UROLOGIC PROBLEMS UPDATE: Practical, Evidence-Based, Clinical Pointers

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UROLOGIC PROBLEMS UPDATEPractical,
Evidence-Based, Clinical Pointers

• B. WAYNE BLOUNT, MD, MPH
• PROFESSOR,
• EMORY UNIVERSITY SOM

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Objectives

• Urinary Incontinence
• Prostate diseases
• Prostatitis
• BPH
• Cancer
• Erectile dysfunction

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QUESTION 1

• 64 YO WF C/O sudden losses of large amounts of
  urine, not always with urgency. you can diagnose
  this patient by history alone.
• A. True
• B. False

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Urinary Incontinence Symptoms
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Primary Underlying Causesof Incontinence

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Other Causes of Accidental Urine Loss

• Overflow
• Functional

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Basic Approach

• Identify and treat reversible causes
• Identify complicating factors -
• that need specialized treatment or additional
  evaluation
• Exclude overflow
• Distinguish stress vs urge
• Treat

Urinary Incontinence in Adults. AHCPR/AHRQ
Clinical Practice Guideline, 2009
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Transient Urinary Incontinence

• D Delirium
• I Infection
• A Atrophy
• P Pharmaceuticals
• P Psychological
• E Endocrine
• R Restricted mobility
• S Stool impaction

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Distinguish Stress from Urge
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Urinalysis

• Bacteriuria
• Hematuria
• Pyuria
• Glycosuria
• Proteinuria

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Other Basic Tests

• Postvoid residual
• Distinction is gt 150-200 ml
• Dont forget that kidneys make about 1 ml per
  minute

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Treatment Strategies

• Increase urethral resistance
• Exercises, injections, medications
• Electrical stimulation, biofeedback, surgery
• Urethral obstruction
• Plugs, patches, continence pessary
• Decrease magnitude of stress on bladder
• Cough control, exercise modification, weight loss

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Behavioral Therapy

• Bladder retraining
• Strongly recommended for treatmentof urge and
  mixed incontinence A NIH, 2009
• Pelvic floor muscle training (pelvic muscle or
  Kegel exercises)
• Strongly recommended for thetreatment of stress
  incontinence A NIH, 2009
• May be augmented by biofeedbackor vaginal weights

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Other Therapies

• All with inconsistent results in trials
• Electrostimulation
• Magnet Therapy (Works for UUI)
• Medical devices pessaries, plugs, etc.
• Injectable bulking agents
• Local estrogen
• NIH Consensus Conference on Urinary Incontinence,
  2008

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Surgery
Colposuspension(Burch MMK)
Elevates and stabilizes urethra by suspending
anterior vaginal wall toiliopectineal
(Coopers)ligaments/pubic symphysis
Suburethral sling(fascial TVT)
Stabilizes urethra by placing it withina sling
suspending it from rectus fasciaor pubic bone
Urethral bulking(collagen carbon)
Injection of bulking materials abouturethra to
increase outlet resistance
MMK Marshall-Marchetti-Krantz.TVT
transvaginal tape.
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Medications

• Currently, there is no medication approved for
  the treatment of SUI

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Off-Label Medications
Pharmacological Action
Examples
Classification
?-adrenergic agonists
Increase urethral tone and closure pressure by
direct stimulation of ?-adrenergic receptors
EphedrineMidodrinePseudoephedrine
Thickens urethral mucosa for a better seal
increases ?-adrenergic response directly affects
all lower urinary tract tissues may increase
sensory threshold of bladder and increase bladder
relaxation
Estradiol
Estrogen
These agents have anticholinergic,direct smooth
muscle relaxant, and norepinephrine-reuptake
inhibition properties
ImipramineAmitriptyline
Tricyclic antidepressants
This information concerns a use that has not
been approved by the US FDA.
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QUESTION 2

• A patient with urge incontinence cannot be
  effectively treated with which of the following
• A. Behahioral therapy
• B. Oxybutinin
• C. Hyoscyamine
• D. Tolterodine
• E. Imipramine

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URGE INCONTINENCE (OAB, DETRUSOR INSTABILITY)

• All of the answers except hyoscyamine are
  correct.
• Anticholinergics meds with such side effects
  are used to treat oab.
• Oxybutynin and tolterodine are the 2 most
  commonly used meds. Level A Rec
• Propanthaline imipramine are 2nd line agents. B
  Rec
• Behavioral therapy e.g. bladder training, is
  effective. A Rec

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Referral/Consultation Criteria

• Uncertain diagnosis
• Uncertain treatment plan
• Failure to respond to therapy
• Consultation regarding surgery
• Hematuria
• Recurrent urinary tract infections
• Abnormal PVR

PVRpostvoid residual.
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4 62 YO WM C/0 2 MOs WORSENING DIFFICULTY
STARTING URINATION WITH LESS FORCE OF STREAM
SOME DRIBBLING.

• PMH Negative
• PE 30 cc prostate rest WNL
• The next recommended step in managing this
  patient is
• A. PSA level
• B. Ultrasound of prostate
• C. Empiric treatment
• D. Prostatic biopsy
• E. All of the above

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BENIGN PROSTATIC HYPERPLASIA

• Prevalence 8 31-40 45 51-60, gt80 80 yo
• SX LUTS reduced force of stream, hesitancy,
  terminal dribbling, sense of incomplete emptying,
  urgency, nocturia, frequency.
• Complications acute urinary retention, recurrent
  UTIs, hydronephrosis Renal failure

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BENIGN PROSTATIC HYPERPLASIA

• Lifetime risk of surgery 29
• 2 Components Dynamic muscle tension Bulky
  structural
• Use AUA symptom scoring index C Rec
• Mild (Score lt 7) Watchful waiting
• Moderate (Score 8 19) Medical RX
• Severe (Score gt 20) Surgery
• SEE www.aafp.org/afp/20020701/77.html end of
  H.O.

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BPH Symptom score
Not at all lt 1 in 5 times lt half the time About half the time gt half the time Almost always
1. In the past month, how often have you had a sensation of not emptying your bladder completely after you finished voiding? 0 1 2 3 4 5
2. In the past month, how often have you had to urinate again less than 2 hours after you finished urinating before? 0 1 2 3 4 5
3. In the past month, how often have you found you stopped and started again several times when you urinated? 0 1 2 3 4 5
4. In the past month, how often have you found it difficult to postpone urination? 0 1 2 3 4 5
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BPH Symptom Score
Not at all lt 1 in 5 times lt half the time About half the time gt half the time Almost always
5. In the past month, how often have you had a weak urinary stream? 0 1 2 3 4 5
6. In the past month, how often have you had to push or strain to begin urination? 0 1 2 3 4 5
7. In the past month, how many times did you typically get up to urinate from the time you went to bed until you arose in the morning? 0 1 2 3 4 5
SCORING KEY 0 to 7 mild 8 to 19 moderate 20 or more severe. SCORING KEY 0 to 7 mild 8 to 19 moderate 20 or more severe. SCORING KEY 0 to 7 mild 8 to 19 moderate 20 or more severe. SCORING KEY 0 to 7 mild 8 to 19 moderate 20 or more severe. SCORING KEY 0 to 7 mild 8 to 19 moderate 20 or more severe. SCORING KEY 0 to 7 mild 8 to 19 moderate 20 or more severe. SCORING KEY 0 to 7 mild 8 to 19 moderate 20 or more severe.
www.aafp.org/afp/20020701/77.html
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QUESTION 3

• Which of the following meds would be
  inappropriate for this patient?
• A. Saw palmetto
• B. Alpha-1-antagonist
• C. 5-alpha-reductase inhibitor
• D. Ciprofloxacin

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BPH MEDS

• Alpha-1-antagonists (5 approved) Similar
  efficacy different side effect profiles
  Terazosin Doxazosin more SEs Dynamic
  component They work A Rec Cochrane, 2008
• 5-Alpha-reductase inhibitors (2 approved) Reduce
  size Need 6-12 mo.s RX for full effect 2
  approved with similar efficacy Ses
• They work A Rec, Cochrane, 2008
• NNT for hematuria 2 NNT to prevent a TURP 6

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BPH MEDS

• Combination RX MAY help A Rec Cochrane,
  Level B. (esp when gt 30 cc volume)
• Saw Palmetto is as effective as 5-alphas A
  Rec (Cochrane Review)

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Other BPH Treatments

• TUMT Transurethral Microwave Thermotherapy
• Is effective when there is
• No urinary retention
• No previous prostate procedures
• Prostate volumes between 30 100 ml
• Not as effective as TURP
• Cochrane, 2007
• Serenoa repens (Am. Dwarf Palm) does NOT work
  A Cochrane, 2009
• Beta-sitosterols are effective B Cochrane
  2008

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QUESTION 4

• 54 YO WM C/O 6 days of perineal pain, urgency
  frequency, fever myalgias. never had before.
  the most likely Dx. is
• A. Acute prostatitis
• B. Cystitis
• C. Chronic bacterial prostatitis
• D. Chronic nonbacterial prostatitis
• E. Urethritis

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PROSTATITIS

• Acute Bacterial
• Chronic bacterial
• Chronic Nonbacterial (CPPS) Inflammatory
  Noninflammatory

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PROSTATE DX TESTS

• Traditional 4-glass test not done much anymore
  not validated too cumbersome
• Alternative is the Pre- Post-massage test
  (PPMT) As good as 4-glass test, but also not
  validated

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ACUTE PROSTATITIS

• A type of UTI
• SX fever, chills, LBP, perineal pain, dysuria,
  urgency, frequency, myalgias, ? Obstructive sx
• P.E. Tender, warm, swollen, firm irregular
• UA CS sans massage

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ACUTE PROSTATITIS RX

• MEDS C Rec
• TCN
• TMP-SMX
• Quinolone
• Duration 3-4 weeks C Rec

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CHRONIC BACTERIAL PROSTATITIS (CBP)

• Source of recurrent UTIs
• Similar SX as Acute c ASX intervals
• WBCs on pre- post-massage UAs
• - CS on pre- on post-massage

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CBP RX

• TMP-SMX as 1st line C Rec
• Quinolone for RX failures C Rec
• Rarely TUP of infected tissue for very sx
  complete failures on Abx

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Erectile Dysfunction

• Definition The inability to achieve or maintain
  an erection sufficient for satisfactory sexual
  performance
• 18 million men in US

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Erectile Dysfunction

• ED is a robust predictor of all-cause mortality
  CV events in men.
• Hazard ratio for mortality 2.04
• Hazard ratio for CV event 1.62
• With a dose-response increase with ED severity
• Bohm, Circulation, March 15, 2010

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Erectile Dysfunction

• 1st line therapy should consist of oral
  phosphodiesterase 5 inhibitors (PD5s) NNT 2.1,
  A Rec, Cochrane, 2007
• PD5s are most effective in ED assoc with DM,
  spinal cord dysfunction and ED caused by
  antidepressants A Rec Cochrane, 2007
• PD5s can help in ED in nerve-sparing
  prostatectomy B Rec, Bandolier, 2005
• PD5 efficacy side effects among the 3 are
  similar, but drop-out rates are lower for
  sildenafil, A Rec Bandolier, 2005

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Phosphodiesterase 5 Inhibitors Adverse Effects

• Vision disturbances
• Priapism
• Angina
• Sudden, Permanent sensorineural hearing loss (
  May, 2010)

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Erectile Dysfunction

• Vacuum Devices B Rec, Bandolier, 2005
• Yohimbine NNT 6.4, A Rec, Bandolier, 2000
• Testosterone works in men with low testosterone
  (lt12 nmol/L), NNT 2.1 Bandolier, 2005
• Alprostadil works NNT 3.5 Is not a 1st
  line agent 2/2 side effects A Rec, Bandolier,
  2005
• We dont know about apomorphine, phentolamine, or
  intracavernosal VIP I Rec, bandolier,

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Erectile Dysfunction What Doesnt Work

• Trazodone A Rec, Bandolier, 2005
• Fibrates statins may contribute to ED B
  Rec,Bandolier, 2007
• Having a BMI gt 30 is a risk factor for ED, B Rec,
  Bandolier, 2000
• Losing weight in obese patients improves erectile
  function, B Rec, Bandolier, 2005

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BIBLIOGRAPHY

• USPSTF. SCREENING FOR PROSTATE CANCER.
  2005.WWW.ahrq.gov/clinic/3rduspstf/prostatescr/pro
  staterr.htm
• Weiss BD. Selecting Medications for the Treatment
  of Urinary Incontinence. AFP 200571315-22.
• Burgio KL, et al. Combined behavioral drug
  therapy for urge incontinence. J Am Geriatr Soc
  200048370-4
• Burgio,KL, et al. Behavioral training with
  without biofeedback in the treatment of urge
  incontinence. JAMA Nov 13, 2002 2882293-9.
• AAFP. Urinary Incontinence Assessment
  management in Family Practice. Video
  http/www.aafp.org/x17358.xml
• Stevermer JJ, Easley SK. Treatment of
  Prostatitis. AFP 2000613015-22.
• NJAFP. CME Report Diagnosis Management of
  Overactive Bladder in Family Medicine. 2007
  21-14.
• Stenardo S. Caring for Patients Who have BPH.
  AAFP CME Bulletin. 200761-6.

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BIBLIOGRAPHY

• Stern JA, Schaeffer AJ. Chronic Prostatitis. West
  J Med Feb. 2000 17298-101.
• Jang T, Schaeffer A. Chronic Prostatis. (Clinical
  Evidence Concise). AFP Aug 1, 2005
• Shamliyan et al. Trials of Nonsurgical Treatments
  for Urinary Incontinence in Women. Ann Int Med
  2008,148.
• Amer. Cancer Soc. Guideline for the Early
  detection of prostate cancer Update 2010. Cancer
  J Clin 2010.
• Wilbur J. Prostate Cancer Screening. Am Fam
  Physician. 2008781377-84.
• Edwards J. Diagnosis Management of Benign
  Prostatic Hyperplasia. Am Fam Physician.
  2008771403-10.

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• EXTRAS

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Prevalence of Urinary Incontinencein Women
Women Under 60 Years Old
Women Over 60 Years Old
Stress55
Stress30
Urge35
Mixed35
Urge20
Mixed25
.
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Initial Assessment for Urinary Incontinence

• History
• Voiding diary
• Physical/pelvic exam
• Urinalysis and other basic tests

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Stress and Urge IncontinenceScreening Questions

• During the last week, how many timesdid you
  accidentally leak urine with
• A physical activity like coughing,
  sneezing,lifting, or exercising?
• A feeling of strong, sudden need to pass your
  urine that did not allow you to get to the toilet
  fast enough?

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Urine Voiding Diary
Fluid IntakeAmount/Type
Urge Present (yes/no)
Leakage(0-3 scale)
Activity
Amount Voided
Time
16 oz. coffee6 oz. orange juice
650AM
425 mL
Getting up/breakfast
0
Yes
745AM
150 mL
Leaving for work
0
Slight

820AM
350 mL
At work
0
Yes
8 oz. coffee
910AM

Cough
2
Yes

915AM
300 mL
Working
0
Yes
10 oz. water
1225PM
275 mL
Working/at lunch
0
Yes
8 oz. water
245PM
400 mL
Bending
1
Yes
4 oz. water
530PM
250 mL
Leaving work
0
Yes

630PM
125 mL
Exercise class
2
Slight
12 oz. water
745PM

Dinner
0
No
4 oz. wine, 8 oz. water
820PM
375 mL
At home
0
Yes
4 oz. water
1050PM
250 mL
Getting ready for bed
0
Yes

Leakage 0no leakage 1drops 2wet underwear
or light pad 3soaked pad or clothing.
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What Is a Primary Cause of SUI?
?

• a. Diminished urethral sphincter function
• b. Increased afferent stimulation from the
  bladder
• c. Contractile dysfunction of the bladder
• d. Detrusor muscle instability/overactivity

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3 Common Factors Associated With Maintaining
Continence

• Urethral closure pressure
• Pressure transmission
• Abdominal pressure

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Pathophysiology of Stress Urinary Incontinence

• Urethral hypermobility
• Displacement of urethra during sudden increasein
  abdominal pressure
• Decreases pressure transmission
• Intra-abdominalpressure overrides urethral
  resistance

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Pathophysiology ofStress Urinary Incontinence

• Intrinsic sphincter deficiency (ISD)
• Urethra is unable to generate enough outlet
  resistance to keep the urethra closed at rest
  orwith minimalphysical activity

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SUI Occurs When Bladder Pressure gt Urethral
Pressure
(PTD x stress gt urethral pressure)

• Any factor that pushes the equation
  towards a positive urethral pressure
  gradient has the potential to be effective

PTDpressure transmission deficit.
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CHRONIC NONBACTERIAL PROSTATITIS (CNP/CPPS)

• Prostatodynia Abacterial Prostatitis
• Urologic Sx or pelvic/genitalia Pain for at least
  3 mos of the prior 6, sans other causes (Dx of
  Exclusion)
• Inflammatory Noninflammatory
• Inflam Has Inflammatory cells in postprostate
  massage urine
• Noninflam includes the rest
• Etiology not known

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CNP/CPPS DX

• SX c/w Dx
• P.E. Prostate can be tender or not
• Tests PPMT with UA CS
• Consider PVR Cystoscopy

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CNP/CPPS RX

• No EBM RXs Below are all B Recs that do NOT
  work, Cochrane, 2008
• ABX, alpha blockers, 5-alpha reductase
  inhibitors, NSAIDs, sitz baths, Allopurinol

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BPH Meds

• Alpha1 receptors 3 subtypes A, B, D
• A type is 70 of receptors in prostate tissue
• B type are more in smooth muscles of vasculature
• Higher receptor density in BPH tissue

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BPH Meds

• Terazosin, doxazosin, alfuzosin work on all 3
  receptor subtypes
• Tamulosin relatively selects A D
• Silodosin is relatively selective for A receptors

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Erectile Dysfunction

• Principal neurotransmitter for erection is nitric
  oxide
• Regulated by cGMP
• Return to flaccidity, cGMP is hydrolyzed to GMP
  by phosphodiesterase type 5
• ERGO the PHD5 inhibitors

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Prostate Cancer Treatment

• Cryotherapy works for localized Ca B rec
  2007
• Adjuvant hormaonal threrapy is effective in
  localized Ca locally advanced Ca 2009

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STAGING

• Stage cancer by TNM system by Gleason grade
• Bone scan unnecessary in Stage T1/T2, gleason lt 7
  PSA lt 10
• DO Staging CT when Gleason gt 6 or PSA gt 10
• With localized cancer, consider endorectal coil
  MRI (determines extracapsular extension)

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TREATMENT

• Watchful Waiting
• Radiotherapy External seeds
• Prostatectomy
• Hormonal Androgen suppression Medical or
  surgical
• Combined RX
• Pt preference, age, life expectancy
• Follow PSA Q 6 mos x 5 yrs, then annually

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QUESTION 5

• 42 YO AAM, ASX, wants a PSA done. Fam Hx
  negative. what is your evidence based
  recommendation to him?
• A. Do the PSA
• B. Do a digital rectal exam
• C. Do both
• D. Do nothing now
• E. Do a prostatic ultrasound

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PROSTATE CANCER
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PROSTATE CANCER SCREENING EBM

• USPSTF There is insufficient evidence to
  recommend for or against routine screening for
  prostate cancer by PSA or DRE in men lt 75 y.o..
  2008 I Rec (Same from Cochrane)
• D Rec for men gt 75 y.o.

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PROSTATE CANCER SCREENING EBM

• ACP Discuss with patients and individualize
  decision. C Rec, 2008
• AUA Screen gt age 50 with 10 yr life
  expectancy. C Rec, 2008
• ACS Discuss with asymptomatic men with a life
  expectancy of gt 10 years. Use informed, shared
  decision-making. I, 2010

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SCREENING

• If screen, following are suggestions
• Average risk men Annual PSA (with or without
  DRE) starting _at_ 50, until life expectancy lt 10
  yrs. PSA cutoff of 4 C Rec
• African-American men men c F.Hx As above,
  starting _at_ 45
• Newer PSA assays have not resulted in better
  patient outcomes. B Rec
• If PSA lt 2.5, can screen Q 2 yrs

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PT. DISCUSSION POINTS

• PC is an important health concern
• Benefits of screening aggressive RX are not
  proven
• DRE PSA have both false s -s
• High risk for further invasive evaluation
• RXs associated with significant morbidity
• Early detection may save lives avert
  cancer-related morbidity, but there is no proof
  for that

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QUESTION 6

• You get a PSA result of 5.6 on a 51 yo wm. what
  is the next evidence-based step?
• A. Repeat the PSA, now
• B. Repeat the PSA with a free
• C. Refer to urology
• D. Repeat the PSA in 1 year
• E. Do nothing

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? POSITIVE SCREEN ?

• Biopsy is the gold standard
• Transrectal BX (TRUS) Office procedure sans
  sedation or analgesia

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Prostate Cancer

• Most common solid tumor among Am. Men
• Around 200,000 diagnoses per year
• Risks
• Age, Family Hx, Race
• Protection? ?Lycopenes? C level evidence
  selenium B Rec Vit E I Rec
• 5 alpha reductase inhibitors Yes B Rec,
  Prostate Cancer Prevention Trial