CLINICAL UROLOGY
| PROSTATE CANCER AND BENIGN PROSTATIC HYPERPLASIA —Mark S. Litwin, MD, MPH, Professor of Urology and Health Services, David Geffen School of Medicine, University of California, Los Angeles |
Prostate Cancer (PC) | Epidemiology: most common solid tumor and second leading cause of cancer deaths in men; between 250000 and 400000 new cases occur annually; accounts for 45000 deaths annually (slight decline in past 4-5 yr) |
| Risk factors: advancing age most important; family history (fathers and brothers); race (blacks 2 to 3 times more likely to develop and die from PC); dietary fat |
| Screening: controversial for older men, because most with PC die from other medical problems; while screening detects PC at early stage, PC tends to be slow growing, and many of those undergoing treatment develop significant complications |
| Digital rectal examination (DRE): older means of diagnosis; main problem is detectable tumors already at more advanced stage; remarks—tumors in posterior part of prostate palpable; those that arise deep within gland not palpable |
| Prostate-specific antigen: actually more sensitive than specific for detecting prostate disorders; elevated in benign prostatic hyperplasia (BPH), PC, and prostatitis; with cutoff of 4 ng/mL, test reasonably sensitive, but only 50% specific; has much higher specificity (but lower sensitivity) when cutoff higher; Thompson trial involving finasteride (Proscar)— found that 1) finasteride does prevent PC in many men, and 2) fairly large group of men with normal PSAs had PC on biopsy; concluded that normal PSA does not rule out PC |
 | Means for improving accuracy of PSA: calculation of PSA density—involves dividing total PSA by prostate size; if ratio >0.15, suspect cancer; if <0.15, suspect BPH; PSA velocity—increase >1.5 ng/mL over 2 yr suggests presence of PC; subsequent study found that men with more rapid velocities more likely to die from PC |
| Age-specific reference ranges for PSA: increases with age; PSA 4 ng/mL not acceptable for men in their 40s, but tolerable for those in their 60s |
| Free-to-total PSA ratio: ≤19% considered suspicious for PC; lower the ratio, more likely patient has PC, provided total PSA abnormal |
| Reasons PSA screening has not led to decreased mortality: lead-time bias—argues that were it not for PSA screening, diagnosis of PC would occur when it presents clinically and that life span would be from time of clinical diagnosis to death; further argues that survival appears longer because diagnosis made earlier, not because death delayed; length bias— argues that advanced cases of PC not in population long and that PSA screening may be detecting lower-grade indolent cases; comment—slight decline in mortality past few years probably related to widespread application of androgen ablation therapy (leuprolide [Lupron] does prolong survival); arguments for PSA screening—1) advanced disease not curable; 2) without it, most patients would not be diagnosed early; arguments against—1) no population-based studies have shown it clearly decreases mortality; 2) many men with PC die from comorbid diseases; 3) treatment itself not without hazards |
| Screening recommendations: American Urological Association and American Cancer Society—begin routine annual screening (PSA and DRE) at 50 yr of age in men expected to live at least 10 yr; begin screening around 40 to 45 yr of age in men with first-degree relatives with PC and in blacks; US Preventive Services Task Force and Canadian Preventive Services Task Force—evidence insufficient to recommend in favor of or against screening |
| Prostate Cancer Prevention Trial (PCPT): concluded that use of finasteride decreases incidence of PC development in healthy men; however, among those who developed PC, prevalence of high-grade tumors slightly higher |
| Diagnosis: after positive screen with PSA and DRE, insert probe gently into rectum and visualize prostate with transrectal ultrasonography (TRUS); 33% of PCs hypoechoic (dark spots), 33% hyperechoic, and remainder isoechoic (not detectable); therefore, TRUS not useful without biopsy; with TRUS, one can visualize prostate nicely and guide biopsy needle throughout prostate; if entire area isoechoic, get ≥12 dodecant biopsy samples to assess prostate; comment—some tumors small enough to elude biopsy needles; therefore, patient with negative biopsy findings still may have PC |
| Staging of tumors: most tumors diagnosed at T1c stage (PSA elevation); T2 tumor palpable; Gleason scoring system— pathologist looks at biopsy slides and grades 2 most common areas; best possible score 1+1=2; worst score 5+5=10 |
| Other tests: bone scan if PSA >10 ng/dL (to look for bony metastases); computed tomography (CT) if PSA >20 ng/dL |
| Treatment options: surgery; irradiation; watchful waiting |
| Radical prostatectomy: lymph nodes next to prostate also removed; usually takes 2 to 2.5 hr to do; traditionally done via lower midline vertical incision; laparoscopic procedure newest modality; goal to extract prostate and not damage other vital structures (most common complications impotence and incontinence) |
| Pelvic irradiation: can be performed externally by firing x-ray beams into prostate or implanting multiple radioactive pellets into prostate under general anesthesia (brachytherapy); problems include impotence, incontinence, possible bowel irritability, and urethral strictures |
| Watchful waiting: great choice for older individual or someone with significant comorbidity; protocol calls for PSA, DRE, and clinical assessment every 6 mo and bone scan every 2 yr to check for metastasis; when metastasis evident, consider androgen ablation therapy |
| Comments: recent Swedish study suggests long-term survival for men with prostate cancer on watchful waiting good; another Scandinavian study concludes that, compared to watchful waiting, surgery definitely improves overall and disease- specific survival; combination of androgen ablation and radiation therapy indicated for men with high-grade tumors |
| Advanced-stage cancer: management “all about androgen ablation”; for more advanced cases, interest exists in using docetaxel (Taxotere) and other chemotherapeutic agents |
| Follow-up care: any detectable PSA after radical prostatectomy indicates failed procedure (PSA should be zero); after radiation, PSA will not go to zero, but should be <1.0 ng/dL; treatment options for recurrent prostate cancer— observation, irradiation of prostate bed (after surgery), salvage surgery, cryotherapy, and androgen ablation (most commonly done) |
Benign Prostatic Hyperplasia | Epidemiology: prevalence increases with advancing age; men with BPH may or may not be symptomatic |
| Anatomic aspects: as prostate enlarges with age, urethra gets narrower and longer, resulting in obstructive and irritative symptoms; comments—for men on watchful waiting, 50% get worse, ≈33% remain stable, and small percentage improve; more severe symptoms are, more likely patient will develop acute urinary retention; prevalence of transurethral resections of prostate (TURP) lower today than in the past due to advances in medical therapy |
| Diagnostic work-up: begin with history (including medication history); rule out urethral strictures via cystoscopy; utilize International Prostate Symptom Score (IPSS) to assess degree of symptoms; examine prostate; do uroflowmetry and postvoid residual measurements; comment—PSA not part of work-up, but may be appropriate in men with BPH |
| Management: watchful waiting (indicated if symptoms not severe); α-blockers (eg, tamsulosin [Flomax), alfuzosin [Uroxatral], terazosin [Hytrin]; Flomax and Uroxatral do not require titration); 5-α-reductase inhibitors (eg, finasteride, dutasteride [Avodart]); surgery (TURP) generally reserved for worst cases; absolute indications for intervention—refractory hematuria; urinary retention; elevated creatinine; bothersome symptoms most common reason for intervention |
| URINARY TRACT STONES —Michel Pontari, MD, Associate Professor of Urology, Temple University School of Medicine, Philadelphia |
| Epidemiology: affects ≈5% of population; lifetime risk of passing stone 8% to 10%; chance of recurrence 50% |
| Types of stones: radiodense—seen on plain x-rays; subtypes include calcium oxalate (most common), calcium phosphate (second most common), and struvite (infection) stones; struvite stones somewhat lighter on kidney, ureter, and bladder (KUB) x-rays; radiolucent—subtypes include uric acid (most common), cystine (rare; faint on KUB), and indinavir stones (radiolucent on KUB and CT) |
| Factors involved in crystallization: nanobacteria provide nidus for deposition and crystallization; urine volume; solute concentration of factors; rate of stone inhibitors (citrate inhibits formation of stones); diet |
| Metabolic risk factors: hypercalciuria; hyperuricosuria; hyperoxaluria; hypocitraturia; low urine volume and dehydration most common cause |
| Clinical presentation: 70% of stones symptomatic and 30% asymptomatic; symptoms—colicky pain; pain in upper ureter, back, or flank area if stone proximal; pain in lower abdomen, testes, or labia on ipsilateral side if stone in middle and distal; nausea and vomiting; hematuria; frequency, urgency, and other urinary symptoms if stone distal (mimics urinary tract infection [UTI]) |
| Clinical evaluation: urinalysis (absence of hematuria does not rule out stone); urine culture; blood urea nitrogen (BUN), serum creatinine, and electrolytes; usual imaging studies include noncontrast helical CT and KUB to determne whether stone radiodense or radiolucent; intravenous pyelography (IVP) indicated if surgery contemplated; cautions—if patient on glucophage, stop 1-2 days before IVP; avoid IV contrast in patients with renal failure; try to avoid renal ultrasonography (US) |
| Management considerations: presence of obstruction; concurrent infection and fever (surgical emergency if obstruction also present); size and location of stone; other symptoms |
| Indications for admission: presence of infection or fever; pain uncontrollable by oral analgesics; extensive nausea and vomiting, precluding use of oral analgesics |
| Chances of passing stone: <25% if stone >5 mm; 20% to 45% if stone 5 mm; 40% to 50% if stone <5 mm in proximal ureter and 75% if in distal ureter |
| Outpatient management: analgesics (can give oxycodone and acetaminophen [Percocet], ketorolac [Toradol], or tramadol); if obstruction present, get follow-up KUB in 1 wk, followed by weekly visits; if patient not obstructed, get KUB within 2 wk, strain urine, then send patient home with strainer to catch stones; tell patient to seek care if significant pain, fever, or nausea and vomiting develop |
| Indications for referral: stone with obstruction and fever; stone >5 mm; small ureteral stone that has not passed in 4 wk |
| Surgical interventions: ureteral stent; extracorporeal shock-wave lithotripsy (ESWL) for stones in upper urinary tract 1 cm; ureteroscopy with laser lithotripsy for stones in kidney; percutaneous nephrolithotomy for stones >1.5 cm |
| Medical management: uric acid stones—alkalinization (speaker usually gives potassium citrate [Urocit-K] to get urine pH >7 to 7.5; usual starting dose 10 mEq tid; increase to 20 mEq tid); cystine stones—alkalization to increase pH to >7.5; speaker usually uses tiopronin (Thiola); infection stones—remove surgically, then give postoperative antibiotics; all stones—increase fluid intake |
| Indications for metabolic evaluation of stones: patients with ≥2 stones; fever or infection with stone; patient with urinary tract abnormalities; studies—serum studies for calcium, electrolytes, phosphate, and uric acid, and 24-hr urine for calcium citrate, uric acid, and oxalate |
| Stones during pregnancy: diagnosed with renal US; distinguish hydronephrosis of pregnancy from obstruction; place stent under US guidance; remove after delivery |
| Bladder stones: usually associated with bladder outlet obstruction with stasis of urine (eg, BPH, neurogenic bladder from spinal cord injury, after bladder augmentation); also seen with metabolic abnormalities; treatment involves laser lithotripsy |
| Stones in children: ≈50% have abdominal or flank pain, most have hematuria; evaluation includes urinalysis, urine culture, renal US, KUB, and metabolic evaluation |
| Indinavir stones: seen in HIV patients on indinavir; treatment includes temporarily stopping indinavir, hydration, controlling pain, stenting (maybe), and urine acidification |
| UROLOGIC IMAGING STUDIES IN PEDIATRIC PATIENTS —Michael Pergament, MD, Clinical Professor of Urology, University of Minnesota Medical School, Minneapolis, and Pediatric Urologist, Children’s Hospital Clinics of Minneapolis and St. Paul |
| What imaging studies do: identify any underlying urinary tract pathology; localize site of infection; detect renal scarring; follow up urinary tract changes, eg, in children with reflux |
| Studies: US—main screening study, but not always definitive; useful for fetal screening for urinary tract abnormalities; can detect renal scarring, swollen kidney, edema, focal enlargement, hydronephrosis, residual urine, bladder wall thickening, and keyhole anomaly; voiding cystourethrography (VCUG)—can demonstrate bladder and urethral anatomy and grade and detect urethral reflux; nuclear cystography—associated with low radiation exposure; good follow-up study or screen; speaker does on child with evidence suggestive of acute pyelonephritis with high fever and normal VCUG; also useful for evaluating children with reflux; diuretic renography—used to differentiate function between 2 kidneys and determine presence of obstruction; dimercaptosuccinic acid (DMSA) scan—helpful in detecting parenchymal renal scarring; CT—occasionally used to confirm acute pyelonephritis; useful in diagnosing abscesses and malignant lesions and following benign renal tumors; testicular US—useful for detecting intrascrotal pathology and ruling out testicular torsion |
| Recommended imaging protocol: after first UTI—do VCUG and US if child ≤5 yr of age; if child has afebrile UTI and ≥5 yr of age, do only US and follow-up VCUG if US abnormal; also do VCUG if UTI febrile or has second afebrile UTI; protocol for siblings and offspring of children with reflux—limit cystography to those ≤5 yr of age and those ≥5 yr of age with abnormal US; urinary incontinence—in children ≥5 yr of age, screen with renal bladder US; if US abnormal or patient has history of UTI, do VCUG |
Educational Objectives
| The goal of this program is to educate the listener about prostate cancer (PC), benign prostatic hyperplasia (BPH), urinary tract stones, and urologic imaging studies for infants and children. After hearing and assimilating this program, the clinician will be better able to: |
| 1. Screen for PC. |
| 2. Comprehend the various options (eg, radical prostatectomy, irradiation, watchful waiting, androgen ablation) for managing patients with PC. |
| 3. Diagnose and treat men with BPH. |
| 4. Evaluate and manage patients with urinary tract stones. |
| 5. Recommend imaging studies for children with suspected urinary tract problems. |
Discussed on This Program
Alfuzosin HCl [Uroxatral]Docetaxel [Taxotere] Dutasteride [Avodart] Finasteride [Propecia, Proscar] Indinavir sulfate [Crixivan] Ketorolac tromethamine [Acular, Acular LS, Toradol]Leuprolide acetate [Eligard, Lupron, others] Oxycodone and acetaminophen [Percocet, Roxicet, Roxilox, Tylox Capsules] Potassium citrate [Urocit-K]Saw palmetto (Serenoa repens) Tamsulosin HCl [Flomax] Terazosin HCl [Hytrin] Tiopronin [Thiola] Tramadol HCl [Ultram]
Suggested Reading
Benjamin R: Neurologic complications of prostate cancer. Am Fam Physician 65:1834, 2002; Bhatnagar V, Kaplan RM: Treatment options for prostate cancer: evaluating the evidence. Am Fam Physician 71:1915, 2005; Blumenfeld AJ et al: Nutritional aspects of prostate cancer: a review. Can J Urol 7:927, 2000; Corbetta S et al: Risk factors associated to kidney stones in primary hyperparathyroidism. J Endocrinol Invest 28:122, 2005; Dull P et al: Managing benign prostatic hyperplasia. Am Fam Physician 66:77 2002; Gooddin S et al: State-of-the-art treatment of metastatic hormone-refractory prostate cancer. Oncologist 7:927, 2002; Gordon AE, Shaughnessy AF: Saw palmetto for prostate disorders. Am Fam Physician 67:1281, 2003; Holmbergh L et al: A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med 347:781, 2002; Johansson JE et al: Natural history of early, localized prostrate cancer. JAMA 291:2713, 2004; Kalaitzis C et al: Treatment of indinavir sulfate induced urolithiasis in HIV-positive patients. Int Urol Nephrol 34:13, 2002; Kattan MW et al: Pretreatment nomogram for predicting the outcome of three-dimensional conformal radiotherapy in prostate cancer. J Clin Oncol 18:3352, 2000; Lee SK et al: Magnetic resonance voiding cystography in the diagnosis of vesicoureteral reflux: comparative study with voiding cystourethrography. J Magn Reson Imaging 21:406, 2005; Marberger M: Urinary stones. Curr Opin Urol 9:315, 1999; McConnell JD et al: The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 349:2387, 2003; Naderi N et al: Real life practice in the management of benign prostatic hyperplasia. Curr Opin 14:41, 2004; Portis AJ, Sundaram CP: Diagnosis and initial management of kidney stones. Am Fam Physician 63:1329, 2001; Punglia RS et al: Effect of verification bias on screening for prostate cancer by measurement of prostate-specific antigen. N Engl J Med 349:335, 2003; Samson DJ et al: Systematic review and metaanalysis of monotherapy compared to combination androgen blockade for patients with advanced prostate carcinoma. Cancer 95:361, 2002; Stanford JL et al: Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: the Prostate Cancer Outcome Study. JAMA 283:354, 2000; Steineck G et al: Quality of life after radical prostatectomy or watchful waiting. N Engl J Med 347:790, 2002; Stitchantrakul W et al: Effects of calcium supplements on the risk of renal stone formation in a population with low oxalate intake. Southeast Asian J Trop Med Public Health 35:1028, 2004; Sylven ET et al: High strain rate testing for kidney stones. J Mater Sci Mater Med 15:613, 2004; Thompson IM et al: Prevalence of prostate cancer among men with a prostate-specific antigen level ≤4.0 ng/mL. N Engl J Med 350:239, 2004; Thompson IM et al: The influence of finasteride on the development of prostate cancer. N Engl J Med 349:215, 2003; Thompson M et al: Timing of follow-up voiding cystourethrogram in children with primary vesicourethral reflux: development and application of clinical algorithm. Pediatrics 115:426, 2005; Trinchieri A et al: Calcium stone disease; a multiform reality. Urol Res 33:194, 2005; Webber R: Benign prostatic hyperplasia: clinical evidence concise. Am Fam Physician 70:1325, 2004; Wu DS, Stoller ML: Indinavir urolithiasis. Curr Opin Urol 10:557, 2000.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship with the manufacturer or provider of any commercial product or service discussed. The following has been disclosed: Dr. Pontari is co-holder of a patent with Merck & Company, a consultant for the Pfizer US Pharmaceutical Group, and has participated in a clinical trial for Roche Laboratories.
Dr. Litwin was recorded June 4, 2005, at the annual Family Practice Refresher Course, sponsored by the David Geffen School of Medicine at the University of California, Los Angeles. Dr. Pontari spoke March 18, 2005, at the annual Spring Family Practice Review, sponsored by the Temple University School of Medicine, Philadelphia, and Lancaster General Hospital, Lancaster, Pennsylvania, and held in Lancaster. Dr. Pergament spoke May 27, 2005, at the annual Family Medicine Review Update, sponsored by the University of Minnesota Medical School, Minneapolis. The Audio-Digest Foundation thanks the speakers and the sponsors for making this program possible.
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