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BENIGN PROSTATIC HYPERPLASIA
Audio-Digest Urology
Volume 36, Issue 13
July 7, 2013

Evolving Trends in Management – John T. Wei, MD
BPH in a Patient with Urinary Retention, Bladder Stone, and Elevated PSA – Mark D. Stovsky, MD
BPH in a Patient with Parkinson Disease – Gregory J. Lowe, MD

   
From The 2013 Annual Meeting Of The Wisconsin Urological Society
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The following is an abstracted summary, not a verbatim transcript, of the lectures/discussions on this audio program.

Urology Program Info  Accreditation InfoCultural & Linguistic Competency Resources

Benign Prostatic Hyperplasia

From the 2013 Annual Meeting of the Wisconsin Urological Society

Educational Objectives

The goals of this program are to improve diagnosis and treatment of benign prostatic hyperplasia (BPH). After hearing and assimilating this program, the clinician will be better able to:

1. Compare the risks and benefits of the major classes of medications used to treat BPH.

2. Interpret recent trials assessing combinations of medical therapies for BPH.

3. Offer guidance to a patient with BPH who is asking how to choose among several surgical treatment modalities he has read about.

4. Apply American Urological Association guidelines for treatment of BPH in patients with complex clinical presentations, including hematuria or urinary tract stones.

5. Discuss common issues encountered when treating BPH in patients with Parkinson disease.

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. Wei is a consultant (data and safety monitoring board) for NeoTract, has received grant/research support from Exosome Diagnostics and HistoSonics, and has received financial or material support (unspecified) from Johnson & Johnson. Dr. Stovsky is a consultant for Actavis. Dr. Lowe and the planning committee reported nothing to disclose.

Evolving Trends in Management

John T. Wei, MD, Division Head for General Urology and Professor of Urology at University of Michigan Medical Center, Ann Arbor

Spectrum of benign prostatic hyperplasia (BPH): clinically, BPH and overactive bladder (OAB) components of lower urinary tract symptoms (LUTS); on International Prostate Symptom Score (IPSS), typical patient with BPH has high frequency and urgency scores and low obstructive symptom scores; irritative symptoms of LUTS include frequency, urgency, urge incontinence (UI), and nocturia; obstructive symptoms include slow stream, straining, hesitancy, and intermittent stream; male LUTS also caused by neurologic conditions, medical therapies such as furosemide (Lasix), and unknown factors

Prevalence: 42% of men seen in primary care practice have IPSS score >7, half have prostatic enlargement on examination, and 29% have both; among patients with both, only one-third speak with primary care physician about treatment

Pharmacotherapy: α-blockers such as prazosin, doxazosin, and silodosin, and 5α-reductase inhibitors (5-ARIs) mainstay of therapy; newer therapies antimuscarinics, and phosphodiesterase-5 inhibitors (PDE5i)

α-blockers: classified as selective for α1a receptors or nonselective; selective drugs have fewer cardiovascular effects; silodosin promoted as highly selective; trial randomizing men to silodosin vs tamsulosin, no difference in IPSS total score found between groups

Phosphodiesterase-5 inhibitors: now considered standard option; men treated with sildenafil (Revatio, Viagra) or tadalafil (Adcirca, Cialis) demonstrate improved American Urological Association symptom scores (AUASS); dose-finding study of tadalafil demonstrated improvements through 12 wk in all active treatment groups compared with placebo; 2.5 to 5 mg chosen as dose that results in significant improvement; confirmed by randomized controlled trial (RCT)

Combinations: RCT studied tamsulosin alone vs tamsulosin plus tadalafil; incremental benefit in AUASS achieved by adding tadalafil to tamsulosin; no difference between groups in peak flow rate (Qmax); concerns exist about side effects, (eg, myocardial infarction, decreased blood pressure [BP]) when PDE5i combined with α-blocker; in randomized crossover study adding sildenafil or tadalafil in patients continuously using silodosin, initial drop in systolic BP observed in all groups, but only 2 to 3 mm Hg greater in active treatment groups than in placebo group; magnitude of fall in BP not clinically relevant

Antimuscarinic agents: nonuroselective antimuscarinics cross blood-brain barrier and can cause cognitive effects; uroselective drugs bind to M2 and M3 receptors and do not cause cognitive problems; antimuscarinics often used in patients not responding to α-blockers; study randomized men with moderate symptoms as evidenced by IPSS >12, including irritative symptoms, to placebo, tolterodine, tolterodine plus tamsulosin, or tamsulosin; at 12 wk, combination superior to placebo as measured by total AUASS, quality of life (QOL) item on IPSS, and other end points; tamsulosin monotherapy as effective as combination in analysis of total AUASS, but combination produced better QOL score than monotherapy; for storage symptoms, combination therapy better than monotherapy with tamsulosin

Urinary retention: although concerns exist about retention with antimuscarinic agents, increased retention not observed in RCTs; however, studies not powered to evaluate this end point; in meta-analysis of 7 best trials, odds of retention significantly greater with antimuscarinics; nonstatistically significant increase in need for catheterization observed; odds ratio 3 for retention when antimuscarinic added to α–blocker, but absolute risk low; check postvoid residual (PVR) in patients on combination

Laser surgery: noncontact, side-firing, potassium titanyl phosphate (KTP) laser now available in 180-W model; holmium laser used for enucleation of prostate (HoLEP); thulium and diode lasers now available

Utilization: in recent Medicare data, use of transurethral resection of prostate (TURP) falling, probably due to new technologies eg, transurethral microwave thermotherapy (TUMT), lasers, and to lesser extent, transurethral needle ablation of prostate (TUNA)

Efficacy: in meta-analysis of RCTs conducted as noninferiority study, most laser technologies noninferior to TURP; with 8-yr follow-up, TUMT had highest retreatment rate, followed by TUNA, coagulation laser, noncontact vaporization laser, and TURP; study suggested retreatment rate lowest after TURP but did not control for prostate size, symptoms, or anatomic configuration; reoperation rates at 1 yr as low as 0.1% after HoLEP and as high as 20% after diode laser treatment; retreatment rates at 5 yr 9% for 80-W laser and 1.4% for HoLEP; HoLEP may result in lower retreatment rate than other lasers

Prostate-specific antigen (PSA): decrease in PSA 40% after treatment with 80-W laser, 80% after 180-W KTP laser, 70% to 90% after HoLEP, and 82% after thulium laser enucleation of prostate

Sexual function: rates of ejaculatory dysfunction 30% to 50% after treatment with 80-W KTP laser, 75% after HoLEP, and 31% after diode laser; postoperative erectile function similar to preoperative function in most studies

Studies in patients with large prostates: RCT comparing photoselective vaporization with TURP found more bleeding with TURP but higher retreatment rate with KTP laser; study comparing 180-W KTP laser with HoLEP found no differences in AUASS or QOL; greater decreases in prostate volume observed after treatment with HoLEP than KTP; in HoLEP group, Qmax higher, ability to empty bladder superior, and PSA lower; all laser therapies likely equivalent to TURP, but laser may have fewer side effects

Electrovaporization: when used in saline, low risk for TURP syndrome and no need to complete case quickly; bipolar and mushroom button procedures available; RCT comparing bipolar to monopolar TURP found no difference in improvements in AUASS, bladder emptying, or Qmax; larger decrease in postoperative serum sodium (Na) levels in monopolar group statistically but not clinically significant; RCT randomizing patients to bipolar, monopolar, or mushroom button procedure found IPSS significantly lower in mushroom group; interpret such studies carefully because although patients randomized, surgeons not randomized; 3-yr follow-up study in patients with large prostates (>80 g) treated with PlasmaKinetic TURP demonstrated 87% fall in IPSS and 64% fall in PSA; HoLEP, 180-W KTP, and bipolar treatment all effectively debulk prostate; since modalities equivalent, surgeon need only become proficient at 1 or 2 procedures

UroLift: procedure designed to compress adenoma laterally to open urethra; transurethral probe placed through cystoscope; lateral lobe pressed against capsule and held in place with nonabsorbable suture and clips; 2 to 3 clips placed on each side of prostate; improvements in AUASS and QOL demonstrated in case series, without change in PVR; phase 3 studies under way; procedure brief

Robotic enucleation: case series using transvesical approach reported operating time 3 hr, hospital stay 3 days, duration of catheterization 7 days, no transfusions, and significant improvements in AUASS and Qmax

Prostatic injections: onabotulinumtoxinA (Botox) — causes atrophy, decreased proliferation, and apoptosis, possibly due to downregulation of α receptors; uncontrolled study using transperineal injection found improvements in AUASS and QOL; anhydrous ethanol — causes necrosis and thrombosis of vessels; in RCT, 79 men had decreases in AUASS at 3 different doses; side effects hematuria in 46%, irritative symptoms in 42%, transient retention in 23%, and incontinence in 15%; PRX302 — genetically engineered, pore-forming agent; inert until activated by PSA in prostate; causes cell lysis; in randomized phase 1/2 study, produced 3-point decrease in AUASS in 3 mo, but findings at 1 yr not statistically significant; may require modifications to dose, number of injections, and level of PSA

Histotripsy: uses sound waves to mechanically destroy lateral lobes; similar to lithotripsy but uses higher frequencies; causes mechanical cavitation, forming slurry of cells that leak into urethra and wash out; human trial planned

BPH in a Patient with Urinary Retention, Bladder Stone, and Elevated PSA

Mark D. Stovsky, MD, Staff Urologist, Cleveland Clinic, Cleveland, OH

Case: 65-yr-old with diabetes (DM) referred for evaluation of LUTS; history of terminal gross hematuria but no infection, incontinence, or renal insufficiency; PSA 6.3 ng/mL but no previous values available; both white and red blood cells on urinalysis, but culture negative; urine cytology showed atypia consistent with reactive changes; other findings blood urea nitrogen 22 mg/dL and creatinine 1.3 mg/dL; prostate moderately enlarged without nodularity

Clinical issues: BPH, symptoms, incomplete voiding, bladder stone, and elevated PSA; competing issues in this patient require detailed management; patient has no hydronephrosis

Recommended tests: AUASS 18 and QOL score 3; frequency and volume chart allows assessment of polyuria; upper tract imaging in addition to renal ultrasonography dictated by hematuria, but not required for BPH; computed tomographic (CT) urography normal except for 3-cm bladder stone

Optional tests: include uroflowmetry and PVR; objective measurements often valuable; Qmax 12 mL/sec, average flow 3 mL/sec, and PVR 175 mL

Management: lower endoscopy not recommended for evaluation of mild BPH, especially when treated with observation or medication; however, cystoscopy and transrectal ultrasonography (TRUS) important for surgical planning; anatomy of prostate can guide decisions about whether to use HoLEP, other laser vaporization, or staged procedure; cystoscopy performed because of gross hematuria revealed lateral BPH, long prostatic urethra, no median lobe, and large bladder stone; knowing length of prostatic urethra helps assess candidacy for TUMT and need for staged procedure; TRUS helpful for preoperative assessment of size of prostate and volume of transition zone; AUA guidelines consider TRUS optional; voiding dysfunction and bladder stone possible nonmalignant reasons for this patient to have elevated PSA; presence of cancer may change management plan; assessment shows 60-g prostate and BPH; prostatic biopsy showed BPH in all cores

Urodynamics: value questioned in patients with voiding dysfunction, particularly when surgery planned; however, often useful when planning surgery or evaluating complicated patients; in uncomplicated patient, uroflowmetry, PVR, and clinical history adequate; in this patient with incomplete emptying, bladder stone, and DM that may affect bladder function, urodynamic testing important, but must consider whether to do urodynamics in presence of stone or after intervention; study showed that urodynamics did not change in presence of bladder stone; 51% of patients with bladder stone had bladder outlet obstruction before or after treatment of stone, 68% had detrusor instability, 10% had bladder atony, and 20% had normal study after treatment of stone; urodynamics important, since 10% to 20% of patients have component of atony that can alter management decisions

Treatment: BHP and LUTS — options include watchful waiting, pharmacologic therapy with α–blockers, 5-ARIs, anticholinergics, and procedural therapies; surgical treatments include TURP and transurethral incision of prostate (TUIP); well-done TUIP equivalent to TURP; TUIP underused, and achievable with holmium laser; open, laparoscopic, or simple prostatectomies available; bladder stone — may treat with endoscopic fragmentation with laser or other technologies, with or without procedure for BPH; must decide whether to perform simultaneous procedures for stone and BPH, or remove stone, manage patient pharmacologically, and check urodynamics before planning procedure for BHP; if open procedure done for bladder stone, could treat prostate surgically at same time, but many such patients do not require surgical management of BHP; in this patient, may treat stone and follow with urodynamics to detect outlet obstruction or atony; plan minimally invasive laser vaporization or enucleation if medical therapy unsuccessful

BPH in a Patient with Parkinson Disease

Gregory J. Lowe, MD, Assistant Professor of Urology, Ohio State University Medical Center, Columbus

Case: 74-yr-old with Parkinson disease (PD), urgency, urge incontinence (UI), rare stress incontinence (SUI), decreased force of stream, nocturia, and erectile dysfunction; no frequency or incomplete emptying; patients with PD often have more storage than voiding symptoms; nocturia most frequent storage symptom in PD population; patient had relief with 10 mg, but not 5 mg solifenacin; developed retention on 10-mg dose; patient reported physical activity decreased his incontinence dramatically; history of successfully treated thyroid cancer and renal cell carcinoma (RCC); current medications carbidopa/levodopa, pramipexole, and warfarin (Coumadin, Jantoven); patient had tremors and other manifestations of PD, but speech clear; patient ambulatory but moved slowly; PSA 3.4 ng/mL, and urinalysis unremarkable; CT for follow-up of RCC unremarkable and PVR zero

Treatment: voiding diary prescribed to assess whether urgency related to difficulty traveling to bathroom and to detect nocturnal polyuria; desmopressin sometimes effective for nocturnal polyuria, but not recommended for this patient because fluctuations in Na could produce confusion; patient asked to elevate legs for 1 to 2 hr before bedtime; finasteride and tamsulosin prescribed; after 2 mo, patient reported worse motor symptoms, nocturia, and urgency; incontinence stable; motor and urinary symptoms not always correlated; patient had no improvement in force of stream and did not complete voiding diary; switched from tamsulosin to trospium, but returned 1 mo later with PVR 75 mL, having stopped taking trospium 2 wk earlier at request of neurologist; patient asking about TURP

Further evaluation: urodynamic evaluation appropriate per International Continence Society guidelines due to failure of conservative measures, elevated PVR, and mixed urinary symptoms; patient refused urodynamics; deep brain stimulation, posterior tibial nerve stimulation (PTNS), sacral neuromodulation, onabotulinum toxin, and prostatic surgical procedures can relieve urinary symptoms; high rates of incontinence reported after surgical procedures on prostate in studies that included patients with PD and multiple system atrophy (MSA); all patients with MSA have incontinence after prostatic procedures; patient chose PTNS, which improved his nocturia and urgency; in patients with PD, PTNS increases maximal cystometric capacity and decreases uninhibited detrusor contractions

Follow-up: stable PSA after stopping finasteride prompted biopsy that revealed cancer; patient had robotic prostatectomy and returned with SUI and slight increase in UI

Educational Objectives

The goals of this program are to improve diagnosis and treatment of benign prostatic hyperplasia (BPH). After hearing and assimilating this program, the clinician will be better able to:

1. Compare the risks and benefits of the major classes of medications used to treat BPH.

2. Interpret recent trials assessing combinations of medical therapies for BPH.

3. Offer guidance to a patient with BPH who is asking how to choose among several surgical treatment modalities he has read about.

4. Apply American Urological Association guidelines for treatment of BPH in patients with complex clinical presentations, including hematuria or urinary tract stones.

5. Discuss common issues encountered when treating BPH in patients with Parkinson disease.

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. Wei is a consultant (data and safety monitoring board) for NeoTract, has received grant/research support from Exosome Diagnostics and HistoSonics, and has received financial or material support (unspecified) from Johnson & Johnson. Dr. Stovsky is a consultant for Actavis. Dr. Lowe and the planning committee reported nothing to disclose.

Acknowledgements

Drs. Wei, Stovsky, and Lowe were recorded at the 2013 Annual Spring Meeting, presented by Ohio Urological Society and held on March 15-16, 2013, in Sandusky, OH. To learn about upcoming meetings of the Ohio Urological Society, go to ousweb.org or visit our website, audio-digest.org. The Audio-Digest Foundation thanks the speakers and the Ohio Urological Society for their cooperation in the production of this issue.

Suggested Reading

Abrams P et al: Evaluation and treatment of lower urinary tract symptoms in older men. J Urol 2009;181(4):1779-87; American Urological Association: AUA Guidelines. Available at: www.auanet.org/education/clinical-practice-guidelines.cfm. Accessed May 10, 2013; Biester K et al: Systematic review of surgical treatments for benign prostatic hyperplasia and presentation of an approach to investigate therapeutic equivalence (non-inferiority). BJU Int 2012;109(5):722-30; Elmansy H et al: Holmium laser enucleation versus photoselective vaporization for prostatic adenoma greater than 60 ml: preliminary results of a prospective, randomized clinical trial. J Urol 2012;188(1):216-21; Gacci M et al: A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with α-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol 2012;61(5):994-1003; Geavlete B et al: Bipolar plasma vaporization vs monopolar and bipolar TURP-A prospective, randomized, long-term comparison. Urology 2011;78(4):930-5; Horasanli K et al: Photoselective potassium titanyl phosphate (KTP) laser vaporization versus transurethral resection of the prostate for prostates larger than 70 mL: a short-term prospective randomized trial. Urology 2008;71(2):247-51; Kaplan SA et al: Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA 2006;296(19):2319-28; Erratum in: JAMA 2007;298(16):1864; JAMA 2007:297(11):1195; Lemack GE et al: Questionnaire-based assessment of bladder dysfunction in patients with mild to moderate Parkinson’s disease. Urology 2000;56(2):250-4; MacDiarmid SA et al: Lack of pharmacodynamic interaction of silodosin, a highly selective alpha1a-adrenoceptor antagonist, with the phosphodiesterase-5 inhibitors sildenafil and tadalafil in healthy men. Urology 2010;75(3):520-5; Malaeb BS et al: National trends in surgical therapy for benign prostatic hyperplasia in the United States (2000-2008). Urology 2012;79(5):1111-6; Mamoulakis C et al: Results from an international multicentre double-blind randomized controlled trial on the perioperative efficacy and safety of bipolar vs monopolar transurethral resection of the prostate. BJU Int 2012;109(2):240-8; Millán-Rodríguez F et al: Urodynamic findings before and after noninvasive management of bladder calculi. BJU Int 2004;93(9):1267-70; Porst H et al: Efficacy and safety of tadalafil once daily in the treatment of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: results of an international randomized, double-blind, placebo-controlled trial. Eur Urol 2011;60(5):1105-13; Roth B et al: Benign prostatic obstruction and parkinson’s disease — should transurethral resection of the prostate be avoided? J Urol 2009;181(5):2209-13; Teng J et al: Photoselective vaporization with the green light laser vs transurethral resection of the prostate for treating benign prostate hyperplasia: a systematic review and meta-analysis. BJU Int 2013;111(2):312-23; Yu HJ et al: Non-inferiority of silodosin to tamsulosin in treating patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). BJU Int 2011;108(11):1843-8.


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