mens urological health cme bph-luts- final- nov 13 2013

1

BPH-LUTS HOME

1

CLINICAL PRACTICE Q&A A CME PROGRAM FOR MEN’S UROLOGICAL HEALTH

BENIGN PROSTATIC HYPERPLASIA- LOWER URINARY TRACT SYMPTOMS

2

BPH-LUTS HOME

2

STEERING COMMITTEE

Lydia Hatcher, MD, CCFP, FCFP Clinical Associate, Professor of Family Medicine, Memorial University of Newfoundland

Jay Lee, MD, FRCSC Clinical Assistant Professor, Division of Urology, Department of Surgery, University of Calgary

Ghalib Ahmed, MD, CCFP General Family Practitioner, Associate Clinical Professor, Department of Family Practice, University of Alberta

Stacy Elliott, MD Director, BC Center for Sexual Medicine, Sexual Medicine Consultant, Men’s Health Initiative, Vancouver Coastal Health Clinical Professor, Departments of Psychiatry and Urologic Sciences, University of British Columbia

Serge Carrier, MD, FRCSC Associate Professor, Division of Urology, Department of Surgery, McGill University

Murray Awde, MD, CCFP, FCFP Clinical Professor of Family Medicine, University of Western Ontario

Anthony Bella, MD, FRCSC Greta and John Hansen Chair in Men's Health Research, Assistant Professor of Urology, Department of Surgery, Associate Scientist, Neuroscience, University of Ottawa

Gerald Brock, MD, FRCSC Professor of Surgery, Urology Program Director, University of Western Ontario Chair Office of Education, Canadian Urology Association

3

BPH-LUTS HOME

3

STEERING COMMITTEE DISCLOSURES

Ghalib Ahmed, MD, CCFP • Grants/Research Support: AstraZeneca, Bristol-Myers Squibb,

Pfizer, Servier, Sunovion • Speaker’s Bureau/Honoraria: Abbott, AstraZeneca, Eli Lilly,

Lundbeck, Merck, Pfizer, Shire • Consulting Fees: Abbott, AstraZeneca, Bayer, Boehringer

Ingelheim, Bristol-Myers Squibb, Eli Lilly, Lundbeck, Merck, Pfizer

Murray Awde, MD, CCFP, FCFP • Grants/Research Support: Astellas, Bristol-Myers Squibb,

Boehringer Ingelheim, Merck, Novartis, Otsuka, Purdue Pharmaceuticals • Speaker’s Bureau/Honoraria: Abbott, AstraZeneca, Bayer, LEO,

Takeda, Nycomed • Consulting Fees: Boehringer Ingelheim, Bristol-Myers Squibb,

Eli Lilly, Merck, Novartis, Novo Nordisk, Pfizer

Anthony Bella, MD, FRCSC • Grants/Research Support: Acorda Therapeutics, Canadian

Foundation for Innovation, Canadian Male Sexual Health Council, Northeastern Section American Urological Association • Speaker’s Bureau/Honoraria: Abbott, American Medical Systems,

Bayer, Coloplast, Eli Lilly, Pfizer

Gerald Brock, MD, FRCSC • Grants/Research Support: American Medical Systems, Eli Lilly,

GlaxoSmithKline, Pfizer • Speaker’s Bureau/Honoraria: American Medical Systems, Bayer,

Coloplast, Eli Lilly, GlaxoSmithKline, Pfizer • Consulting Fees: Bayer, Eli Lilly, GlaxoSmithKline, Pfizer

Serge Carrier, MD, FRCSC • Grants/Research Support: Bayer, Eli Lilly, Pfizer • Speaker’s Bureau/Honoraria: Abbott, Bayer, Eli Lilly, Pfizer

Stacy Elliott, MD • Speaker’s Bureau/Honoraria: Abbott, Bayer, Eli Lilly, Pfizer • Consulting Fees: Abbott, Bayer, Eli Lilly, Pfizer

Lydia Hatcher, MD, CCFP, FCFP • Grants/Research Support: Servier • Speaker’s Bureau/Honoraria: AstraZeneca, Boehringer Ingelheim,

Eli Lilly, Janssen-Ortho, Merck, Nycomed, Pfizer, Purdue Pharmaceuticals, Takeda, Valeant • Consulting Fees: AstraZeneca

Jay Lee MD, FRCSC • Speaker’s Bureau/Honoraria: Abbott, Bayer, Eli Lilly,

GlaxoSmithKline, Pfizer

4

HOME

4

SPEAKER DISCLOSURES

• Faculty: [Speaker’s name]

• Grants/Research Support:

• Speaker’s Bureau/Honoraria:

• Consulting Fees:

• Other:

5

HOME

5

DISCLOSURE OF COMMERCIAL SUPPORT

• This program has received financial support from Eli Lilly Canada Inc in the form of an educational grant

• This program has received in-kind support from Eli Lilly Canada Inc in the form of logistical support.

• Potential for conflict(s) of interest: • [Speaker/Faculty name] has received funding Eli Lilly Canada Inc.

• Eli Lilly markets tadalafil, a product that will be discussed in this program.

6

HOME

6

MITIGATING POTENTIAL BIAS

• All content in this presentation has been developed, reviewed and approved by the Steering Committee

• All the recommendations involving clinical medicine are based on evidence from well-designed clinical trials published in peer-reviewed journals

7

BPH-LUTS HOME

7

BPH-LUTS

• The goal of this module is to address common questions in the area of BPH-LUTS

• Benign prostatic hyperplasia is the histological pattern of the prostate, characterized by proliferation of smooth muscle and epithelial cells within the prostatic transition zone. This may lead to prostatic enlargement.

• Lower urinary tract symptoms refer to storage and/or voiding disturbances.

• BPH-LUTS refers to bothersome lower urinary tract symptoms linked to the prostate

BPH: benign prostatic hyperplasia; LUTS: lower urinary tract symptoms. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS; 2. Abrams et al. J Urol. 2009; 181:1779-87.

8

BPH-LUTS HOME

8


How should I evaluate a patient with BPH-LUTS?

1 Is there evidence of a relationship between

BPH-LUTS and ED? 2

How do I decide which agent to prescribe for

BPH-LUTS? 3 When should I refer a

patient to a urologist? 4

How should I follow-up with a BPH-LUTS patient? 5

9

BPH-LUTS HOME

9

BPH-LUTS HOME

How should I evaluate a patient with BPH-LUTS? 1


10

BPH-LUTS HOME BPH-LUTS HOME

10

LEARNING OBJECTIVES

• After completing this question participants will be able to:

• Identify diagnostic assessments for BPH-LUTS and integrate these into clinical practice

• Evaluate the utility of PSA testing and recognize the CUA’s position on testing

• Distinguish the signs and symptoms of OAB from BPH-LUTS

CUA: Canadian Urological Association; OAB: overactive bladder; PSA: prostate-specific antigen.

11


11 HOW SHOULD I EVALUATE A PATIENT WITH BPH-LUTS?

• Medical history • Directed physical exam • Urinalysis • PSA testing • Symptom assessment

PSA: prostate-specific antigen.

12


12

MEDICAL HISTORY

• Medical history should assess:1,2

• Nature and duration of symptoms

• Fluid intake – amount and types of fluid

• Comorbid conditions

• Prior and current illness

• Prior surgery and trauma

• Current medications

Do you routinely ask about sexual function when evaluating a

patient for LUTS?

1. Nickel et al. CUAJ. 2010;4:310-6; 2. Abrams et al. J Urol. 2009;181:1779-87.

13


13

BPH-LUTS AND ED

• BPH-LUTS and ED are common comorbid conditions

0

10

20

30

40

50

60

70

80

90

100

No symptoms Mild Moderate Severe

% o

f P

ati

en

ts w

ith

Ere

cti

le P

rob

lem

s

Severity of LUTS

50-59 yrs (n=5,786)

60-69 yrs (n=4,191)

70-79 yrs (n=2,828)

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

14


14

DIRECTED PHYSICAL EXAM

• Physical examination for patients with BPH-LUTS:1,2

• MANDATORY EVALUATION – DIGITAL RECTAL EXAM

• Evaluate prostate for size, consistency, shape and abnormalities suggestive of prostate cancer (such as nodules or asymmetry)

• Assess suprapubic area to rule out bladder distention

• Evaluate overall motor and sensory function of the perineum and lower limbs especially with a history of stroke or neurologic disease

1. Nickel et al. CUAJ. 2010;4:310-6; 2. Abrams et al. J Urol. 2009;181:1779-87.

15


15

URINALYSIS

• Dipstick urinalysis should be performed in all BPH-LUTS patients to rule out other diagnoses that may cause LUTS:

UTI: urinary tract infection. 1. Abrams et al. J Urol. 2009;181:1779-87.

Abnormal/borderline urinalysis results should be repeated and/or followed with a urine culture1

Urinalysis Result Possible Diagnosis

• Hematuria • Kidney stones • Bladder cancer

• Pyuria or presence of nitrates

• UTI • Urethral stricture

• Proteinuria • Underlying renal disease

• Glucosuria • Diabetes

16


16

PSA TESTING

Do you currently recommend PSA testing for your patients

with BPH-LUTS?

PSA: prostate-specific antigen.

17


17

WHY PSA TESTING?

DRE: digital rectal exam; PSA: prostate-specific antigen. 1. Roehrborn et al. Urology. 1999;53:581-9.

Adapted from Roehrborn et al. Urology. 1999;53:581-9.

60

50

40

30 1 2 3 4 5 6 7

Serum PSA ng/mL-1

Pro

stat

e V

olu

me

(m

l)

50

55

60

65

70

75

PSA can Help Predict Prostate Size

18


18 PSA CAN IDENTIFY PATIENTS WITH HIGHER RISK

OF RETENTION OR SURGICAL INTERVENTION

PSA: prostate-specific antigen. 1. Roehrborn et al. Urology. 1999;53:473-80.

Need for BPH-related surgery Acute urinary retention

Baseline PSA Thresholds

Fou

r Ye

ar In

cid

en

ce (

%)

>0 >1 >2 >3 >4 >5 >6 >7

2

6

10

14

18

20

24

26

>8

19


19 CUA RECOMMENDATIONS FOR PSA TESTING

• The CUA position on PSA as a screening test for prostate cancer DIFFERS from the USPSTF1

• CUA recommends PSA testing be offered to all men ≥50 years of age with a life expectancy of ≥10 years.

• Canadian guidelines for the management of BPH-LUTS suggest PSA testing for:2

• Patients who have at least a 10 year life expectancy, and for whom the presence of prostate cancer would change management

• Patients for whom PSA measurement may change the management of their voiding symptoms (estimate for prostate volume)

CUA: Canadian Urological Association; PSA: prostate-specific antigen; USPSTF: United States Preventive Services Task Force. 1. CUA position statement on PSA testing. November 2011; 2. Nickel et al. CUAJ. 2010;4:310-6.

20


20

SYMPTOM ASSESSMENT

• Assess the severity of symptoms and degree of bother1

• Evaluate response to treatment

• Validated symptom assessment tools are available: • International Prostate Symptom Score (IPSS)

• American Urological Association (AUA) symptom score

• Lower urinary tract symptoms classified as:2

• Storage symptoms

• Voiding symptoms

• Post-micturition symptoms

1. Nickel et al. CUAJ. 2010;4:310-6; 2. Abrams et al. Urology. 2003;61:37-49.

Click here for more info on IPSS

21


21

STORAGE (IRRITATIVE) SYMPTOMS

1. Abrams et al. Urology. 2003;61:37-49.

• Frequency • Nocturia • Urgency • Urinary incontinence • Stress incontinence • Urge incontinence

What are the characteristic storage symptoms? Q

22


22

VOIDING (OBSTRUCTIVE) SYMPTOMS


• Slow stream • Splitting or spraying • Intermittent stream • Hesitancy • Straining • Terminal dribble

What are the characteristic voiding symptoms? Q

23


23

POST-MICTURITION SYMPTOMS


• Feeling of incomplete emptying • Post-micturition dribble

What are the characteristic post-micturition symptoms? Q

24


24

SYMPTOM BOTHER

Mild Symptoms Moderate – Severe Symptoms

No Significant Bother Moderate – Severe Bother

LUTS Presentation

IPSS: International Prostate Symptom Score. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Barry et al. J Urol. 1992;148:1549-57.

IPSS Quality of Life Assessment2

“If you were to spend the rest of your life with your urinary condition as is, how would you feel about it?”

25


25

OPTIONAL ASSESSMENTS

• Optional assessments for BPH-LUTS include: • Post-void residual

• Sexual function questionnaire (i.e. SHIM)2

• Serum creatinine

• Urine cytology

• Uroflow

• Voiding diary

SHIM: Sexual Health Inventory for Men. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Rosen et al. Int J Imp Res. 1999;11:319-26.

Click here for more info on SHIM

26


26 OTHER ASSESSMENTS (NOT RECOMMENDED)

• Other assessments can be considered, however these are not recommended for BPH-LUTS: • Cystoscopy

• Cytology

• Urodynamics

• Radiological evaluation of upper urinary tract (CT/MRI)

• Prostate ultrasound

• Prostate biopsy

CT: computed tomography; MRI: magnetic resonance imaging. 1. Nickel et al. CUAJ. 2010;4:310-6.

27


27

OAB: overactive bladder.

DISTINGUISHING BPH-LUTS FROM OAB

Typically distinguished by: • Voiding symptoms • Failure of standard BPH-LUTS therapy to

resolve symptoms

How do you distinguish between BPH-LUTS and OAB? Q

28


28

BPH-LUTS VS. OAB

OAB: overactive bladder. 1. Clemens et al. J Urol. 2007;178:1354-8.

BPH-LUTS OAB

• Prostate-mediated bladder voiding obstruction symptoms

• Frequency, nocturia, urgency

• Intermittent stream, straining

• Weak urinary stream

• Sense of incomplete emptying

• BPH-LUTS medications fail to resolve storage symptoms

• Urgency (+/- urge incontinence)

• Frequency, nocturia

29


29 PERSISTENT STORAGE SYMPTOMS MAY BE A SIGN OF OTHER PROBLEMS

WARNING Persistent storage symptoms

may be related to other conditions

• Higher risk in smokers and patients with microscopic hematuria

• Storage symptoms secondary to neurologic disease may be more difficult to treat

30


30

TAKE HOME MESSAGES

• Evaluation of BPH-LUTS includes: • Medical history (including comorbid conditions)

• BPH-LUTS and ED are common comorbid conditions

• Physical exam (with DRE)

• Urinalysis

• PSA testing

• Sensitive marker for prostate volume

• Recommended in patients with BPH-LUTS and a life-expectancy >10 years

• Symptom bother assessment

• OAB is characterized by storage symptoms which persist upon treatment of BPH-LUTS

DRE: digital rectal exam; ED: erectile dysfunction; OAB: overactive bladder; PSA: prostate-specific antigen. 1. Nickel et al. CUAJ. 2010;4:310-6.

31

BPH-LUTS HOME

31

BPH-LUTS HOME

Is there evidence of a relationship between

BPH-LUTS and ED? 2


32


32

LEARNING OBJECTIVES


• Recognize the link between BPH-LUTS and ED and its implications for treatment

• Assess recent data for PDE5 inhibitors in BPH-LUTS and integrate this new indication into clinical practice

PDE: phosphodiesterase.

33


33 IS THERE EVIDENCE OF A RELATIONSHIP BETWEEN BPH-LUTS AND ED?

• Epidemiological • Pathophysiological

34


34 EPIDEMIOLOGICAL LINK BETWEEN BPH-LUTS & ED

• Erection problems strongly associated with LUTS (p<0.001)1

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

0102030405060708090

100

Nosymptoms

Mild Moderate Severe

% o

f P

atie

nts

wit

h

Ere

ctio

n P

rob

lem

s

Severity of LUTS

50-59 yrs (n=5,786)60-69 yrs (n=4,191)70-79 yrs (n=2,828)

35


35

• Original thinking was that BPH-LUTS was the result of: • Physical obstruction by the prostate

• Contraction of the bladder neck

CAUSE OF BPH-LUTS

Mechanisms now implicated in BPH-LUTS:1

• Altered smooth muscle relaxation or contractility • Reduced blood flow • Reduced function of nerves and endothelium

1. Gacci et al. Eur Urol. 2011;60:809-25.

36


36 LOCALIZATION OF PDE5: IMPLICATIONS FOR BPH-LUTS

• PDE5 enzyme blocks NO mediated smooth muscle relaxation

• The PDE5 enzyme is found in tissues of the:1

• Penis

• Bladder

• Prostate

• Urethra

NO: nitric oxide; PDE5: phosphodiesterase 5. 1. Fibbi et al. J Sex Med. 2010;7:59-69.

PDE5

BPH-LUTS HOME

37

BPH-LUTS HOME

37 SMOOTH MUSCLE CONTRACTION: IMPLICATIONS FOR BPH-LUTS

• PDE5 inhibitor increases:1

• NO, causing smooth muscle relaxation

• Blood flow to the pelvis and penis

cGMP: cyclic guanosine monophosphate: GMP: guanosine monophosphate; NO: nitric oxide; PDE5: phosphodiesterase 5; PDE5i: phosphodiesterase 5 inhibitor. 1. Wang. Curr Opin Urol. 2010;20:49-54.

Smooth muscle contraction

Smooth muscle relaxation

cGMP

cGMP

GMP PDE5

PDE5i

BPH-LUTS HOME

38

BPH-LUTS HOME

38 ALL PDE5 INHIBITORS HAVE BEEN SHOWN TO IMPROVE BPH-LUTS

*Not indicated for the treatment of BPH-LUTS. PDE5: phosphodiesterase 5. 1. McVary et al. J Urol. 2007;177:1071-7; 2. Stief et al. Eur Urol. 2008;53:1236-44.; 3. McVary et al. J Urol. 2007;177:1401-7.

-7

-6

-5

-4

-3

-2

-1

0

0 8

VardenafilPlacebo

Weeks

Mea

n C

han

ge

in S

ymp

tom

Sco

re

Vardenafil2* Weeks

-7

-6

-5

-4

-3

-2

-1

0

0 12

PlaceboSildenafilM

ean

Ch

ange

in

Sym

pto

m S

core

Sildenafil1*

4 6

-10

-8

-6

-4

-2

0

0 6 12

PlaceboTadalafil 5 mg

Mea

n C

han

ge

in S

ymp

tom

Sco

re

Tadalafil 20 mg

Weeks Tadalafil3

BPH-LUTS HOME

39

BPH-LUTS HOME

39

Study Description Length Effect on LUTS

McVary et al, 2007

•369 men with LUTS and ED •Daily sildenafil* vs. placebo

12 weeks • Significant ↓ IPSS • Significant ↑ QoL •↔ Qmax and Qav

Tuncel et al, 2010

•60 men with BPH-LUTS • Sildenafil* (4 days/week) or

tamsulosin or combination 8 weeks

• Improved urinary symptoms with tamsulosin/combination •↑ erectile function with sildenafil/combination

McVary et al, 2007

•281 men with BPH-LUTS •Tadalafil once daily

12 weeks • Significant ↓ IPSS at 6 and 12 weeks •↔ Qmax and Qav

Roehrborn et al, 2008

•886 men with BPH-LUTS •Daily tadalafil

12 weeks • Significant improvement in urinary symptoms

Stief et al, 2008

•222 men with BPH-LUTS •Vardenafil* twice daily

8 weeks • Significant improvement in irritative/obstructive

symptoms and general QoL

Gacci et al, 2011

•60 men with persistent irritative urinary symptoms •Vardenafil* + tamsulosin vs.

tamsulosin

12 weeks • Significant reduction of irritative symptoms with

combined therapy

PDE5 INHIBITORS FOR BPH-LUTS

*Not indicated for the treatment of BPH-LUTS. IPSS: International Prostate Symptom Score; Qav: average flow rate; Qmax: maximum flow rate; QoL: quality of life; PDE5: phosphodiesterase 5. 1. Gacci et al. Eur Urol. 2011;60:809-25.

No change in urinary flow rate with PDE5 inhibitors

BPH-LUTS HOME

40

BPH-LUTS HOME

40 REASONS FOR LACK OF LUTS IMPROVEMENT WITH PDE5I FOR ED

• Treatment of BPH-LUTS with PDE5 inhibitors requires daily dosing

• Many patients use PDE5 inhibitors on-demand for ED

• Short-acting PDE5 inhibitors (sildenafil/vardenafil) require TID dosing to

reach appropriate plasma levels

• Only long-acting PDE5 inhibitors are clinically relevant for BPH-LUTS

In the past, why have patients not reported improvements in LUTS when

they have used a PDE5 inhibitor for ED? Q

PDE5: phosphodiesterase 5; PDE5i: phosphodiesterase 5 inhibitor; TID: three-times daily.

BPH-LUTS HOME

41

BPH-LUTS HOME

41 TADALAFIL 5 MG BUT NOT 2.5 MG IS EFFECTIVE FOR THE TREATMENT OF BPH-LUTS

-9

-8

-7

-6

-5

-4

-3

-2

-1

0

PLA Run InWeek - 4

BaselineWeek 0 Week 4 Week 8 Week 12

Me

an C

han

ge in

To

tal I

PSS

Sco

re

fro

m B

ase

line

to

En

dp

oin

t

Placebo

TAD 2.5 mg

TAD 5.0 mg

TAD 10.0 mg

TAD 20.0 mg

Tadalafil 2.5 mg p<0.05 at week 4 Tadalafil 5, 10, and 20 mg p<0.01 for weeks 4, 8, and 12 compared to placebo

Clinically meaningful improvement

IPSS: International Prostate Symptom Score; PLA: placebo; TAD: tadalafil. 1. Roehrborn et al. J Urol. 2008;180:1228-34.

BPH-LUTS HOME

42

BPH-LUTS HOME

42

EFFICACY OF PDE5I’S FOR BPH-LUTS

IPSS: International Prostate Symptom Score; LS: least squares; PDE5I: phosphodiesterase 5 inhibitor. 1. Oelke et al. Eur Urol. 2012;61:917-25.

-7

-6

-5

-4

-3

-2

-1

0

0 2 4 6 8 10 12

LS M

ean

Ch

ange

fro

m B

ase

line

in

IPSS

To

tal S

core

Duration of Treatment (weeks)

Placebo

Tadalafil

Tamsulosin

43


43

TADALAFIL FOR BPH

• On June 28, 2012 Health Canada approved tadalafil for the treatment of:1

• The signs and symptoms of benign prostatic hyperplasia (BPH)

• Erectile dysfunction (ED) and the signs and symptoms of BPH

1. Cialis Product Monograph. Eli Lilly Canada Inc.

44


44

TAKE HOME MESSAGES

• BPH-LUTS and ED often occur together

• Pathophysiological link between BPH-LUTS and ED • Suggests a role for the NO/cGMP pathway (which regulates smooth muscle

relaxation)

• PDE5 inhibitors improve smooth muscle relaxation and are an effective treatment for both ED and BPH-LUTS

• Once daily tadalafil is approved in Canada for the treatment of BPH-LUTS

cGMP: cyclic guanosine monophosphate: NO: nitric oxide; PDE5: phosphodiesterase 5.

45

BPH-LUTS HOME

45

BPH-LUTS HOME

BENIGN PROSTATIC HYPERPLASIA-LOWER URINARY TRACT SYMPTOMS

3 How do I decide which agent to prescribe for BPH-LUTS?

46


46

LEARNING OBJECTIVES


• Evaluate factors that influence treatment decisions for BPH-LUTS

• Assess the pharmacological treatment options for BPH-LUTS, including a recently approved PDE5 inhibitor

PDE5: phosphodiesterase 5.

47


47 HOW DO I DECIDE WHICH AGENT TO PRESCRIBE FOR BPH-LUTS?

• Symptom severity • Bother • Prostate size

Other factors: • Side effects • Tolerability

48


48

CUA TREATMENT ALGORITHM

5-ARI: 5-alpha reductase inhibitor; PSA: prostate-specific antigen. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Barkin J. Can J Urol. 2011;18 Suppl:14-9; 3. Roehrborn et al. Urology. 1999;53:581-9.

Alpha-Blocker or

5-ARI or

Combination Therapy or

Surgical Options

Mild Symptoms Moderate – Severe Symptoms

Small Prostate Large Prostate

No Significant Bother Moderate – Severe Bother

Watchful Waiting or

5-ARI

Small Prostate Large Prostate Small Prostate Large Prostate

Watchful Waiting Watchful Waiting or

5-ARI

Alpha-Blocker or

Surgical Options

LUTS Presentation

Watchful Waiting

Click on the underlined “criteria” for a specific focus on that algorithm stage

Large prostate is considered to be >30 g

(correlates to a PSA of ≥1.5 ng/mL)2,3

49


49

ALPHA-BLOCKERS

• Selective antagonist of α1-adrenoceptors located in:

• Prostate

• Prostatic capsule

• Bladder base

• Bladder neck

• Prostatic urethra

• Help relax smooth muscle in the bladder neck and prostate; allow urine to flow more freely

• Selective and non-selective alpha-blockers exist • Non-selective alpha-blockers are not commonly used for BPH-LUTS

1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS.

50


50

ALPHA-BLOCKER OPTIONS

• First-line options include:1,2 • Selective:

• Alfuzosin

• Tamsulosin

• Silodosin

• Equal clinical effectiveness for LUTS secondary to BPH

• Do not alter the natural progression of the disease

• Choice of agent should depend on comorbidities, side effect profile and tolerance

1. Nickel et al. CUAJ. 2010;4:310-6; 2. Rapaflo Product Monograph. Watson Laboratories Inc.

• Non-selective: • Doxazosin • Terazosin

51


51

5-ALPHA REDUCTASE INHIBITORS

• Indicated as first-line therapy for men with enlarged prostates: 1,2 • Finasteride inhibits 5α-reductase Type 2 (prostate)

• Dutasteride inhibits 5α-reductase Type 1 AND 2 (liver, skin and prostate)

• Blocks the conversion of testosterone to DHT (responsible for prostate growth)

• Treatment with 5-ARIs reduce:1

• Prostate size

• PSA

• Long-term risk of acute urinary retention

• Need for surgery

5-ARIs: 5-alpha reductase inhibitors; DHT: dihydrotestosterone; PSA: prostate-specific antigen. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS; 2. Nickel et al. CUAJ. 2010;4:310-6.

52


52

5-ARIs AND PROSTATE CANCER

• Proposed explanations for the increased incidence of high-grade tumours in 5-ARI arm over placebo:3

• 5-ARIs shrink prostate volume: ↑ likelihood of detecting high-grade disease

• 5-ARIs reduce BPH: ↑ sensitivity of PSA and DRE in detecting disease

5-ARIs: 5-alpha reductase inhibitors; DRE: digital rectal exam; mGs: modified Gleason score; PCPT: Prostate Cancer Prevention Trial; PSA: prostate-specific antigen; REDUCE: Reduction by dutasteride of prostate cancer. 1. Thompson et al. NEJM. 2003;349:215-24; 2. Andriole et al. NEJM. 2010;362:1192-202; 3. Hamilton et al. BMC Med. 2011;9:105.

0

5

10

15

20

25

30

Overall mGs 5-6 mGs 7-10 mGs 8-10Inci

de

nce

of

Pro

stat

e C

ance

r (%

)

DutasteridePlacebo

REDUCE2

0

5

10

15

20

25

30

Overall mGs 5-6 mGs 7-10 mGs 8-10Inci

de

nce

of

Pro

stat

e C

ance

r (%

)

Finasteride

Placebo

PCPT1

53


53

COMBINATION THERAPY

• Combined alpha-blocker and 5-ARI therapy is effective for LUTS associated with prostatic enlargement

• Improves symptom score and peak urinary flow greater than either monotherapy option

• Delays symptomatic disease progression

• Decreased risk of urinary retention and/or prostate surgery

5-ARI: 5-alpha reductase inhibitor. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS; 2. Nickel et al. CUAJ. 2010;4:310-6.

54


54 NEW THERAPEUTIC OPTION: PDE5 INHIBITOR

Smooth muscle contraction

Smooth muscle relaxation

cGMP

cGMP

GMP PDE5

PDE5i

• PDE5 inhibitors* promote smooth muscle relaxation to:1

• Improve LUTS

• Improve quality of life

• Effective in men with or without ED2

Click here for data on PDE5i’s

*Tadalafil is the only PDE5 inhibitor approved for BPH-LUTS (approved in Canada June 2012). cGMP: cyclic guanosine monophosphate; GMP: guanosine monophosphate; PDE5: phosphodiesterase 5; PDE5i: phosphodiesterase 5 inhibitor. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS; 2. Broderick et al. Urology. 2010;75:1452-8.

55


55 WHEN SHOULD PDE5 INHIBITORS BE CONSIDERED?

Where would you place PDE5 inhibitors in your

BPH-LUTS armamentarium?

PDE5: phosphodiesterase 5.

56


56 PHYTOTHERAPEUTIC AGENTS FOR BPH-LUTS

• Phytotherapies for BPH-LUTS:1

• Serenoa repens (saw palmetto berry extract)

• Pygeum africanum (African plum)

1. Nickel et al. CUAJ. 2010;4:310-6.

Do you recommend phytotherapy to your patients

for BPH-LUTS treatment?

57


57 NO SIGNIFICANT IMPROVEMENT OF BPH-LUTS WITH SAW PALMETTO

• Treatment with saw palmetto resulted in no significant improvement in symptoms or objective measures of BPH2

1. Nickel et al. CUAJ. 2010;4:310-6; 2. Bent et al. NEJM. 2006; 354:557-66.

CUA guidelines do not recommend phytotherapy for standard care of BPH-LUTS1

Click here for data on Saw Palmetto

58


58

BPH-LUTS MEDICATIONS SIDE EFFECTS

1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS; 2. Cialis Product Monograph. Eli Lilly Canada Inc.

Click on drug class for complete

listing of side effects

What are the most common side effects with BPH-LUTS medications? Q

How do you educate patients to manage side effects?

Alpha-blockers:1 • Retrograde ejaculation • Erectile dysfunction • Asthenia • Dizziness • Orthostatic hypotension • Nasal congestion

5α-reductase inhibitors:1 • Reduced libido • Erectile dysfunction • Decreased ejaculate

volume • Breast tenderness

PDE5 inhibitors:2 • Headache • Facial flushing • Dyspepsia

59


59

CASE SCENARIOS

5-ARI: 5-alpha reductase inhibitor; PDE5i: phosphodiesterase 5 inhibitor; PSA: prostate-specific antigen.

Which therapy would you prescribe to a patient with moderate-severe BPH-LUTS? Q

Case Description Recommendation

Moderate-severe bother (PSA 1.3 ng/mL) α-blocker

What if he also had...

Diabetes?

Hypertension?

ED?

Signs of prostatic enlargement (PSA >1.5 ng/mL)?

Signs of prostatic enlargement (PSA >1.5 ng/mL) and ED?

Bothersome sexual side effects with α-blocker or 5-ARI?

α-blocker

α-blocker

α-blocker or PDE5i

5-ARI

5-ARI and/or PDE5i

PDE5i

60


60 TAKE HOME MESSAGES:

TREATMENT OPTIONS FOR PATIENTS WITH LUTS

• Alpha-blockers are a first-line option for men with symptomatic bother who desire treatment

• 5ARI’s are an effective option for symptomatic patients with demonstrable prostatic enlargement

• Combination alpha-blocker and 5-ARI therapy improves symptom score and peak urinary flow vs. monotherapy; appropriate for patients with LUTS associated with prostatic enlargement

• A PDE5 inhibitor can be used once-daily in men with moderate to severe symptoms and bother, to effectively reduce symptoms of BPH-LUTS while maintaining sexual function

• Phytotherapy is not recommended by the CUA

5-ARI: 5-alpha reductase inhibitor; PDE5: phosphodiesterase 5.

61

BPH-LUTS HOME

61

BPH-LUTS HOME


4 When should I refer a patient to a urologist?

62


62

LEARNING OBJECTIVES


• Recognize when referral to a specialist is appropriate for an efficient shared-care approach

• Assess indications for surgery and be aware of surgical options for patients with BPH-LUTS

63


63 WHEN SHOULD I REFER A PATIENT TO A UROLOGIST?

DRE: direct rectal exam; PSA: prostate-specific antigen. 1. Nickel JC. Can Urol Assoc J. 2010;4:127-8.

Considerations: • To rule out prostate cancer (abnormal

PSA level and/or abnormal DRE) • Hematuria • Unresponsive to therapy • Patient preference • Surgical management

64


64 WHAT IS CONSIDERED AN ABNORMAL PSA VALUE?

• Rapid change in PSA over 1 year1

• 0.75 ng/mL/year when PSA is 4-10 ng/mL

• High PSA value for age1,2

• 4.0 ng/mL was originally used to differentiate normal PSA level from pathologic elevation

• Age-specific references have been used to improve sensitivity

PSA: prostate-specific antigen. 1. Izawa et al. 2011. Can Urol Assoc J. 2011;5:235-40; 2. Oesterling et al. JAMA. 1993;270:860-4; 3. Moul et al. J Urol 2007;177:499-503.

Parameter3

Age Group

40-49 50-59 60-69 70-79

Serum PSA Concentration (ng/mL)

0-2.5 0-3.5 0-4.5 0-6.5

65


65

BPH-LUTS ON THE RISE

• Approximately 40% of Canadian men >50 years of age are thought to have moderate-severe LUTS1

• Require an approach involving both the primary care practitioner and a urologist for efficient management1,2

• Urologist confirms the diagnosis, rules out prostate cancer, initiates therapy (either watchful waiting, medical or surgical); transfers patient back to primary care practitioner

• Primary care practitioner follows LUTS; monitors for progression or complications, monitor PSA (and DRE) if indicated; refer back to urologist, as necessary

DRE: direct rectal exam; PSA: prostate-specific antigen. 1. Rawson NS and Saad F. Can Urol Assoc J. 2010;4:123-7; 2. Nickel. Can Urol Assoc J. 2010;4:127-8.

66


66

PROSTATE OBSTRUCTION

67


67

PATIENT SELECTION

1. Nickel et al. CUAJ. 2010;4:310-6; 2. Novara et al. European Urology Supplements. 2006;5:418-29.

• Renal insufficiency • LUTS complications • Patient requests surgical treatment • Medication is ineffective • Medication side effects are intolerable

When is surgery indicated for BPH-LUTS? Q

68


68

SURGICAL OPTIONS

*Not insured in Canada. TUMT: transurethral microwave therapy; TUNA: transurethral needle ablation; TURP: transurethral resection of the prostate. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS.

Click on the underlined

“procedures” for more specific

information

What are the surgical options for BPH-LUTS? Q

Prostate Size

Very Large (Volume ≥ 80-100 g)1

Large (Volume 30-80 g)1

Smaller (Volume <30 g)1

Open prostatectomy Laser prostatectomy

• Holmium • Green light

TURP Laser prostatectomy

• Holmium • Green light

TURP Minimally Invasive

• TUMT* • TUNA*

69


69

RISKS OF SURGERY

• Excessive bleeding requiring blood transfusion

• TUR syndrome

• Permanent sexual side effects: • Retrograde ejaculation

• Erectile dysfunction (less common)

• Urinary tract infections

• Urinary incontinence

• Need for retreatment: • Prostate regrowth

• Bladder/urethral strictures

TUR: transurethral resection. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS.

70


70 TAKE HOME MESSAGES: REFERRAL AND SURGERY

• Consider referral to a specialist: • To rule out prostate cancer (abnormal PSA/DRE)

• If presence of hematuria

• If patient is unresponsive to therapy

• For surgical management

• If patient indicates a preference for referral

• Surgery should be considered in patients with LUTS complications or where medication is ineffective/intolerable

• Patients can be managed in a shared-care approach • Majority of patients with BPH-LUTS will never require a urologist

DRE: direct rectal exam; PSA: prostate-specific antigen. 1. Nickel JC. Can Urol Assoc J. 2010;4:127-8.

71

BPH-LUTS HOME

71

BPH-LUTS HOME

5 How should I follow-up with a BPH-LUTS patient?


72


72

LEARNING OBJECTIVES


• Assess time-to-symptom improvement for each pharmacological option and establish a follow-up strategy

• Evaluate options for non-responders

73


73 HOW SHOULD I FOLLOW-UP WITH A BPH-LUTS PATIENT?

1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS.

• Symptom assessment 4-12 weeks following diagnosis

• Subsequent follow-up should occur at 6 months and then annually

74


74

ASSESS TREATMENT RESPONSE

• The time required to observe improvement of symptoms varies depending upon the class of medication

*Silodosin shows statistically significant symptom improvement after 3-4 days. PDE5: phosphodiesterase 5. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS; 2. Rapaflo Product Monograph. Watson Laboratory Inc; 3. Proscar Product Monograph. Merck Canada Inc; 4. Porst et al. Eur Urol. 2011;60:1105-13.

Drug Class Time for Symptom Improvement

α-blockers • 2-4 weeks to develop fully • Hours to days for statistically significant

difference over placebo*1,2

5α-reductase inhibitors • At least 6 months1,3

PDE5 inhibitors • 4 weeks to reach statistically significant

symptom improvement4

75


75

NON-RESPONSE TO TREATMENT

Consider: • Optimizing current treatment regimen:

• Increase dose • Switch agent • Add agent

• Re-evaluate diagnosis (consider OAB) • Refer to urologist

OAB: overactive bladder.

What should be done if symptoms have not improved? Q

76


76

TAKE HOME MESSAGES

• Follow-up 4-12 weeks following diagnosis

• Follow-up should include symptom assessment

• Optimize treatment regimen or re-evaluate diagnosis if symptoms have not improved: • Increase dose

• Switch agent

• Add agent

1. Nickel et al. CUAJ. 2010;4:310-6; 2. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS.

77

BPH-LUTS HOME

77

BPH-LUTS HOME

BENIGN PROSTATIC HYPERPLASIA-LOWER URINARY TRACT SYMPTOMS

Supplementary Slides

78


78

SYMPTOM SEVERITY MEASURE

• International Prostate Symptom Score (IPSS) • Assessed based on reported frequency of 7 symptoms and impact on quality of life

• Patients rate questions on a scale of 0-5

• 0 = not at all

• 5 = almost always

• Sum of answers determines the severity of symptoms

1. Barry et al. J Urol. 1992;148:1549-57.

Mild: 1-7 Moderate: 8-19 Severe: 20-35

Next

79


79

IPSS ASSESSMENT

*Rated on a scale of 0-6, with 0 being delighted and 6 being terrible. IPSS: International Prostate Symptom Score. 1. Barry et al. J Urol. 1992;148:1549-57.

Return to Slide 18

Symptom Question

1. Incomplete emptying: How often have you had the sensation of not emptying your bladder?

2. Frequency: How often have you had to urinate less than every 2 hours?

3. Intermittency: How often have you found you stopped and started again several times when you urinate?

4. Urgency: How often have you found it difficult to postpone urination?

5. Weak stream: How often have you had a weak urinary stream?

6. Straining: How often have you had to strain to start urinating?

7. Nocturia: How many times did you typically get up at night to urinate?

8. Quality of life:* If you were to spend the rest of your life with your urinary condition as is, how would you feel about it?

80


80

SEXUAL HEALTH INVENTORY FOR MEN

• Used to assess the severity of ED in sexually active men • Shortened validated version of the IIEF

IIEF: International Index of Erectile Function. 1. Rosen et al. Int J Imp Res. 1999;11:319-26.

Over the Past 6 months:

1. How do you rate your confidence that you could get and keep an erection?

2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration?

3. During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner?

4. During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse?

5. When you attempted sexual intercourse, how often was it satisfactory to you?

Return to Slide 23

81


81

MILD SYMPTOMS

LUTS Presentation

Mild Symptoms

Watchful Waiting or

5-ARI

Large Prostate Small Prostate

Watchful Waiting

5-ARI: 5-alpha reductase inhibitor. 1. Nickel et al. CUAJ. 2010;4:310-6.

Return to Slide 48

82


82 MODERATE-SEVERE SYMPTOMS: NO BOTHER

Moderate – Severe Symptoms

No Significant Bother


Watchful Waiting Watchful Waiting or

5-ARI

LUTS Presentation


Return to Slide 48

83


83 MODERATE-SEVERE SYMPTOMS: MODERATE-SEVERE BOTHER

Alpha-Blocker or

5-ARI or

Combination Therapy or

Surgical Options

Moderate – Severe Symptoms

Moderate – Severe Bother


Alpha-Blocker or

Surgical Options

LUTS Presentation


Return to Slide 48

84


84 ALL PDE5 INHIBITORS HAVE BEEN SHOWN TO IMPROVE BPH-LUTS

*Not indicated for the treatment of BPH-LUTS. PDE5: phosphodiesterase 5. 1. McVary et al. J Urol. 2007;177:1071-7; 2. Stief et al. Eur Urol. 2008;53:1236-44.; 3. McVary et al. J Urol. 2007;177:1401-7.

-7

-6

-5

-4

-3

-2

-1

0

0 8

VardenafilPlacebo

Weeks

Mea

n C

han

ge

in S

ymp

tom

Sco

re

Vardenafil2* Weeks

-7

-6

-5

-4

-3

-2

-1

0

0 12

PlaceboSildenafilM

ean

Ch

ange

in

Sym

pto

m S

core

Sildenafil1*

4 6

-10

-8

-6

-4

-2

0

0 6 12

PlaceboTadalafil 5 mg

Mea

n C

han

ge

in S

ymp

tom

Sco

re

Tadalafil 20 mg

Weeks Tadalafil3

Next

BPH-LUTS HOME

85

BPH-LUTS HOME

85

Study Description Length Effect on LUTS

McVary et al, 2007

•369 men with LUTS and ED •Daily sildenafil* vs. placebo

12 weeks • Significant ↓ IPSS • Significant ↑ QoL •↔ Qmax and Qav

Tuncel et al, 2010

•60 men with BPH-LUTS • Sildenafil* (4 days/week) or

tamsulosin or combination 8 weeks

• Improved urinary symptoms with tamsulosin/combination •↑ erectile function with sildenafil/combination

McVary et al, 2007

•281 men with BPH-LUTS •Tadalafil once daily

12 weeks • Significant ↓ IPSS at 6 and 12 weeks •↔ Qmax and Qav

Roehrborn et al, 2008

•886 men with BPH-LUTS •Daily tadalafil

12 weeks • Significant improvement in urinary symptoms

Stief et al, 2008

•222 men with BPH-LUTS •Vardenafil* twice daily

8 weeks • Significant improvement in irritative/obstructive

symptoms and general QoL

Gacci et al, 2011

•60 men with persistent irritative urinary symptoms •Vardenafil* + tamsulosin vs.

tamsulosin

12 weeks • Significant reduction of irritative symptoms with

combined therapy

PDE5 INHIBITORS FOR BPH-LUTS

*Not indicated for the treatment of BPH-LUTS. IPSS: International Prostate Symptom Score; Qav: average flow rate; Qmax: maximum flow rate; QoL: quality of life; PDE5: phosphodiesterase 5. 1. Gacci et al. Eur Urol. 2011;60:809-25.

No change in urinary flow rate with PDE5 inhibitors Next

BPH-LUTS HOME

86

BPH-LUTS HOME

86 REASONS FOR LACK OF LUTS IMPROVEMENT WITH PDE5I FOR ED

• Treatment of BPH-LUTS with PDE5 inhibitors requires daily dosing

• Many patients use PDE5 inhibitors on-demand for ED

• Short-acting PDE5 inhibitors (sildenafil/vardenafil) require TID dosing to

reach appropriate plasma levels

• Only long-acting PDE5 inhibitors are clinically relevant for BPH-LUTS

In the past, why have patients not reported improvements in LUTS when they have

used a PDE5 inhibitor for ED? Q

PDE5: phosphodiesterase 5; PDE5i: phosphodiesterase 5 inhibitor; TID: three-times daily.

Next

BPH-LUTS HOME

87

BPH-LUTS HOME

87 TADALAFIL 5 MG BUT NOT 2.5 MG IS EFFECTIVE FOR THE TREATMENT OF BPH-LUTS

-9

-8

-7

-6

-5

-4

-3

-2

-1

0

PLA Run InWeek - 4

BaselineWeek 0 Week 4 Week 8 Week 12

Me

an C

han

ge in

To

tal I

PSS

Sco

re

fro

m B

ase

line

to

En

dp

oin

t

Placebo

TAD 2.5 mg

TAD 5.0 mg

TAD 10.0 mg

TAD 20.0 mg

Tadalafil 2.5 mg p<0.05 at week 4 Tadalafil 5, 10, and 20 mg p<0.01 for weeks 4, 8, and 12 compared to placebo

Clinically meaningful improvement

IPSS: International Prostate Symptom Score; PLA: placebo; TAD: tadalafil. 1. Roehrborn et al. J Urol. 2008;180:1228-34.

Next

BPH-LUTS HOME

88

BPH-LUTS HOME

88

EFFICACY OF PDE5I’S FOR BPH-LUTS

IPSS: International Prostate Symptom Score; LS: least squares; PDE5I: phosphodiesterase 5 inhibitor. 1. Oelke et al. Eur Urol. 2012;61:917-25.

-7

-6

-5

-4

-3

-2

-1

0

0 2 4 6 8 10 12

LS M

ean

Ch

ange

fro

m B

ase

line

in

IPSS

To

tal S

core

Duration of Treatment (weeks)

Placebo

Tadalafil

Tamsulosin

Return to Slide 52

89


89 SAW PALMETTO DOES NOT IMPROVE BPH-LUTS

• No significant differences were observed in symptom improvement between saw palmetto and placebo

Return to Slide 55

Changes in Primary and Secondary Outcome Measures

Measure Saw Palmetto

(n=112) Placebo (n=113)

Difference between Groups (95% CI)

mean (±SE) change

Primary outcomes

AUASI score -0.68±0.35 -0.72±0.35 0.04 (-0.93 to 1.01)

Peak urinary flow rate (ml/sec) 0.42±0.34 -0.01±0.34 0.43 (-0.52 to 1.38)

AUASI: American Urological Association Symptom Index; CI: confidence interval. 1. Bent et al. NEJM. 2006;354:557-66.

90


90

α-Blocker Side-effect Profile

Alfuzosin1 Dizziness and headache, low incidence of postural symptoms, potential for syncope, priaprism and atrial fibrillation

Doxazosin2

Dizziness/light-headedness, hypotension/syncope, drowsiness, fatigue (tiredness), swelling of the feet, shortness of breath, painful erection, ejaculation disorders (e.g. retrograde ejaculation)

Tamsulosin3

Dizziness, headache, palpitations, hypotension, rhinitis, diarrhea, nausea and vomiting, constipation, asthenia, itching and hives (urticaria), abnormal/retrograde ejaculation, fainting, priaprism

Terazosin4

Dizziness/faintness (as a result of blood pressure drop), back pain, constipation, diarrhea, drowsiness or sleepiness, dry mouth, flatulence, headache, impotence, indigestion, decreased libido, nasal congestion, nausea, urinary frequency, weakness or weight gain

Silodosin5 Retrograde ejaculation, dizziness, diarrhea, light-headedness upon standing or sitting up abruptly, headache, nasopharyngitis and nasal congestion

ALPHA-BLOCKER SIDE EFFECTS

5-ARIs: 5-alpha reductase inhibitors. 1. Xatral Product Monograph. Sanofi-Aventis Canada Inc; 2. Cardura Product Monograph. Pfizer Canada Inc; 3. Flomax Product Monograph. Boehringer Ingelheim (Canada) Ltd; 4. Hytrin Product Monograph. Abbott Laboratories; 5. Rapaflo Product Monograph. Watson Laboratories Inc.

5-ARIs Return to Slide 56

91


91

5-ARI Side-effect Profile

Finasteride1

• Impotence/inability to have an erection that continues after stopping the medication

• Decreased libido • Problems with ejaculation, such as a decrease in the amount of semen released

during sex • Male infertility and/or poor quality of semen • Breast tenderness or swelling • Testicular pain • Depression

Dutasteride2

• Impotence • Decreased libido • Breast disorders (including breast enlargement and tenderness) • Ejaculation disorders • Dizziness • Hair loss • Abnormal hair growth

5-ARI SIDE EFFECTS

5-ARI: 5-alpha reductase inhibitor; PDE5i: phosphodiesterase 5 inhibitor. 1. Proscar Product Monograph. Merck Canada Inc; 2. Avodart Product Monograph. GlaxoSmithKline Inc.

PDE5i’s Return to Slide 56

92


92

PDE5 INHIBITOR SIDE EFFECTS

PDE5i: phosphodiesterase 5 inhibitor. 1. Viagra Product Monograph. Pfizer Canada Inc; 2. Cialis Product Monograph. Eli Lilly Canada Inc; 3. Staxyn Product Monograph. Bayer Inc.

PDE5i Side-effect Profile

Sildenafil1

• Headache • Facial flushing • Dyspepsia • Nasal congestion • Abnormal vision colour tinge

Tadalafil2

• Headache • Dyspepsia • Back pain • Myalgia • Nasal congestion

Vardenafil3

• Headache • Flushing • Rhinitis • Dyspepsia • Sinusitis Return to

Slide 56

93


93 TRANSURETHRAL RESECTION OF THE PROSTATE

• Electric current can be monopolar or bipolar

• Similar safety and efficacy profiles1

• Bipolar TURP thought to be advantageous2

• Use of isotonic irrigating fluid eliminates need for grounding pads and risk of TUR syndrome

TUR: transurethral resection; TURP: transurethral resection of the prostate. 1. Méndez-Probst et al. CUAJ. 2011;5:385-9; 2. Hueber et al. Can Urol Assoc J. 2011;5:390-1.

Uses electric current to remove tissue from the transition zone of the prostate

Next

94


94

DISADVANTAGES OF TURP

• Contraindicated in patients on anticoagulants

Return to Slide 66

TUR: transurethral resection. TURP: transurethral resection of the prostate. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS; 3. Yang et al. J Urol. 2001;165:1526-32.

Disadvantages:1,2,3

• Risk of blood transfusion • TUR syndrome • Need for retreatment (14.7% in 8 year follow-up) • Retrograde ejaculation • Risk of impotency

95


95

LASER PROSTATECTOMY

1. Holmium laser:1

• Operational wavelength 2140 nm in pulsed mode

• Performed at 60-80 W

• HoLRP on glands <60 g, HoLEP on glands >60 g

2. Green light laser (PVP):2

• Wavelength of 532 nm

• Available in 80-W, 120-W and 180-W models3

HoLRP: holmium laser resection; HoLEP: holmium laser enucleation; PVP: photoselective vaporization prostatectomy. 1. Tooher et al. J Urol. 2004;171:1773-81; 2. Hai. Urology. 2009;73:807-10.

Uses laser energy to remove obstructing tissue from the prostate through tissue coagulation or

vaporization/ablation1

Return to Slide 66

96


96

HOLMIUM LASER

• 10 year follow-up study has found HoLEP to be equivalent to TURP • Reduced requirement for re-operation1

• May safely be considered a new, size independent, gold standard for symptomatic BPH1

• In prostates >100 g, HoLEP was as effective as open prostatectomy in reducing micturition and the need for re-operation2

• Suitable for patients on anticoagulants3

Disadvantages:4

• Retrograde ejaculation (75-80%) • Dysuria is common • Longer operation time than TURP

HoLEP: holmium laser enucleation; TURP: transurethral resection of the prostate. 1. Elmansy et al. J Urol. 2011;186:1972-6; 2. Kuntz et al. Eur Urol. 2008;53:160-6; 3. Elzayat et al. J Urol. 2006;175:1428-32; 4. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS.

Return to Slide 66

97


97

GREEN LIGHT LASER

• Ideal for large prostates (30-80 g)

• Improvement in symptoms and re-operation rate comparable to TURP1

• Safe and effective in patients on anticoagulants2

TURP: transurethral resection of the prostate. 1. Ruszat et al. Eur Urol. 2008;54:893-901; 2. Ruszat et al. Eur Urol. 2007;1031-41; 3. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS.

Disadvantages:3

• Limited long-term data, particularly with 120-W and 180-W

• Longer operation time than TURP • Dysuria is common Return to

Slide 66

98


98

OPEN PROSTATECTOMY

• Oldest surgical treatment for BPH

• Considered when prostate is too large (80-100 g) for TURP for fear of:2

• Incomplete resection

• Significant bleeding

• Risk of TUR syndrome (dilutional hyponatremia)

Obstructive prostatic adenomas are surgically removed through incisions from the inside of the

bladder or through the anterior prostatic capsule1

TUR: transurethral resection; TURP: transurethral resection of the prostate. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS; 2. Nickel et al. CUAJ. 2010;4:310-6.

Next

99


99 DISADVANTAGES OF OPEN PROSTATECTOMY

• Most invasive of the surgical procedures

• Risk of bladder stone development

• Risk of bladder diverticula

• Risk of incontinence

• Risk of bladder neck contracture and urethral stricture

Return to Slide 66

1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS.

100


100

• No tissue is removed1

• Ideal for prostate volumes <30 g

Advantages over TURP1 Disadvantages1

• Reduced bleeding incidents • Shorter operation time • Avoidance of TUR syndrome • Minimal and shorter post-operative

bladder irrigation • Low risk of retrograde ejaculation • Shorter times for catheterization • Shorter hospitalization

• Higher rate of symptom recurrence • Need for additional surgery

TRANSURETHRAL INCISION OF THE PROSTATE

Incisions are made in the bladder outlet to improve symptoms

TUR: transurethral resection; TURP: transurethral resection of the prostate. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS.

Return to Slide 66

101


101

MINIMALLY INVASIVE: TUMT

• Considered in patients with: • Moderate symptoms

• Small to moderate sized prostate gland

• Desire to avoid more invasive therapy

• Associated with a higher 5 year re-treatment rate than TURP

TURP: transurethral resection of the prostate. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Illing. Eur Urol Suppl. 2007;6:701-9.

Transurethral microwave therapy (TUMT)1

Microwave heating destroys excess prostate tissue2

Return to Slide 66

102


102

MINIMALLY INVASIVE: TUNA

• Considered for younger, active individuals where sexual function is an important quality of life issue

• Limited data on long term outcomes

• Higher re-treatment rate than TURP2

TURP: transurethral resection of the prostate. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Illing. Eur Urol Suppl. 2007;6:701-9.

Transurethral needle ablation (TUNA)1

Generates necrosis by heat application using two needles2

Return to Slide 66

mens urological health cme bph-luts- final- nov 13 2013

Health & Medicine