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UROLOGIC CONCERNS IN MEN
Audio-Digest Family Practice
Volume 61, Issue 27
July 21, 2013

Lower Urinary Tract Symptoms/ Sexual Dysfunction/Scrotal Pain – Carol Kashefi, MD
Prostate Cancer Screening – Howard L. Adler, MD

   
Digital Media $24.99
Audio CD $27.99
 


The following is an abstracted summary, not a verbatim transcript, of the lectures/discussions on this audio program.

Family Practice Program Info  Accreditation InfoCultural & Linguistic Competency Resources

Urologic Concerns in Men

Educational Objectives

The goals of this program are to improve diagnosis and management of urologic problems and prostate cancer in men. After hearing and assimilating this program, the clinician will be better able to:

1. Prescribe drugs for treatment of lower urinary tract symptoms and erectile dysfunction.

2. Identify causes of scrotal pain.

3. Recognize groups at higher risk for prostate cancer.

4. Consider recommendations from the United States Preventive Services Task Force and American Urological Association for prostate-specific antigen-based screening for prostate cancer.

5. Counsel appropriate patients with prostate cancer about the option of active surveillance.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee 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. Kashefi is on the Speakers’ Bureaus for Astellas Pharma US, Pfizer, and Warner Chilcott. Dr. Adler and the planning committee reported nothing to disclose. In her lecture, Dr. Kashefi presents information that is related to the off-label or investigational use of a therapy, product, or device.

Lower Urinary Tract Symptoms/
Sexual Dysfunction/Scrotal Pain

Carol Kashefi, MD, Urologist, Scripps Green Hospital, La Jolla, CA

Lower urinary tract symptoms (LUTS): urinary storage (irritative) — urgency; increased daytime frequency; nighttime frequency; incontinence; voiding — slow stream; difficulty starting; spraying; incomplete voiding; intermittency; terminal dribbling; postmicturition symptoms

Differential diagnosis: benign prostatic hyperplasia (BPH); ureteral stones; tumor; stricture; prostatitis; nocturnal polyuria associated with obstructive sleep apnea

Management: no treatment required if patient able to urinate comfortably (discuss prevention, eg, avoiding cold medications); if LUTS bothersome, start with behavioral management (eg, stopping fluids 3 hr before bedtime); elevating legs 2 to 3 hr before bedtime helpful; indications for referral to urologist — suspicious rectal examination; blood in urine; elevated prostate-specific antigen (PSA); pain

First-line treatments for BPH related to LUTS

α-blockers: doxazosin (start with 1-2 mg; titrate up weekly to 8 mg); terazosin (titrate up to 5 mg); no dose escalation required with newer selective α-blockers (eg, tamsulosin [Flomax] or alfuzosin [Uroxatrol]); side effects — anejaculation (least with alfuzosin); onset of action — with silodosin (Rapaflo), occurs within hours rather than days

5α-reductase inhibitors: when starting finasteride or dutasteride, check baseline PSA and recheck after 6 mo (patients may have clinically important prostate cancer; refer to urologist if PSA does not drop by 50%); patients likely to benefit — those with gland 40 g; those with PSA 1.5 ng/mL; can be helpful in reducing risk for retention and need for surgery in patients with elevated postvoid residual urine volume and severe symptoms; time to clinical benefit — 6 to 12 mo (α-blocker should be used immediately as well); takes 2 to 4 yr of use for full benefits; reduces prostate size by 30% and increases flow rate by 2 mL/sec

Combination therapy: studies done over 6 to 12 mo showed α-blocker alone equivalent to combination of α-blocker and 5α-reductase inhibitor; Medical Therapy of Prostatic Symptoms trial showed synergistic benefit of combination therapy over 4.5 yr, compared to α-blocker alone

5α-reductase inhibitors and cancer: Prostate Cancer Prevention Trial — 18,000 men 55 yr of age with normal prostate examinations and PSA <3.0 ng/mL given finasteride or placebo; men underwent annual PSA testing and digital rectal examination (DRE; men underwent prostate biopsy if PSA elevated, DRE abnormal, or completed study after 7 yr); found that high-risk prostate cancers (Gleason score 8-10) more prevalent in men treated with finasteride than in those treated with placebo; later study showed similar results with dutasteride at 4 yr; meta-analysis showed 25% relative risk reduction in lower-risk cancers (Gleason score ≤7) with use of 5α-reductase inhibitors; theories — higher likelihood of cancer detection with reduced prostate size; natural selection (ie, selecting out higher-grade cancers unaffected by inhibitory effects of 5α-reductase inhibitors)

Erectile dysfunction (ED): incidence increases with each 10 yr above age 40 yr; prevalence higher with age and medical comorbidities; risk factors — ≤75% of men with diabetes have some degree of ED; cardiovascular (CV) disease (consider CV assessment); chronic renal failure; hyperthyroidism; pelvic or abdominal surgery; exposure to radiation or trauma; priapism; Peyronie disease; scarring of tunica albuginea; long-standing bicycling; depression; central nervous system pathology; medications (eg, antihypertensives, psychotropics, antiandrogens); smoking

Prevention of ED: avoid smoking; use bicycle seat with no nose; cross-sectional study saw significantly lower relative risk of developing ED in men who had sex 3 times/wk, compared to men who had sex ≤1 time/wk

Pathophysiology of ED: organic ED — problems with blood flow (eg, venous leak; penile ring can help significantly); neurogenic, anatomic, or endocrinologic cause (check prolactin, testosterone, and thyroid hormones); psychogenic ED — ask about nocturnal erections; adrenaline and stress potent inhibitors of erections

First-line therapies: CV assessment — if patient at low risk (<3 risk factors), give phosphodiesterase type 5 (PDE-5) inhibitors; if patient at high risk, make sure condition stable before beginning treatment; PDE-5 inhibitors — gold standard; vardenafil (Levitra, Staxyn [10 mg sublingually; can be taken with or without meals]); no concerns about timing and concomitant use with α-blocker; sildenafil (Viagra) and vardenafil should be taken on empty stomach (1 hr before meal or 3 hr after meal; not as relevant with tadalafil [Cialis])

Second-line therapies: intracavernous injections — alprostadil, papaverine, or phentolamine delivered directly to cavernosal tissues to create erection; should be avoided in patients on warfarin (eg, Coumadin, Jantoven, Marevan) or patients with poor manual dexterity; can cause penile fibrosis in <3% of patients; concern for hematoma; teach patient technique (do trial in office and look for good response; make sure patient does not develop priapism); has high efficacy; intraurethral injections — alprostadil in pellet form inserted into penis diffuses into cavernosal bodies; causes penile pain (can transmit and cause vaginal pain); has lower efficacy than intracavernous injections; vacuum erectile devices — advantages include no use of medications and no side effects; risk for penile ischemia when used for >30 min; surgery — penile prostheses (semirigid or inflatable); penile revascularization (rare; used in avid bicyclists or patients with trauma to groin)

Premature ejaculation: ejaculation ≤1 min from start of vaginal entry (normal 5 min); unsatisfactory for both partners; common at 40 to 50 yr of age; possible causes include serotonin receptor stimulation and penile hypersensitivity (contradicted by circumcision studies); associated with ED, but mostly with psychologic problems

Treatments: behavioral modification; sexual psychotherapy; no medications approved by Food and Drug Administration (FDA) in United States; prilocaine and lidocaine to minimize sensitivity (condoms must be used); selective serotonin reuptake inhibitors (SSRIs) — off-label use; paroxetine (Paxil, Paxil CR, Pexeva) typically used as on-demand dose (eg, 5 hr before sex); dapoxetine (approved in Europe)

Scrotal pain: differential diagnosis — hydrocele; spermatocele; varicocele (more common on left side); torsion; testicular cancer; trauma; patient history — onset; duration; quality; exacerbating and alleviating factors; stressors; relationships; history of scrotal or inguinal surgeries; physical examination — palpation; DRE (prostatitis can masquerade as scrotal pain [particularly if pain bilateral]); urinalysis or culture to rule out infection; sensitivity and specificity of semen culture or expressed prostatic secretions low (no longer used); high-resolution ultrasonography recommended to rule out tumor in all men with orchalgia; treatment — first-line treatment includes nonsteroidal anti-inflammatory drugs (NSAIDs) and sitz baths if 2 courses of antibiotics for epididymitis ineffective; tailor antibiotics based on suspicion of sexually transmitted disease (STD; if patient <35 yr of age, treat for STD; if patient >35 yr of age and STD unlikely, then fluoroquinolone adequate); start trial of α-blocker (off-label use) to relax pelvic floor tension (effective in ≤50% of patients); gabapentin, tricyclic antidepressants, or carbamazepine may be helpful; complementary or alternative medicine (eg, biofeedback) and pelvic floor physical therapy helpful; surgery — epididymectomy ineffective; patients who undergo orchiectomy may have residual pain; some studies show good results with vasovasostomy or vasoepididymostomy in patients with vasectomy, but can also induce more pain; hydrocelectomy preferred over needle aspiration due to higher risk for infection and recurrence

Prostate Cancer Screening

Howard L. Adler, MD, Clinical Associate Professor of Urology and Medical Director of Prostate Care Program, State University of New York, School of Medicine, Stony Brook

Prostate cancer (PC): risk for diagnosis increases with age; most common in men >60 yr of age; average age at diagnosis in white men 69 yr (67 yr in blacks); colorectal, lung, and prostate cancers top causes of cancer death; most patients with PC who die have hormone-refractory (castration-resistant) disease; 85% of patients have bone metastases; death rate declining over time (may be due to early androgen deprivation; many patients undergo hormonal therapy); lifetime risk of dying from PC 2% to 3%; 90% to 95% of patients who have PC die from unrelated cause; no curative therapy available for advanced PC; survival rates of men who undergo radical prostatectomy for organ-confined disease equivalent to those of age-matched controls; early-stage cancers not palpable; microscopic cancers can have high malignant potential and lead to lethal disease; most palpable PCs not curable

Prostate-specific antigen: serine protease; produced by prostatic epithelium and periurethral glands; liquefies coagulum and seminal fluid

Evaluation: consecutive annual evaluations by PSA testing and DRE; older recommendations — start screening white men with no family history at age 50 yr; start screening black men and men with positive family history at age 40 yr; less frequent (eg, every 4-5 yr) screening being considered in patients with low PSA; American Urological Association (AUA) recommendations (2009) — attain baseline PSA in all men 40 yr of age; single threshold value of PSA to prompt prostate biopsy no longer recommended; decision to proceed should be based primarily on PSA and DRE results, while considering free and total PSA, patient’s age, PSA velocity, PSA density (PSA relative to prostate size), family history, ethnicity, biopsy history, and comorbidities; AUA strongly supported that men need to be informed of risks and benefits of PC screening before biopsy and option of active surveillance in lieu of immediate treatment for certain men

United States Preventive Services Task Force (USPSTF): in 2008, concluded with moderate certainty that harms of PSA screening outweighed benefits in men 75 yr of age; clinicians should not order PSA testing for men <75 yr of age without first discussing potential but uncertain benefits and known harms of screening and treatment; in 2011, USPSTF stated that there is moderate or high certainty that testing has no net benefit, or that harms outweigh benefits (grade D recommendation), and discouraged use of service; Affordable Care Act — mandated that USPSTF must assess, develop, and update clinical preventive recommendations; requires that Medicare and qualified commercial plans provide 100% coverage for preventive services graded A or B by USPSTF, and services graded C or D require copayment; following release of recommendation, Obama Administration told Associated Press that Medicare would continue to pay for PSA testing

PSA testing: goals to prevent mortality and morbidity associated with metastatic PC, including urinary tract obstruction, fractures, and significant bone pain; early detection most effective way to prevent or minimize morbidity of advanced (metastatic) PC; some PCs aggressive and advance quickly, but many indolent, slow-growing, and may never become life threatening; PSA testing most widely available method for identifying changes in prostate; when used appropriately, PSA provides valuable information that aids in diagnosis, follow-up, and treatment; patients who have symptomatic tumors have higher-grade, more advanced (often deadly) disease; data show 75% reduction in proportion of men who present with metastatic PC; metastatic PC in new diagnosis extremely rare; 42% reduction in age-adjusted PC mortality seen over last 20 yr; various models suggest 40% to 70% of reduction due to early detection; most studies analyzed by USPSTF demonstrate benefits from PSA testing; USPSTF underestimated benefits and overestimated harms of testing

Studies: Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial — among >76,000 men 55 to 74 yr of age, PC detection rate 12% higher in screening arm; study considered imperfect due to prescreening contamination of control arm, thereby invalidating original comparison hypotheses; 60% to 70% of men with abnormal PSA failed to get timely prostate biopsy; European Randomized Study of Screening for Prostate Cancer — recent data show 21% risk reduction in PC-related deaths (≤29% after accounting for noncompliance of patients); benefits primarily seen in men <70 yr of age; number of PCs needed to be detected to prevent 1 death 37; PSA screening significantly reduced risk of developing metastatic PC; Goteborg randomized population-based PC screening trial — looked at 20,000 men 50 to 64 yr of age; showed 41% decrease in advanced PC and 44% relative risk reduction in PC mortality after median of 14 yr

AUA Best Practice Statement (2009): early detection and risk assessment should be offered to asymptomatic men 40 yr of age who wish to be screened, and have estimated life expectancy >10 yr; men who wish to be screened should undergo PSA testing and DRE; decisions to use PSA for early detection should be individualized; inform patients about known risks and potential benefits; AUA strongly supports that men be informed of risks and benefits of PC screening before biopsy and option of active surveillance for certain men diagnosed with PC

High-risk patients who may benefit from screening: patients with African ancestry (50% more likely to be diagnosed with PC; have 245% greater PC mortality rate); patients with positive family history of PC; patients with PSA 1 ng/mL at age 40 yr

Diagnosis and treatment: diagnosis does not automatically indicate need for active treatment; current standard to offer active surveillance to appropriate patients (eg, patients with low-risk disease, patients with limited life expectancy, patients who do not wish to pursue aggressive interventions)

Questions and answers: free PSA — fraction of total PSA that is unbound; not routinely used by speaker; mostly used to determine need for second biopsy; <21% considered abnormal or suspicious; can be reduced by inflammation or infection; tested in research laboratories; benign PSA and intact or inactive PSA correlate with BPH; pro PSA correlates with PC and aggressiveness; testosterone replacement — not recommended for patients under active surveillance but reasonable on individual basis in patients treated successfully with no disease; prostate intraepithelial neoplasia (PIN) — premalignant lesion; some patients diagnosed with PC found to have high-grade PIN; patients with small amount of focal PIN less likely to be diagnosed with PC; if multiple cores positive, recommend repeat biopsy sooner; markers — PC antigen 3 testing (urine-based marker that can help select patients who may benefit from repeat biopsy); absence of phosphatase and tensin homolog (immunohistochemical marker) in many malignancies associated with presence of aggressive disease

Acknowledgements

Dr. Kashefi spoke in Wailea Beach, Maui, HI, at the 18th Annual Primary Care in Paradise: Medical Specialties from the Primary Care Perspective, presented March 25-28, 2013, by Scripps Conference Services and CME. Please visit www.scripps.org/for-health-care-professionals for information about other course offerings from this sponsor. Dr. Adler spoke in Stony Brook, NY, at Maurice Goldenhar 39th Annual Family Medicine Update 2013, presented March 20-22, 2013, by the Department of Family Medicine at Stony Brook School of Medicine. Please visit http://medicine.stonybrookmedicine.edu/cme/courses for information about course offerings from this sponsor. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Suggested Reading

Agalliu I et al: Prostate cancer mortality in relation to screening by prostate-specific antigen testing and digital rectal examination: a population-based study in middle-aged men. Cancer Causes Control. 2007 Nov;18(9):931-7; Andriole GL et al: PLCO Project Team. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009 Mar 26;360(13):1310-9; Aus G et al: Prostate cancer screening decreases the absolute risk of being diagnosed with advanced prostate cancer — results from a prospective, population-based randomized controlled trial. Eur Urol. 2007 Mar;51(3):659-64; Chapple CR: A Comparison of Varying alpha-Blockers and Other Pharmacotherapy Options for Lower Urinary Tract Symptoms. Rev Urol. 2005;7 Suppl 4:S22-30; Etzioni R et al: Limitations of basing screening policies on screening trials: The US Preventive Services Task Force and Prostate Cancer Screening. Med Care. 2013 Apr;51(4):295-300; Etzioni R et al: Impact of PSA screening on the incidence of advanced stage prostate cancer in the United States: a surveillance modeling approach. Med Decis Making. 2008 May-Jun;28(3):323-31; McMahon CG: Dapoxetine: a new option in the medical management of premature ejaculation. Ther Adv Urol. 2012 Oct;4(5):233-51; Melnikow J et al: Counterpoint: Randomized trials provide the strongest evidence for clinical guidelines: The US Preventive Services Task Force and Prostate Cancer Screening. Med Care. 2013 Apr;51(4):301-3; Moyer VA: U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012 Jul 17;157(2):120-34; Munarriz R et al: Only the nose knows: penile hemodynamic study of the perineum-saddle interface in men with erectile dysfunction utilizing bicycle saddles and seats with and without nose extensions. J Sex Med. 2005 Sep;2(5):612-9; Pinsky PF et al: Prostate cancer specific survival in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Cancer Epidemiol. 2012 Dec;36(6):e401-6; Qin Z et al: Impact of frequency of intercourse on erectile dysfunction: a cross-sectional study in Wuhan, China. J Huazhong Univ Sci Technolog Med Sci. 2012 Jun;32(3):396-9; Van der Meer S et al: Impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC) on prostate-specific antigen (PSA) testing by Dutch general practitioners. BJU Int. 2013 Mar 6 [Epub ahead of print].


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