking: Often only if bothersome LUTS, & conservative management unsuccessful or not appropriate. Do not offer homeopathy, phytotherapy or acupuncture. LUTS 61 LUTS 62 LUTS 63 7
% of men with AUR (2years) 14/07/2015 Overactive bladder: Offer an anticholinergic Overactive bladder: mirabegron (Betmiga), 50mg od β3-adrenoceptor agonist Newly licensed 2013 for OAB NICE: only if anticholinergic is ineffective, contraindicated or not tolerated 1. Moderate to severe LUTS (not OAB predominant): Offer an α-blocker 2. LUTS with PSA >1.4, prostate >30g: - high risk of progression: Offer a 5-α reductase inhibitor (5-ARI) 1 and 2: Offer combination treatment LUTS 64 LUTS 65 LUTS 66 Progression = Worsening symptoms Acute retention BPH-related surgery Risk factors: Age over 70 Moderate to severe symptoms that are bothersome PSA > 1.4 ng/ml, Prostate volume >30ml Risk of AUR by Baseline Serum PSA in Untreated Men (Placebo Group) 5 4 3 2 1 0 9-fold increase in risk (p<0.001) 0.4 Serum PSA level <1.4 ng/ml (n=705) 3.9 Serum PSA level 1.4 ng/ml (n=1394) LUTS Management: α-blockers Reduce tone of bladder neck / prostate Ideal first line in primary care for mixed LUTS Rapid onset 4-6 weeks No effect on PSA level or prostate size LUTS 67 Adapted from Marberger MJ et al Eur Urol 2000;38:563-568. LUTS 68 LUTS 69 LUTS Management: α-blockers BUT do not prevent progression S/E include: dizzy, faint, weak, bowel effects, headache, ejaculatory dysfunction LUTS Management: 5-ARIs Inhibit conversion of T to DHT prostate volume Most effective in larger prostates LUTS Management: 5-ARIs Beneficial effects start at 6-9 months, fully develop over years symptoms & rate of AUR / surgery S/E include: fatigue, ED, libido, gynaecomastia LUTS 70 LUTS 71 LUTS 72 8
Mean change in PSA (%) 14/07/2015 5-ARIs reduce PSA level Double-blind 1 Open phase 2 20 15.0 5.5 10.7 10 2.8 6.8 2.2 0 10 9.2 20 30 40 35.7 50 43.5 48.6 60 50.5-52.9 48.4 57.2 LUTS Management: 5-ARIs & PSA Any confirmed increase from lowest PSA level may signal non-compliance to therapy, or prostate cancer (particularly high-grade) should be carefully evaluated Can still use PSA to help risk assessment of PCa, after a new baseline established LUTS Management: Combination 0 6 12 18 24 30 36 42 48 placebo dutasteride Treatment month LUTS 74 LUTS 75 1. Adapted from Roehrborn CG et al. Urology 2002; 60: 434-441. 2. Adapted from Debruyne F et al. Eur Urol 2004; 46: 488-495. LUTS Management: Combination Studies show combination Rx: Most effective for controlling symptoms Most effective for reducing progression e.g. At 4 years, combination vs tamsulosin alone reduced risk of AUR / surgery by 70% 7.7% actual risk reduction (NNT=13) Roehrborn CG et al. J Urol 2008;179:616 21; Siami P et al. Contemp Clin Trials 2007;28:770 9 McConnell JD et al. NEJM 2003;349:2387 98 LUTS 76 LUTS 77 LUTS 78 2012: Cialis (tadalafil) 5 mg od: Licensed for treating the signs & symptoms of BPH SLS restrictions amended, so can prescribe for condition other than ED Tadalafil for LUTS: IPSS scores do improve May be more effective combined with α-blocker (caution) NICE 2015: Do not offer solely for LUTS, unless part of a trial LUTS 79 LUTS 80 LUTS 81 9
IPSS: Tadalafil vs placebo & Tamsulosin vs placebo Male LUTS EAU Guidelines 2015 (without indications for surgery) Bothersome - symptoms? + - - Prostate volume >40 ml? Storage symptoms predominant? + - Nocturnal polyuria predominant? + + with or without α 1-blocker/PDE5-I - Long-term treatment? Residual storage symptoms + * Please note that tamsulosin is an active control. This study was powered for direct comparisons between tadalafil and placebo and between tamsulosin and placebo. Watchful waiting with or without Add muscarinic receptor antagonist + continue with with or without 5-ARI ± α 1-blocker/ PDE5-I with or without Anti cholinergic with or without Vasopressin Analogue Oelke et al. Eur Urol 2012;61: 917-925 Back to NICE: Consider adding an anticholinergic if storage symptoms after α blocker alone for LUTS LOW risk of retention Back to NICE: Nocturnal polyuria (>1/3 urine at night) Consider late-afternoon loop diuretic Consider oral desmopressin, if other medical causes have been excluded Gratzke C et al. Eur Urol 2015;67:1099-1109 LUTS 86 LUTS 87 LUTS: Referral Bothersome LUTS not responded to conservative & drug management LUTS complicated by: recurrent or persistent UTI retention (acute / chronic) renal impairment thought due to LUT dysfunction stress urinary incontinence Flow-rate Post-void residual LUTS: Secondary Care Flow-rate Post-void residual LUTS: Secondary Care Possibly: Cystoscopy Upper tract imaging LUTS 88 LUTS 89 LUTS 90 10
Flow-rate Post-void residual LUTS: Secondary Care Possibly: Cystoscopy Upper tract imaging Urodynamics (if considering surgery) Voiding: TURP TUVP HoLEP (laser) LUTS: Surgery TUIP (often smaller prostates, younger men) Urolift for some LUTS: Surgery Storage: Botox injections Sacral / tibial nerve stimulation Cystoplasty LUTS 91 LUTS 92 LUTS 93 LUTS: Surgery Stress incontinence: Implantation of an artificial sphincter LUTS: SUMMARY Common, under-reported Ask: what is bothering the patient? Strong link with ED / Metabolic Syndrome Holistic assessment Think: balls LUTS: SUMMARY Lifestyle intervention especially fluid intake Medical therapy according to symptoms Find & treat nocturnal polyuria Remember: a progressive condition Refer if not responding / atypical / complicated LUTS 94 LUTS 95 LUTS 96 11