CLINICAL UROLOGY
From the 33rd Annual Family Medicine Update, sponsored by the University of Minnesota Medical School,
Minneapolis
| PROSTATE CANCER —Kenneth S. Koeneman, MD, Associate Professor, Department of Urologic Surgery, Dougherty Endowed
Chair in Urologic Oncology, and Director, Center for Prostate Cancer, University of Minnesota Medical School, Minneapolis
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| Introduction: occurs in 1 in 6 men; more likely in black men; survival rates—5-yr, 98% to 99%; 10-yr, 80%; 15-yr,
50%; ≈100% with early localized detection; risk for prostate cancer increases after age 50 yr; risk factors—age; ethnicity;
positive family history; high dietary fat intake; number of men presenting with metastasis decreasing, due to awareness
and earlier case finding
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| Staging: T1—“chips” on transurethral resection or presence of prostate-specific antigen (PSA); T1C most common
stage; T2—nodule on ≥50% of lobe; T3—extension into prostate capsule; T3C, invasion of seminal vesicles; T4—
invasion of pelvic organs
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| Natural history of prostate cancer: heterogeneous; Gleason scoring—grades 6 to 10; grade 6 cancers grow more
slowly than grades 8 to 10
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| Detection: American Urological Association (AUA) recommends annual digital rectal examination (DRE) and PSA screening
starting at age 50 yr; American Cancer Society (ACS) recommends discussing risks and benefits; ≈80% of cancers detected
by PSA, 20% by DRE; refer to urologist if uncomfortable about DRE; offer PSA screening; PSA—normal, 0.0 to 4.0
ng/mL; dependent on age, baseline of last PSA, prostate size, and change over time; consider age-adjusted PSA (eg, normal
PSA in patient 70-79 yr of age can be up to 6.5 ng/mL); PSA velocity >0.75 ng/mL over 12 to 18 mo usually cancer, rather
than benign prostatic hyperplasia (BPH; PSA rises slowly [eg, 0.1-0.2 ng/mL over 2 yr]); PSA changes can occur from prostatitis
and urinary tract infection (UTI; treat with antibiotics for 2 wk and repeat PSA testing in 1 mo); check free to total
PSA (<15% indicates higher risk for cancer); PSA <4.0 ng/mL in 25% of diagnosed prostate cancers; problems with PSA
testing—not all men with prostate cancer have elevated PSA; elevated PSA also seen in BPH; testing anxiety; no definite
proof of improved survival; not supported by many organizations
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| Mass screening: AUA guidelines—annual DRE and PSA at age 45 yr in men at increased risk (eg, black men, men
with positive family history); screening not recommended in men with life expectancy <10 yr because 10% to 30% of
men progress and can undergo biopsy and begin hormone therapy (removal of male hormone causes regression of prostate
and prostate cancer); higher PSA level indicates higher risk; perform imaging studies in patients with metastatic disease
and Gleason grade 6 to 10
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| PSA monitoring after therapy: PSA should be nondetectable 2 to 4 wk after surgery; half-life 3 to 4 days (longer with
more sensitive PSA testing); radiation therapy—takes 1.0 to 2.0 yr after external beam radiation and 1.0 to 2.5 yr after iodine
brachytherapy seed implant for PSA to reach nadir of 0.5 ng/mL; in patients with advanced disease who undergo castration,
degree and duration of PSA nadir predictive of outcome
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| Treatment options: watchful waiting or active surveillance in men with life expectancy <10 yr; biopsy every 1 to 2 yr;
PSA monitoring and DRE; may pursue treatment in patients with higher grade on repeat biopsy; watchful waiting or surveillance
not recommended unless disease Gleason grade 6; external beam irradiation, eg, intensity-modulated radiation
therapy (IMRT) or tomotherapy combines imaging of computed tomography (CT) with accelerator (new protocol of 5
treatments instead of 42 can result in better therapy and fewer side effects); brachytherapy seed implantation—
effective for early-stage disease and intermediate risk; treats prostate and not seminal vesicles or lymph nodes; seeds implanted
over 1 to 2 hr with needles through perineum; good outcomes; minimally invasive; side effects include bowel and
bladder irritation and risk (1%-2%) for incontinence; cryotherapy—used by urologists to freeze prostate or seminal vesicles;
causes impotence in 70% of men; effective cancer control; surgery—open surgery (infraumbilical incision to remove
prostate and seminal vesicles; sew bladder to urethra); hormone therapy—remove testosterone; injections or pills
or medication combined with surgery; combination therapy—radiation and hormone therapy for intermediate- to high-
risk disease; 6 mo of hormone therapy for intermediate risk, 2 yr for high-risk disease; tomotherapy to pelvic lymph
nodes and seed implantation to prostate; chemotherapy—for high-risk disease, primary treatment surgery or irradiation,
followed by systemic treatment; goal to prevent or cure microscopic metastases
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| Treatment strategy: bone metastasis—lethal phenotype of prostate cancer; propensity to spread to lymph nodes; patients
die from cachexia, anemia, and weakening; preoperative magnetic resonance imaging (MRI)—before surgery
and radiation therapy; spectroscopy shows different levels of chemicals, due to blood flow and anatomic images, to determine
involvement of prostate or capsule; used in research, and clinical use increasing; look at age of patient, health, longevity,
needs of family, lifestyle, biases (eg, some patients do not want surgery), and cost; low risk—Gleason grade ≤6;
PSA <10 ng/mL; Gleason grades 3 + 4 = 7; stage T1 found by PSA screening or small nodule; watchful waiting if patient
older; other patients can undergo one treatment (eg, surgery, seed implantation, or cryotherapy); higher risk for incontinence
with surgery; higher risk for bowel dysfunction with irradiation; effects on sexual function with seed implantation
or nerve-sparing surgery; intermediate risk—Gleason grade 7 (4 + 3); PSA >10 ng/mL, or larger nodule; surgery or
lymph node dissection; external beam radiation and hormone therapy; seed implantation to prostate and external beam radiation;
be more aggressive; 20% to 40% of patients may fail 5 to 7 yr later; high risk—Gleason grade high; PSA level
high; obvious extension outside of capsule; be aggressive (eg, extensive lymph node dissection); irradiation to pelvis;
hormone therapy for 2 to 3 yr and external beam radiation; seed implantation and open and robotic surgery; faster recovery,
and quicker return to normal activities with laparoscopic surgery
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| Questions and answers: after prostatectomy, PSA levels should fall to nondetectable levels (eg, <0.1 ng/mL) in ≈6
wk; may cause patients significant anxiety; PSA nadir after radiation therapy predictive of clinical failure; may take 2.5
yr for PSA to fall from 5.0 to 6.0 ng/mL to <0.5 ng/mL; PSA nadir should be <0.5 ng/mL
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| HEMATURIA —J. Kyle Anderson, MD, Assistant Professor, Department of Urologic Surgery, University of Minnesota
Medical School, Minneapolis
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| Take-home points: hematuria from malignancy can be intermittent; in patients with infection and anticoagulation, hematuria
requires further work-up; risk factors—age >40 yr; tobacco smoking or secondhand smoke exposure; irritative
symptoms (ie, burning or pain with urination); gross hematuria
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| Definitions: microscopic hematuria—>3 red blood cells on high-power field on microscopic component of UA; for low-
risk patients, 2 of 3 specimens; for patients with risk factors, one specimen sufficient; whether positive results on dipstick
only counts as hematuria controversial; gross hematuria—visible blood
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| Differential diagnosis: upper tract—kidney stones; strictures; cancer (renal cell or transitional cell carcinoma); infarction;
trauma; papillary necrosis; sickle cell disease; pyelonephritis; infection; tuberculosis; glomerular—IgA nephropathy;
thin basement membrane disease; Alport’s syndrome; glomerular disease; lower tract—infection;
inflammation; cystitis; prostatitis; bladder cancer; prostate cancer; strictures; schistosomiasis; urethritis
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| Familial hematuria: Alport’s syndrome—can lead to progressive loss of renal function; characterized by hearing loss,
ocular abnormalities, and hematuria; uncommon (1 in 5000); comprises ≤5% of end-stage renal disease; thin basement
membrane disease—benign; incidence ≤5%; microscopic hematuria; no progressive renal failure; no proteinuria; no
hypertension; differential diagnosis—exercise-induced hematuria; overanticoagulation; factitious causes (eg, red urine
from, eg, blackberries or beets); positive results on dipstick only can be due to myoglobinuria from rhabdomyolysis, hemoglobinuria
from hemolysis, povidone iodine, or bacterial peroxidases
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| Work-up: patient history; gross hematuria—determine how long present; determine location of bleeding in urinary
tract (if bleeding occurs early in urine stream, consider urethra; if late in stream, prostate; if in entire stream, kidney or
bladder); ask about flank pain (to rule out kidney stones or pyelonephritis) and irritative voiding; risk factors—consider
age, occupational chemical exposure, tobacco smoking, and chemotherapy (eg, cyclophosphamide); physical
examination—edema for nephrotic syndrome; atrial fibrillation for embolism; flank mass for renal tumor; tenderness
for kidney stone or pyelonephritis; DRE for prostatitis or prostate cancer; laboratory testing—determine whether patient
has renal parenchymal disease, glomerular problem, or UTI; obtain UA; look for proteinuria, positive culture, infection,
and renal insufficiency; consider PSA testing
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| Special circumstances: anticoagulation—not explanation for hematuria if international normalized ratio (INR) normal
(2-3); some evidence that 15% to 45% of anticoagulated patients with hematuria have significant genitourinary condition;
other causes—menstrual cycle; vigorous exercise; sexual activity; infection—in low-risk patients, recheck
urine in 6 wk; in high-risk patients, consider full evaluation
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| Further work-up: low-risk patients—upper tract imaging in addition to UA and urine cytology; if negative, proceed
to follow-up regimen (ie, check blood pressure and repeat UA and cytology at 6, 12, 24, and 36 mo); if patient has proteinuria,
refer to nephrologist for biopsy; if patient has gross hematuria or test results suspicious for malignancy, repeat
work-up; if cytology abnormal, perform cystoscopy; high-risk patients—perform cystoscopy, upper tract imaging, and
urine cytology; treat findings or proceed to follow-up regimen
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| Upper tract imaging: ultrasonography—does not require intravenous (IV) contrast; easy to perform; operator-dependent;
sensitivity and specificity low; inexpensive; widely available; cystoscopy and retrograde pyelography (contrast
injected into ureter and kidneys)—can be performed in patients with renal failure, but sedation required; IV pyelography
(IVP)—requires IV contrast; inexpensive; CT urography—image abdomen and pelvis without contrast for kidney
stones, and image with contrast for renal parenchyma; after 5 min, look for filling defects; higher radiation level, cost, sensitivity,
and specificity than IVP for renal masses; gold standard for renal masses
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| Future: CT virtual cystoscopy—computer reconstruction of CT image; not currently in use; new urine tests—focus on
transitional cell carcinoma; role undefined; screening for hematuria currently not recommended as standard practice; new
urinary markers in development
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| INCONTINENCE —Michael L. Tran, MD, Assistant Professor, Department of Urologic Surgery, University of Minnesota
Medical School, and Director of Urodynamics, Columbia Park Medical Group, Minneapolis
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| Types: overflow—results from urinary retention from prostate condition or neurogenic bladder from spinal cord injury;
mixed—symptoms of urge and stress incontinence; more common in women; stress incontinence rarely seen in men unless
history of plastic surgery; nighttime—consider lower extremity edema and sleep apnea; postvoid dribble—in men >40 yr
of age “nothing we can do about it”; part of aging process; functional—causes include delirium, dementia, infection, atrophic
vaginitis, medications, psychologic condition, excess urine, restricted mobility, and constipation or stool impaction;
overactive bladder and urge incontinence in women—symptoms include frequency (voiding ≥8 times), urgency (strong
urge to urinate), and incontinence (loss of urine)
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| Etiology: neurogenic—loss of inhibition of pontine micturition center leads to increased excitability of smooth muscle;
associated with multiple sclerosis, stroke, spinal cord injury, and Parkinson’s disease; myogenic—thickening of muscle
within bladder with increasing age; can be idiopathic
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| Physical examination: vaginal atrophy; pelvic prolapse; medication history; urinalysis; blood in urine; voiding diary
helpful; diagnosis based on patient history and physical examination
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| Management: medical management mainstay of therapy; behavioral therapy and pelvic floor muscle training effective
≈50% of time; InterStim device—electrodes placed in S3 nerve roots; useful in patients who do not respond to medical
management or physical therapy or who have side effects from medications; efficacy rate 80%
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| Medications: aimed at muscarinic receptors (M2 and M3 receptors dominant in bladder; M3 more specific to bladder contractions);
most common side effects include dry mouth and constipation; blurred vision rare (anticholinergics contraindicated
in patients with narrow-angle glaucoma); tachycardia rare; some effects on cognitive function in older patients;
efficacy, mechanisms, and side effect profiles similar; oxybutynin (eg, Ditropan)—may be difficult to tolerate; causes
constipation; effective; metabolized by liver; tolterodine (Detrol)—commonly used; nonselective; effective; fewer side
effects than oxybutynin; metabolized by liver; solifenacin (Vesicare)—more selective for M3 receptors; prolongs QT interval
when combined with certain medications; trospium (Sanctura)—commonly used in Europe; effective; fewer effects
on central nervous system; taken bid; metabolized by kidney (use in patients with liver problems); darifenacin
(Enablex)—highly selective for M3 receptors; may be useful in patients who failed treatment with tolterodine or oxybutynin
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| Stress incontinence: loss of urine with exertion, eg, coughing; coexists with urge incontinence ≈33% of time;
childbirth—incidence of stress incontinence lower in nulliparous women and women who underwent cesarean delivery;
vaginal fistula prevalent in third-world countries; ≈50% of patients with stress incontinence have pelvic organ prolapse
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| Risk factors: stress; age; obesity (unclear); estrogen and constipation may play role; tobacco smoking; ≈20% of women
>60 yr of age may develop some form of leakage over 1 yr, but ≈6% resolve over time; angiotensin-converting enzyme
(ACE) inhibitors cause cough; diuretics; á-blockers; urinary tract infections; stool impaction
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| Physical examination: mobility; cognition; peripheral edema; retention in bladder or neurogenic bladder; pelvic organ
prolapse; health of vaginal lining; strength of pelvic floor muscles; check for leakage (ask patient to stand and cough);
check urethral hypermobility (angle of urethra >30º); stress incontinence more prevalent among whites than blacks (least
common in Asian women); UA to rule out infection; check postvoid residual urine; start therapy or perform further work-
up with urodynamics or cystoscopy as needed; treatment of pelvic organ prolapse with pessary may unmask incontinence
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| Treatment: pelvic muscle training—appears more effective in overactive bladder than in stress incontinence;
medications—cause many side effects; no drugs currently available for treatment; pseudoephedrine (eg, Sudafed) ineffective;
surgery—substance injected into urethra; must be repeated every 2 mo; success rate variable; retropubic
suspension and sling procedures effective; sling procedures performed more often than Burch procedures, due to
shorter surgery and recovery; transvaginal tape—success rate, 80% to 90%; outpatient surgical procedure; long-term
results as good as Burch procedure; supportive tape applied under urethra; failure rate, 5% to 8%
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Suggested Reading
Barzilay J et al: Getting to goal blood pressure: why reserpine deserves a second look. J Clin Hypertens (Greenwich)
9:591, 2007; Barzilay JI et al: Fasting glucose levels and incident diabetes mellitus in older nondiabetic adults randomized
to receive 3 different classes of antihypertensive treatment: a report from the Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial (ALLHAT). Arch Intern Med 166:2191, 2006; Black HR et al: Metabolic and clinical outcomes
in nondiabetic individuals with the metabolic syndrome assigned to chlorthalidone, amlodipine, or lisinopril as initial
treatment for hypertension: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
(ALLHAT). Diabetes Care 31:353, 2008; Bloch J et al: Thresholds for diastolic blood pressure reduction in older patients
with isolated systolic hypertension appear to be different depending on the presence or absence of underlying coronary heart disease.
J Clin Hypertens (Greenwich) 9:977, 2007; Bloch MJ et al: Hypertension prevalence increases and hypertension
control rates improve in the United States: 2003-2004. J Clin Hypertens (Greenwich) 9:147, 2007; Burgio KL: Current
perspectives on management of urgency using bladder and behavioral training. J Am Acad Nurse Pract 16:4, 2004; Cushman
WC et al: Rationale and design for the blood pressure intervention of the Action to Control Cardiovascular Risk in Diabetes
(ACCORD) trial. Am J Cardiol 99:44i, 2007; Hashim H et al: Drug treatment of overactive bladder: efficacy, cost
and quality-of-life considerations. Drugs 64:1643, 2004; Jamerson K et al: Exceptional early blood pressure control rates:
the ACCOMPLISH trial. Blood Press 16:80, 2007; Leenen FH et al: Clinical events in high-risk hypertensive patients randomly
assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-
lowering treatment to prevent heart attack trial. Hypertension 48:374, 2006; Madersbacher H: Overactive bladder--a practical
approach to evaluation and management. J Med Liban 52:220, 2004; Wallace SA et al: Bladder training for urinary
incontinence in adults. Cochrane Database Syst Rev:CD001308, 2004; Wein AJ: Diagnosis and treatment of the overactive
bladder. Urology 62:20, 2003; Wright JT Jr et al: Clinical Outcomes by Race in Hypertensive Patients With and
Without the Metabolic Syndrome: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
Arch Intern Med 168:207, 2008.
Educational Objectives
| The goal of this program is to improve management of prostate cancer, hematuria, and incontinence. After hearing and assimilating
this program, the clinician will be better able to:
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 | 1. Describe advantages and disadvantages of using prostate-specific antigen testing for prostate cancer.
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| 2. Select appropriate treatment for prostate cancer, based on risk and clinical findings.
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| 3. List the differential diagnosis of patients with hematuria.
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| 4. Work up patients with hematuria, based on patient history and physical examination.
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| 5. Choose drugs with fewer side effects when treating overactive bladder.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee
members to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of
interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and
not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Koeneman is on
the Speakers’ Bureaus for GlaxoSmithKline, Sanofi-Aventis, and Pfizer. Dr. Tran is a Consultant for Colpoplast and
Medtronics. Dr. Anderson and the planning committee reported nothing to disclose.
Acknowledgments
Drs. Koeneman, Anderson, and Tran spoke at the 33rd Annual Family Medicine Update 2007, sponsored by the University
of Minnesota Medical School, and held May 7-11, 2007, in Minneapolis, MN. The Audio-Digest Foundation thanks the
speakers and the sponsor for their cooperation in the production of this program.
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