- Email: [email protected]
Introduction and Conclusions
european urology supplements 6 (2007) 695–700
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Introduction and Conclusions Claude Schulman a,*, Christopher Chapple b a b
University Clinics of Brussels, Erasme Hospital, Brussels, Belgium Royal Hallamshire Hospital, Sheffield, UK
Article info
Abstract
Keywords: Bladder cancer Benign bladder diseases Expert meeting Kidney cancer Prostate cancer Stone disease Surgery Urology
Every year, an increasing quantity of new information is presented at the major urologic and oncologic congresses such as the European Association of Urology (EAU), the American Urological Association (AUA), the American Society of Clinical Oncology (ASCO), and so forth. Because of the delay until final publication of these data, it is very difficult for urologists to keep up to date with the new scientific information relevant for their own clinical practise. In light of this difficulty, a closed expert meeting ‘‘New Horizons in Urology’’ (NHU) was held in October 2006 in Marbella, Spain. The objective of this meeting was to provide practising urologists with the most important information with practical clinical relevance to urologists presented during the major urologic and oncologic meetings. This information was selected and presented by leading experts in the field of functional and oncologic urology. Nonmalignant disease areas that were considered were surgical interventions for lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), benign bladder diseases, and stone disease. Malignant disease topics were prostate cancer, bladder cancer, and kidney cancer. Each session started with a clinical case workshop during which the attendee’s opinion on the management of the clinical case was assessed via interactive voting, followed by a discussion of the expert panel. The sessions were closed with a brief update lecture. The current paper summarises the highlights of the closed expert meeting. # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. University Clinics of Brussels, Hoˆpital Erasme, Department of Urology, Route de Lennik 808, 1070 Brussels, Belgium. Tel. +32 2 555 36 14; Fax: +32 2 555 36 99. E-mail address: [email protected] (C. Schulman).
1.
Introduction
In October 2006, a closed expert meeting, ‘New Horizons in Urology’ (NHU), was held in Marbella, Spain, which included about 135 practising urologists and leading experts from different European countries. The objective of this meeting was to
provide urologists with up-to-date scientific information on various subjects in the field of functional and oncologic urology. The scientific sessions dealt with three nonmalignant disease subjects (ie, surgical interventions for lower urinary tract symptoms suggestive of benign prostatic hyperplasia [LUTS/BPH], benign bladder diseases,
1569-9056/$ – see front matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eursup.2007.03.012
696
european urology supplements 6 (2007) 695–700
and stone disease) and three malignant disease subjects (ie, prostate cancer, bladder cancer, and kidney cancer). Each session started with a clinical case workshop including two cases to illustrate new insight in the disease area and/or new management guidelines. The attendee’s opinion on the management of the clinical case was assessed via interactive voting. Each vote was followed by a discussion with the expert panel. The sessions were closed with a brief update lecture covering new insights in the disease area with a discussion on potential impacts on clinical practise. Senior urologists attending the 2006 major urology and oncology meetings selected the key information that was presented during the update lectures. This paper summarises the main outcomes of the different topics discussed during the closed expert meeting.
2.
Conclusions
2.1. Highlights on nonmalignant diseases—functional urology 2.1.1.
Surgical interventions for LUTS/BPH
At this year’s European Association of Urology (EAU) and American Urological Association (AUA) meetings, various randomised controlled trials comparing (minimally invasive) surgical interventions with transurethral resection of the prostate (TURP) for patients with LUTS/BPH were presented. Rowland Illing presented the outcomes of some of these trials including at least 100 LUTS/BPH patients and with at least 1-yr follow-up [1]. Electrosurgical or laser alternatives for TURP such as bipolar transurethral resection in saline, transurethral vaporisation of the prostate, and holmium laser resection/enucleation were found to have an efficacy comparable to TURP and good safety profiles [2–5]. Energy-based ablative techniques like transurethral needle ablation, transurethral microwave therapy, and photoselective vaporisation of the prostate were also suggested as possible alternatives for TURP. These therapies seem to be associated with a lower risk of complications than TURP [6–8]. Mechanical stenting was suggested as a possible treatment for high-risk patients who cannot be anaesthetised [9]. Finally, there were promising preliminary data with regard to the use of botulinum toxin A injections into the prostate [10,11]. It was emphasised that more prospective trials are needed to assess the long-term efficacy and safety (>5-yr follow-up) of these surgical and minimally invasive interventions.
2.1.2.
The bladder
Emmanuel Chartier-Kastler summarised the most relevant new findings on functional bladder problems, focusing on bladder outlet obstruction (BOO) and painful bladder syndrome/interstitial cystitis (PBS/IC) [12]. It was stated that, as the diagnosis and treatment of patients with functional bladder problems varies considerably among practising urologists, continuous medical education of urologists is needed. With regard to BOO, the role of uroflowmetry and ultrasound as potential noninvasive diagnostic tools and the use of a1-adrenoceptor antagonists as a therapeutic aid were discussed [13– 15]. With respect to PBS/IC, it was emphasised that there is need for a standardised definition. Tenderness on bladder palpation was considered to be useful observation in the initial screening and evaluation of IC patients in clinical practise [16]. Finally, botulinum toxin A and cyclosporine A have been suggested as promising treatments for PBS/IC [17,18], but further research is warranted to evaluate their long-term efficacy and safety. 2.1.3.
Stone disease
The highlights of 2006 on stone disease were presented by Thomas Knoll [19]. Nowadays, highrisk patients, patients with kidney stones that fail to pass spontaneously, and those with stones larger than 5 cm can be adequately treated with minimally invasive surgical procedures such as extracorporeal shock wave lithotripsy (ESWL), ureteroscopy (URS), and percutaneous nephrolithotomy (PNL). Both ESWL and URS are considered excellent procedures for removing ureteral stones. The choice of treatment depends on size and location of the stones, available equipment, expertise of the physician, cost of the procedure, and the patient’s preference. Currently, URS is gaining popularity, while the use of ESWL gradually decreases. ESWL is not invasive, but it is less effective than URS and should only be considered as initial treatment for small stones in the proximal ureter [20]. URS is more cost-effective for the removal of larger proximal and distal ureteral stones. The use of PNL is recommended as first-line therapy for patients with lower pole stones [21]. The a1-adrenoceptor antagonists including tamsulosin have shown promise as medical therapy that aids expulsion of distal ureteral stones [22,23]. However, further research is needed to confirm these initial clinical observations. 2.1.4. Nocturia and tamsulosin oral controlled absorption system (OCAS)
Philip Van Kerrebroeck presented interesting data on the control of nocturia in patients with LUTS/BPH
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[24]. Nocturia, or the complaint that an individual has to wake at night one or more times to void, is considered one of the most bothersome LUTS. It can considerably affect the patient’s sleep pattern and lead to daytime sleepiness and even health problems [25]. In view of the problems related to nocturia, treatments for LUTS/BPH should be evaluated for their effect on nocturia, quality of sleep (QoS), and quality of life (QoL) [26]. The first 3–4 h of sleep, when deep, slow-wave sleep predominates, are thought to be essential for a good night’s sleep and thus a good QoL [27]. Therefore, sleep interruption during this part of sleep should be prevented as much as possible. The hours of undisturbed sleep (HUS), defined as the time from falling asleep until the first awakening to void, may be a valuable tool to measure the impact of treatment on QoS [26]. The new tamsulosin OCAS was developed to provide persistent release of tamsulosin throughout the entire gastrointestinal tract, including the colon [28]. Consequently, the new tamsulosin tablet has a favourable pharmacokinetic profile characterised by a consistent and continuous 24-h plasma concentration. It was suggested that, because of these qualities, tamsulosin OCAS would alleviate nocturia and improve QoL.
histopathologic data are important pieces of information within a global set of parameters that should all be considered when deciding on a suitable treatment strategy. With respect to the treatment of patients with localised disease, it was shown that the biochemical disease-free survival of patients with positive surgical margins 1 mm after laparoscopic RP is comparable to that of patients with a negative margin status after surgery [35]. However, follow-up data are needed to verify these results in the long run. External beam radiation therapy and RP were found to result in comparable survival and progression rates in patients with localised PCa [36]. With respect to advanced disease, a randomised phase 3 study presented at the American Society of Clinical Oncology (ASCO) 2006 annual meeting suggested that intermittent hormonal therapy might be an option for regular practise because it yields comparable survival and progression rates as continuous hormonal therapy and has less impact on the patient’s sexual function [37]. However, these data should be confirmed in a larger scale study with a longer follow-up period. Finally, zoledronic acid was suggested to prevent bone complications in patients treated with androgen-deprivation therapy. 2.2.2.
2.2.
Highlights on malignant diseases—oncologic urology
2.2.1.
Prostate cancer
Interesting new data on the screening, detection, and management of prostate cancer (PCa) that were presented at the major 2006 urologic and oncologic meetings were discussed by Pierre Teillac [29]. One of the most relevant new findings with respect to the screening for PCa came from a study investigating the diagnostic yield of two prostate-specific antigen (PSA) cut-off values, 2.5 ng/mL and 4.0 ng/mL, respectively, for the detection of PCa. There seems to be no distinct PSA threshold suitable for the early detection of clinically relevant PCa [30]. Another study suggested that active surveillance could be a possible treatment strategy for selected PCa patients with good prognosis [31]. The PSA doubling time (PSADT) can be an important aid in this active surveillance. It was shown that patients with a PSADT < 12 mo are at elevated risk of progression and PCa-specific death [32]. In addition, histopathologic data of radical prostatectomy (RP) specimens should be treated with caution since there seems to be low agreement for extracapsular extension and margin status among pathologists [33]. Partin tables are not suited for the prediction of lymph node involvement in patients with clinically localised PCa [34]. It was concluded that the Partin tables and
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Bladder cancer
Antonio Alcaraz summarised many interesting new data on the surveillance and treatment of patients with bladder cancer (BCa) that were presented at the key urologic congresses in 2006 [38]. A number of studies in the field of BCa evaluated the diagnostic and prognostic value of the biomarkers survivin and nuclear matrix protein (NMP)-22. However, these studies had rather inconsistent outcomes regarding the specificity and sensitivity of these markers for the detection and follow-up of BCa. It was emphasised that more research is warranted to assess whether either of these biomarkers can replace voided urine cytology or cystoscopy in daily practise. A major revelation at this year’s urology congresses was the introduction of the European Organisation for Research and Treatment of Cancer (EORTC) tables to calculate the risk of recurrence and progression of superficial BCa patients [39]. These tables are considered to be very important decisionmaking tools for the treatment and follow-up of patients with superficial disease. Radical cystectomy is still the treatment of choice for patients with recurrent superficial BCa after Bacillus CalmetteGue´rin (BCG) failure. However, several more conservative second-line treatments are under investigation. For example, a phase 2 multicentre trial presented at the 2006 AUA annual meeting showed that patients with recurrent superficial BCa after
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>12 mo of remission have a similar cancer-free survival rate as BCG-naive patients after BCG + interferon-a (IFN-a) treatment [40]. At the closed meeting, the experts stated that a bladder-sparing treatment could be indicated for selected patients with minimally invasive BCa. With respect to muscle-invasive and metastatic tumours, one study showed that BCa patients with a pT0N0M0 radical cystectomy specimen, and especially those with lymphovascular invasion, cannot be considered cured and still need lifelong surveillance [41]. One study presented at the 2006 ASCO meeting showed promising results with paclitaxel, ifosfamide, and nedaplatin combination chemotherapy as salvage treatment for patients with recurrent urothelial cancer [42]. Finally, the oncologic outcome of laparoscopic cystectomy seems to be comparable to that of open radical cystectomy or nephroureterectomy [43,44]. However, it was stated that longterm outcomes are needed to confirm these data. 2.2.3.
Kidney cancer
As discussed by Francesco Montorsi, several relevant new data on surgical and minimally invasive treatment of localised renal cell carcinoma (RCC) and systemic treatments for advanced RCC were presented in 2006 at the urologic and oncologic meetings [45]. Previous research demonstrated that partial nephrectomy provides recurrence-free and long-term survival rates similar to those observed after radical neprectomy in patients with a tumour <4 cm. Nevertheless, data from a retrospective study presented at the AUA meeting in 2006 indicated that urologists are still reluctant to use this technique, even for small tumours [46]. A study presented at the 2006 EAU meeting showed that tumour size is positively correlated with aggressiveness [47]. Promising results with minimally invasive techniques such as cryoablation and radiofrequency ablation were presented, but the long-term oncologic efficacy and safety of these techniques need to be evaluated. A number of important studies further evaluated the efficacy and safety of several angiogenesis inhibitors for the treatment of advanced RCC. One study suggested that sunitinib is superior to IFN-a as first-line treatment for patients with advanced clear-cell RCC [48]. Sorafenib was found to prolong the progression-free survival of patients previously treated for advanced RCC significantly more than placebo [49]. Finally, monotherapy with temsirolimus increased the overall survival time in poor-risk patients significantly more than IFN-a alone or combination therapy with temsirolimus and IFN-a [50].
2.2.4.
Optimal testosterone control and Eligard
The importance of optimal testosterone control in PCa and the advantages of the luteinising hormone releasing hormone (LHRH) agonist Eligard in this respect were discussed by Bertrand Tombal and Richard Berges [51]. LHRH agonists are developed to reduce testosterone levels to a similar degree as surgical castration. However, a percentage of patients treated with conventional LHRH agonists do not achieve these levels [52–54]. Moreover, many patients experience injection-related and breakthrough testosterone escapes during treatment [54,55]. In contrast to these conventional formulations, Eligard offers 1-, 3-, and 6-mo depot formulations using a superior delivery system. All three formulations of Eligard successfully reduce and maintain testosterone levels comparable to orchidectomy in the majority of patients [56–58]. The Eligard 6-mo formulation is the first LHRH agonist that extends treatment for 6 mo. In addition, it allows flexible monitoring of patients as the need for visits to administer injections is removed. Fewer visits to the physician also imply that the patient is less often reminded of his condition, which may reduce emotional distress. References [1] Illing R. Surgical and minimally invasive interventions for LUTS/BPH: highlights from 2006. Eur Urol Suppl 2007;6: 701–9. [2] Terrone C, Scoffone C, Cracco C, et al. Bipolar versus monopolar TURP: a randomised study. Eur Urol Suppl 2006;5:235 (abstract no. 849). [3] Ho H, Yip S, Lim KB, et al. A prospective randomised controlled trial comparing bipolar transurethral resection in saline (TURIS) system and conventional monopolar transurethral resection of prostate in men with benign prostatic hyperplasia: 1 year’s clinical efficacy and safety. Eur Urol Suppl 2006;5:308 (abstract no. 1143). [4] Chandrasekar P, Kapasi F, Virdi J. A prospective randomised study between transurethral vaporisation using plasmakinetic energy and transurethral resection of prostate – 5-year results. Eur Urol Suppl 2006;5:309 (abstract no. 1148). [5] Wilson LC, Gilling PJ, Williams A, et al. A randomised trial comparing holmium laser enucleation versus transurethral resection in the treatment of prostates larger than 40 grams: results at 2 years. Eur Urol 2006;50:569–73. [6] Mattiasson A, Wagrell L, Schelin S, et al. Five-year followup of feedback microwave thermotherapy versus TURP for clinical BPH: a prospective randomized multicenter study. Urology 2007;69:91–6. [7] Hill B, Belville W, Bruskewitz R, et al. Five year results of a prospective randomized trial comparing transurethral needle ablation (TUNA) to TURP for treatment of symptomatic BPH. J Urol 2002;167(suppl 4):294.
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[8] Bachmann A, Ruszat R, Straumann U, et al. Photoselective vaporisation of the prostate (PVP) versus transurethral resection of the prostate (TURP). Eur Urol Suppl 2006;5:236 (abstract no. 855). [9] Armitage JN, Rashidian A, Cathcart PJ, et al. The thermoexpandable metallic stent for managing benign prostatic hyperplasia: a systematic review. BJU Int 2006;98:806–10. [10] Chuang YC, Chiang PH, Yoshimura N, et al. Sustained beneficial effects of intraprostatic botulinum toxin type A on lower urinary tract symptoms and quality of life in men with benign prostatic hyperplasia. BJU Int 2006;98: 1033–7. [11] Chuang YC, Giannantoni A, Chancellor MB. The potential and promise of using botulinum toxin in the prostate gland. BJU Int 2006;98:28–32. [12] Chartier-Kastler E. Functional bladder problems. Eur Urol Suppl 2007;6:710–6. [13] Al-Hayek S, Belal M, Abrams P. How reliable is non-invasive uroflowmetry in predicting the presence of bladder outlet obstruction in men? J Urol 2006;175:437 (abstract no. 1356). [14] Oelke M, Ho¨fner K, de la Rosette JJ, et al. What is the most precise cut-off value of detrusor wall thickness measurement to classify bladder outlet obstruction? Neurourol Urodyn 2006;25 (abstract no. 28). [15] Tubaro A, Sironi D, Pizzoccaro M, et al. Effect of tamsulosin on bladder wall hypertrophy in patients with lower urinary tract symptoms suggestive of bladder outlet obstruction. Eur Urol Suppl 2003;2(1):158 (abstract no. 624). [16] Botros S, Miller J, Goldberg R, et al. A simple test to aid in the diagnosis of interstitial cystitis. Neurourol Urodyn 2006;25 (abstract no. 403). [17] Giannantoni A, Costantini E, Di Stasi SM, et al. Botulinum A toxin intravesical injections in the treatment of painful bladder syndrome: a pilot study. Eur Urol 2006;49:704–9. [18] Sairanen J, Tammela TL, Leppilahti M, et al. Cyclosporine A and pentosan polysulfate sodium for the treatment of interstitial cystitis: a randomized comparative study. J Urol 2005;174:2235–8. [19] Knoll T. Stone disease. Eur Urol Suppl 2007;6:717–22. [20] Honeck P, Hacker A, Alken P, et al. Shock wave lithotripsy versus ureteroscopy for distal ureteral calculi: a prospective study. Urol Res 2006;34:190–2. [21] Albala DM, Assimos DG, Clayman RV, et al. Lower pole I: a prospective randomized trial of extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy for lower pole nephrolithiasis-initial results. J Urol 2001;166:2072–80. [22] De Sio M, Autorino R, Di Lorenzo G, et al. Medical expulsive treatment of distal-ureteral stones using tamsulosin: a single-center experience. J Endourol 2006;20:12–6. [23] Devasia A, Bhagat S, Chacko N, et al. Is there a role for tamsulosin in extra corporeal shockwave lithotripsy for renal and ureteric calculi? J Urol 2006;175:549–50 (abstract no. 1710). [24] Van Kerrebroeck P. Nocturia and tamsulosin OCAS. Eur Urol Suppl 2007;6:723–7. [25] Asplund R. Nocturia: consequences for sleep and daytime activities and associated risks. Eur Urol Suppl 2005;3(6): 24–32.
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[26] Chapple CR, Batista JE, Berges R, et al. The impact of nocturia in patients with LUTS/BPH: Need for new recommendations. Eur Urol Suppl 2006;5:12–8. [27] Stanley N. The physiology of sleep and the impact of ageing. Eur Urol Suppl 2005;3(6):17–23. [28] Stevens NHE, Speakman M. Behaviour and transit of tamsulosin Oral Controlled Absorption System (OCAS1) in the gastrointestinal tract. Curr Med Res Opin 2006;22:2323–8. [29] Teillac P, Mongiat-Artus P. Prostate cancer: highlights from 2006. Eur Urol Suppl 2007;6:728–36. [30] Muntener M, Kunz U, Eichler K, et al. Diagnostic yield of a PSA threshold for prostate biopsy of 2.5 ng/ml compared to 4 ng/ml. Eur Urol Suppl 2006;5:237 (abstract no. 859). [31] Master VA, Konety BR, Perez N, et al. Prostate cancer progression in a watchful waiting cohort: the UCSF experience. J Urol 2006;175:158–9 (abstract no. 488). [32] Collette L, Studer UE, Whelan P, et al. PSA doubling time as predictor of objective progression and death in patients with T0-T4 N0-2 M0 prostate cancer not suitable for local definitive treatment on watchful waiting (EORTC 30891). Eur Urol Suppl 2006;5:203 (abstract no. 721). [33] van der Kwast TH, Collette L, Van PH, et al. Impact of pathology review of stage and margin status of radical prostatectomy specimens (EORTC trial 22911). Virchows Arch 2006;449:428–34. [34] Heidenreich A, Ohlmann C, Engelmann U, et al. Partin tables do not adequately predict the risk of lymph node involvement in patients undergoing radical prostatectomy for clinically localised prostate cancer. Eur Urol Suppl 2006;5:280 (abstract no. 1032). [35] Cathelineau X, Harmon J, Rozet F, et al. The significance of positive surgical margins 1mm after laparoscopic radical prostatectomy. Eur Urol Suppl 2006;5:52 (abstract no. 118). [36] Di Stasi SM, Giannantoni A, Virgili G, et al. Radical retropubic prostatectomy versus external beam radiotherapy for localised prostate cancer: an interim report of a multicentre, prospective, phase III randomised study. Eur Urol Suppl 2006;5:204 (abstract no. 728). [37] Calais Da Silva FM, Calais Da Silva F, Bono A, et al. Phase III intermittent MAB vs continuous MAB. J Clin Oncol 2006;24:220 (abstract no. 4513). [38] Alcaraz A. Bladder cancer: highlights from 2006. Eur Urol Suppl 2007;6:737–44. [39] Sylvester RJ, van der Meijden AP, Oosterlinck W, et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 2006;49:466–75. [40] Gallagher BL, Joudi FN, O’Donnell MA. Response to intravesical immunotherapy in BCG naı¨ve and BCG treated patients. J Urol 2006;175:268 (abstract no. 831). [41] Kassouf W, Spiess PE, Brown GA, et al. Natural history of bladder cancer in patients with PO disease at radical cystectomy. J Urol 2006;175(suppl):397 (abstract no. 1233). [42] Shinohara N, Harabayashi T, Suzuki S, et al. Salvage chemotherapy with paclitaxel, ifosfamide, and nedaplatin in patients with urothelial cancer who had received
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prior cisplatin-based therapy. Cancer Chemother Pharmacol 2006;58:402–7. Gaston R, Barmoshe S, Pansadoro A, et al. Laparoscopic radical cystectomy: review of 100 cases. Eur Urol Suppl 2006;5:23 (abstract no. 2). Manabe D, Saika T, Ebara S, et al. Comparative study for oncological outcome following laparoscopic nephroureterectomy or standard nephroureterectomy for upper urinary tract transitional cell carcinoma. Eur Urol Suppl 2006;5:23 (abstract no. 1). Montorsi F. Kidney cancer: highlights from 2006. Eur Urol Suppl 2007;6:745–53. Miller DC, Hollingsworth JM, Hafez KS, et al. Partial nephrectomy for small renal masses: an emerging quality of care concern? J Urol 2006;175:229 (abstract no. 708). ¨ szoy M, et al. Renal tumours Remzi M, Klingler HC, O between 3 and 4cm show significantly more aggressive parameters than tumours equal or less than 3cm. An analysis of 287 renal tumours 4cm. Eur Urol Suppl 2006;5:107 (abstract no. 339). Motzer RJ, Hutson TE, Tomczak P, et al. Phase III randomized trial of sunitnib malate (SU1 1248) versus interferonalfa (IFN-a) as first-line systemic therapy for patients with metastatic renal cell carcinoma (mRCC). J Clin Oncol 2006;24:2 (abstract no. LBA3). Escudier B, Szczylik C, Eisen T, et al. Randomised phase III trial of the multikinase inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). Eur Urol Suppl 2006;5:287 (abstract no. 1058). Hudes G, Carducci M, Tomczak P, et al. A phase III, randomized, 3-arm study of temsirolimus (TEMSR) or interferon-alfa (IFN) or the combination of TEMSR + IFN in the treatment of first-line, poor-prognosis patients with advanced renal cell carcinoma. J Clin Oncol 2006;24:2 (abstract no. LBA4).
[51] Tombal B, Berges R. Optimal testosterone control and Eligard1. Eur Urol Suppl 2007;6:745–60. [52] Morote J, Esquena S, Abascal JM, et al. Failure to maintain a suppressed level of serum testosterone during longacting depot luteinizing hormone-releasing hormone agonist therapy in patients with advanced prostate cancer. Urol Int 2006;77:135–8. [53] Oefelein MG, Cornum R. Failure to achieve castrate levels of testosterone during luteinizing hormone releasing hormone agonist therapy: the case for monitoring serum testosterone and a treatment decision algorithm. J Urol 2000;164:726–9. [54] Sarosdy MF, Schellhammer PF, Soloway MS, et al. Endocrine effects, efficacy and tolerability of a 10-8-mg depot formulation of goserelin acetate administered every 13 weeks to patients with advanced prostate cancer. BJU Int 1999;83:801–6. [55] Sharifi R, Browneller R. Serum testosterone suppression and potential for agonistic stimulation during chronic treatment with monthly and 3-month depot formulations of leuprolide acetate for advanced prostate cancer. J Urol 2002;168:1001–4. [56] Chu FM, Jayson M, Dineen MK, et al. A clinical study of 22.5 mg. LA-2550:A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. J Urol 2002;168:1199–203. [57] Crawford ED, Sartor O, Chu F, et al. A 12-month clinical study of LA-2585 (45.0 mg): a new 6-month subcutaneous delivery system for leuprolide acetate for the treatment of prostate cancer. J Urol 2006;175:533–6. [58] Perez-Marreno R, Chu FM, Gleason D, et al. A six-month, open-label study assessing a new formulation of leuprolide 7.5 mg for suppression of testosterone in patients with prostate cancer. Clin Ther 2002;24: 1902–14.
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Introduction and Conclusions Claude Schulman a,*, Christopher Chapple b a b
University Clinics of Brussels, Erasme Hospital, Brussels, Belgium Royal Hallamshire Hospital, Sheffield, UK
Article info
Abstract
Keywords: Bladder cancer Benign bladder diseases Expert meeting Kidney cancer Prostate cancer Stone disease Surgery Urology
Every year, an increasing quantity of new information is presented at the major urologic and oncologic congresses such as the European Association of Urology (EAU), the American Urological Association (AUA), the American Society of Clinical Oncology (ASCO), and so forth. Because of the delay until final publication of these data, it is very difficult for urologists to keep up to date with the new scientific information relevant for their own clinical practise. In light of this difficulty, a closed expert meeting ‘‘New Horizons in Urology’’ (NHU) was held in October 2006 in Marbella, Spain. The objective of this meeting was to provide practising urologists with the most important information with practical clinical relevance to urologists presented during the major urologic and oncologic meetings. This information was selected and presented by leading experts in the field of functional and oncologic urology. Nonmalignant disease areas that were considered were surgical interventions for lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), benign bladder diseases, and stone disease. Malignant disease topics were prostate cancer, bladder cancer, and kidney cancer. Each session started with a clinical case workshop during which the attendee’s opinion on the management of the clinical case was assessed via interactive voting, followed by a discussion of the expert panel. The sessions were closed with a brief update lecture. The current paper summarises the highlights of the closed expert meeting. # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. University Clinics of Brussels, Hoˆpital Erasme, Department of Urology, Route de Lennik 808, 1070 Brussels, Belgium. Tel. +32 2 555 36 14; Fax: +32 2 555 36 99. E-mail address: [email protected] (C. Schulman).
1.
Introduction
In October 2006, a closed expert meeting, ‘New Horizons in Urology’ (NHU), was held in Marbella, Spain, which included about 135 practising urologists and leading experts from different European countries. The objective of this meeting was to
provide urologists with up-to-date scientific information on various subjects in the field of functional and oncologic urology. The scientific sessions dealt with three nonmalignant disease subjects (ie, surgical interventions for lower urinary tract symptoms suggestive of benign prostatic hyperplasia [LUTS/BPH], benign bladder diseases,
1569-9056/$ – see front matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eursup.2007.03.012
696
european urology supplements 6 (2007) 695–700
and stone disease) and three malignant disease subjects (ie, prostate cancer, bladder cancer, and kidney cancer). Each session started with a clinical case workshop including two cases to illustrate new insight in the disease area and/or new management guidelines. The attendee’s opinion on the management of the clinical case was assessed via interactive voting. Each vote was followed by a discussion with the expert panel. The sessions were closed with a brief update lecture covering new insights in the disease area with a discussion on potential impacts on clinical practise. Senior urologists attending the 2006 major urology and oncology meetings selected the key information that was presented during the update lectures. This paper summarises the main outcomes of the different topics discussed during the closed expert meeting.
2.
Conclusions
2.1. Highlights on nonmalignant diseases—functional urology 2.1.1.
Surgical interventions for LUTS/BPH
At this year’s European Association of Urology (EAU) and American Urological Association (AUA) meetings, various randomised controlled trials comparing (minimally invasive) surgical interventions with transurethral resection of the prostate (TURP) for patients with LUTS/BPH were presented. Rowland Illing presented the outcomes of some of these trials including at least 100 LUTS/BPH patients and with at least 1-yr follow-up [1]. Electrosurgical or laser alternatives for TURP such as bipolar transurethral resection in saline, transurethral vaporisation of the prostate, and holmium laser resection/enucleation were found to have an efficacy comparable to TURP and good safety profiles [2–5]. Energy-based ablative techniques like transurethral needle ablation, transurethral microwave therapy, and photoselective vaporisation of the prostate were also suggested as possible alternatives for TURP. These therapies seem to be associated with a lower risk of complications than TURP [6–8]. Mechanical stenting was suggested as a possible treatment for high-risk patients who cannot be anaesthetised [9]. Finally, there were promising preliminary data with regard to the use of botulinum toxin A injections into the prostate [10,11]. It was emphasised that more prospective trials are needed to assess the long-term efficacy and safety (>5-yr follow-up) of these surgical and minimally invasive interventions.
2.1.2.
The bladder
Emmanuel Chartier-Kastler summarised the most relevant new findings on functional bladder problems, focusing on bladder outlet obstruction (BOO) and painful bladder syndrome/interstitial cystitis (PBS/IC) [12]. It was stated that, as the diagnosis and treatment of patients with functional bladder problems varies considerably among practising urologists, continuous medical education of urologists is needed. With regard to BOO, the role of uroflowmetry and ultrasound as potential noninvasive diagnostic tools and the use of a1-adrenoceptor antagonists as a therapeutic aid were discussed [13– 15]. With respect to PBS/IC, it was emphasised that there is need for a standardised definition. Tenderness on bladder palpation was considered to be useful observation in the initial screening and evaluation of IC patients in clinical practise [16]. Finally, botulinum toxin A and cyclosporine A have been suggested as promising treatments for PBS/IC [17,18], but further research is warranted to evaluate their long-term efficacy and safety. 2.1.3.
Stone disease
The highlights of 2006 on stone disease were presented by Thomas Knoll [19]. Nowadays, highrisk patients, patients with kidney stones that fail to pass spontaneously, and those with stones larger than 5 cm can be adequately treated with minimally invasive surgical procedures such as extracorporeal shock wave lithotripsy (ESWL), ureteroscopy (URS), and percutaneous nephrolithotomy (PNL). Both ESWL and URS are considered excellent procedures for removing ureteral stones. The choice of treatment depends on size and location of the stones, available equipment, expertise of the physician, cost of the procedure, and the patient’s preference. Currently, URS is gaining popularity, while the use of ESWL gradually decreases. ESWL is not invasive, but it is less effective than URS and should only be considered as initial treatment for small stones in the proximal ureter [20]. URS is more cost-effective for the removal of larger proximal and distal ureteral stones. The use of PNL is recommended as first-line therapy for patients with lower pole stones [21]. The a1-adrenoceptor antagonists including tamsulosin have shown promise as medical therapy that aids expulsion of distal ureteral stones [22,23]. However, further research is needed to confirm these initial clinical observations. 2.1.4. Nocturia and tamsulosin oral controlled absorption system (OCAS)
Philip Van Kerrebroeck presented interesting data on the control of nocturia in patients with LUTS/BPH
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[24]. Nocturia, or the complaint that an individual has to wake at night one or more times to void, is considered one of the most bothersome LUTS. It can considerably affect the patient’s sleep pattern and lead to daytime sleepiness and even health problems [25]. In view of the problems related to nocturia, treatments for LUTS/BPH should be evaluated for their effect on nocturia, quality of sleep (QoS), and quality of life (QoL) [26]. The first 3–4 h of sleep, when deep, slow-wave sleep predominates, are thought to be essential for a good night’s sleep and thus a good QoL [27]. Therefore, sleep interruption during this part of sleep should be prevented as much as possible. The hours of undisturbed sleep (HUS), defined as the time from falling asleep until the first awakening to void, may be a valuable tool to measure the impact of treatment on QoS [26]. The new tamsulosin OCAS was developed to provide persistent release of tamsulosin throughout the entire gastrointestinal tract, including the colon [28]. Consequently, the new tamsulosin tablet has a favourable pharmacokinetic profile characterised by a consistent and continuous 24-h plasma concentration. It was suggested that, because of these qualities, tamsulosin OCAS would alleviate nocturia and improve QoL.
histopathologic data are important pieces of information within a global set of parameters that should all be considered when deciding on a suitable treatment strategy. With respect to the treatment of patients with localised disease, it was shown that the biochemical disease-free survival of patients with positive surgical margins 1 mm after laparoscopic RP is comparable to that of patients with a negative margin status after surgery [35]. However, follow-up data are needed to verify these results in the long run. External beam radiation therapy and RP were found to result in comparable survival and progression rates in patients with localised PCa [36]. With respect to advanced disease, a randomised phase 3 study presented at the American Society of Clinical Oncology (ASCO) 2006 annual meeting suggested that intermittent hormonal therapy might be an option for regular practise because it yields comparable survival and progression rates as continuous hormonal therapy and has less impact on the patient’s sexual function [37]. However, these data should be confirmed in a larger scale study with a longer follow-up period. Finally, zoledronic acid was suggested to prevent bone complications in patients treated with androgen-deprivation therapy. 2.2.2.
2.2.
Highlights on malignant diseases—oncologic urology
2.2.1.
Prostate cancer
Interesting new data on the screening, detection, and management of prostate cancer (PCa) that were presented at the major 2006 urologic and oncologic meetings were discussed by Pierre Teillac [29]. One of the most relevant new findings with respect to the screening for PCa came from a study investigating the diagnostic yield of two prostate-specific antigen (PSA) cut-off values, 2.5 ng/mL and 4.0 ng/mL, respectively, for the detection of PCa. There seems to be no distinct PSA threshold suitable for the early detection of clinically relevant PCa [30]. Another study suggested that active surveillance could be a possible treatment strategy for selected PCa patients with good prognosis [31]. The PSA doubling time (PSADT) can be an important aid in this active surveillance. It was shown that patients with a PSADT < 12 mo are at elevated risk of progression and PCa-specific death [32]. In addition, histopathologic data of radical prostatectomy (RP) specimens should be treated with caution since there seems to be low agreement for extracapsular extension and margin status among pathologists [33]. Partin tables are not suited for the prediction of lymph node involvement in patients with clinically localised PCa [34]. It was concluded that the Partin tables and
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Bladder cancer
Antonio Alcaraz summarised many interesting new data on the surveillance and treatment of patients with bladder cancer (BCa) that were presented at the key urologic congresses in 2006 [38]. A number of studies in the field of BCa evaluated the diagnostic and prognostic value of the biomarkers survivin and nuclear matrix protein (NMP)-22. However, these studies had rather inconsistent outcomes regarding the specificity and sensitivity of these markers for the detection and follow-up of BCa. It was emphasised that more research is warranted to assess whether either of these biomarkers can replace voided urine cytology or cystoscopy in daily practise. A major revelation at this year’s urology congresses was the introduction of the European Organisation for Research and Treatment of Cancer (EORTC) tables to calculate the risk of recurrence and progression of superficial BCa patients [39]. These tables are considered to be very important decisionmaking tools for the treatment and follow-up of patients with superficial disease. Radical cystectomy is still the treatment of choice for patients with recurrent superficial BCa after Bacillus CalmetteGue´rin (BCG) failure. However, several more conservative second-line treatments are under investigation. For example, a phase 2 multicentre trial presented at the 2006 AUA annual meeting showed that patients with recurrent superficial BCa after
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>12 mo of remission have a similar cancer-free survival rate as BCG-naive patients after BCG + interferon-a (IFN-a) treatment [40]. At the closed meeting, the experts stated that a bladder-sparing treatment could be indicated for selected patients with minimally invasive BCa. With respect to muscle-invasive and metastatic tumours, one study showed that BCa patients with a pT0N0M0 radical cystectomy specimen, and especially those with lymphovascular invasion, cannot be considered cured and still need lifelong surveillance [41]. One study presented at the 2006 ASCO meeting showed promising results with paclitaxel, ifosfamide, and nedaplatin combination chemotherapy as salvage treatment for patients with recurrent urothelial cancer [42]. Finally, the oncologic outcome of laparoscopic cystectomy seems to be comparable to that of open radical cystectomy or nephroureterectomy [43,44]. However, it was stated that longterm outcomes are needed to confirm these data. 2.2.3.
Kidney cancer
As discussed by Francesco Montorsi, several relevant new data on surgical and minimally invasive treatment of localised renal cell carcinoma (RCC) and systemic treatments for advanced RCC were presented in 2006 at the urologic and oncologic meetings [45]. Previous research demonstrated that partial nephrectomy provides recurrence-free and long-term survival rates similar to those observed after radical neprectomy in patients with a tumour <4 cm. Nevertheless, data from a retrospective study presented at the AUA meeting in 2006 indicated that urologists are still reluctant to use this technique, even for small tumours [46]. A study presented at the 2006 EAU meeting showed that tumour size is positively correlated with aggressiveness [47]. Promising results with minimally invasive techniques such as cryoablation and radiofrequency ablation were presented, but the long-term oncologic efficacy and safety of these techniques need to be evaluated. A number of important studies further evaluated the efficacy and safety of several angiogenesis inhibitors for the treatment of advanced RCC. One study suggested that sunitinib is superior to IFN-a as first-line treatment for patients with advanced clear-cell RCC [48]. Sorafenib was found to prolong the progression-free survival of patients previously treated for advanced RCC significantly more than placebo [49]. Finally, monotherapy with temsirolimus increased the overall survival time in poor-risk patients significantly more than IFN-a alone or combination therapy with temsirolimus and IFN-a [50].
2.2.4.
Optimal testosterone control and Eligard
The importance of optimal testosterone control in PCa and the advantages of the luteinising hormone releasing hormone (LHRH) agonist Eligard in this respect were discussed by Bertrand Tombal and Richard Berges [51]. LHRH agonists are developed to reduce testosterone levels to a similar degree as surgical castration. However, a percentage of patients treated with conventional LHRH agonists do not achieve these levels [52–54]. Moreover, many patients experience injection-related and breakthrough testosterone escapes during treatment [54,55]. In contrast to these conventional formulations, Eligard offers 1-, 3-, and 6-mo depot formulations using a superior delivery system. All three formulations of Eligard successfully reduce and maintain testosterone levels comparable to orchidectomy in the majority of patients [56–58]. The Eligard 6-mo formulation is the first LHRH agonist that extends treatment for 6 mo. In addition, it allows flexible monitoring of patients as the need for visits to administer injections is removed. Fewer visits to the physician also imply that the patient is less often reminded of his condition, which may reduce emotional distress. References [1] Illing R. Surgical and minimally invasive interventions for LUTS/BPH: highlights from 2006. Eur Urol Suppl 2007;6: 701–9. [2] Terrone C, Scoffone C, Cracco C, et al. Bipolar versus monopolar TURP: a randomised study. Eur Urol Suppl 2006;5:235 (abstract no. 849). [3] Ho H, Yip S, Lim KB, et al. A prospective randomised controlled trial comparing bipolar transurethral resection in saline (TURIS) system and conventional monopolar transurethral resection of prostate in men with benign prostatic hyperplasia: 1 year’s clinical efficacy and safety. Eur Urol Suppl 2006;5:308 (abstract no. 1143). [4] Chandrasekar P, Kapasi F, Virdi J. A prospective randomised study between transurethral vaporisation using plasmakinetic energy and transurethral resection of prostate – 5-year results. Eur Urol Suppl 2006;5:309 (abstract no. 1148). [5] Wilson LC, Gilling PJ, Williams A, et al. A randomised trial comparing holmium laser enucleation versus transurethral resection in the treatment of prostates larger than 40 grams: results at 2 years. Eur Urol 2006;50:569–73. [6] Mattiasson A, Wagrell L, Schelin S, et al. Five-year followup of feedback microwave thermotherapy versus TURP for clinical BPH: a prospective randomized multicenter study. Urology 2007;69:91–6. [7] Hill B, Belville W, Bruskewitz R, et al. Five year results of a prospective randomized trial comparing transurethral needle ablation (TUNA) to TURP for treatment of symptomatic BPH. J Urol 2002;167(suppl 4):294.
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[51] Tombal B, Berges R. Optimal testosterone control and Eligard1. Eur Urol Suppl 2007;6:745–60. [52] Morote J, Esquena S, Abascal JM, et al. Failure to maintain a suppressed level of serum testosterone during longacting depot luteinizing hormone-releasing hormone agonist therapy in patients with advanced prostate cancer. Urol Int 2006;77:135–8. [53] Oefelein MG, Cornum R. Failure to achieve castrate levels of testosterone during luteinizing hormone releasing hormone agonist therapy: the case for monitoring serum testosterone and a treatment decision algorithm. J Urol 2000;164:726–9. [54] Sarosdy MF, Schellhammer PF, Soloway MS, et al. Endocrine effects, efficacy and tolerability of a 10-8-mg depot formulation of goserelin acetate administered every 13 weeks to patients with advanced prostate cancer. BJU Int 1999;83:801–6. [55] Sharifi R, Browneller R. Serum testosterone suppression and potential for agonistic stimulation during chronic treatment with monthly and 3-month depot formulations of leuprolide acetate for advanced prostate cancer. J Urol 2002;168:1001–4. [56] Chu FM, Jayson M, Dineen MK, et al. A clinical study of 22.5 mg. LA-2550:A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. J Urol 2002;168:1199–203. [57] Crawford ED, Sartor O, Chu F, et al. A 12-month clinical study of LA-2585 (45.0 mg): a new 6-month subcutaneous delivery system for leuprolide acetate for the treatment of prostate cancer. J Urol 2006;175:533–6. [58] Perez-Marreno R, Chu FM, Gleason D, et al. A six-month, open-label study assessing a new formulation of leuprolide 7.5 mg for suppression of testosterone in patients with prostate cancer. Clin Ther 2002;24: 1902–14.