Best of the AUA Annual Meeting

Meeting Review

9a. RIU0500_07-31.qxd 8/4/10 4:28 PM Page e134 MEETING REVIEW Best of the AUA Annual Meeting Highlights From the 2010 American Urological Association Meeting, May 29-June 3, 2010, San Francisco, CA [Rev Urol. 2010;12(2/3):e134-e146 doi: 10.3909/riu0500] © 2010 MedReviews®, LLC Key words: Urosepsis • Transrectal ultrasound prostate • Escherichia coli • Autologous muscle-derived cells • Botulinum toxin • Synthetic mesh sling • Prostate-specific antigen • Nocturia • Prostatic urethral lift • PRX3.02 • Shock wave lithotripsy ver 2100 posters, abstracts, and videos were presented at the 2010 annual meeting of the American Urological Association (AUA), held this year in San Francisco, CA, from May 29 through June 3. The editors of Reviews in Urology have culled the enormous volume of infor- O Reviewed by J. Curtis Nickel, MD, Queen’s University, Kingston, Ontario, Canada; Akira Furuta, MD, Jikei University School of Medicine, Tokyo, Japan; Michael B. Chancellor, MD, William Beaumont Hospital, Royal Oak, MI; Claus G. Roehrborn, MD, FACS, University of Texas Southwestern Medical Center, Dallas, TX; Dean G. Assimos, MD, Wake Forest University School of Medicine, WinstonSalem, NC; Ellen Shapiro, MD, FACS, FAAP, New York University School of Medicine, New York, NY; Michael K. Brawer, MD, URIDEA, Seattle, WA. e134 VOL. 12 NO. 2/3 2010 mation from this premier source and present here the findings most relevant to the practicing urologist. Infectious Complications of Prostate Biopsies Urosepsis is one the most feared complications of transrectal ultrasound prostate (TRUSP) biopsies and as the number of biopsies worldwide increases, we have noticed an increase in the number of centers reporting this complication. Five separate groups presented their post-TRUSP biopsy infectious complication rate at the 2010 AUA meeting. There are serious lessons to be learned from these presentations. Table 1 summarizes these reports, which are remarkably consistent. The risk of serious infectious complications requiring hospitalization from TRUSP biopsy is not trivial. In total, 791 of 66,811 men undergoing TRUSP (1.2%) developed REVIEWS IN UROLOGY urosepsis, with the majority being admitted to hospital. A number of these studies clearly show that this problem has been increasing over time.1,2,6 These studies indicate that most of the TRUSP-associated infectious complications are secondary to Escherichia coli. It is likely that this problem is related to evolving antimicrobial resistance patterns. Penna and colleagues7 reported a metaanalysis of antimicrobial resistance patterns of E coli in uncomplicated, community-acquired urinary tract infections among adults. Studies (84,074 North American and European isolates between 1998 and 2007) generally showed significantly increased resistance to our frontline antibiotics starting after 2000, in particular with increasing patterns of ciprofloxacin resistance. There is no doubt that resistance is increasing in our urological population by injudicious 9a. RIU0500_07-31.qxd 8/4/10 4:28 PM Page e135 Best of the AUA Annual Meeting Table 1 Rate of Infectious Complications in Men Undergoing TRUSP Biopsy of the Prostate Authors Country Men at Risk 1 Canada 2 Loeb S et al Casey JT et al3 Cermak A et al4 Nam R et al Jung S et al5 6 Uddin MM et al Prophylaxis Rate % (n) Organism Outcome 41,482 ND 1.4% (562) ND Hospitalization USA 17,472 ND 0.38% (67) ND Hospitalization USA 945 Ciprofloxacin 1.6% (15) E coli in 83.3% ND Czech Republic 1943 Fluoroquinolone  metronidazole 2.42% (47) E coli in 68% Hospitalization (30/47) Korea 2013 Ciprofloxacin 0.4% (9) E coli in 100% Hospitalization Singapore 2956 Ciprofloxacin  gentamicin  augmentin 3.1% (91) E coli in 94.4% ND E coli, Escherichia coli; ND, not documented; TRUSP, transrectal ultrasound prostate. use of antibiotic prophylaxis and treatment regimens. The somewhat popular regimen of subjecting men with mildly elevated prostate-specific antigen (PSA) levels to 4 to 6 weeks of antibiotics to see if the PSA drops (and biopsy can be avoided) should be put to rest by the randomized, controlled trial presented by Bhaysar and colleagues.8 This practice is ineffective and not only increases the risk of emergence of resistance in the local population but would theoretically put those men who will likely require a biopsy at higher risk of urosepsis with resistant organisms. So what can we do about this very real risk? More antibiotic prophylaxis is not the ultimate solution. The following suggestions are recommended: 1. Wait for a period of time (4-6 weeks?) after previous antibiotic treatment of whatever cause. 2. Carefully monitor bacterial sensitivity results of all local infectious events so that prophylaxis may be adjusted according to local resistance rates of the most common organisms (in particular, E coli). 3. Encourage careful stewardship of antibiotics in your area (rationale short-course prophylaxis for uro- logical conditions as suggested in AUA guidelines). 4. Make sure that sterile urine is documented prior to the procedure. 5. In patients at higher risk for harboring multiple resistant organisms (recent immigrant, long-term antibiotic use, physician or hospital worker exposed to these organisms, previous recent procedures including TRUSP biopsies), consider prebiopsy anal swab or stool cultures. These AUA presentations were a wake-up call for the urological community. The problem will not go away, but will become more significant over time. Above all, we must strive to do no harm to patients who are involved in our prostate cancer screening and detection efforts. [Reviewed by J. Curtis Nickel, MD, FRCSC] Incontinence Dr. Lesley Carr from Toronto, Ontario, Canada, presented a multicenter Canadian study of autologous musclederived cell (AMDC) injection for the treatment of stress urinary incontinence (SUI).9 This study was sponsored by Cook Medical Incorporated (Bloomington, IN) and was approved by Health Canada and the institutional ethics committees. This study enrolled 38 women whose SUI had not improved with standard therapy for at least 12 months. AMDCs were biopsied from patients’ quadriceps femoris using a needle device under local anesthesia. In the first, double-blind phase, 20 patients were randomized into 5 groups to receive 1, 2, 4, 8, or 16 million AMDCs via cystoscope-assisted periurethral cell injection. The second, single-blind phase sequentially enrolled 9 patients, 3 per group, to receive 32, 64, or 128 million AMDCs. The third, single-blind phase of the study utilized ultrasound guidance to inject 9 patients, 3 per group, with 16, 32, or 64 million AMDCs. All patients could elect a second injection of the same dose after 3-month follow-up with measures at 1, 3, 6 and 12 months after the last injection. Twenty-nine women have reached 12-month follow-up; no serious adverse events were encountered. Minor events included pain and bruising at the muscle biopsy site, mild local reactions to cell injection, mild self-limited urinary retention lasting a few hours without need for catheterization, and VOL. 12 NO. 2/3 2010 REVIEWS IN UROLOGY e135 9a. RIU0500_07-31.qxd 8/4/10 4:28 PM Page e136 Best of the AUA Annual Meeting continued urinary tract infection; 1 patient reported worsened incontinence after the second injection. Of the 4 patients who received a single injection and completed 12 months of follow-up, all reported  50% reduction in stress leak numbers. Of the 25 patients with 2 injections who have reached the 12-month follow-up, 12 patients (48%) reported no stress leaks at 12 months after the second injection; 16 patients (64%) had  50% reduction in the number of stress leaks over a 3-day period. In addition, at 12 months after the second injection, 40% of the patients experienced  50% improvement in quality of life. More women with the larger dose injection trended to greater improvement, but more of the higher dose women are currently pending follow-up. Dr. Carr concluded that AMDCs are safe for treating patients with SUI with promising efficacy at 1 year follow-up in relieving symptoms and improving quality of life. Bladder botulinum toxin injection has gained considerable attention for the treatment of the refractory overactive bladder (OAB); however, the rate of occurrence of adverse events (AE) may be a concern. Dr. Chen and associates from Taiwan evaluated a series of botulinum toxin A (BoNT-A) bladder injections to assess potential risk factors of adverse events that may help improve patient selection.10 From 2004 through 2009, patients who received BoNT-A injections for refractory OAB were reviewed and acute urinary retention (AUR), elevated postvoid residual urine (PVR), straining to void, urinary tract infection (UTI), hematuria, and general weakness were assessed as AE. The incidence of AE was analyzed according to the dose of BoNT-A, site of injection, sex difference, age, comorbidities, presence of benign prostatic hyperplasia (BPH) in men, and urodynamic parameters. e136 VOL. 12 NO. 2/3 2010 There were 112 men and 105 women. Mean age was 71 years (range, 18-94). At 3 months, a successful result was reported in 144 (66%) of patients; 36 (17%) had mild improvement and 37 (17%) had no improvement. AUR occurred in 18 (8%), with PVR  150 mL in 103 patients (48%). One hundred one (47%) patients reported straining to void. Gross hematuria occurred in 17 (8%) patients, UTI developed in 31 (14%), and general weakness was noted in 6 (3%). A larger dose of BoNT-A correlated with a higher incidence of elevated PVR and straining to void. Increased incidence of AUR was noted in men, age  75 years old, and patients with baseline PVR  100 mL or voiding efficiency  70%. Interestingly no patients receiving only bladder base and trigonal BoNT-A injections had AUR. Dr. Chen reported that male sex, aging, elevated baseline residual urine volume, and higher botulinum toxin dose are risk factors for potential AEs. The authors noted that clinical efficacy was similar with or without risk for AE and they noted minimal adverse events with 100 U and bladder base and trigonal injection of BoNT-A. Dr. Burnett and associates from Jacksonville, Florida, performed an analysis of a longitudinal database update of repair of female prolapse with synthetic prosthetics.11 Patients undergoing anterior, posterior, or combined anterior and posterior repair using synthetic mesh material were enrolled. The authors reported retrospectively prior to September 2006 and prospectively since September 2006 on this internal review board (IRB)–approved database. Patients were followed at 3- to 6-month intervals and given a complete pelvic examination and inquiry as to sexual activity and new onset or recurrent prolapse symptoms. Data were analyzed using logistic regression analy- REVIEWS IN UROLOGY sis. The authors reported no source of funding. From 2003 to 2009, 310 patients underwent synthetic mesh prolapse repair, of which 166 underwent anterior repair, 104 underwent posterior repair, and 40 combined anterior and posterior repair. Mean follow-up was approximately 40 months (range, 1-76 months). Three of 310 patients experienced major complications: 1 bleeding requiring re-operation, 1 delayed rectovaginal fistula at 9 months postoperatively, and 1 urinary retention requiring suprapubic tube that gradually resolved her symptoms. Dr. Burnett concluded that at their institution, synthetic mesh material used for reconstruction of pelvic organ prolapse has an acceptable complication rate and an excellent success and satisfaction rate at mean follow-up of almost 40 months. Obesity is known to be associated with SUI, and recent epidemiological studies have also demonstrated a link between obesity and OAB. Dr. Tyagi and associates explored a new hypothesis that appetite-inducing peptide hormone ghrelin (the hunger protein) is a key link between obesity and bladder contractility,12 and were awarded the AUA best abstract prize. At a podium presentation, Dr. Tyagi reported new linkage between obesity and incontinence. Human bladders were obtained from organ donors and effect of ghrelin peptide was investigated in precontracted isolated human bladder strips by cumulative dose addition. Cumulative addition of ghrelin into the muscle strip bath evoked concentration-dependent reduction in the frequency of spontaneous contractions of human bladder strips. The ghrelin addition to isolated rat bladder strips precontracted with potassium choride produced a dose-dependent reduction in contractility. 9a. RIU0500_07-31.qxd 8/4/10 4:28 PM Page e137 Best of the AUA Annual Meeting Dr. Tyagi concluded that this was the first study to demonstrate the functional role of ghrelin in human bladder and its inhibitory effect on bladder contractions. Peripheral ghrelin receptors on nitrergic nerves in bladder may aid bladder relaxation by releasing nitric oxide. These findings shed light on the mechanism of the association of obesity with OAB because ghrelin, released from the stomach and/or pancreas, acts on the hypothalamus and stimulates appetite, leading to inhibition of insulin release. Dr. Peters from Beaumont Hospital in Michigan reported on a multicenter, double-blind, IRB-approved trial sponsored by Uroplasty Inc. (Minnetonka, MN), which enrolled 220 subjects: 110 randomized to percutaneous tibial nerve stimulation (PTNS) and 110 randomized to a validated sham intervention.13 PTNS stimulation was delivered through a 34-gauge needle electrode inserted near the posterior tibial nerve using the Urgent PC™ device for 12 weekly 30-minute sessions. Subjects and study coordinators were blinded to the intervention. A surface electrode and 2 sham electrode pads were placed for consistency with the sham. The sham used a Streitberger placebo needle that provided the sensation of a needle, but did not pierce the skin as it retracted into its shaft. TENS electrode pads were placed above and below the small toe, providing the sensation of stimulation without tibial nerve activation. An inactive surface electrode was placed as in PTNS. The audible PTNS device sounds were also reproduced in the sham intervention to diminish auditory variation between groups. Voiding diaries and validated questionnaires were completed at baseline and after 6 and 12 interventions. The primary endpoint was global response assessment (GRA). No serious AEs were noted. Interestingly, 52% of PTNS and 58% of sham subjects correctly guessed their intervention. The GRA noted 55% responders moderately or markedly improved in the PTNS group compared with 21% in the sham group (P  .001). The Overactive Bladder Questionnaire symptom severity score and quality of life scores showed significant improvement in the PTNS group compared with the sham group (P  .01). Dr. Peters concluded that this study provides evidence that PTNS is superior to placebo with significant improvement in OAB symptoms. PTNS lacks major side effects and may become an important new treatment of OAB symptoms. [Reviewed by Akira Furuta, MD, Michael B. Chancellor, MD] Male Lower Urinary Tract Symptoms (LUTS) and BPH Etiology, Epidemiology, and Natural History of Male LUTS/BPH Male LUTS and BPH continue to occupy a significant proportion of the annual AUA meeting. A search yields 99 documents with the keyword “BPH” and 60 documents with the keyword “LUTS.” The topics regarding male LUTS and BPH were presented in both moderated poster and podium sessions divided into epidemiology and natural history, basic science, medical therapy, surgical therapy, and technology. Considerable attention was also paid to issues of male LUTS and BPH in the sessions on general and epidemiological trends and the socioeconomics of evidence-based medicine, quality of life, and practice patterns. This ever-growing and very popular topic in urology occupied 5 sessions, with a considerable number of presentations including male LUTS and BPH. The idea that the serum levels of male androgen steroids such as testosterone and dihydrotestosterone would in some way be linked to male LUTS, PSA, and prostate size is intriguing, and, indeed, has been researched in the past. Baseline data and follow-up data from the Dutasteride phase III studies have shown that even men with a low serum testosterone level, that is, hypogonadal men, may have completely normal prostate sizes and, in fact, experience prostate growth over time similar to those men with normal testosterone levels.14 At this year’s AUA meeting, data were presented from the Prostate Cancer Awareness Week.15 In 13,487 participants from 2003 and 2008, appropriate testing was performed and a univariate analysis, age, digital rectal examination (DRE), estimated prostate volume, and serum PSA were significantly and positively correlated with AUA Symptom Score, whereas serum total testosterone and body mass index were not. In a multiple regression analysis, age, DRE, and PSA maintained a significant relationship, but, overall, there was no association between total testosterone and male LUTS and DRE estimated prostate size. Jennifer St. Sauver and colleagues from the Olmsted County Study of Urinary Tract Symptoms in Men correlated rates of decline in serum testosterone levels and rates of changes in LUTS and prostate size and maximum urinary flow rate in 648 men over an 8-year follow-up. 16 They found that the testosterone levels declined over time by a median grade of 0.19%/y, and that the rate of change in testosterone levels was correlated with an increase in LUTS and maximum lower urinary flow rate, but not with changes in the rate of change in the prostate volume. Of interest, the same group reported on 616 men from the Olmsted County study and found that, over the obser- VOL. 12 NO. 2/3 2010 REVIEWS IN UROLOGY e137 9a. RIU0500_07-31.qxd 8/4/10 4:28 PM Page e138 Best of the AUA Annual Meeting continued vation period, 9.4% were diagnosed with prostate cancer.17 The researchers calculated the median PSA velocity in patients with and without prostate cancer at 6.0%/y versus 3.3%/y, whereas prostate volume increase was 2.2%/y in both groups. In other words, in those patients developing prostate cancer, the rate of PSA increase was 2.5 times the rate of prostate volume increase compared with a rate of 1.5 for those who did not develop prostate cancer. Whether such subtle differences can be used in discerning the implications of PSA increases in men followed in practitioners’ clinics remains to be determined, as the differences seem to be small with great overlap. It is well understood that the introduction of medical therapy for male LUTS and BPH in the 1990s reduced the number of transurethral resections of the prostate (TURP) dramatically; Izard and Nickel found a 60% decrease from 1988 to 1998 with a moderate increase in the numbers in more recent years in Kingston, Ontario, Canada.18 They asked an interesting question regarding the presentation and outcome of patients who underwent TURP in their center over this time period and found a significant rise in patients presenting with acute or chronic urinary retention at the time of the TURP. The rates for AUR were 22.9%, 54.2%, and 42.9%, respectively, in 1988, 1998, and 2008, and those with residual urine volume of  300 cc or chronic urinary retention were 14.6%, 20.3%, and 39.3%. It was equally interesting that the number of patients discharged with a catheter, that is, patients who failed to void postoperatively, increased over 2 decades from 3.2% to 12.5% and, ultimately, 28.6%, respectively, for the 3 time points. The researchers speculated that medical therapy has delayed surgical treatment for many patients and, thus, the capacity of these e138 VOL. 12 NO. 2/3 2010 patients to improve following surgery appears to be significantly reduced as the patients present for surgery later in the natural history of their disease. In this context, it is of some interest to review the data presented from the BPH Registry by John Wei.19 What proportion of patients continue medical therapy for male LUTS and BPH even if they do not respond? In this analysis of 8280 person-months of follow-up, lack of response was defined as a decrease of less than 4 points on the International Prostate Symptom Score; 48% of 264 patients did not achieve a decrease of 4 points, out of which 221 or 84% continued to take medication. Why would 84% of patients who have only marginal benefit continue taking a rather costly medication? Are these the patients that ultimately present with disease progression and, perhaps, with chronic or acute urinary retention, only to experience less improvement in their symptoms than might have been experienced had the surgery been performed earlier? These are obviously controversial hypotheses and the data do not support firm conclusions; however, it would be important to determine whether patients not responsive to medical therapy should be more aggressively counseled to undergo surgery earlier in the disease course. Several authors have reported on the economic burden of nocturia and on mortality risks associated with it— a somewhat surprising finding.20,21 From the Boston Area Community Health (BACH) study, an age- and sex-adjusted prevalence of nocturia (defined as 2 voids per night or more) was estimated as affecting 28 million people over the age of 30 years in the United States. The team from the BACH study estimated that the economic value of productivity lost in 2008 was $61 billion, and the proportion of the population at risk of REVIEWS IN UROLOGY falling due to nocturia was 16.2% with estimated medical costs of an additional $1.5 billion.22 An even more provocative study was presented by Kupelian and colleagues, who analyzed the Third National Health and Nutrition Examination Survey (NHANES III) study.23 By defining the prevalence of nocturia as 2 or more episodes per night, the researchers calculated a prevalence of 15.5 among men and 20.9 among women, increasing rapidly with age. The most stunning finding of the multivariate analysis is the statistically significant trend towards increased mortality risks with an increased number of voiding episodes among both men and women (Table 2). A similar observation was reported by Japanese investigators who studied 788 subjects with the mean age of 76 years and demonstrated that hazard ratios for mortality were 1.59-, 2.34-, and 2.6fold for people who voided 2, 3, or 4 or more times per night compared with those individuals with  1 voiding episode per night.24 Medical Therapy for Male LUTS and BPH Vis-à-vis the problem with nocturia, it has been shown that conventional medical therapy is not very effective in the reduction of nocturnal voiding episodes. In fact, several analyses of the medical therapy for prostatic symptoms, or the Medical Therapy of Prostatic Symptoms (MTOPS) study revealed that on average the reduction ranges from 0.3 to 0.6 episodes only.25 Desmopressin is an antidiuretic that has been shown to effectively reduce nocturnal polyuria and nocturia.26,27 A new orally disintegrating formulation was developed that permits sublingual administration without water.28 A multicenter, randomized, phase III trial involving a broad population of adults with an average of 2 9a. RIU0500_07-31.qxd 8/4/10 4:28 PM Page e139 Best of the AUA Annual Meeting Table 2 Association of Nocturia and Mortality by Sex and Agea Men Women Unadjusted HR (95% CI) Adjusted HRb (95% CI) Unadjusted HR (95% CI) Adjusted HRb (95% CI) 20-49 4.09 (2.20, 7.63) 2.56 (1.32, 4.94) 2.70 (1.53, 4.76) 1.10 (0.66, 1.86) 50-64 2.05 (1.40, 3.02) 1.60 (1.06, 2.41) 2.25 (1.56, 3.25) 1.94 (1.27, 2.96) 65-90 1.65 (1.36, 2.00) 1.35 (1.11, 1.63) 1.54 (1.31, 1.82) 1.19 (1.04, 1.37) Overall 4.75 (3.95, 5.72) 1.49 (1.25, 1.78) 3.58 (3.05, 4.20) 1.32 (1.14, 1.51) Age Unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) comparing respondents with nocturia  2 to those with nocturia  2 per night. b Adjusted for age, body mass index, marital status, education, smoking, cardiovascular disease, diabetes, hypertension, medication use (diuretic, antihypertensive, lipid lowering, antidepressant). a Change From Baseline in Number of Nocturnal Voids/Night Change From Baseline in Initial Period of Undisturbed Sleep –2.5 Day 28 180 1 year –1.43 –1.4 –1.18 –1.0 1 year 140 –1.77 –1.0 161 107 100 80 126 119 120 Minutes Number of Voids/Night –2.0 –1.5 Day 28 160 –2.11 83 85 25 g 50 g 60 40 –0.5 20 0 25 g 50 g 100 g 0 100 g n at day 28  417; n at 1 year  235 Figure 1. The durable effect of desmopressin orally disintegrating tablet. or more voids per night was conducted; desmopressin was administered in comparison with placebo at dosages of 10, 25, 50, and 100 g. Efficacy assessment was conducted at day 28 and patients were followed to 1 year. The 25- g dose was found to be ineffective in comparison with placebo. At baseline, the mean nocturnal urine volume was 850 mL, which decreased in all treatment groups including placebo. However, greater reductions were observed with increasing doses of desmopressin. The reductions at 28 days ranged from 109 cc for the placebo group to 313 in the 100-g group. The onset of effect was visible at day 8, maintained to day 28, and ultimately carried out to 1 year of follow-up. At the same time, the period of uninterrupted sleep was increased between 83 and 107 minutes in the actively treated patients. When patients were followed for 1 year, the nocturnal void episodes decreased from 1.4 for the 25-g dose to 2.11 for the 100-g dose, and the period of undisturbed sleep increased from 119 to 161 minutes (Figure 1). The researchers concluded that in this cohort of patients with nocturnal polyuria, the desmopressin orally disintegrating tablet reduced nocturnal diuresis, the mean number of nighttime voids, and prolonged initial periods of undisturbed sleep with a rapid and durable effect to 1 year. It will be interesting to observe whether these findings can be corroborated with VOL. 12 NO. 2/3 2010 REVIEWS IN UROLOGY e139 9a. RIU0500_07-31.qxd 8/4/10 4:28 PM Page e140 other studies and whether this particular formulation of desmopressin will be submitted to the US Food and Drug Administration for approval. Regarding combination medical therapy for BPH, an updated analysis of the combination of dutasteride and tamsulosin (CombAT [Combination of Avodart and Tamsulosin] trial) was reported.29 In this particular analysis, men were divided into tertiles by baseline prostate volume ( 42 mL, 42 to 58 mL, and  58 mL).30 As Figure 2 demonstrates, the relative risk reduction for AUR or BPH-related surgery induced by combination therapy compared with tamsulosin alone increases dramatically with increasing prostate volume. The incidence rates for combination therapy ranged from 3.6% to 5.6%, whereas the incidence rate for tamsulosin ranged from 6.1% to 18.4%, leading to a risk reduction range from 39.4% to 72.6%. Thus, it is clear that the efficacy of combination therapy in terms of risk reduction increases linearly with increasing prostate size. In the same analysis, it was shown that the superiority of combination therapy compared with -blocker therapy with tamsulosin alone regarding symptom score and maximum urinary flow rate also increases the increasing prostate volume. The symptom score improvement for the prostate volume of  42g was 6.2 versus 4.7, whereas it was 6.6 versus 3.4 for prostates  58g. The peak flow rate improvements were 2.4 versus 1.0 and 2.9 versus 0.6, respectively, for prostates  42 g and those  58 g. Along similar lines, an analysis of BPH-related outcomes in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study according to baseline symptom score and prostate volume was performed and reported.31,32 Men eligible for REDUCE were between age 50 and 75 years with a PSA  2.5 ng/mL but  e140 VOL. 12 NO. 2/3 2010 Incidence of AUR/BPH-Related Surgery (%) Best of the AUA Annual Meeting continued 24 22 RRR = 39.4% RRR = 69.3% RRR = 72.6% *** 18.4 20 18 16 14 RRR = 15.5% RRR = 29.6% 12 RRR = 15.1% 10.7 10 572 8 6.6 6.1 6 4.4 4 3.6 2 533 550 5.6 4.7 507 3.4 526 552 521 515 551 0 < 42 42-58 > 58 Baseline Prostate Volume (cc) Combination Dutasteride Tamsulosin *** P < .001 vs combination Figure 2. Combination 4-year therapy reduces incidence of acute urinary retention (AUR) or benign prostatic hyperplasia (BPH)–related surgery. RRR, risk reduction range. 10 ng/mL, a prostate volume  80 g, and a symptom score of  21 points. Four subgroups were created: patients with a symptom score and a prostate volume  8 and  30 g, respectively;  8 and  30 g, respectively;  8 and  30 g, respectively; and  8 and  30 g, respectively. As Figure 3 demonstrates, the incidence rate of either AUR or surgery in the placebo arm was 2.6 and 6.1 in the patients with prostate volumes  30 g and 6.2 and 12.6 in the patients with prostate volumes  30 g. In patients with prostate volumes  30 g, the incidence was significantly dependent on symptom severity; that is, those with a symptom score  8 had an incidence of only 6.2 versus those with a symptom score of  8 (12.6). This clearly shows that AUR and BPH-related surgery is not only dependent on prostate volume, but also on symptom severity. In addition, from this prostate cancer prevention study, one can clearly deduce that treatment with the 5 -reductase in- REVIEWS IN UROLOGY hibitor dutasteride is most effective in patients with moderate symptoms and in large prostates ( 30 g) as the relative risk reduction is most cost effective in those patients. The relative risk reduction is 73%, 81%, and 74% in the 3 groups with the greatest risk in the placebo arm versus 48% in the group of patients with minimal symptoms and small prostates. However, the absolute risk reduction is significantly greater and, thus, the cost effectiveness is significantly better in the group of patients with both moderate symptoms and enlarged prostates. The last interesting analysis of the REDUCE study was presented by Nickel and colleagues.33 In the REDUCE study, the Chronic Prostatitis Symptom Index (CPSI) was administered every 6 months. Two groups of patients were identified: 337 patients with prostatitis-like pain and 182 patients with prostatitis-like syndrome. Prostatitislike syndrome patients were defined as those with perineal and/or 9a. RIU0500_07-31.qxd 8/4/10 4:28 PM Page e141 Best of the AUA Annual Meeting response on the CPSI. It is interesting to observe that, as this study aimed to demonstrate the ability of dutasteride to prevent prostate cancer, another significant insight was gained regarding the ability of this drug to prevent male LUTS and BPH progression as well as to treat prostatitis-like pain and syndromes in men. Risk of AUR or BPH-related surgery was significantly lower with dutasteride within each subgroup (P < .001), except within the IPSS < 8, PV < 30 cc subgroup (P = .22) 14 Placebo RRR: 74% Dutasteride 12.6% Incidence of AUR/BPHRelated Surgery at 4 Years (%) 12 10 RRR: 48% RRR: 73% RRR: 81% 8 6.2% 6.1% 1300 359 6 1891 4 3.4%* 2.6% 2 378 1.4% 1.7%* 370 1317 1.2%* 1877 333 0 IPSS < 8 PV < 30 cc IPSS < 8 PV > – 30 cc *P < .001 dutasteride vs placebo IPSS > –8 PV < 30 cc IPSS > –8 PV > – 30 cc Figure 3. Reduced incidence of acute urinary retention (AUR) or benign prostatic hyperplasia (BPH)–related surgery with dutasteride over a 4-year study. IPSS, International Prostate Symptom Score; PV, prostate volume; RRR, risk reduction range. Adjusted Mean Change From Baseline (Units) –7 –6 –5 * * * Dutasteride (n = 324) * * * –4 –3 Placebo (n = 323) –2 –1 0 Prostatitis-Like Pain Population *P < – 0.05 for dutasteride vs placebo Figure 4. Reduction in Chronic Prostatitis Symptom Index score in prostatitis-like pain subgroup. ejaculatory pain plus a CPSI pain subscore 4. In the group of patients with prostatitis-like pain, the reduction in the baseline score was significantly greater for the dutasteride group versus the placebo group (Figure 4). Also, in the prostatitis-like pain and prostatitis-like syndrome subgroup, there were significantly more 4- and 6-point responders in the dutasteride group versus the placebo group. The relevance of this is that a 4-point and 6-point response is defined as a minimal versus a moderate Device Treatment for Male LUTS and BPH There are several start-up companies that are developing devices for the treatment of male LUTS and BPH. Among them is NxThera Inc. (St. Paul, MN), a firm that is developing a device that utilizes vapor injections and thermal energy to close tissue in the prostate. The technology can be used to treat other urological problems, including prostate cancer, but at the moment the company is pursuing the BPH market and is embarking on early phase II trials to explore the feasibility and safety of the device. Another company that has been developing minimally invasive, non–heat-based technology is NeoTract (Pleasanton, CA). NeoTract has developed a procedure called prostatic urethral lift, trademarked as the UroLift® system. The UroLift delivers the device transurethrally through a urethral lift sheath under cystoscopic visualization. Sutures are deployed from the UroLift device through a small needle and positioned in the prostate tissue to retract the obstructing lobes. At the AUA meeting, an update was provided on a number of patients who had been treated at different sites, mostly in Australia.34 The device showed rapid improvement of symptoms by 2 weeks with a reduction in the International Prostate Symptom Score from 22.8 to 13.8 points with the results durable to 12 months. The device did not affect sexual function nor did it induce retrograde ejaculation. In fact, as a VOL. 12 NO. 2/3 2010 REVIEWS IN UROLOGY e141 9a. RIU0500_07-31.qxd 8/4/10 4:28 PM Page e142 Best of the AUA Annual Meeting continued e142 VOL. 12 NO. 2/3 2010 jection of a PSA-activated, channelforming toxin as a therapeutic intervention. Researchers from Johns Hopkins University, Baltimore, MD, modified a proaerolysin with this inactive precursor of a bacterial psycholytic for forming protein to produce a PSA-activated protoxin (PRX3.02).36 They showed that a single tumor injection of PRX3.02 produced substantial, if not complete, regression of PSA-secreting human prostate cancer zenografts. The prostates of monkeys injected with a single dose are quite extensive for organ-confined damage, with no toxicity of neighboring organs for general morbidity as a result of the unique specificity with PSA- secreting cells. Elhilali and colleagues reported on the evaluation of transperineal administration of PRX3.02 in men with voiding symptoms and BPH. In early phase II studies, the efficacy regarding IPSS and quality of life and maximum urinary flow rates have been demonstrated with no effect on erectile function. A phase IIb study was conceived and the results reported at this year’s AUA meeting.37 Ninetytwo patients were randomized 2:1 to receive PRX3.02 versus placebo. At baseline, patients had a prostate volume of  49 g with a PSA of  3.2 ng/mL and a symptom score of 23 points with a flow rate of 8.3 to 8.4 mL/s. Symptom improvement at 3 and 6 months was 9.1 and 8.9 points with a PRX3.02 versus 5.8 and 4.6 with the placebo. Improvement in maximum flow rate was 3.1 and 3.9 versus 1.3 and 1.3, respectively (Figure 5). Both irritative and obstructive symptoms improved in a similar manner. Adverse events were observed in 74.2% versus 80.3%, and the most common adverse events in the PRX3.02 group were dysuria, frequency of urination with urgency, some hematuria, and perineal pain. In phase I, II, and IIb studies, the drug appeared to be well tolerated with a dose response, had no effect on erectile function, and had overall minimal and short-term adverse events. It is expected that the PRX3.02 will be further explored in phase III studies in Figure 5. Efficacy results: mean change in International Prostate Symptom Score (IPSS) (PRX3.02 vs placebo). ANCOVA, analysis of covariance. –10 Mean Change in IPSS From Baseline measure of sexual function, the International Index of Erectile Function Questionnaire score improved from 34 to 45 from baseline to month 12. The company is currently planning to expand into the European market, but will also have to perform a pivotal trial in the United States. An interesting technological advancement was presented in regard to microwave thermotherapy for male LUTS and BPH. A group of investigators injected beagles with 0.5 mL of phospholipid polyethylene glycol– coated 2 mg/mL 4 nm Fe304 nanoparticles.35 Fiber optic thermistors were placed on both sides of the prostate. The Urologix Targis® (Urologix, Inc., Minneapolis, MN) microwave catheter was then placed in the urethra and microwaves were applied up to 40 W for 18 minutes with recording of temperatures. The researchers found that the nanoparticles are able to appropriately heat and ablate prostate tissue, and this increased the efficacy of the microwave treatment substantially. Areas injected with nanoparticles showed a 7.5°C increase in temperature compared with contralateral counterparts. Hematoxylin and eosin staining demonstrated focal necrosis and hemorrhage in the site of nanoparticle injection. The heating profile was dependent on the concentration, with a maximum response seen with a concentration of 6.65 mg/mL with the difference in temperature being 60°C versus 45°C with water injection alone. It does appear that the use of nanoparticles in urology is being explored in various areas. However, because nanoparticles, depending on size, shape, and composition, can be used to enhance energy, it seemed reasonable to explore it in the field of energy ablation of prostate tissue. Another novel treatment for male LUTS and BPH as well as prostate cancer prevention consists of the in- REVIEWS IN UROLOGY –9 Placebo PRX3.02 P = .0238 P = .0541 –8 –7 P = .1576 –6 –5 –4 –3 –2 –5 (6.1) –7 (5.6) –9.1 (6.0) –5.8 (5.4) –8.9 (6.7) –4.6 (9.4) –1 0 Month 1 Month 3 Month 6 Computed using ANCOVA model with terms for treatment group, age, baseline IPSS, and baseline prostate volume 9a. RIU0500_07-31.qxd 8/4/10 4:28 PM Page e143 Best of the AUA Annual Meeting males with BPH as well as in prostate cancer applications. [Reviewed by Claus G. Roehrborn, MD, FACS] Shock Wave Lithotripsy A number of strategies have been proposed to improve results with shock wave lithotripsy. The utilization of a slower wave delivery rate to improve fragmentation was based on in vitro and in vivo animal model study results eventually confirmed in clinical trials.38-41 In vitro studies have shown that the gradual ramping up of shock wave energy improved fragmentation as compared with maintaining the same energy level or a gradual reduction in shock wave energy.42 Honey and colleagues previously reported on a randomized, prospective study to assess the clinical benefits of gradually ramping up shock wave energy in those with solitary, opaque renal stones 20 mm in size using a Phillips LithoTron® device (Healthtronics, Marietta, GA).43 In this study, the immediate escalation group received treatment energy started at 14 to 15 kV, depending on whether the electrode was new or used, and increased 1 kV every 10 shocks to a maximum of 23 kV. The delayed protocol involved increasing the kilovolts from 14 to 15 after 10 seconds, maintaining the kilovolts at 15 for 1500 shocks, and thereafter increasing it by 1 every 10 seconds for a maximum of 23 kV. Shock wave treatment was terminated when it was believed the stone was effectively fragmented or a total of 3000 shock waves were delivered. Despite a significantly higher number of shock waves delivered to the delayed dose escalation group, there were no differences in the stone-free rates at 3 months in this study. At the 2010 AUA meeting, Honey and associates presented results of another prospective, randomized study in which a rapid energy escalation from 14 kV to 22 kV was compared to a gradual protocol (18 kV for the first 900 shocks, 20 kV for the next 900, and 22 kV for the remainder).44 One hundred eighty-eight patients with previously untreated renal stones  5 mm participated in this study. Sex, pretreatment stone surface area, and the percentage with lower pole stones were similar in both groups. At 3 months, success as defined by the percentage stone free or with fragments 4 mm were similar as assessed with kidney-ureterbladder radiography and renal ultrasound: 55.8% for rapid dose escalation versus 65.6% for gradual dose escalation (P  .169). There were no differences in morbidity or the need for ancillary procedures. Both studies reported by this group demonstrate that delayed dose escalation does not result in improved stone fragmentation or clearance, which is contrary to the aforementioned in vitro study. This demonstrates the importance of confirming in vitro studies with properly designed clinical trials. However, there may be some benefits in this strategy with regard to pain tolerance if intravenous sedation is used for anesthesia. The potential renoprotective benefits of this approach have not yet been adequately addressed.45 [Reviewed by Dean G. Assimos, MD] Pediatric Urology The 1st World Congress of Pediatric Urology was held in conjunction with the annual AUA national meeting. Ten pediatric urology societies from around the world were represented in the podium, poster, and video sessions. Cuda and Kirsch reported on changing trends in the surgical approach to the undescended testis (UDT).46 Classically, a standard orchiopexy was performed through an inguinal or high inguinal incision. The nonpalpable testis was managed with a high inguinal or abdominal approach, but more recently laparoscopy has been utilized for these testes. In the early 1980s, orchiopexy through a transscrotal incision was described. These investigators reviewed 413 orchiopexies performed in 344 patients between 2003 and 2009. The patients were divided into 3 groups based on the time intervals of May 2003-October 2004, April 2006January 2008, and January 2008-July 2009. The groups had similar numbers of patients with no difference in mean age. The researchers found that over a 6-year period, the number of orchiopexies performed through a scrotal incision more than doubled, whereas the number of inguinal procedures diminished. They note that the scrotal incision is used if the testis can be mobilized into the scrotum. The inguinal approach should continue to be used in the setting of a concomitant hernia. Marschall-Kehrel and colleagues performed a multicenter analysis of 487 enuretic children to determine whether structured withdrawal improves long-term antidiuretic treatment outcomes.47 Children were treated with desmopressin (0.2 mg or 0.4 mg), which was either abruptly terminated or progressively withdrawn by lengthening the treatment intervals (structured withdrawal every second day, third day, etc). At 1 year, 361 children were available for followup (129 in the abrupt termination group and 232 in the structured withdrawal group). The abrupt termination group had a 51% response at the end of therapy, whereas the withdrawal group had a 72% response. The group undergoing structured withdrawal had more favorable outcomes at 1 year following treatment when compared with the abrupt termination group (85.5% vs 72%). The authors VOL. 12 NO. 2/3 2010 REVIEWS IN UROLOGY e143 9a. RIU0500_07-31.qxd 8/4/10 4:28 PM Page e144 Best of the AUA Annual Meeting continued suggest that at the end of treatment, desmopressin should be progressively withdrawn. Moore and colleagues examined the natural history and management of the nonfunctioning versus very low functioning kidney.48 Multicystic kidneys (MCDK) show 0% function on renal scintigraphy and are thought to have a benign natural history. It is controversial whether very low functioning kidneys have the same benign course. The renal units of interest had 0% function on dimercaptosuccinic acid scanning and represented the MCDK group, whereas the dysplastic/ dysmorphic (DK) group demonstrated 1% to 9% function. There were 120 MCDKs and 42 DKs. In the MCDK group, 16 of 120 (13%) developed recurrent UTI or hypertension and 7 patients underwent nephrectomy. In the DK group, 13 of 42 patients (31%; P  .01) developed UTI, hypertension, or carcinoma. Seven patients underwent nephrectomy for UTI or hypertension. One 14-year-old girl showed progressive enlargement in the DK. At nephrectomy, the pathology on the DK was renal cell carcinoma. The authors concluded that patients with DKs with very low function require closer long-term follow-up because about one third of patients develop UTI, hypertension, or, more rarely, carcinoma. Gatti and colleagues studied whether effacement of a ureteral orifice or the inconspicuous crescentlike slit appearance that is achieved following endoscopic treatment of vesicoureteral reflux with dextranomer-hyaluronic acid (DHA) could be used as a predictor of success.49 A prospective study was perfomed in 42 patients with 63 refluxing ureters. After the injection, reflux was predictable if there was any grade of persistent hydrodistensibility of the ureteral orifice. This occurred in only 3 ureters. In 48 ureters (76%), no e144 VOL. 12 NO. 2/3 2010 reflux was observed on the voiding cystourethrogram performed at 8 to 12 weeks. When the VCUG was repeated at 1 year in 29 patients, only 3 patients had reflux despite the negative study at 2 to 3 months. At cystoscopy, effacement was absent in 2 of the failures but present in 1. The authors conclude that effacement of the orifice is a very good predictor of reflux resolution. They also note that although effacement and a nondistensible orifice were present at the end of the procedure in all patients who had successful injections, it did not discriminate success versus failure. [Reviewed by Ellen Shapiro, MD, FACS, FAAP] Prostate Cancer Markers As has been the case over the past 2 decades, prostate cancer markers were a major topic of discussion at the 2010 AUA meeting. Only a few of the many outstanding abstracts can be reviewed here. PSA Velocity Loeb and colleagues utilized PSA velocity (PSAV) risk count (the number of times a PSAV exceeds a specific cut point to improve specificity in a screening population).50 Two PSAV values were calculated in 18,214 men and the number of times (0, 1, 2) a velocity  0.4 ng/mL/y was determined. The count was 2 in 40% of men with malignancy as compared with 4% of those without malignancy. Compared with those with a count of 0 or 1, there was a 5.4-fold increase in men with Gleason score 8 to 10 prostate cancer after adjusting for age and PSA. This is a novel enhancement on PSAV; unfortunately, it requires a long PSA history in the individual patient. Concomitant Medications The effect of concomitant medications on serum PSA levels has not REVIEWS IN UROLOGY been well investigated. Chang and associates performed a cross-sectional analysis utilizing the National Health and Nutrition Examination Survey.51 Men who had recent prostate manipulations or who were receiving hormone therapy were excluded. Among 1846 men, nonsteroidal anti-inflammatory agents (NSAIDs), statins, and thiazide diuretics were associated with lower PSA levels. A model predicted that, at 10 years, the PSA reduction for NSAIDs, statins, and thiazide diuretics was 11%, 26%, and 47%, respectively. These data need confirmation in biopsy trials, but if the findings prevail the effect of these agents, particularly in men undergoing surveillance or monitoring of prostate cancer, may need to be considered. Androgen Receptors The evolution to castration-resistant prostate cancer is an inevitable consequence of hormonal therapy. An intriguing observation in this complex process was reported by Thalmann and coworkers.52 The researchers looked at the differential androgen receptor expression in primary and lymph node metastases in 119 men undergoing radical prostatectomy and extended pelvic lymph node dissection. Immunohistochemical quantization of the androgen receptor expression was utilized. Although androgen receptor expression was significantly upregulated in the primary compared with benign prostate, it was significantly reduced in the metastases. Androgen receptor expression in the primary and metastases did not predict survival nor was it correlated with age, cancer volume, or number or size of metastases. This study suggests that at an early step in the progression of prostate cancer there may be mechanisms in place to advantage the castration-resistant phenotype. 9a. RIU0500_07-31.qxd 8/4/10 4:28 PM Page e145 Best of the AUA Annual Meeting Body Mass Index PSA level has been shown to be inversely related to body mass index (BMI). Wright and colleagues studied additional demographic and clinical factors associated with BMI.53 Seven hundred eighty seven control patients formed a population-based, casecontrol study of prostate cancer. The mean serum PSA level was 1.20, 1.14, and 0.91 ng/mL for BMI  25, 26-29, and  30, respectively. Statin and aspirin use, as well as diabetes mellitus, were associated with decreased PSA; BPH and a family history of prostate cancer was seen in those with higher PSA level. In multivariate analysis, BMI was not associated with PSA level (P  .06); however, BPH and family history were associated with an increase and starting use of these agents led to a decrease in PSA level. These factors may need to be considered when interpreting PSA levels. Nomograms The use of nomograms to predict biochemical recurrence (BR) after radical prostatectomy is widespread. Teeter and associates looked at whether commonly utilized nomograms predicted more distant endpoints, including prostate-cancer–specific mortality.54 The researchers evaluated 1819 men in the SEARCH database who underwent radical prostatectomy between 1988 and 2009. They observed that the Kattan, Johns Hopkins, and Center for Prostate Disease Research (CapSURE) approaches all were able to predict prostate-cancer– specific mortality—even better than they are able to foretell BR. This is an important investigation of the merit of these predictive models. Tumor Vasculature Tumors must establish a robust vasculature to grow. The extent of neovascularity has been correlated with higher malignant potential in a num- ber of organ sites, including the prostate. Namdarian and associates quantified circulating endothelial cells and their progenitors in men who were free of disease 1 year following radical treatment, men with localized prostate cancer pretherapy, and patients with metastatic disease.55 They noted that in men with metastases, the median levels of circulating endothelial cells were higher (P  .05). Moreover, they observed that the only men to recur following radical prostatectomy were those with the highest 10% of circulating endothelial cells. This may offer a novel approach for identifying men destined to fail single-modality therapy by exploiting one of the universal hallmarks of cancer progression. [Reviewed by Michael K. Brawer, MD] Dr. Chancellor is a consultant and investigator for Cook and Allergan. Dr. Roehrborn is or has been investigator or consultant to companies and organizations studying, manufacturing, and/or marketing products aimed for the treatment of male LUTS and BPH: Eli Lilly, GSK, Pfizer, Sanofi Aventis, Merck, Watson Pharmaceuticals, NIH/NIDDK. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. Nam R, Klotz L, Loblaw A, et al. Rising hospital admission rates for urologic complications after transrectal ultrasound-guided prostate biopsy [abstract 2097]. J Urol. 2010;183(suppl): e815. Loeb S, Carter HB, Berndt S, et al. How safe is prostate biopsy? Rate of complications requiring hospitalization following prostate biopsy in SEER-Medicare [abstract 2096]. J Urol. 2010; 183(suppl):e815. Casey JT, Kim RJ, Alpha HH, et al. Hospitalization for fever after transrectal ultrasound-guided prostate needle biopsy [abstract 609]. J Urol. 2010;183(suppl):e240. Cermak A, Mareckova N, Pacik D. Infectious complications of prostate biopsy: the changes in antibiotics resistance patterns–the review of a 5-year period [abstract 2101]. J Urol. 2010;183(suppl):e817. Jung S, Park JB, Hwang EC, et al. Clinical aspect of post TRUS biopsy infection caused by quinolone-resistant bacteria [abstract 808]. J Urol. 2010;183(suppl):e315-e316. Uddin MM, Ho HSS, Ng LG, Cheng CWS. Transrectal prostate biopsy sepsis: trends in its 16. 17. 18. 19. 20. bacteriology and antibiotic prophylaxis in a single center over 8 years [abstract 807]. J Urol. 2010;183(suppl):e315. Penna FJ, Elder JS, Diaz M. Antimicrobial resistance patterns of Escherichia coli in uncomplicated community-acquired urinary tract infections among adults: a meta-analysis [abstract 597]. J Urol. 2010;183(suppl): e235. Bhaysar R, El-Zawahry A, Caulder S, et al. Six weeks of fluoroquinolone antibiotic for patients with elevated PSA is not clinically beneficial: a randomized controlled clinical trial [abstract 2095]. J Urol. 2010;183(suppl): e814-e815. Carr L, Herschorn S, Birch C, et al. Autologous muscle-derived cells as therapy for stress urinary incontinence: a randomized, dose-ranging trial [abstract 1524]. J Urol. 2010;183(suppl): e587-e588. Chen C-Y, Chancellor M, Kuo H-C. Risk factors of adverse events after intravesical botulinum toxin A injections for refractory overactive bladder syndrome [abstract 1519]. J Urol. 2010; 183(suppl):e586. Burnett E, Schurfranz B, Goldwasser S, Costa J. Updated review of prospective/retrospective outcomes and complications with use of synthetic mesh for reconstruction of anterior and posterior vaginal prolapse in a single institution [abstract 1393]. J Urol. 2010;183(suppl):e538. Tyagi V, Tyagi P, Peters K, et al. Ghrelin-A putative mechanistic link between OAB and obesity [abstract 1525]. J Urol. 2010;183(suppl):e588. Peters K, Carrico D, Perez-Marrero R, et al. Percutaneous tibial nerve stimulation: a multicenter, randomized, sham-controlled trial for overactive bladder syndrome [abstract 1515]. J Urol. 2010;183(suppl):e584. Marberger M, Roehrborn CG, Marks LS, et al. Relationship among serum testosterone, sexual function, and response to treatment in men receiving dutasteride for benign prostatic hyperplasia. J Clin Endocrinol Metab. 2006;91: 1323-1328. Tandberg DJ, O’Donnell C, Hughes A, Crawford ED. Total testosterone not associated with lower urinary tract symptoms in a prostate cancer screening population [abstract 1629]. J Urol. 2010;183(suppl):e629-e630. St. Sauver J, Jacobson D, McGree M, et al. Correlations between rates of decline in testosterone level and rates of change in lower urinary tract symptoms, prostatic enlargement, and maximum urinary flow rate [abstract 1633]. J Urol. 2010;183(suppl):e631. Breau R, Karenes RJ, Jacobson D, et al. Longitudinal PSA and prostate volume changes in men who develop prostate cancer [abstract 2102]. J Urol. 2010;183(suppl):e817. Izard J, Nickel JC. Impact of medical therapy on transurethral resection of the prostate (TURP): two decades of change [abstract 2086]. J Urol. 2010;183(suppl):e811. Wei J, Carman W, Rosen R, et al. High rates for continued BPH medical therapy among non responders [abstract 498]. J Urol. 2010; 183(suppl):e197. Cornu JN, Roupret M. Impact of nocturia on the daily life of patients with lower urinary tract VOL. 12 NO. 2/3 2010 REVIEWS IN UROLOGY e145 9a. RIU0500_07-31.qxd 8/4/10 4:28 PM Page e146 Best of the AUA Annual Meeting continued 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. symptoms due to benign prostatic hyperplasia. Prog Urol. 2007;17(5 suppl 1):1033-1036. Temml C, Ponholzer A, Gutjahr G, et al. Nocturia is an age-independent risk factor for hip-fractures in men. Neurourol Urodyn. 2009;28:949-952. Holm-Larsen T, Weiss JP, Langkilde LK. Economic burden of nocturia in the US adult population [abstract 2]. J Urol. 2010;183(suppl):e1. Kupelian V, Fitzgerald M, Kaplan S, et al. Nocturia is a marker of increased mortality risk: results from the Third National Health and Nutrition Examination [abstract 56]. J Urol. 2010; 183(suppl):e24. Nakagawa H, Niu K, Kaiho Y, et al. Mortality in the elderly correlates with the frequency of nighttime voiding: results of a 5-year prospective cohort study in Japan [abstract 3]. J Urol. 2010;183(suppl):e1-e2. Johnson TM 2nd, Burrows PK, Kusek JW, et al; Medical Therapy of Prostatic Symptoms Research Group. The effect of doxazosin, finasteride and combination therapy on nocturia in men with benign prostatic hyperplasia. J Urol. 2007;178:2045-2050; discussion 2050-2051. Chancellor MB, Atan A, Rivas DA, et al. Beneficial effect of intranasal desmopressin for men with benign prostatic hyperplasia and nocturia: preliminary results. Tech Urol. 1999;5:191-194. Azzouzi AR, Fourmarier M, Desgrandchamps F, et al. Other therapies for BPH patients: desmopressin, anti-cholinergic, anti-inflammatory drugs, and botulinum toxin. World J Urol. 2006;24:383-388. Weiss JP, Snyder JA, Ellison WT, et al. Fastdissolving desmopressin (MELT) is well tolerated in nocturia: results of a randomized, placebocontrolled study [abstract 1528]. J Urol. 2010; 183(suppl):e589-e590. Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4year results from the CombAT study. Eur Urol. 2010;57:123-131. Roehrborn CG, Barkin J, Siami PF, et al. Clinical outcomes by baseline prostate volume in men with benign prostatic hyperplasia: 4 year results from the combination of Avodart and tamsulosin (CombAT) trial [abstract 1782]. J Urol. 2010; 183(suppl):e690-e691. Andriole GL, Bostwick DG, Brawley OW, et al; REDUCE Study Group. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010; 362:1192-1202. Roehrborn CG, Pettaway CA, Somerville MC, et al. Efficacy of dutasteride on benign prostatic e146 VOL. 12 NO. 2/3 2010 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. hyperplasia endpoints in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study according to baseline international prostate symptom score and prostate volume [abstract 1783]. J Urol. 2010;183(suppl):e691. Nickel JC, Tammela TLJ, Teloken C, et al. Dutasteride reduces prostatitis symptoms compared to placebo in men enrolled in the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) study [abstract 797]. J Urol. 2010;183(suppl): e311-e312. Woo H, Chin P, Bolton D, et al. Update on the prostatic urethral lift, a novel minimally invasive treatment for symptomatic benign prostatic hyperplasia [abstract 1918]. J Urol. 2010;183(suppl):e746. Lee R, Rey D, Bardliving C, et al. Nanoparticleenhanced microwave thermotherapy [abstract 1788]. J Urol. 2010;183(suppl):e693-e694. Williams SA, Merchant RF, Garrett-Mayer E, et al. A prostate-specific antigen-activated channel-forming toxin as therapy for prostatic disease. J Natl Cancer Inst. 2007;99:376-385. Elhilali M, Pommerville P, Steinhoof G, et al. Evaluation of transperineal prostatic administration of a PSA-activated protoxin (PRX302) in men with LUTS secondary to BPH [abstract 1787]. J Urol. 2010;183(suppl):e693. Greenstein A, Matzkin H. Does the rate of extracorporeal shock wave delivery affect stone fragmentation? Urology. 1999;54:430-432. Weir MJ, Tariq N, Honey RJ. Shockwave frequency affects fragmentation in a kidney stone model. J Endourol. 2000;14:547-550. Paterson RF, Lifshitz DA, Lingeman JE, et al. Stone fragmentation during shock wave lithotripsy is improved by slowing the shock wave rate: studies with a new animal model. Urology. 2002;168:2211-2215. Semins MJ, Trock BJ, Matlaga BR. The effect of shock wave rate on the outcome of shock wave lithotripsy: a meta-analysis. J Urol. 2008;179: 194-197. Zhou Y, Cocks FH, Preminger GM, Zhong P. The effect of treatment strategy on stone comminution efficiency in shock wave lithotripsy. J Urol. 2004;172:349-354. Honey RJ, Ray AA, Ghiculete D; University of Toronto Lithotripsy Associates, Pace KT. Shock wave lithotripsy: a randomized, doubleblind trial to compare immediate versus delayed voltage escalation. Urology. 2010;75:38-43. Honey RJ, Chiculete D, Wiesenthal JD, Pace KT. A randomized, double-blinded clinical trial of shock wave lithotripsy voltage escalation techniques for renal calculi [abstract 1893]. J Urol. 2010;183(suppl):e736. REVIEWS IN UROLOGY 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. McAteer JA, Evan AP, Williams JC Jr, Lingeman JE. Treatment protocols to reduce renal injury during shock wave lithotripsy. Curr Opin Urol. 2009;19:192-195. Cuda S, Kirsch A. Changing trends in the surgical approach to undescended testes [abstract 14]. Presented at: 1st World Congress of Pediatric Urology; May 27-31, 2010; San Francisco, CA. Marschall-Kehrel D, Harms TW, Devey S, Tolle A. Structured withdrawal improves long-term antidiuretic treatment outcome—a multicentric national analysis of 487 enuretic children [abstract 16]. Presented at: 1st World Congress of Pediatric Urology; May 27-31, 2010; San Francisco, CA. Moore K, Leslie B, Mahdi M, et al. Is it zero? The natural and management history of nonfunctioning versus very low functioning kidneys [abstract MP31]. Presented at: 1st World Congress of Pediatric Urology; May 27-31, 2010; San Francisco, CA. Gatti JM, Windsperger AP, Graham SM, et al. Effacement as a predictor of success: a prospective clinical trial correlating the appearance of refluxing ureteral orifices after injection with long-term resolution [abstract P19]. Presented at: 1st World Congress of Pediatric Urology; May 27-31, 2010; San Francisco, CA. Loeb S, Metter EJ, Kan D, et al. Prostate-specific antigen velocity risk count improves the specificity of screening for clinically significant prostate cancer [abstract 2043]. J Urol. 2010;183(suppl):e793. Chang S, Harshman L, Bhattacharya J, Presti J. The impact of common medications on serum prostate-specific antigen levels: analysis of National Health and Nutrition Examination Survey [abstract 2044]. J Urol. 2010;183(suppl): e793-e794. Thalmann GN, Rocha C, Schobinger S, et al. Androgen receptor expression is decreased in matched prostate cancer lymph node metastases [abstract 2056]. J Urol. 2010;183(suppl):e799. Wright JL, Lin DW, Stanford JL. The effect of demographic and clinical factors on the relationship between BMI and PSA levels [abstract 2059]. J Urol. 2010;183(suppl):e800. Teeter A, Aronson W, Presti J, et al. Do nomograms designed to predict biochemical recurrence (BCR) do a better job of predicting more distant prostate cancer outcomes than BCR?—a report from the Search Database Group [abstract 241]. J Urol. 2010;183(suppl):e94. Namdarian B, Georgiou H, Corcoran N, et al. Circulating endothelial cells: a new biomarker in prostate cancer [abstract 2129]. J Urol. 2010;183(suppl):e827.