Benign Prostatic Hyperplasia · –Recognize and diagnose LUTS secondary to benign prostatic...

transcript

Benign Prostatic Hyperplasia

Jay Lee, MD, FRCSC

Clinical Associate Professor

University of Calgary

by any means – graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of

Sea Courses Inc. except where permitted by law.

Sea Courses is not responsible for any speaker or participant’s statements, materials, acts or omissions.

• At the end of this program, participants will be able to:– Define terminology related to lower urinary tract

symptoms (LUTS)

– Recognize and diagnose LUTS secondary to benign prostatic hyperplasia (BPH)

– Predict progression in terms of symptoms, acute urinary retention and need for surgery

– Determine the appropriate care path for each patient

Definition of Terms

BPH – Benign Prostatic

Hyperplasia

BOO – Bladder Outlet Obstruction

LUTS – Lower Urinary Tract Symptoms

Hypertrophied detrusor muscle

Obstructed urinary flow

Natural History of BPH: Symptoms Worsen

Kirby RS et al. Benign prostatic hyperplasia. Health Press, 1995.

Remain Stable ImproveWorsen

Richard F et al., Prog Urol 2001; 11(2):250-63.

50-59 years

15%17%

60-69 years

35%33%

70-79 years

0 1-7 8-19 20-35 pointsIPSS

2,372 French menIIEF

Diabetes 20.2% 3.2%

Hypertension 32.0% 13.6%

Pelvic surgery 18.8% 2.4%

LUTS 72.2% 37.7%

Smoker 29.6% 34.6%

Regular alcohol 37.5% 42.4%

ED(n=853)

No ED(n=3581)

Braun M et al., Int J Impot Res 2000; 12:305-311

Risk Factors for BPH Progression

• Age 50 years or older

• Enlarged prostate (≥ 30 mL)

– PSA ≥ 1.4 ng/mL as a marker for prostate volume

• Moderate-to-severe urinary symptoms (AUA-SI score > 7)

McConnell JD et al. N Engl J Med. 2003;349:23872398. Roehrborn CG et al. Urology.1999;53:473480.

Clinical Outcomes in BPH vs. Other Diseases

Condition Clinical Outcome Incidence (%)*

Osteoporosis Vertebral fracture 1.5Hip fracture 18

Atherosclerosis Fatal/nonfatal MI 2.1

Superficial bladder cancer Recurrence 30–88

Kidney stones Recurrence 2–47

BPH AUR 7Surgical Intervention 10

*Annual incidence or rate per person-years

Adapted from Roehrborn CG et al. Urology 2000;56:9-18; McConnell JD et al. N Engl J Med 1998; 338:557-563.

BPH – Key Components of Diagnosis: History

General medical history– LUTS/severity/bother; hematuria, UTI, retention, incontinence– Review of nervous system (evidence of neurogenic bladder) – MS, spinal cord

injury…– DM– Family history of prostate cancer

Past surgical history– APR, spinal surgery– Urethral Surgery/instrumentation

Medications– Note use of diuretics, antihypertensives, psychotropics, anticholinergics, hormones,

some OTC cold medications– Current BPH treatment – Smoking, caffeine, EtOH intake

BPH / LUTS Symptoms Obstructive Symptoms

Hesitancy

Weak stream

Straining to pass urine

Prolonged micturition

Post-void dribbling

Sensation of incomplete bladder emptying

Acute or chronic urinary retention

Overflow incontinence

Irritative Symptoms

Frequency

Urgency

Nocturia

Urge incontinence

Dysuria

Hematuria

*Now: Storage and voiding

BPH – Key Components of Diagnosis: Focused Physical Exam

Digital rectal examination (DRE)

– Assess prostate size, consistency, symmetry, presence of nodules or indurations

– Size does not predict severity of symptoms or obstruction

– Check for suprapubic fullness (i.e., retention)

– Neurologic Exam

BPH – Key Components of Diagnosis

– Urinalysis• Abnormalities could suggest other problems – hematuria, UTI,

proteinuria

– Discuss PSA measurement if:• Age > 50, life expectancy > 10 years (diagnosis of prostate cancer

would change management)

• Family history of prostate cancer (age 40)

• African American (age 40)

*** Serum creatinine • High creatinine necessitates imaging of upper tract

A Word On PSA

• DO NOT DO PSA IF:

– ACUTE RETENTION

– INFECTION

– LIFE EXPECTANCY < 10 YEARS

BPH - Complications

• If untreated, can progress to serious complications including:

– Acute Urinary Retention (AUR)– Bladder decompensation– Upper urinary tract compromise – obstructive

uropathy & renal failure– Recurrent UTI– Bleeding– Stones– Bladder diverticuli– Decreased quality of life

Anderson JB et al. Eur Urol 2001;39:390-399.

Treatment Options - Overview

• Watchful Waiting

• Lifestyle Modifications – ↓hs fluids, limit alcohol/caffeine, timing of diuretic use…

• Medical Therapy - -blockers, 5--reductase inhibitors….

• Surgery – TURP, minimally invasive strategies

- Blockers

Alpha Blockers: General• Established Mechanism of Action

– Blockade of sympathetic activity

– Relaxation of prostatic and bladder-neck smooth muscle

• Effects– Have rapid onset of action and are well tolerated– Improve urinary flow and reduce LUTS

• Flow rates ↑ by ~ 25%• Sx Scores ↓ by 20-40% (4-6 points)

– Do not affect prostate enlargement or PSA

*** Little effect on disease progression wrt rate of AUR/surgery

Adapted from Kirby RS. Eur Urol 1999;36(suppl 1):48-53.

Common -Blocker Side Effects

• Orthostatic hypotension

• Dizziness (central versus vascular phenomenon)

• Nasal Congestion

• Fatigue

• Head-ache

• GI Upset

• RETROGRADE EJACULATION

1A Blockers – Long-acting, Subtype Selective

• Tamsulosin (Flomax CR) - 0.4 mg – 0.8mg/day

• Alfuzosin (Xatral) – 10mg po qd

• Silodosin (Rapaflo) – 8 mg po qd

– Exhibits greater uro-selectivity

• Selective antagonist of 1A-receptor subtype

• Subtype makes up ~70% of all 1-receptors in the prostate

– Once daily dosing

– No antihypertensive properties therefore no dose adjustments are necessary

5--Reductase

Inhibitors

dutasteride

finasteride

Prostate Size Reduced

DHTTestosterone

5-α Reductase Inhibitors (5ARI’s)

Steers WD. Urology. 2001;58(suppl 6A):17–24.Bartsch G et al. Eur Urol. 2000;37:367380.

5-AR = 5-alpha reductase; DHT = dihydrotestosterone

Type I 5AR

Type II 5AR

5--Reductase Inhibitors

Mechanism of action

– Regulates conversion of Tt to DHT

– ↓ Prostatic levels of DHT by 80-90%

– Slows rate of prostate enlargement

Effects (may take 6-9mo)

– Decreases prostate volume by ~ 20%

– Reduces the risk of AUR and the need for BPH-related surgery

– not appropriate for men with LUTS who do not have prostatic enlargement

*** Will lower PSA by 50% over 12 months

Indications for 5- Reductase Inhibitors

• Monotherapy or Combination therapy with

-blocker

• Large prostate - men with larger prostates

(> 40 g) respond more favorably(Response can be predicted by PSA - poor response if < 1.3 ng/ml)

• Hematuria 2° BPH

5ARI Efficacy: Summary• Data from robust randomized placebo-controlled studies has

confirmed that both dutasteride and finasteride have a significant

effect in men with enlarged prostates:

✓ Reducing symptoms (30% from baseline) and impact of BPH

✓ Reducing prostate size (20-30%)

✓ Improving urinary stream (1-2 ml/sec)

✓ Reducing risk of urinary retention and surgery (>50%)

• Improvements are generally seen after ~6 months or more and

continue to build beyond 2 years of therapy

McConnell JD et al. N Engl J Med 1998;338:557–63 Roehrborn CG et al. Urology 2002; 60: 434-441

PSA Testing in Patients on Medical Therapy for LUTS/BPH

• α-blocker therapy has no effect on PSA

• 5α-Reductase Inhibitors lower PSA by 40-50% in 6 months

– Critical to have baseline PSA

• Refer for biopsy if elevated

– Repeat PSA after 6 months treatment

• If does not fall, indicates non-compliance or cancer risk

– Double PSA value to determine cancer risk

– Progressively rising PSA on treatment is indication for referral and

biopsy

Combination TherapyModerate-Severe Symptoms and Enlarged Prostate

✓Rapid onset✓ Improvements in

symptoms and stream

✓Further improvement in symptoms and stream

✓Long-lasting symptom benefit

✓Prevent disease progression

✓Reduce risk of AUR and surgery

-blocker Combination 5-ARI

COMBINATION THERAPY

McConnell JD, et al. N Engl J Med 2003;349:2387-98.

Combination therapy is better than monotherapy at reducing risk of clinical progression

Roehrborn CG, et al. Eur Urol. 2010 Jan;57(1):123-31.

Combination therapy is better than monotherapy at improving symptoms

What to do with the α-Blocker?

• With combination therapy, removal of the α-blocker after 6-9 months of therapy is reasonable1,4

• Majority of men will continue to enjoy good symptom control2,3,4

• More severe baseline symptoms may require that the α-blocker be continued longer-term2

1) Nickel CJ et al. Can J Urol; 2005;12(3);2677-2683 2) J Barkin et al. European Urology (2003): 44; 461-466. 3) Baldwin KC et al: Urology 58(2), 2001 3) Nickel et al. CUAJ 2008;2(1):16-21.

• Tadalafil 5mg currently indicated for men with BPH-related LUTS

• Recent clinical studies investigating PDE5-inhibitors in BPH

McVary KT, et al. J Urol. 2007 Apr;177(4):1401-7.

WeeksEfficacy of Tadalafil

WeeksM

Tadalafil 20 mg

Efficacy of Vardenafil

Efficacy of Sildenafil

PLA Run InWeek - 4

BaselineWeek 0 Week 4 Week 8 Week 12

tal IP

Placebo

Tad 2.5

Tad 5.0

Tad 10.0

Tad 20

Tadalafil Dosing For BPH

Compared to placebo (Ancova analysis)

* Tadalafil 2.5mg p<.05 at week 4, and Tadalafil 5, 10, and 20 mg p<.01 for Weeks 4, 8, and 12 compared to placebo

Clinical meaningfulimprovement

*P < .05 versus placebo-7

Baseline Week 4 Week 8 Week 12

Placebo

Tadalafil

Tamsulosin

Study LVID

Tadalafil vs Placebo and Tamusolsin vs Placebo

• Some plant extracts have shown some efficacy in small clinical trials

• Serenoa repens (saw palmetto berry extract)

• Pygeum africanum (African plum)

Bent S, et al. N Engl J Med 2006;354:557-66.

No statistically significant difference between treatment with saw palmetto and placebo

Absolute Indications for Surgery

• Refractory retention

• Renal failure – obstructive uropathy

• Recurrent infections

• Recurrent Bleeding

• Stones

BPH - When to Refer

• Referral warranted in patients with:

– IPSS > 20 (severe)

– Urinary retention

– Recurrent UTI

– Hematuria

– Bladder stones

– Renal insufficiency

– Failure of medical treatment

– Abnormal DRE or Elevated PSA

Key Messages

• BPH is very common in men

• BPH is progressive

• Multiple medications are available for treatment

• Some men will require intervention past medical therapy

Benign Prostatic Hyperplasia · –Recognize and diagnose LUTS secondary to benign prostatic...

Documents