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BPH / LUTS

Dr Jonny Coxon

GP

Beaconsfield Medical Practice

Brighton

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“As man draws near the common goal

Can anything be sadder

Than he who, master of his soul

Is servant to his bladder‟

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Plan of attack

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Plan of attack

• Prevalence including ‘under-reporting’

• Presentation

• What are lower urinary tract symptoms (LUTS)?

• Distinction between storage / voiding etc

• Initial assessment in primary care

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Plan of attack

• Overactive bladder

• Medical management

• Who to refer

• What happens in secondary care

• Case scenarios

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Prevalence

• Depends who you ask

• Not all male LUTS = BPH

• Not all BPH causes LUTS

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Prevalence

0

10

20

30

40

50

60

70

80

90

100

20-29 30-39 40-49 50-59 60-69 70-79 80-89

Pre

vale

nce (

%) Pradhan (1975)

Swyer (1944)

Franks (1954)

Moore (1943)

Harbitz (1972)

Holund (1980)

Baron (1941)

Fang-Liu (1991)

Karube (1961)

Age (y)

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Prevalence

It is abnormal NOT to have benign growth of the prostate with

increasing age

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Prevalence

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Prevalence

• Approximately 1/3 of men over 50 have moderate to severe lower urinary tract symptoms

• = 3.2 million men in UK

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• Huge issue = getting men to report symptoms in first place

• Some can be rather stoical: “just part of growing old”

Presentation: what do patients say?

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Presentation: 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 awful.”

• “Do you know the public toilets round here are awful…”

• “I have to plan my day around toilet breaks”

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• “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.”

Presentation: what do patients say?

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• “I’m worried about me prostrate”

• “While I’m here doc…”

• “I’m here because the wife sent me in.”

Presentation: what do patients say?

Lack of

physical

intimacy

Anger or

conflict

Avoidance

or withdrawal

A feeling of

distance or

isolation

Lack of

communication

Pro

po

rti

on

of

me

n w

ith

en

larg

ed

pro

sta

te a

nd

th

eir

sp

ou

se

s r

ep

orti

ng

sp

ec

ific

re

lati

on

sh

ip c

on

ce

rn

s Men with mild symptoms (n=216)

Men with moderate-to-severe symptoms (n=203)

Spouses of men with enlarged prostate (n=77)

Roehrborn CG et al. Prostate Cancer Prostatic Dis 2006;9:30–34.

Presentation

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Worry that patient may have cancer 71%

Worry about patient’s need for surgery 66%

Deterioration in sex life due to symptoms 66%

Social life affected by patient’s symptoms 47%

Become tired because of waking at night 42%

Sells, Donovan, Ewings & MacDonagh. BJU Int 2000, 85, 440-445

Presentation: what do partners say?

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• GPs worry about missing prostate cancer – only 11% confident in distinguishing between BPH

& Prostate Cancer

• 54% refer men before maximising medical

therapy

• GPs seek specialist advice in 1/3 of men with LUTS

Presentation: what do we say?

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• Urologists feel that approx 40% of BPH referrals could be managed in primary care

• 68% of urologists agree that interpreting PSA results is difficult for GPs

Presentation: what do we say?

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What are LUTS?

• What happened to “prostatism”?

• Or at least “BPH”?

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LUTS =

Lower Urinary Tract Symptoms

BPH =

Benign Prostatic Hyperplasia

BPE =

Benign Prostatic Enlargement

BOO =

Bladder Outlet Obstruction

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What are LUTS?

BPH

BOO

CNS Renal

Cardiac Pituitary

BPE

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LUTS: Storage symptoms

• Urgency +/- Urge Incontinence

• Frequency

• Nocturia

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LUTS: Storage symptoms

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LUTS: Voiding symptoms

• Poor flow

• Intermittency

• Hesitancy

• Straining

• Terminal dribble

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LUTS: Post-micturition

• Post micturition dribble

• Incomplete emptying

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LUTS: Assessment

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LUTS: Assessment

4 pages of interest:

• Initial assessment

• Referral

• Conservative management

• Drug treatment

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LUTS: Assessment

Consider as 2-part consultation:

• Initial Hx & Ex

• Provide info

• Tests & forms to fill in

• Review and choose management

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LUTS Assessment: History

• Storage symptoms

• Voiding symptoms

• How much bother from symptoms?

• What is the patient’s worry?

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LUTS Assessment: History

• Other elements of PMH, e.g.

– Diabetes

– Heart failure

– Kidney failure

– Liver failure

– OSA

– Oedema

– Chronic venous stasis

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LUTS Assessment: History

• Medications, eg:

– α-blockers

– Diuretics

– Ca channel blockers

– SSRIs

– Bronchodilators (anti-cholinergics)

– Antihistamines

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LUTS Assessment: History

• Medications, eg:

– Lithium

– Benzodiazepines

– NSAIDs

– Pioglitazone

– Gabapentin

– Pregabalin

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LUTS Assessment: Examination

• Abdomen

• External genitalia

• PR / DRE

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LUTS Assessment: Examination

PR / DRE:

• Is it smooth?

• Is it big?

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LUTS Assessment: Examination

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LUTS Assessment: Examination

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LUTS Assessment: Investigations

• Urine dipstick test

• Bloods:

– “Offer a serum creatinine test (+ eGFR) only if you suspect renal impairment”

– PSA?

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• 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 Assessment: PSA?

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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).”

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LUTS Assessment: Investigations

• What’s normal?

• Void: 250ml

• Fluid in: approx 1.5L / 24 hrs

• Urine out: approx 1.5L / 24 hrs

• Frequency defined as > than 8 voids/day

• Nocturia defined as > 1 void at night

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LUTS Assessment: Investigations

• Reduced volume voids with marked variation in voided volume – characteristic of OAB

• Reduced volume voids without significant variation in voided volume – ‘red flag’

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• Ask re ED

• Measure BP

• Might add to bloods:

– Lipids

– Glucose

LUTS Assessment: Not NICE

• MSAM: Multinational Survey of the Ageing Male

• N =12,815 men aged 50-80 years

0

20

40

60

80

100

Mild Moderate Severe

LUTS severity

Inc

ide

nc

e e

rec

tio

n p

rob

lem

s (

%)

Rosen R et al. Eur Urol 2003;44:637-49

LUTS & ED

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LUTS & ED

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• Interest in sex declines with worsening LUTS

• Several studies shown association of LUTS with ED & premature ejaculation

• Treatment itself can worsen or even improve sexual function

• Unclear how much association is physiological or related to sleep disturbance/anxiety

LUTS & ED

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• PDE-5 inhibitors improve both ED & LUTS in men with both conditions

• Significant improvement in IPSS scores

• (No change seen in urodynamic variables)

• May see more effective combined with α-blocker (but caution giving together)

LUTS & ED

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LUTS & Metabolic Syndrome

Gacci et al, Eur Urol 2011; 60: 809-825

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LUTS & Metabolic Syndrome

N=409, men

presenting with LUTS

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LUTS & Metabolic Syndrome

N=409, men

presenting with LUTS

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LUTS & Metabolic Syndrome

Kellogg Parsons J et al Eur Urol 2011

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LUTS & Metabolic Syndrome

St Sauver JL et al BJU Int 2010

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LUTS & Metabolic Syndrome

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LUTS & Metabolic Syndrome

• Primary Care = ideal setting for holistic management of male LUTS

• The prostate as the “gateway to men’s health”

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LUTS Management

Uncomplicated LUTS Complicated LUTS

• Gradual onset

• Impalpable bladder

• Normal external genitalia

• Benign feeling prostate

• Normal PSA

• No infection / haematuria

• Raised PSA / Abnormal DRE

• Pelvic / Urogenital pain

• UTI / Dysuria

• Palpable bladder

• Incontinence

• Haematuria

• Severe symptoms

• Bladder stones!

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LUTS Management

• If LUTS not bothersome or complicated, reassure

• Offer:

– advice on lifestyle interventions (for example, fluid intake)

– information on the condition.

• Offer review if symptoms change.

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LUTS Management

• For men with mild-moderate bothersome LUTS, discuss:

• Active surveillance:

– reassurance & lifestyle advice without immediate treatment and with regular follow-up, or

• Active intervention:

– conservative management

– drug treatment

– surgery

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LUTS Management - Conservative

• If you suspect OAB, offer:

– supervised bladder training

– advice on fluid intake

– lifestyle advice and,

– if needed, containment products.

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LUTS Management - Conservative

• If you suspect OAB, offer:

– supervised bladder training

– advice on fluid intake

– lifestyle advice and,

– if needed, containment products.

• Do not offer penile clamps

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LUTS Management - Conservative

• For men with storage LUTS (particularly urinary incontinence):

– Offer temporary containment products (e.g. pads or collecting devices) to achieve social continence until a diagnosis and management plan have been discussed

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LUTS Management - Conservative

• Voiding symptoms:

–Offer ISC before indwelling catheter if LUTS cannot be corrected by less invasive measures.

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LUTS Management - Conservative

• Explain to men with post micturition dribble how to perform urethral milking

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LUTS Management – Drug Rx

• Only if bothersome LUTS, & conservative management unsuccessful or not appropriate.

• Do not offer homeopathy, phytotherapy or acupuncture.

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LUTS Management – Drug Rx

• Overactive bladder:

–Offer an anticholinergic

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LUTS Management – Drug Rx 1. Moderate to severe LUTS:

–Offer an α-blocker • Alfuzosin, doxazosin, tamsulosin or terazosin

2. LUTS with prostate >30g , PSA >1.4, high risk of progression:

–Offer a 5-α reductase inhibitor (5-ARI) • Dutasteride, finasteride

1 and 2:

–Offer combination treatment

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• Progression =

– Deterioration in symptoms

– Acute retention

– BPH-related surgery

• Risk factors:

– Age over 70 with LUTS

– Moderate to severe symptoms that are bothersome i.e. IPSS ≥8 (QoL question over 3)

– PSA > 1.4 ng/ml, Prostate volume >30ml

LUTS Management – Drug Rx

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Adapted from Marberger MJ et al Eur Urol 2000;38:563-568.

Risk of AUR by Baseline Serum PSA in Untreated Men (Placebo Group)

% o

f m

en

wit

h A

UR

(2

ye

ars

)

Serum PSA level <1.4 ng/ml

(n=705)

Serum PSA level ≥1.4 ng/ml

(n=1394)

9-fold increase in risk (p<0.001)

0.4

3.9

5

4

3

2

1

0

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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

• BUT do not prevent progression

• S/E include: dizzy, faint, weak, bowel effects, headache (see SmPC for full list)

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LUTS Management: 5-ARIs

• Finasteride or Dutasteride (Avodart/Combodart )

• Inhibit conversion of testosterone to DHT

• ↓prostate volume

• Most effective in larger prostates

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LUTS Management: 5-ARIs

• Beneficial effects start at 9 months, fully develop over years

• ↓symptoms & ↓rate of AUR / surgery

• S/E include: fatigue, ED, loss of libido, gynaecomastia (see SmPC for full list)

–60

–50

–40

–30

–20

–10

0

10

20

0 6 12 18 24 30 36 42 48

Treatment month

Me

an

ch

an

ge

in

PS

A (

%)

Double-blind1 Open phase2

placebo

dutasteride

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.

5.5 2.2

10.7 6.8

15.0

2.8

–50.5

–35.7

–48.6 –43.5

–9.2

-52.9

–48.4

–57.2

5-ARIs reduce PSA level

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LUTS Management: Combination

• MTOPS & CombAT studies

• Most effective for controlling symptoms

• Most effective for reducing progression

• At 4 years in CombAT, combination reduced risk of AUR / surgery by 70% vs tamsulosin alone

• 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

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LUTS Management: Combination

• In CombAT, More men in the combination group (0.9%) had cardiac failure versus dutasteride (0.2%) & tamsulosin (0.6%)

• Also seen in REDUCE study

• No difference in overall cardiovascular events

• Rates of cardiac failure in all treatment groups were low compared with the placebo group of pooled Phase III BPH studies (1.3%)

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LUTS Management: 5-ARIs & PSA

REDUCE study:

• Extent of PSA decrease in the first 6 months does not predict the diagnosis of prostate cancer

• Patients should have a new PSA baseline established after 6 months

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LUTS Management: 5-ARIs & PSA

REDUCE study:

• Any confirmed increase from lowest PSA level may signal non-compliance to therapy or the presence of prostate cancer (particularly high-grade)

– should be carefully evaluated

• Treatment does not interfere with the use of PSA to assist diagnosis of prostate cancer, after a new baseline has been established

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LUTS Management – Drug Rx

Back to NICE:

• Consider adding an anticholinergic if storage symptoms after α–blocker alone for LUTS

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LUTS Management – Drug Rx 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

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LUTS: Referral

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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

– suspected urological cancer

– stress urinary incontinence.

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LUTS: Secondary Care

• Flow-rate

• Post-void residual

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LUTS: Secondary Care

• Flow-rate

• Post-void residual

• Possibly:

– Cystoscopy

– Upper tract imaging

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LUTS: Secondary Care

• Flow-rate

• Post-void residual

• Possibly:

– Cystoscopy

– Upper tract imaging

– Urodynamics (if considering surgery)

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LUTS: Surgery

Voiding:

• TURP

• TUVP

• HoLEP (laser)

• TUIP (often smaller prostates, younger men)

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LUTS: Surgery

Storage:

• Botox injections

• Cystoplasty

• Sacral nerve stimulation

Stress incontinence:

• Implantation of an artificial sphincter

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LUTS: SUMMARY

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LUTS: SUMMARY

• Common, under-reported

• Ask: what is bothering the patient?

• Strong link with ED / Metabolic Syndrome

• Holistic assessment

• Think: balls

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LUTS: SUMMARY

• Lifestyle intervention especially fluid intake

• Medical therapy according to symptoms

• Find and treat nocturnal polyuria

• Remember: a progressive condition

• Refer if not responding / atypical / complicated