Douglas C. Bauer, MD University of California, San Francisco

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Urology Update

• Douglas C. Bauer, MD
• University of California, San Francisco
• No disclosures

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Overview

• Microscopic hematuria
• Urinary incontinence
• Benign prostatic hypertrophy
• Impotence
• Prostatitis
• Prostate cancer treatment

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Cases

• 26 WF, 3rd episode of gross hematuria, one
  following URI
• 77 BM, microscopic hematuria. Smoker.
  Asymptomatic.

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Microscopic hematuria

• Defined as gt3-5 RBC/HPF
• Common (even in young)
• Yearly UAs in soldiers for 16 yr 39
• Fear of malignancy

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Etiology age dependent

• Glomerular IgA, thin basement (lt50), Alports
  (gt50), other GN
• Non-glomerular (upper) nephrolith, renal cell CA
  (gt50), polycystic kidney
• Non-glomerular (lower) cytitis, prostatitis,
  urethritis, bladder CA (gt50)
• Other exercise, anti-coag, factitious

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Diagnostic evaluation

• Repeat dipstick unless risk factors
• Rule out proteinuria, azotemia, infection
• Imaging helical CT vs. sono
• Procedures cystoscopy if risk factors for cancer
  or gt50

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Other issues

• Cytology not recommended
• Phase contrast microscopy identifies glomerular
  source (dysmorphic)
• Screening not cost-effective
• Natural history of IgA uncertain
• Fish oil?

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Cases

• 56 female, 30 years of worsening UI with cough,
  exercise.
• 40 female, several years of episodic urgency,
  occasional UI. Worse with coffee, EtOH

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Urinary incontinence

• Common
• 25 reproductive age women
• 40 postmenopausal women
• Chronic - social seclusion
• ?Falls Fractures
• ?3x Nursing home admits
• Costly
• 26 billion annually
• More than all cancer care for women

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Incontinence definitions

• Overactive Bladder (OAB)
• - urge incontinence , frequency, nocturia
• Stress -coughing, sneezing, straining, exercise
• Mixed - both urge and stress
• Other - neurologic, obstruction

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Stress vs. urge incontinence

• Symptom Stress Urge
• Precipitant activity urge
• Timing immediate delayed
• Amount small-mod large
• Nocturia rare common
• Remissions rare common

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Evidence-based guidelines

• 1996 AHRQ Clinical Practice Guidelines
• ? Primary Care diagnosis treatment
• History, neurologic pelvic exam, PVR, U/A
• 10 years later, where are we?
• Barriers for Primary Care
• Work up too time consuming complex
• No pelvic exam tables
• PVR frequently not possible

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Diagnostic Aspects of Incontinence Study (DAISy)

• Cross-sectional study (N 301), 6 US centers
• 3 incontinence questions (3 IQ) vs. full
  evaluation
• 3 questions
• 1. During the last 3 months, have you leaked
• urine, even a small amount? If yes
• 2. Stress UI physical activity, coughing,
  sneezing, lifting, or exercise
• Urge UI urge, feeling need to empty but
  could not get to the toilet fast enough
• 3. Type of UI most often Stress, Urge, Mixed,
  Other Brown Annals 2006

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Accuracy of 3 IQ compared to full evaluation
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Summary screening for incontinence

• Primary Care Clinicians
• 3 IQ to classify type of UI
• DAISy Take Home Message
• 3 IQ is a good test for type of UI, especially
  because the risk of missed Dx and Rx low
• Indentification is critical to reducing burden of
  UI!

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Initial visit

• Clinical diagnosis - 3 IQ, UA
• Patient information
• Urinary diary
• Bedside commode
• Topical estrogens?
• Weight loss?
• Consider Rx

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Behavioral vs. meds

• 197 women with Urge UI RCT
• ? UI
• Biofeedback/behavioral 81
• Medication 69
• Placebo 40
• Greater satisfaction in behavioral group
• Burgio 1998

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Patient information

• 222 women with Urge UI RCT
• Improved
• Biofeeback 63
• Verbal/vaginal instruct 69
• Self-help booklet 59
• Not statistically different
• Burgio JAMA 2002

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Urinary diary

• Simple form for recording voids, incontinent
  episodes, fluid intake
• Excellent education intervention!
• Very useful in planning therapy
• -fluid adjustment
• -timing and type of medications

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Incontinence treatment

• Initial Rx similar for stress urge
• Behavioral Management
• - Fluids modification
• - Pelvic Floor Exercises
• - Bladder training
• Verbal and written instructions

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Successful pelvic floor exercises

• Strengthen levator ani and sphincter
• Two fingers in the vagina, one hand on the
  abdomen
• Two types rapid and prolonged
• Individualized program
• Coughing

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Bladder training

• Re-establishing voluntary control
• Schedule voids q 30-60 minutes
• Diary, relaxation, urge suppression
• RCT demonstrated
• 50 improvement in 75 of participants
• Stress and Urge UI (Fantyl 1991)

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OAB medication effectiveness

• Subjective cure 40-60 vs. placebo
  20-40
• Long-term success 50
• Side effects 50
• Discontinuation 10-65
• Bottom line Medications very similar!

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OAB medications

• Side effects dry mouth
• constipation
• drowsiness
• blurred vision
• dizziness
• Contraindications narrow angle glaucoma
• hepatic/renal disease

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Medication prescribing guideline

• Immediate Release
• Oxybutynin (Ditropan) ?
• Tolterodine (Detrol) ?
• Trospium (Santura)

• Extended release
• Darifenacin (Enablex)
• Ditropan XL
• Solifenacin (Vesicare)
• Detrol LA
• Oxybutynin transdermal (Oxytrol)

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Case

• 63 WM, progressive nocturia, hesitancy. PSA 6.

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Benign prostatic hypertrophy

• 80 by age 80 years
• 50 have had a prostatectomy
• Prostate grows throughout life
• Until (unless) testosterone is gone
• Two components of BPH
• Dynamic
• Mechanical

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Assessing BPH severity

• 0 to 35 AUA scale (7 questions)
• Moderate symptoms 8 to 18
• Peak urine flow lt 10 ml/sec (requires 150cc)

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Dynamic therapy of BPH

• Contraction ? adrenergic-mediated
• ? blockers relax smooth muscle
• prostate, blood vessels
• prazosin, terazosin
• ?1A receptors in prostate only
• tamsulosin specific ?1A blocker

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Mechanical therapy of BPH

• Curious genetic abnormality
• 5?-reductase deficiency
• fail to convert T to DHT
• no baldness, prostatic hypertrophy
• Finasteride
• specific 5?-reductase blocker
• marked reduction in DHT levels

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Finasteride and BPH

• Somewhat better than placebo (1.5 points!)
• Not as good as ?-blockers in VA study
• Combined with ?-blockers (NEJM, 12/03)
• Slower progression vs. either one alone
• Retention, surgery similar to finasteride
• May depend upon gland size
• works better in large glands, higher PSA

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Herbs and BPH

• Beta-sitosterol (plant phytosterol)
• 1 RCT
• Saw palmetto
• 18 RCTs
• Both better than placebo

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Surgery (TUR-P) and BPH

• Works better than watchful waiting
• RCT of 556 men
• Especially if sx moderate or severe
• Surgery group had less
• urinary retention, urinary symptoms
• No diff. in impotence, incontinence

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Cases

• 38 WM with impotence. Gradual worsening. Poor
  libido, no depression.
• 58 male, 3 year S/P total prostatectomy, impotent
  ever since. Intact libido.

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Impotence

• No new developments in diagnosis
• Common (25 gt65), iatrogenic causes
• Laboratory evaluation
• not evidence-based
• glucose or glycosylated hemoglobin
• TSH
• testosterone x 2, then LH/FSH, prolactin
• ? free testosterone if boarderline

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Hypogonandism and impotence

• Testosterone falls with age (nl gt325 ng/dl)
• low in 40 age 50-60, 70 age 70-80
• Little evidence that low testosterone is a common
  cause of impotence
• Long-term effects of testosterone replacement
  still unknown (IOM report)

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Sildenafil

• Phosphodiesterase (PDE)-5 inhibitor
• PDEs normally breaks down cGMP
• PDE-5 localizes in prostate
• cGMP is a second messenger
• Sexual stimulationgt nitric oxide release gt cGMP
  release gt vasodilation gt obstructs venules gt
  erection
• Sildenafil prolongs half-life of cGMP

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Nitrates and nitric oxide

• Nitrates are metabolized to nitric oxide
• Nitric oxide regulates resting vascular tone
• cGMP is a common second messenger for nitric
  oxide
• Inhibition of cGMP prolongs nitric oxide action

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Clinical implications

• Basal NO release means that sildenafil normally
  reduces BP by 10-20 mm Hg
• developed as an anti-anginal
• Exogenous nitrates substantial effects
• 25 - 50 mm Hg drop in SBP
• sildenafil half-life of 4 hours
• Bottom line nitrates, no sildenafil vice-versa

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Sildenafil practicalities

• 10 per pill (25, 50, 100 mg size)
• Easy to split in half
• Works in 30 minutes
• Requires NO release
• Prescribe 3 x 50 mg
• try 25 mg first, then 50, then 75

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Me too drugs

• Vardenafil (Levitra)
• similar efficacy, no direct comparisons
• less effect on PDE-6 (fewer visual effects?)
• Tadalafil (Cialis, Le Weekend pill)
• up to 36 hr. of efficacy

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Other modalities

• Erec-Aid suction device
• Alprostadil intra-urethral pellets
• smooth muscle relaxant (direct)
• determine dose (125, 250, 500, 1000 ug)
• Success in 65
• Penile pain in one-third
• Yohimbine (? 2 antagonist) ?

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Case

• 66 male with urgency, hesitancy, nocturia

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Prostatitis

• Ascending infection
• Often with partners GU organism(s)
• Zinc levels low ?value of supplements
• Symptoms variable
• Pain between umbilicus and knees

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Prostatitis diagnosis
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Common errors

• Using normal exam, UA to r/o prostatitis
• Overdiagnosis of acute prostatitis
• Undertreatment (time-wise)
• Extra-prostatic sources
• Unusual organisms with Foley
• Diagnosis w/o leukocytes

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Treatment of prostatitis

• Bacterial
• Acute for 4 weeks
• TMX/Sulfa, CBCN, quinolone
• Chronic for 2 to 4 months
• TMX/Sulfa, nitrofurantoin
• Non-bacterial (2, then 4 weeks)
• Erythromycin, TCN or doxycycline
• Prostadynia ?

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Prostate cancer

• 350,000 new cases in U.S. each year
• 50,000 deaths per year
• 8.5 million men with the disease (30)
• Leveling off now (PSA penetration)
• Average age 73 years
• One in six dxed, one in thirty die

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Is early detection and treatment good?

• Early detection early treatment
• Early treatment early side effects
• Early side effects loss of quality-of-life
• Loss of 2 to 7 days of QA life
• Early treatment ? late benefit
• If Tx works pt. lives long enough

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Prostate cancer classification

• Official system, Stages 0 to IV
• Most pathologist still use dual Gleason
• Worst Gleason is 10 5 5, written 5/5

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Localized disease 15-year mortality in untreated
55-year-old men
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Prostate cancer treatment (usual)

• Stage 0 watch
• Stage I, II surgery (?radiation)
• Stage III radiation
• Stage IV hormonal therapy

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Early prostate cancer treatment, ? needed

• Initial non-randomized studies watchful waiting
  as good as treatment for most localized dz.
• Therapies have complications
• Radical prostatectomy
• 8 incontinence
• 60 (55) impotent

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Does surgery improve outcomes?

• RCT of watchful waiting vs. surgery in 695 men
  with local dz (Holmberg, 2002)
• 75 had palpable dz, 10 detected from PSA
• Mean age 64, 6.2 years follow up
• Prostate cancer death RR 0.50 (0.27, 0.91)
• Distant metastases RR 0.63 (0.41, 0.96)
• Ongoing trials in US

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Advanced cancer hormonal treatment

• Surgical or medical castration
• LHRH agonists (leuprolide, goserelin)
• Constant stimulation of LH tachyphylaxis
• No LH no testosterone
• Suppress early LH surge
• Androgen receptor blockade (flutamide)
• Adrenal androgen production (ketoconazole)

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Surgery vs. medical castration

• Similar effects on survival
• Surgery one-time cost of 7,000
• But surgery more cost-effective

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Confusing results

• Waiting hormones orchiectomy
• Flutamide orchiectomy gt orchiectomy
• 5-year survival 28 vs. 25
• Radiation goserelin gt radiation
• Hit advanced disease early and hard

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Summary

• Urologic conditions are common in primary care
• Many can be successfully managed, at least
  initially, without referral