European Urology - Articles in Press

Glycine Transporter Type 2 (GlyT2) Inhibitor Ameliorates Bladder Overactivity and Nociceptive Behavior in Rats - Uncorrected Proof

2012-02-03

Abstract: Background: Glycine is a major inhibitory neurotransmitter in the spinal cord, the concentration of which is regulated by two types of glycine transporters (GlyTs): GlyT1 and GlyT2. We hypothesized that the inhibition of GlyTs could ameliorate bladder overactivity and/or pain sensation in the lower urinary tract.Objective: Investigate the effects of GlyT inhibitors on bladder overactivity and pain behavior in rats.Design, setting, and participants: Cystometry was performed under urethane anesthesia in cyclophosphamide (CYP)–treated rats. In behavioral studies using conscious rats, nociceptive responses were induced by intravesical administration of resiniferatoxin (3μM). Selective GlyT1 or GlyT2 inhibitors were administered intrathecally to evaluate their effects.Measurements: Cystometric parameters, nociceptive behaviors (licking and freezing), and messenger RNA (mRNA) levels of GlyTs and glycine receptor (GlyR) subunits in the dorsal spinal cord (L6–S1) were measured.Results and limitations: During cystometry in CYP-treated rats, significant increases in intercontraction interval and micturition pressure threshold were elicited by ALX-1393, a selective GlyT2 inhibitor, but not by sarcosine, a GlyT1 inhibitor. These effects were completely reversed by strychnine, a GlyR antagonist. ALX-1393 also significantly suppressed nociceptive behaviors in a dose-dependent manner. In sham rats, GlyT2 mRNA was expressed at a much higher level (23-fold) in the dorsal spinal cord than GlyT1 mRNA. In CYP-treated rats, mRNA levels of GlyT2 and the GlyR α1 and β subunits were significantly reduced.Conclusions: These results indicate that GlyT2 plays a major role in the clearance of extracellular glycine in the spinal cord and that GlyT2 inhibition leads to amelioration of CYP-induced bladder overactivity and pain behavior. GlyT2 may be a novel therapeutic target for the treatment of overactive bladder and/or bladder hypersensitive disorders such as bladder pain syndrome/interstitial cystitis.Take Home Message: Inhibition of glycine transporter type 2 (GlyT2) ameliorated bladder overactivity and pain responses induced by bladder irritation in rats. This result suggests that GlyT2 inhibitors might be useful for the treatment of overactive and hypersensitive bladder conditions, including bladder pain syndrome.

Androgen-Deprivation Therapy for Nonmetastatic Prostate Cancer Is Associated With an Increased Risk of Peripheral Arterial Disease and Venous Thromboembolism - Uncorrected Proof

2012-02-03

Abstract: Background: Previous studies demonstrate that androgen-deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and orchiectomy for prostate cancer (PCa) is associated with cardiovascular disease. However, few studies have examined its effect on the peripheral vascular system.Objective: To study the risk of peripheral artery disease (PAD) and venous thromboembolism associated with ADT for PCa.Design, settings, and participants: This was a population-based observational study of 182 757 US men ≥66 yr of age who were diagnosed with nonmetastatic PCa from 1992 to 2007, with a median follow-up of 5.1 yr, of whom 47.8% received GnRH agonists and 2.2% orchiectomy.Measurements: We used Cox proportional hazards models with time-varying treatment variables to adjust for demographic and tumor characteristics in assessing whether treatment with GnRH agonists or orchiectomy were associated with PAD and/or venous thromboembolism.Results and limitations: GnRH agonist use was associated with an increased risk of incident PAD (adjusted hazard ratio [HR]: 1.16; 95% confidence interval [CI], 1.12–1.21) and incident venous thromboembolism (adjusted HR: 1.10; 95% CI, 1.04–1.15). In addition, orchiectomy was associated with an increased risk of peripheral arterial disease (adjusted HR: 1.13; 95% CI, 1.02–1.26) and venous thromboembolism (adjusted HR: 1.27; 95% CI, 1.11–1.45). Limitations include the observational study design and the inability to assess the use of oral antiandrogens.Conclusions: ADT for nonmetastatic PCa is associated with an increased risk of PAD and venous thromboembolism. Additional research is needed to better understand the potential risks and benefits of ADT, so that this treatment can be targeted to patients for whom the benefits are clearest.Take Home Message: Androgen-deprivation therapy (ADT) for nonmetastatic prostate cancer is associated with an increased risk of peripheral artery disease and venous thromboembolism, and men must be counseled of these risks prior to the administration of ADT. Additional research is needed to elucidate indications and relative harms and benefits of ADT.

Spread of OnabotulinumtoxinA After Bladder Injection. Experimental Study Using the Distribution of Cleaved SNAP-25 as the Marker of the Toxin Action - Uncorrected Proof

Ana Coelho, Francisco Cruz, Célia D. Cruz, António Avelino — 2012-02-03

Abstract: Background: OnabotulinumtoxinA (Onabot/A) has been used to treat detrusor overactivity disorders. The treatment is based on several injections of toxin throughout the bladder wall. However, injection protocols are not well established among clinicians, varying in dose and dilution.Objective: Study the distribution and neurochemistry of cleaved synaptosome-associated protein of 25 kDa (cSNAP-25) after Onabot/A administration in the guinea pig bladder. In addition, we analyzed which factor, dose or volume, contributes more to the diffusion of the toxin.Design, setting, and participants: Guinea pig bladders were treated with Onabot/A via intramural injection or an instillation.Measurements: Bladder cryostat sections were processed for single or dual immunohistochemistry staining with antibodies against cSNAP-25, vesicular acetylcholine transporter, tyrosine hydroxylase, and calcitonin gene-related peptide. Different administration methods and doses were analyzed. Statistical analysis was performed using the chi-square test for colocalization studies after multiple injections and the t test for the evaluation of affected fibers after a single injection.Results and limitations: CSNAP-25 immunoreactive fibers were abundant throughout the bladder tissue in the mucosa and muscular layer. Double labeling showed that parasympathetic fibers are more affected than sympathetic or sensory. A single Onabot/A injection is more effective if diluted in a higher volume. Onabot/A instillation in the bladder does not cleave SNAP-25 protein.Conclusions: A single Onabot/A injection spreads the neurotoxin activity to the opposite side of the guinea pig bladder. This action is more evident when high saline volumes are used to dissolve Onabot/A. The toxin cleaves the SNAP-25 protein mainly in cholinergic but also in adrenergic and sensory fibers. In contrast with intramural injection, instillation of Onabot/A does not cleave SNAP-25 in nerve fibers.Take Home Message: A single intramural injection of onabotulinumtoxinA spreads to the opposite side of the guinea pig bladder. This action, evaluated through synaptosome-associated protein of 25 kDa cleavage, is more evident if higher-volume dilutions are performed.

Three-Tesla Magnetic Resonance–Guided Prostate Biopsy in Men With Increased Prostate-Specific Antigen and Repeated, Negative, Random, Systematic, Transrectal Ultrasound Biopsies: Detection of Clinically Significant Prostate Cancers - Uncorrected Proof

2012-02-03

Abstract: Background: Patients with elevated prostate-specific antigen (PSA) and one or more previous negative transrectal ultrasound (TRUS) biopsy sessions are subject to diagnostic uncertainty due to TRUS-biopsy undersampling. Magnetic resonance (MR)–guided biopsy (MRGB) has shown high prostate cancer (PCa)–detection rates in studies with limited patient numbers.Objective: Determine the detection rate of clinically significant PCa for MRGB of cancer-suspicious regions (CSRs) on 3-T multiparametric MR imaging (MP-MRI) in patients with elevated PSA and one negative TRUS-biopsy session or more.Design, setting, and participants: Of 844 patients who underwent 3-T MP-MRI in our referral centre between March 2008 and February 2011, 438 consecutive patients with a PSA >4.0 ng/ml and one negative TRUS-biopsy session or more were included. MRGB was performed in 265 patients. Exclusion criteria were existent PCa, endorectal coil use, and MP-MRI for indications other than cancer detection.Intervention: Patients underwent MRGB of MP-MRI CSRs.Measurements: Clinically significant MRGB cancer-detection rates were determined. Clinically significant cancer was defined based on PSA, Gleason score, stage, and tumour volume. Follow-up PSA and histopathology were collected. Sensitivity analysis was performed for patients with MP-MRI CSRs without MRGB.Results and limitations: In a total of 117 patients, cancer was detected with MRGB (n=108) or after negative MRGB (n=9). PCa was detected in 108 of 438 patients (25%) and in 41% (108 of 265) of MRGB patients. The majority of detected cancers (87%) were clinically significant. During follow-up, clinically significant cancers were detected in six of nine (67%) negative MRGB patients. Sensitivity analysis resulted in increased cancer detection (47–56%). Complications occurred in 0.2% of patients (5 of 265).Conclusions: In patients with elevated PSA and one negative TRUS-biopsy session or more, MRGB of MP-MRI CSRs had a PCa-detection rate of 41%. The majority of detected cancers were clinically significant (87%).Take Home Message: In patients with an elevated prostate-specific antigen level and one or more previous negative, random, systematic, transrectal ultrasound biopsy sessions, magnetic resonance (MR)–guided biopsy of detected cancer-suspicious regions on 3-T multiparametric MR imaging had a detection rate of 41% for predominantly clinically significant prostate cancers (87%).

Use of Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer Is Low Among Major European Centres: Results of a Feasibility Questionnaire - Uncorrected Proof

Maximilian Burger, Peter Mulders, Wim Witjes — 2012-02-02

The poor outcome of muscle-invasive bladder cancer (MIBC) is challenging . Neoadjuvant cisplatin-containing combination chemotherapy increases survival by 5–7% and is a grade A recommendation in the current European Association of Urology (EAU) guidelines . The few data on the pattern of care of MIBC suggest great variability. The use of neoadjuvant chemotherapy (NCT) seems to be low; the US National Cancer Database registers that only 11% of MIBC patients undergo chemotherapy, with the majority of those in the adjuvant, rather than the neoadjuvant, setting . The adoption of NCT across Europe is entirely uncertain .

Reply From the Authors re: Quoc-Dien Trinh, Jesse Sammon, Maxine Sun, et al. Perioperative Outcomes of Robot-Assisted Radical Prostatectomy Compared With Open Radical Prostatectomy: Results From the Nationwide Inpatient Sample. Eur Urol. In press. DOI:10.1016/j.eururo.2011.12.027: Robotic Prostatectomy: Men Versus Machines—The Machines Are Already Here - Corrected Proof

Quoc-Dien Trinh, Maxine Sun, Jesse Sammon, Mani Menon, Pierre I. Karakiewicz — 2012-02-02

We read with great interest the editorial by Meeks and Eastham commenting on our paper , which showed that robot-assisted radical prostatectomy (RARP) is associated with better perioperative outcomes relative to open radical prostatectomy (ORP). Several important points were raised that merit further discussion.

Reply from Authors re: Propensity-Score-Matched Comparison of Perioperative Outcomes Between Open and Laparoscopic Nephroureterectomy: A National Series. Eur Urol. In press. DOI:10.1016/j.eururo.2011.12.051 - Corrected Proof

Nawar Hanna, Maxine Sun, Marco Bianchi, Pierre I. Karakiewicz — 2012-02-02

We read with interest the editorial comment made by Inman on our recent paper that compared short-term in-hospital outcomes between open nephroureterectomy (ONU) versus laparoscopic nephroureterectomy (LNU) . The propositions made within the comment summarize the inherent considerations that should be accounted for, not only of our report, but also of the bulk of existing literature addressing the same topic . Given the low incidence and rarity of upper tract urothelial carcinomas (UTUCs) , it is not surprising that no randomized trial has been designed to compare morbidity or mortality between ONU and LNU. In the future, despite the necessity, such a trial will remain unlikely to happen. What is left are institutional and population-based data, both study cohorts holding advantages and disadvantages of their own. Ultimately, the goal of all such reports is to reach a consensus for both the patient and the clinician. To date, no study, including our recent report , can reliably and validly cover all the unknowns of the topic. Nonetheless, the totality of all such reports, whether institutional or population based, prospectively or retrospectively designed, sheds light on what has been addressed as well as what remain to be addressed.

Management of Small Renal Masses: Watch, Cut, Freeze, or Fry? - Uncorrected Proof

Jose A. Karam, Christopher G. Wood — 2012-02-02

The American Cancer Society estimated that >58 000 patients will be diagnosed with a renal malignancy in 2011, resulting in 13 000 deaths , with renal cell carcinoma constituting most of those tumors . The diagnosis of small renal masses (SRMs), usually defined as a renal mass <4cm, has increased in recent years, especially in patients in their eighth decade, mostly due to the increased use of ultrasound and computed tomography (CT) . Most of the SRMs are currently detected incidentally, as a result of imaging performed for unrelated complaints . Fortunately, most SRMs, if malignant, are of low stage and grade . As such, urologists are currently encountering an increased number of patients with SRMs and are challenged as to the most appropriate course of management.

Laparoendoscopic Single-Site and Conventional Laparoscopic Radical Nephrectomy Result in Equivalent Surgical Trauma: Preliminary Results of a Single-Centre Retrospective Controlled Study - Uncorrected Proof

2012-02-02

Abstract: Background: Laparoendoscopic single-site surgery (LESS) has been developed in an attempt to further reduce the morbidity and scarring associated with surgical intervention, and it has been proposed to result in less induced surgical trauma than conventional laparoscopy.Objective: Investigate the surgical trauma after LESS radical nephrectomy (LESS-RN) and laparoscopic radical nephrectomy (LRN).Design, setting, and participants: This was a retrospective single-centre study including 66 patients: 31 patients underwent LESS-RN and 35 historical control patients who had undergone LRN. LRNs were performed between April 2008 and May 2009; LESS-RNs were performed between May 2009 and February 2011.Intervention: LESS-RN and LRN were both performed via a transperitoneal access. Blood samples were collected pre- and intraoperatively at 6, 24, and 48h, and at 5 d postoperatively.Measurements: Serum concentrations of acute-phase markers, C-reactive protein (CRP), serum amyloid A (SAA) antibody, and interleukin 6 (IL-6) and interleukin 10 (IL-10) were measured at each time point by enzyme-linked immunosorbent assay. Clinical data were collected by reviewing the patient's records.Results and limitations: There were no differences in serum CRP and SAA levels between the groups (CRP: p=0.12; SAA: p=0.09) at all time points. The changes in IL-6 levels in the LRN group were statistically significantly higher compared with the LESS-RN group at 6h after surgery (p=0.02), whereas the LESS-RN group showed statistically significantly higher IL-6 levels than the LRN group at 24h after surgery (p=0.02).Also, the serum levels of the anti-inflammatory cytokine IL-10 showed different kinetics in each group, being higher in the LESS-RN during the early postoperative phase (at 6h: p=0.01) and higher in the LRN group at 48h after surgery (p=0.01). The limitations of this study were its nonrandomized character and the small cohort of patients.Conclusions: LESS-RN is as effective as LRN without compromising surgical and postoperative outcomes, but it does not add any significant advantage in comparison with traditional LRN in terms of systemic stress response and surgical trauma.Take Home Message: Laparoendoscopic single-site radical nephrectomy is as effective as laparoscopic radical nephrectomy (LRN) without compromising surgical and postoperative outcomes, but it does not add any significant advantage in comparison with traditional LRN in terms of systemic stress response and surgical trauma.

Tension-Free Vaginal Tape for the Treatment of Urodynamic Stress Incontinence: Efficacy and Adverse Effects at 10-Year Follow-Up - Corrected Proof

2012-01-30

Abstract: Background: One of the most effective and popular current procedures for the surgical treatment of stress urinary incontinence (SUI) is tension-free midurethral slings.Objective: To evaluate the outcomes of women with retropubic tension-free vaginal tape (TVT) for urodynamic stress incontinence (USI) after 10-yr follow-up.Design, setting, and participants: This was a prospective observational study. Consecutive women with proven USI were treated with TVT. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded.Intervention: Standard retropubic TVT.Measurements: Patients underwent preoperative clinical and urodynamic evaluations. During follow-up examinations, women were assessed for subjective satisfaction and objective cure rates. Multivariable analyses were performed to investigate outcomes.Results and limitations: A total of 63 women were included. After 10 yr, 5 patients (8%) were lost or no longer evaluable. The 10-yr subjective, objective, and urodynamic cure rates were 89.7%, 93.1%, and 91.4%, respectively. These rates were stable across the whole study period (p>0.99). De novo overactive bladder was reported by 30.1% and 18.9% of patients at 3-mo and 10-yr follow-up, respectively (p for trend = 0.19). A total of 84.2% of women with detrusor overactivity received antimuscarinic drugs, but 43.8% were nonresponders 12 wk later. At multivariable analysis, maximum detrusor pressure during the filling phase >9cm H2O (hazard ratio [HR]: 16.2; p=0.01) and maximum detrusor pressure during the voiding phase ≤29cm H2O (HR: 8.0; p=0.01) were independent predictors for the recurrence of SUI, as well as obesity was for the recurrence of objective SUI (HR: 17.1; p=0.01] and of USI (HR: 8.9; p=0.02), respectively. Intraoperatively, bladder perforation occurred in two cases; no severe bleeding or other complications occurred.Conclusions: The 10-yr results of this study seem to demonstrate that TVT is a highly effective option for the treatment of female SUI, recording a very high cure rate with low complications after a 10-yr follow-up.Take Home Message: The long-term results of this prospective observational study seem to demonstrate that the tension-free vaginal tape procedure is a highly effective treatment for female stress urinary incontinence. It also presents a very high cure rate and a low complication rate after a 10-yr follow-up.

A Novel Automated Platform for Quantifying the Extent of Skeletal Tumour Involvement in Prostate Cancer Patients Using the Bone Scan Index - Corrected Proof

2012-01-27

Abstract: Background: There is little consensus on a standard approach to analysing bone scan images. The Bone Scan Index (BSI) is predictive of survival in patients with progressive prostate cancer (PCa), but the popularity of this metric is hampered by the tedium of the manual calculation.Objective: Develop a fully automated method of quantifying the BSI and determining the clinical value of automated BSI measurements beyond conventional clinical and pathologic features.Design, setting, and participants: We conditioned a computer-assisted diagnosis system identifying metastatic lesions on a bone scan to automatically compute BSI measurements. A training group of 795 bone scans was used in the conditioning process. Independent validation of the method used bone scans obtained ≤3 mo from diagnosis of 384 PCa cases in two large population-based cohorts. An experienced analyser (blinded to case identity, prior BSI, and outcome) scored the BSI measurements twice. We measured prediction of outcome using pretreatment Gleason score, clinical stage, and prostate-specific antigen with models that also incorporated either manual or automated BSI measurements.Measurements: The agreement between methods was evaluated using Pearson's correlation coefficient. Discrimination between prognostic models was assessed using the concordance index (C-index).Results and limitations: Manual and automated BSI measurements were strongly correlated (ρ=0.80), correlated more closely (ρ=0.93) when excluding cases with BSI scores ≥10 (1.8%), and were independently associated with PCa death (p<0.0001 for each) when added to the prediction model. Predictive accuracy of the base model (C-index: 0.768; 95% confidence interval [CI], 0.702–0.837) increased to 0.794 (95% CI, 0.727–0.860) by adding manual BSI scoring, and increased to 0.825 (95% CI, 0.754–0.881) by adding automated BSI scoring to the base model.Conclusions: Automated BSI scoring, with its 100% reproducibility, reduces turnaround time, eliminates operator-dependent subjectivity, and provides important clinical information comparable to that of manual BSI scoring.Take Home Message: We developed and evaluated the first unbiased, fully automated software system to systematically calculate skeletal tumour burden in patients with metastatic cancer in the bone, simplifying a valuable but cumbersome technology with shortcomings that had prevented its widespread clinical use.

Subclassification of pT3 Urothelial Carcinoma of the Renal Pelvicalyceal System is Associated With Recurrence-Free and Cancer-Specific Survival: Proposal for a Revision of the Current TNM Classification - Corrected Proof

2012-01-25

Abstract: Background: The clinical course of pT3 upper tract urothelial carcinoma (UTUC) is highly variable.Objectives: The aim of the current study was to validate the clinical and prognostic importance of pT3 subclassification in the renal pelvicalyceal system in a large international cohort of patients.Design, setting, and participants: From a multi-institutional international database, 858 renal pelvicalyceal tumors treated with radical nephroureterectomy (RNU) were systematically reevaluated by genitourinary pathologists. Category pT3 pelvic tumors were categorized as pT3a (infiltration of the renal parenchyma on a microscopic level only) versus pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue).Intervention: RNU.Measurements: Associations of pT3 subclassifications with clinicopathologic features were assessed with the chi-square test. Prognostic impact was assessed with the log-rank test and multivariable Cox regression analyses.Results and limitations: Of 858 patients with renal pelvicalyceal tumors, 266 (31%) had pT3 disease. Of these, 146 (54.9%) were classified as pT3a and 120 (45.1%) as pT3b. Compared with pT3a, pT3b cancers were associated with higher tumor grade, nodal disease, and tumor necrosis. Ten-year recurrence-free (pT3a 58% vs pT3b 38%; p<0.001) and cancer-specific (pT3a 60% vs pT3b 39%; p=0.002) survival rates were lower for patients with pT3b disease. In multivariable analyses, classification pT3b was an independent predictor of both disease recurrence (hazard ratio [HR]: 1.8, p=0.003) and cancer-specific mortality (HR: 1.7; p=0.02). The major limitation is the retrospective character of the study.Conclusions: Subclassification of pT3 renal pelvicalyceal UTUC helps identify patients who are at increased risk of disease progression and cancer-related death. Further research may help assess the value of subclassification and its inclusion in future editions of the American Joint Committee on Cancer–International Union Against Cancer TNM classification system.Take Home Message: Subclassification of pT3 urothelial carcinoma of the renal pelvicalyceal system into pT3a and pT3b revealed remarkable outcome differences. Stage pT3b was an independent prognostic indicator regarding disease recurrence and cancer-specific mortality with possible impact on follow-up regimens and adjuvant clinical trials in future.

Comment on the US Preventive Services Task Force's Draft Recommendation on Screening for Prostate Cancer - Corrected Proof

Maciej Kwiatkowski, Laurence Klotz, Jonas Hugosson, Franz Recker — 2012-01-25

Only 3 yr from the date of its last publication , the US Preventive Services Task Force (USPSTF) has updated its recommendations for prostate cancer (PCa) screening. In the 2008 version, prostate-specific antigen (PSA) screening was discouraged for men aged ≥75 yr, whereas for younger men, there was no recommendation based on grade 1, as “the current evidence is considered … insufficient to assess the balance of benefits and harms” . In the current version, the USPSTF postulates a grade D recommendation regardless of age, thus discouraging PSA-based screening for PCa. The question is, what happened in the last 3 yr to justify this shift?

Re: Kari A.O. Tikkinen, Anssi Auvinen. Does the Imprecise Definition of Overactive Bladder Serve Commercial Rather than Patient Interests? Eur Urol. In press. DOI: 10.1016/j.eururo.2011.12.013: The Origin of the Term Overactive Bladder, Industry, and Patient Care - Corrected Proof

Paul Abrams, Alan Wein — 2012-01-25

Thank you for allowing us to comment on this interesting editorial that raises a number of important points. The term overactive bladder (OAB) was introduced by us against the wishes of the company that asked us to organise a symposium on “unstable bladder” in 1996. The history of the introduction of the term OAB has been previously documented in detail . The company objected to our idea because the drug that the company intended to bring to market would have been granted a licence for use in patients with the diagnosis of unstable bladder, which, Tikkinen et al. rightly point out, was the term accepted by the regulators at that time. We insisted on the use of OAB, the company finally conceded, and the term was used in all the publications that resulted from that scientific meeting, which covered all aspects of the subject area from basic science to surgical management .

Validation of Serum Amyloid α as an Independent Biomarker for Progression-Free and Overall Survival in Metastatic Renal Cell Cancer Patients - Corrected Proof

2012-01-24

Abstract: Background: We recently identified apolipoprotein A2 (ApoA2) and serum amyloid α (SAA) as independent prognosticators in metastatic renal cell carcinoma (mRCC) patients, thereby improving the accuracy of the Memorial-Sloan Kettering Cancer Center (MSKCC) model.Objective: Validate these results prospectively in a separate cohort of mRCC patients treated with tyrosine kinase inhibitors (TKIs).Design, setting, and participants: For training we used 114 interferon-treated mRCC patients (inclusion 2001–2006). For validation we studied 151 TKI-treated mRCC patients (inclusion 2003–2009).Measurements: Using Cox proportional hazards regression analysis, SAA and ApoA2 were associated with progression-free survival (PFS) and overall survival (OS). In 72 TKI-treated patients, SAA levels were analyzed longitudinally as a potential early marker for treatment effect.Results and limitations: Baseline ApoA2 and SAA levels significantly predicted PFS and OS in the training and validation cohorts. Multivariate analysis identified SAA in both separate patient sets as a robust and independent prognosticator for PFS and OS. In contrast to our previous findings, ApoA2 interacted with SAA in the validation cohort and did not contribute to a better predictive accuracy than SAA alone and was therefore excluded from further analysis. According to the tertiles of SAA levels, patients were categorized in three risk groups, demonstrating accurate risk prognostication. SAA as a single biomarker showed equal prognostic accuracy when compared with the multifactorial MSKCC risk mode. Using receiver operating characteristic analysis, SAA levels >71 ng/ml were designated as the optimal cut-off value in the training cohort, which was confirmed for its significant sensitivity and specificity in the validation cohort. Applying SAA >71 ng/ml as an additional risk factor significantly improved the predictive accuracy of the MSKCC model in both independent cohorts. Changes in SAA levels after 6–8 wk of TKI treatment had no value in predicting treatment outcome.Conclusions: SAA but not ApoA2 was shown to be a robust and independent prognosticator for PFS and OS in mRCC patients. When incorporated in the MSKCC model, SAA showed additional prognostic value for patient management.Take Home Message: Serum amyloid α may be used (alone or as part of the Memorial Sloan-Kettering Cancer Center model) as an objective prognostic marker in future clinical trials in metastatic renal cell carcinoma patients and may improve the a priori selection of appropriate risk-directed therapy for every individual.

Predicting Clinical Outcomes After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma - Corrected Proof

2012-01-24

Abstract: Background: Novel prognostic factors for patients after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) have recently been described.Objective: We tested the prognostic value of pathologic characteristics and developed models to predict the individual probabilities of recurrence-free survival (RFS) and cancer-specific survival (CSS) after RNU.Design, setting, and participants: Our study included 2244 patients treated with RNU without neoadjuvant or adjuvant therapy at 23 international institutions. Tumor characteristics included T classification, grade, lymph node status, lymphovascular invasion, tumor architecture, location, and concomitant carcinoma in situ (CIS). The cohort was randomly split for development (12 centers, n=1273) and external validation (11 centers, n=971).Interventions: All patients underwent RNU.Measurements: Univariable and multivariable models addressed RFS, CSS, and comparison of discrimination and calibration with American Joint Committee on Cancer (AJCC) stage grouping.Results and limitations: At a median follow-up of 45 mo, 501 patients (22.3%) experienced disease recurrence and 418 patients (18.6%) died of UTUC. On multivariable analysis, T classification (p for trend <0.001), lymph node metastasis (hazard ratio [HR]: 1.98; p=0.002), lymphovascular invasion (HR: 1.66; p<0.001), sessile tumor architecture (HR: 1.76; p<0.001), and concomitant CIS (HR: 1.33; p=0.035) were associated with disease recurrence. Similarly, T classification (p for trend<0.001), lymph node metastasis (HR: 2.23; p=0.001), lymphovascular invasion (HR: 1.81; p<0.001), and sessile tumor architecture (HR: 1.72; p=0.001) were independently associated with cancer-specific mortality. Our models achieved 76.8% and 81.5% accuracy for predicting RFS and CSS, respectively. In contrast to these well-calibrated models, stratification based upon AJCC stage grouping resulted in a large degree of heterogeneity and did not improve discrimination.Conclusions: Using standard pathologic features, we developed highly accurate prognostic models for the prediction of RFS and CSS after RNU for UTUC. These models offer improvements in calibration over AJCC stage grouping and can be used for individualized patient counseling, follow-up scheduling, risk stratification for adjuvant therapies, and inclusion criteria for clinical trials.Take Home Message: We developed prognostic models for prediction of clinical outcomes following radical nephroureterectomy using clinical and pathologic variables. These models are highly accurate and offer improvements in calibration over American Joint Committee on Cancer stage grouping.

Cancer Control and Functional Outcomes of Salvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Systematic Review of the Literature - Corrected Proof

2012-01-24

Abstract: Context: Prostate cancer (PCa) recurrence following definitive radiation therapy (RT) remains a vexing challenge for the practicing physician. Salvage radical prostatectomy (SRP) has not been recognized yet as a valuable therapeutic option.Objective: We critically analyzed the currently available evidence on SRP as to patient selection, predictive oncologic factors, surgical technique, cancer control, surgical complications, functional outcomes, and comparison to other salvage therapies.Evidence acquisition: A systematic review of the literature was performed in June 2011 using the Medline, Embase, and Web of Science databases, limiting the review to English-language articles published between January 1980 and June 2011. All authors reviewed the list of references and added papers relevant to the topic of the review prior to the analysis. The panel selected 40 articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria.Evidence synthesis: Positive surgical margins in SRP varied from 43% to 70% in earlier publications versus 0–36% in recent publications, and pathologic organ-confined disease (OCD) was found in 22–53% versus 44–73% in earlier versus recent publications. Biochemical recurrence–free probability after SRP ranged from 47% to 82% at 5 yr and from 28% to 53% at 10 yr. Cancer-specific survival (CSS) and overall survival varied from 70% to 83% and 54% to 89% at 10 yr. Pre-SRP prostate-specific antigen value and prostate biopsy Gleason score were the strongest prognostic risk factors for progression-free survival, OCD, and CSS. Open, laparoscopic, and robotic techniques were shown to be feasible in the hands of experienced surgeons. The most frequent complications included anastomotic stricture (7–41%) followed by rectal injury (0–28%). Major complications (modified Clavien classification grade 3–5) varied from 0% to 25%. Most complications were less frequent in more recent series, except for anastomotic stricture. The majority of patients had erectile dysfunction prior to SRP (50–91%) and 80–100% after SRP. Urinary continence ranged from 21% to 90% after surgery. Limitations of this review include the absence of prospective studies and lack of comparative analyses between SRP and other therapies.Conclusions: In selected patients with confirmed, localized, radiation-recurrent PCa, SRP may effectively promote durable cancer control with acceptable associated surgical morbidity and variable functional recovery.Take Home Message: Salvage radical prostatectomy for radiation-recurrent prostate cancer may provide durable cancer control when performed by experienced surgeons. Perioperative complications and incontinence rates are acceptable, although erectile dysfunction is still significant.

Monotherapy with Tadalafil or Tamsulosin Similarly Improved Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia in an International, Randomised, Parallel, Placebo-Controlled Clinical Trial - Corrected Proof

2012-01-20

Abstract: Background: Tadalafil improved lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH; LUTS/BPH) in clinical studies but has not been evaluated together with an active control in an international clinical study.Objective: Assess tadalafil or tamsulosin versus placebo for LUTS/BPH.Design, setting, and participants: A randomised, double-blind, international, placebo-controlled, parallel-group study assessed men ≥45 yr of age with LUTS/BPH, International Prostate Symptom Score (IPSS) ≥13, and maximum urinary flow rate (Qmax) ≥4 to ≤15ml/s. Following screening and washout, if needed, subjects completed a 4-wk placebo run-in before randomisation to placebo (n=172), tadalafil 5mg (n=171), or tamsulosin 0.4mg (n=168) once daily for 12 wk.Measurements: Outcomes were assessed using analysis of covariance (ANCOVA) or ranked analysis of variance (ANOVA) (continuous variables) and Cochran-Mantel-Haenszel test or Fisher exact test (categorical variables).Results and limitations: IPSS significantly improved versus placebo through 12 wk with tadalafil (−2.1; p=0.001; primary efficacy outcome) and tamsulosin (−1.5; p=0.023) and as early as 1 wk (tadalafil and tamsulosin both −1.5; p<0.01). BPH Impact Index significantly improved versus placebo at first assessment (week 4) with tadalafil (−0.8; p<0.001) and tamsulosin (−0.9; p<0.001) and through 12 wk (tadalafil −0.8, p=0.003; tamsulosin −0.6, p=0.026). The IPSS Quality-of-Life Index and the Treatment Satisfaction Scale–BPH improved significantly versus placebo with tadalafil (both p<0.05) but not with tamsulosin (both p>0.1). The International Index of Erectile Function–Erectile Function domain improved versus placebo with tadalafil (4.0; p<0.001) but not tamsulosin (−0.4; p=0.699). Qmax increased significantly versus placebo with both tadalafil (2.4ml/s; p=0.009) and tamsulosin (2.2ml/s; p=0.014). Adverse event profiles were consistent with previous reports. This study was limited in not being powered to directly compare tadalafil versus tamsulosin.Conclusions: Monotherapy with tadalafil or tamsulosin resulted in significant and numerically similar improvements versus placebo in LUTS/BPH and Qmax. However, only tadalafil improved erectile dysfunction.Trial registration: Clinicaltrials.gov ID NCT00970632Take Home Message: Monotherapy with tadalafil or tamsulosin for 12 wk resulted in similar, significant improvements versus placebo in lower urinary tract symptoms suggestive of benign prostatic hyperplasia and maximum flow rate. However, only tadalafil significantly improved measures of treatment satisfaction and erectile dysfunction. Adverse events and related discontinuations were few.

Prognostic Role and HER2 Expression of Circulating Tumor Cells in Peripheral Blood of Patients Prior to Radical Cystectomy: A Prospective Study - Corrected Proof

2012-01-20

Abstract: Background: Preliminary research has suggested the potential prognostic value of circulating tumor cells (CTC) in patients with advanced nonmetastatic urothelial carcinoma of the bladder (UCB).Objective: Prospectively analyze the clinical relevance and human epidermal growth factor receptor 2 (HER2) expression of CTC in patients with clinically nonmetastatic UCB.Design, setting, and participants: Blood samples from 100 consecutive UCB patients treated with radical cystectomy (RC) were investigated for the presence (CellSearch system) of CTC and their HER2 expression status (immunohistochemistry). HER2 expression of the corresponding primary tumors and lymph node metastasis were analyzed using fluorescence in situ hybridization.Intervention: Blood samples were taken preoperatively. Patients underwent RC with lymphadenectomy.Measurements: Outcomes were assessed according to CTC status. HER2 expression of CTC was compared with that of the corresponding primary tumor and lymph node metastasis.Results and limitations: CTC were detected in 23 of 100 patients (23%) with nonmetastatic UCB (median: 1; range: 1–100). Presence, number, and HER2 status of CTC were not associated with clinicopathologic features. CTC-positive patients had significantly higher risks of disease recurrence and cancer-specific and overall mortality (p values: ≤0.001). After adjusting for effects of standard clinicopathologic features, CTC positivity remained an independent predictor for all end points (hazard ratios: 4.6, 5.2, and 3.5, respectively; p values ≤0.003). HER2 was strongly positive in CTC from 3 of 22 patients (14%). There was discordance between HER2 expression on CTC and HER2 gene amplification status of the primary tumors in 23% of cases but concordance between CTC, primary tumors, and lymph node metastases in all CTC-positive cases (100%). The study was limited by its sample size.Conclusions: Preoperative CTC are already detectable in almost a quarter of patients with clinically nonmetastatic UCB treated with RC and were a powerful predictor of early disease recurrence and cancer-specific and overall mortality. Thus CTC may serve as an indication for multimodal therapy. Molecular characterization of CTC may serve as a liquid biopsy to guide individual targeted therapy in future clinical trials.Take Home Message: Circulating tumor cells (CTC) are detectable in almost 25% of patients with clinically nonmetastatic bladder cancer prior to radical cystectomy. Presence of precystectomy CTC was a strong independent predictor for disease recurrence and mortality. The molecular profile of CTC may help guide individualized targeted therapy.

A Randomized Prospective Trial to Assess the Impact of Transurethral Resection in Narrow Band Imaging Modality on Non–Muscle-Invasive Bladder Cancer Recurrence - Corrected Proof

2012-01-20

Abstract: Background: Narrow band imaging (NBI) is an optical enhancement technology that filters white light into two bandwidths of illumination centered on 415nm (blue) and 540nm (green). NBI cystoscopy can increase bladder cancer (BCa) visualization and detection at the time of transurethral resection (TUR). NBI may therefore reduce subsequent relapse following TUR.Objective: Assess the impact of NBI modality on 1-yr non–muscle-invasive BCa (NMIBC) recurrence risk.Design, setting, and participants: Consecutive patients with overt or suspected BCa were included in a prospective study powered to test a 10% difference in 1-yr recurrence risk in favor of cases submitted to NBI TUR. Excluding patients with muscle-invasive BCa, negative pathologic examination, or without follow-up, the study population was composed of 148 subjects randomized from August 2009 to September 2010 to NBI TUR (76 cases) or white light (WL) TUR (72 cases).Intervention: TUR was performed in NBI or standard WL modality.Measurements: The 1-yr recurrence risks in NBI or WL TUR groups were compared using odds ratio (OR) point and interval estimates derived from logistic regression modeling.Results and limitations: The 1-yr recurrence-risk was 25 of 76 patients (32.9%) in the NBI and 37 of 72 patients (51.4%) in the WL group (OR=0.62; p=0.0141). Simple and multiple logistic regression analyses provided similar OR points and interval estimates.Conclusions: TUR performed in the NBI modality reduces the recurrence risk of NMIBC by at least 10% at 1 yr.Take Home Message: Transurethral resection with narrow band imaging improves 1-yr recurrence-free survival of non–muscle-invasive bladder cancer.

Genome-wide Analysis of CpG Island Methylation in Bladder Cancer Identified TBX2, TBX3, GATA2, and ZIC4 as pTa-Specific Prognostic Markers - Corrected Proof

2012-01-19

Abstract: Background: DNA methylation markers could serve as useful biomarkers, both as markers for progression and for urine-based diagnostic assays.Objective: Identify bladder cancer (BCa)–specific methylated DNA sequences for predicting pTa-specific progression and detecting BCa in voided urine.Design, setting, and participants: Genome-wide methylation analysis was performed on 44 bladder tumours using the Agilent 244K Human CpG Island Microarray (Agilent Technologies, Santa Clara, CA, USA). Validation was done using a custom Illumina 384-plex assay (Illumina, San Diego, CA, USA) in a retrospective group of 77 independent tumours. Markers for progression were identified in pTa (n=24) tumours and validated retrospectively in an independent series of 41 pTa tumours by the SNaPshot method (Applied Biosystems, Foster City, CA, USA).Measurements: The percentage of methylation in tumour and urine samples was used to identify markers for detection and related to the end point of progression to muscle-invasive disease with Kaplan-Meier models and multivariate analysis.Results and limitations: In the validation set, methylation of the T-box 2 (TBX2), T-box 3 (TBX3), GATA binding protein 2 (GATA2), and Zic family member 4 (ZIC4) genes was associated with progression to muscle-invasive disease in pTa tumours (p=0.003). Methylation of TBX2 alone showed a sensitivity of 100%, a specificity of 80%, a positive predictive value of 78%, and a negative predictive value of 100%, with an area under the curve of 0.96 (p<0.0001) for predicting progression. Multivariate analysis showed that methylation of TBX3 and GATA2 are independent predictors of progression when compared to clinicopathologic variables (p=0.04 and p=0.03, respectively). The predictive accuracy improved by 23% by adding methylation of TBX2, TBX3, and GATA2 to the European Organisation for Research and Treatment of Cancer risk scores. We further identified and validated 110 CpG islands (CGIs) that are differentially methylated between tumour cells and control urine. The limitation of this study is the small number of patients analysed for testing and validating the prognostic markers.Conclusions: We have identified four methylation markers that predict progression in pTa tumours, thereby allowing stratification of patients for personalised follow-up. In addition, we identified CGIs that will enable detection of bladder tumours in voided urine.Take Home Message: This study identified novel biomarkers for the detection of bladder cancer in voided urine as well as pTa-specific prognostic markers.

Clinical, Molecular, and Genetic Correlates of Lymphatic Spread in Clear Cell Renal Cell Carcinoma - Corrected Proof

2012-01-19

Abstract: Background: While it is well known that clear cell renal cell carcinoma (ccRCC) that presents with lymphatic spread is associated with an extremely poor prognosis, its molecular and genetic biology is poorly understood.Objective: Define the clinicopathologic, molecular, and genetic biological characteristics of these tumors in comparison to nonmetastatic (N0M0) renal cell carcinomas.Design, setting, and participants: A retrospective study defined clinicopathologic features, expression of 28 molecular markers, and occurrence of chromosomal aberrations for their correlation with lymphatic spread in three cohorts of 502, 196, and 272 patients, respectively.Measurements: Fisher exact test or the χ2 test were used to compare categorical variables; continuous variables were compared with the Mann-Whitney U test or student t test. Cut-off values were calculated based on receiver operating characteristic curves and the Youden Index. Uni- and multivariate regression analyses were used to investigate the correlation with lymphatic spread.Results and limitations: In clinical analyses, a predictive model consisting of smoking history (p=0.040), T stage (p<0.0001), Fuhrman grade (p<0.0001), Eastern Cooperative Oncology Group performance status (p<0.0001), and microvascular invasion (p<0.0001) was independently associated with lymphatic spread. After adjustment with these clinical variables, low carbonic anhydrase IX (CAIX) (p=0.043) and high epithelial vascular endothelial growth factor receptor 2 (p=0.033) protein expression were associated with a higher risk of lymphatic spread, and loss of chromosome 3p (p<0.0001) with a lower risk. The current study is limited by its retrospective design, small sample size, and single-center experience.Conclusions: The low rates of CAIX expression and loss of chromosome 3p suggest that lymphatic spread in ccRCC occurs independently of von Hippel-Lindau tumor suppressor inactivation.Take Home Message: Lymph node–positive clear cell renal cell carcinomas (RCCs) are more likely to be wild-type von Hippel-Lindau tumors, to express low carbonic anhydrase IX, and to have the worst prognosis and are poor immunotherapy responders, like non–clear cell RCCs.

EAU Guidelines on Laser Technologies - Corrected Proof

2012-01-18

Abstract: Context: The European Association of Urology (EAU) Guidelines Office has set up a guideline working panel to analyse the scientific evidence published in the world literature on lasers in urologic practice.Objective: Review the physical background and physiologic and technical aspects of the use of lasers in urology, as well as current clinical results from these new and evolving technologies, together with recommendations for the application of lasers in urology. The primary objective of this structured presentation of the current evidence base in this area is to assist clinicians in making informed choices regarding the use of lasers in their practice.Evidence acquisition: Structured literature searches using an expert consultant were designed for each section of this document. Searches were carried out in the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and Medline and Embase on the Dialog/DataStar platform. The controlled terminology of the respective databases was used, and both Medical Subject Headings and EMTREE were analysed for relevant entry terms. One Cochrane review was identified.Evidence synthesis: Depending on the date of publication, the evidence for different laser treatments is heterogeneous. The available evidence allows treatments to be classified as safe alternatives for the treatment of bladder outlet obstruction in different clinical scenarios, such as refractory urinary retention, anticoagulation, and antiplatelet medication. Laser treatment for bladder cancer should only be used in a clinical trial setting or for patients who are not suitable for conventional treatment due to comorbidities or other complications. For the treatment of urinary stones and retrograde endoureterotomy, lasers provide a standard tool to augment the endourologic procedure.Conclusions: In benign prostatic obstruction (BPO), laser vaporisation, resection, or enucleation are alternative treatment options. The standard treatment for BPO remains transurethral resection of the prostate for small to moderate size prostates and open prostatectomy for large prostates. Laser energy is an optimal treatment method for disintegrating urinary stones. The use of lasers to treat bladder tumours and in laparoscopy remains investigational.Take Home Message: This paper reviews the use of lasers in a number of clinical applications in urologic disorders. Lasers are widely used in the treatment of benign prostatic obstruction, benign prostatic enlargement, bladder and kidney cancer, and urothelial tumours and structures. They represent the state of the art in disintegrating urinary stones. Knowledge of the lasers currently in use and the principles of tissue interaction will assist clinicians in making informed choices.

Re: Gianluca Giannarini, Thomas M. Kessler, Frédéric D. Birkhäuser, George N. Thalmann, Urs E. Studer. Antegrade Perfusion With Bacillus Calmette-Guérin in Patients With Non–Muscle-Invasive Urothelial Carcinoma of the Upper Urinary Tract: Who May Benefit? Eur Urol 2011;60:955–60 - Corrected Proof

Apul Goel, Swarnendu Mandal, Sachin B. Patil — 2012-01-18

The literature regarding the long-term efficacy and tolerability of antegrade bacillus Calmette-Guerin (BCG) for non–muscle-invasive upper tract urothelial cancer is scarce. The present study by Giannarini and colleagues in a large number of patients has proved its effectiveness on long-term follow-up (up to 237 mo; mean: 42 mo). Kidney preservation could be achieved in 89% of the cases using the study protocol.

Reply to Apul Goel, Swarnendu Mandal, Sachin B. Patil's Letter to the Editor re: Gianluca Giannarini, Thomas M. Kessler, Frédéric D. Birkhäuser, George N. Thalmann, Urs E. Studer. Antegrade Perfusion With Bacillus Calmette-Guérin in Patients With Non–Muscle-Invasive Urothelial Carcinoma of the Upper Urinary Tract: Who May Benefit? Eur Urol 2011;60:955-60 - Corrected Proof

Gianluca Giannarini, Urs E. Studer — 2012-01-18

We appreciate the interest of Goel et al. in our recent article, published in the Platinum Journal, which reports on our long-term experience with antegrade bacillus Calmette-Guérin (BCG) perfusion of the upper urinary tract (UUT) in the management of non–muscle-invasive urothelial carcinoma . We are pleased to address their queries.

How Should We Understand the Term Androgen Deprivation Therapy? - Corrected Proof

Tomasz Drewa, Mark S. Soloway — 2012-01-18

Many authors use the term androgen deprivation therapy (ADT) to indicate any treatment that decreases testosterone either to the prostate or in the serum. Is this usage correct?

Robotic Partial Nephrectomy Versus Laparoscopic Cryoablation for the Small Renal Mass - Corrected Proof

2012-01-16

Abstract: Background: Open partial nephrectomy (OPN) remains the gold standard for treatment of small renal masses (SRMs). Laparoscopic cryoablation (LCA) has provided encouraging outcomes. Robotic partial nephrectomy (RPN) represents a new promising option but is still under evaluation.Objective: Compare the outcomes of RPN and LCA in the treatment of patients with SRMs.Design, setting, and participants: We retrospectively analyzed the medical charts of patients with SRMs (≤4cm) who underwent minimally invasive nephron-sparing surgery (RPN or LCA) in our institution from January 1998 to December 2010.Intervention: RPN and LCA.Measurements: Perioperative complications and functional and oncologic outcomes were analyzed.Results and limitations: A total of 446 SRMs were identified in 436 patients (RPN, n=210; LCA, n=226). Patients undergoing RPN were younger (p<0.0001), had a lower American Society of Anesthesiologists score (p<0.001), and higher baseline preoperative estimated glomerular filtration rate (eGFR) (p<0.0001). Mean tumor size was smaller in the LCA group (2.2 vs 2.4cm; p=0.004). RPN was associated with longer operative time (180 vs 165min; p=0.01), increased estimated blood loss (200 vs 75ml; p<0.0001), longer hospital stay (72 vs 48h; p<0.0001), and higher morbidity rate (20% vs 12%, p=0.015). Mean follow-ups for RPN and LCA were 4.8 mo and 44.5 mo, respectively (p<0.0001). Local recurrence rates for RPN and LCA were 0% and 11%, respectively (p<0.0001). Mean eGFR decrease after RPN and LCA was insignificant at 1 mo, at 6 mo after surgery, and during last follow-up. Limitations include retrospective study design, length of follow-up, and selection bias.Conclusions: Both techniques remain viable treatment options in the management of SRMs. A higher incidence of perioperative complications was found in patients undergoing RPN. However, the technique was not predictive of the occurrence of postoperative complications. Early oncologic outcomes are promising for RPN, which also seems to be associated with better preservation of renal function. Long-term follow-up and well-designed prospective comparative studies are awaited to corroborate these findings.Take Home Message: Robotic partial nephrectomy (RPN) and laparoscopic cryoablation (LCA) represent viable treatment options in the management of small renal masses. Early oncologic outcomes are promising for RPN, which also seems to be associated with better preservation of renal function. LCA should be reserved for patients with comorbidities who desire active treatment. Long-term follow-up and well-designed prospective comparative studies are awaited to corroborate these findings.

The Impact of Interscreening Interval and Age on Prostate Cancer Screening With Prostate-Specific Antigen - Corrected Proof

2012-01-16

Abstract: Background: Population-based screening for prostate cancer (PCa) has used serum prostate-specific antigen (PSA) since the early 1990s. However, the efficacy could be affected by screening interval, age ranges of screening, attendance, and contamination of the control group in randomised controlled trials.Objective: Assess the impact of the above-mentioned factors on screening efficacy.Design, setting, and participants: Parameters pertaining to the natural history of PCa and sensitivity were estimated using data from the Finnish quadrennial screening program starting at 55 yr of age and terminating at 71 yr of age and comprising 80 458 men (32 000 in the screening arm and 48 458 in the control arm). We performed Markov decision analyses for different screening policies with a simulated 25-yr follow-up.Intervention: PSA screening.Measurements: The impact of different interscreening intervals and target age ranges on advanced PCa (stage III or worse) and PCa mortality was assessed.Results and limitations: With 65% attendance and 20% contamination, as in the Finnish trial, screening would result in an 11.1% (95% confidence interval [CI], 9.1–13.3%) reduction in advanced cancers and a 7.3% (95% CI, 5.3–9.7%) reduction in PCa death, with corresponding absolute risk difference of 2.6% (95% CI, 1.9–3.5%) and 1.8% (95% CI, 1.4–2.2%), respectively. Numbers needed to screen were 385 to prevent one case of advanced PCa and 556 to prevent one PCa death at 25 yr. Those figures remained similar from 12 yr onwards. Reduction in advanced PCa increased to 40% with annual screening and to 24% with biennial screening. When the age at screening initiation was increased by 5 yr, the benefit was reduced by 9% with annual screening and by 3% with biennial screening.Conclusions: We predicted the impact of basic screening characteristics on the benefit of the program. The screening interval (1–4 yr) had a greater impact on mortality reduction than did the age at start of screening (55–65 yr).Clinical trial registration: International Standard Randomised Controlled Trial Number (ISRCTN): ISRCTN49127736.Take Home Message: The current study provides an in-depth quantitative analysis of the impact of the subsidiary issues of screening, including interscreening interval and age of starting and terminating screening, on the effectiveness of prostate-specific antigen (PSA) screening. The interscreening interval had a greater impact on mortality reduction than did the target age range. Elucidation of these findings provides insight into the inconsistent and heterogeneous results of several previous randomised controlled trials with PSA testing.

Contemporary Management of Ureteral Stones - Corrected Proof

2012-01-16

Abstract: Context: Ureteral calculi represent a common condition that urologists encounter in everyday practice. Several treatment options are available for calculi that do not pass spontaneously or are unlikely to do so.Objective: In this nonsystematic review, we summarize the existing data on contemporary management of ureteral stones focusing on medical expulsive therapy (MET) and different treatment modalities.Evidence acquisition: A PubMed search was performed. We reviewed the recent literature on the management of ureteral calculi. Articles were considered between 1997 and 2011. Older studies were included selectively if historically relevant.Evidence synthesis: For stones that do not pass spontaneously or with MET, shock wave lithotripsy (SWL) and ureteroscopy (URS) are the most common and efficient treatment modalities. Both techniques have obvious advantages and disadvantages as well as different patterns of complications. For select cases or patients, other modalities may be useful.Conclusions: Ureteral stones of up to 10mm and eligible for observation may be offered MET. For most ureteral calculi that require treatment, advances in SWL and URS allow urologists to take a minimally invasive approach. Other more invasive treatments are reserved for select “nonstandard” cases.Take Home Message: Removal of stones from the ureter is an important and extensive part of the care of patients with urinary tract stone disease. For smaller (<10-mm) ureteral stones in a reasonable asymptomatic patient, medical expulsive therapy is an excellent initial form of treatment. In terms of active stone removal, both shock wave lithotripsy and ureteroscopy have been shown to be useful alternatives.

Vesicoureteral Reflux: Current Trends in Diagnosis, Screening, and Treatment - Corrected Proof

2012-01-12

Abstract: Context: Vesicoureteral reflux (VUR) is present in approximately 1% of children in North America and Europe and is associated with an increased risk of pyelonephritis and renal scarring. Despite its prevalence and potential morbidity, however, many aspects of VUR management are controversial.Objective: Review the evidence surrounding current controversies in VUR diagnosis, screening, and treatment.Evidence acquisition: A systematic review was performed of Medline, Embase, Prospero, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, clinicaltrials.gov, and the most recent guidelines of relevant medical specialty organizations.Evidence synthesis: We objectively assessed and summarized the published data, focusing on recent areas of controversy relating to VUR screening, diagnosis, and treatment.Conclusions: The evidence base for many current management patterns in VUR is limited. Areas that could significantly benefit from additional future research include improved identification of children who are at risk for VUR-related renal morbidity, improved stratification tools for determining which children would benefit most from which VUR treatment option, and improved reporting of long-term outcomes of VUR treatments.Take Home Message: Many aspects of vesicoureteral reflux (VUR) management are controversial, and the evidence base for many current management patterns is limited. We review the current literature surrounding VUR diagnosis, screening, and treatment.

Percutaneous Nephrolithotomy in the United Kingdom: Results of a Prospective Data Registry - Corrected Proof

2012-01-12

Abstract: Background: Percutaneous nephrolithotomy (PCNL) is commonly used in the management of large upper renal tract stones. It is highly effective but carries a greater risk of significant morbidity than less invasive treatment options such as ureteroscopy or extracorporeal shock wave lithotripsy.Objective: Evaluate the current practice and outcomes of PCNL using a national prospective data registry.Design, setting, and participants: All surgeons undertaking PCNL in the United Kingdom were invited to submit data to an online registry.Measurements: Effectiveness was assessed by stone-free rates and safety according to complications including blood transfusion, fever, and sepsis rates.Results and limitations: Since January 2010, data on 987 patients who had 1028 PCNL procedures were collected. A total of 299 of 1012 procedures (30%) were for staghorn calculi, 299 (30%) for stones >2cm, 329 (33%) for stones 1–2cm, and 89 (9%) for stones <1cm. There were no significant differences in rates of failed access or complications according to whether a urologist or radiologist obtained renal access. There was a nonsignificant trend to a higher transfusion rate with balloon dilatation (7 of 222 [3.2%]) compared with serial dilatation (2 of 245 [0.8%]) of the renal tract (p=0.093). Totally tubeless procedures were not associated with higher complication rates but did lead to a significant reduction in median length of stay (3 d vs 1.5 d; p<0.0001). Intraoperatively, 78% of patients were believed to be stone free, which was confirmed in 68% with postoperative imaging. Blood transfusion was required in 24 of 968 patients (2.5%). The incidence of postoperative fever was 16% and of sepsis was 2.4%.Conclusions: The PCNL data registry is a unique resource providing vital information on current practice and critical outcome data. Using the registry, endourologists can audit their practice against national outcome data for this benchmark procedure. It will help surgeons counsel patients during consent for this complex endourologic procedure about the possible outcome in their hands.Take Home Message: The British Association of Urological Surgeons percutaneous nephrolithotomy (PCNL) data registry represents the largest prospective multicentre series in the United Kingdom with information on >1000 procedures. It provides unique information on contemporary practice and national outcomes of PCNL. It facilitates audit and revalidation and may be used by surgeons to counsel patients regarding the treatment of their renal stones.

Radical Prostatectomy for Long-Term Functional and Oncologic Outcomes - Corrected Proof

Herbert Lepor — 2012-01-12

The management of prostate cancer (PCa) is controversial and is under intense public scrutiny. PCa deserves the limelight because it is the most common cancer diagnosed and the second most common cause of cancer mortality for men living in the developed world. Its impact on the health and well-being of men and the economics of health care policy is astounding. In addition, there is a paucity of level 1 evidence to definitively influence guidelines for screening, diagnosis, or treatment. It is unimaginable that in 2012, there are no contemporary randomized studies comparing functional or oncologic outcomes following radical prostatectomy (RP) versus radiation therapy and only one published randomized study with long-term follow-up comparing RP and watchful waiting (WW).

Re: Bas W.G. van Rhijn, Theo H. van der Kwast, Sultan S. Alkhateeb, et al. A New and Highly Prognostic System to Discern T1 Bladder Cancer Substage. Eur Urol 2012;61:378–84 - Corrected Proof

Maximilian Burger, Wolfgang Otto, Arndt Hartmann — 2012-01-12

Recently, van Rhijn et al. presented the validation of a novel substaging system of pT1 bladder cancer (BCa) in European Urology, reporting microinvasive and extensive-invasive T1 BCa as independent prognostic groups for progression and survival . Microinvasive and extensive-invasive pT1 were defined as a single focus of lamina propria invasion ≤0.5mm and larger or multiple areas, respectively. Previously, a system for pT1 substaging was suggested, assessing the depth of invasion in relation to the muscularis mucosae–vascular plexus (ie, defining T1a, T1b, and T1c as invasion above, into, and beyond this plexus, respectively). In their data, van Rhijn et al. found the latter system was not prognostic of either end point. We congratulate the authors on this paramount contribution and underscore its meaning.

Reply to Maximilian Burger, Wolfgang Otto, and Arndt Hartmann's Letter to the Editor re: Bas W.G. van Rhijn, Theo H. van der Kwast, Sultan S. Alkhateeb, et al. A New and Highly Prognostic System to Discern T1 Bladder Cancer Substage. Eur Urol 2012;61:378–84 - Corrected Proof

2012-01-12

Improvement of care is the ultimate goal in oncology. T1 bladder cancer (BCa) is an entity in which such an improvement is urgently needed because, as urologists, we lack accurate prognostic parameters to decide who needs radical surgery and who will find repeat transurethral resection (TUR) with adjuvant bacillus Calmette-Guérin (BCG) immunotherapeutic instillations sufficient to control this disease. A randomized study to answer this important clinical question has not been done and will probably never take place. Although far from ideal, variables to predict prognosis in T1 BCa are grade, size, multifocality, carcinoma in situ, and residual T1 BCa at re-TUR .

Predictors of Attendance for Prostate-Specific Antigen Screening Tests and Prostate Biopsy - Corrected Proof

2012-01-11

Abstract: Background: Little is known about factors influencing men's decisions to undergo screening and diagnostic tests for prostate cancer (PCa).Objective: Identify predictors of attendance for prostate-specific antigen (PSA) testing and prostate biopsy.Design, setting, and participants: Literature searches and interviews with men undergoing PSA testing and prostate biopsy formed the basis of a self-report questionnaire designed to identify predictors of health behaviour, which was completed by men eligible for PSA invitation and prostate biopsy. Multitrait scaling analyses established the final questionnaire content. This revised instrument was distributed to a new cohort of men before PSA testing and biopsy invitations were received. Ethical committee approval was obtained from Trent Multicentre Research Ethics Committee (MREC/01/4/025 – 21/06/2001).Measurements: Predictors of health behaviour and attendance rates for PSA test or prostate biopsy were measured. Associations between questionnaire scores and health behaviour (PSA and prostate biopsy attendance) were examined using logistic regression.Results and limitations: The provisional 49-item health behaviour questionnaire was completed by 468 of 810 men (57.8%). Multitrait scaling refined the questionnaire to 26 items in six scales (A: health benefits, B: threats to health, C: barriers to testing, D: health intentions, E: external influences, F: current general health). A total of 1455 of 2657 men (54.8%) completed the revised instrument before invitations for PSA test or biopsy were received; 395 (43.4%) and 434 (91.6%) attended. Strong associations between men's health intentions (scale D) and PSA and biopsy attendance (odds ratio: 1.56 or 3.67, respectively; p<0.001) were observed with modest associations between the other five scales and attendance for PSA testing. Average questionnaire response rates represent the major limitation of this study.Conclusions: Knowledge and beliefs about PCa and testing predict men's intentions and attendance for PSA testing and prostate biopsy. Understanding men's health behaviour is important for the management of patients seeking PSA testing in general practice.Take Home Message: Knowledge and beliefs about prostate cancer and testing influence the behaviour of men invited for prostate-specific antigen testing and prostate biopsy. Efforts to optimize uptake may be informed by targeting these areas.

Radiofrequency Ablation Versus Partial Nephrectomy in Patients with Solitary Clinical T1a Renal Cell Carcinoma: Comparable Oncologic Outcomes at a Minimum of 5 Years of Follow-Up - Corrected Proof

2012-01-11

Abstract: Background: Long-term comparative outcomes for radiofrequency ablation (RFA) versus partial nephrectomy (PN) for the primary treatment of clinical T1a renal cell carcinoma (RCC) have not previously been reported.Objective: Report comparative 5-yr oncologic outcomes for RFA versus PN in patients with clinical T1a RCC.Design, setting, and participants: Observational single-institution cohort study, involving consecutive patients with a solitary histologically confirmed T1a RCC treated by RFA or PN and followed for a minimum of 5 yr. Those presenting with synchronous multiple, metachronous, bilateral, and/or metastatic disease, a history of hereditary RCC syndromes, a family history of RCC, and with post-treatment follow-up <5 yr were excluded from analysis.Measurements: The Kaplan-Meier method was used to determine 5-yr overall survival (OS), cancer-specific survival (CSS), local recurrence-free survival (local RFS), overall disease-free survival (DFS), and metastasis-free survival (MFS) for RFA versus PN. Survival curves were compared using the log-rank test. A p value ≤0.05 was considered statistically significant.Results and limitations: A total of 37 patients in each group met the selection criteria. The RFA cohort was significantly older and had more advanced comorbidities, but other patient characteristics were similar. For RFA versus PN, median follow-up was 6.5 yr (interquartile range [IQR]: 5.8–7.1) versus 6.1 yr (IQR: 5.4–7.3) (p=0.68), respectively. The 5-yr OS was 97.2% versus 100% (p=0.31), CSS was 97.2% versus 100% (p=0.31), DFS was 89.2% versus 89.2% (p=0.78), local RFS was 91.7% versus 94.6% (p=0.96), and MFS was 97.2% versus 91.8% (p=0.35), respectively. Study limitations are retrospective data analysis, loss to follow-up, limited statistical power, and limited generalizability of our data.Conclusions: In appropriately selected patients, RFA is an effective minimally invasive therapy for the treatment of cT1a RCC, yielding comparable long-term oncologic outcomes to nephron-sparing surgery.Take Home Message: When comparing homogeneous, matched, and concurrent patient cohorts, radiofrequency ablation for solitary T1a renal cell carcinoma results in long-term (≥5 yr) oncologic outcomes that are comparable with those for partial nephrectomy.

Does the Imprecise Definition of Overactive Bladder Serve Commercial Rather than Patient Interests? - Corrected Proof

Kari A.O. Tikkinen, Anssi Auvinen — 2012-01-06

The tendency has always been strong to believe that whatever received a name must be an entity or being, having an independent existence of its own. And if no real entity answering to the name could be found, men did not for that reason suppose that none existed, but imagined that it was something peculiarly abstruse and mysterious. —John Stuart Mill

Extent of Cancer of Less Than 50% in Any Prostate Needle Biopsy Core: How Many Millimeters Are There? - Corrected Proof

2012-01-06

The primary goal of needle biopsy is to diagnose prostatic adenocarcinoma. Once prostate cancer (PCa) is detected, further descriptive information regarding the type of cancer, the amount of tumor, and the grade in prostate needle cores (Appendix 1) forms the cornerstone for contemporary management of the patient and for assessment of the potential for local cure and risk for distant metastasis . The information provided in the needle biopsy report regarding the attributes of carcinoma is used depending on the individual patient's medical condition and preference and for the treating physician's evaluation to determine (1) whether any form of treatment is indicated and, if so, (2) the type of therapy. The information in the biopsy report may be valuable in further determining potential treatment strategies, such as the field and/or type of radiation therapy (eg, brachytherapy, external beam); the need for adjuvant hormonal therapy; the eligibility for clinical trials, including active surveillance (AS); the type of surgery (nerve sparing, bladder neck sparing); and sometimes the intraoperative course (eg, using frozen sections for lymph nodes, neurovascular bundle involvement, apical and bladder neck margin or type of operation) .

Robotic Prostatectomy: The Rise of the Machines or Judgment Day - Corrected Proof

Joshua J. Meeks, James A. Eastham — 2012-01-06

Utilization of robotic prostatectomy has increased since its introduction in 2000 . Trinh et al provide a national snapshot of the current trends in surgical treatment of prostate cancer (PCa) . Although the enthusiasm for robotic prostatectomy is driven by surgeons, consumers, and the robot manufacturer, the size of the shift is presented clearly in this manuscript. In 2008 and 2009, >60% of all prostatectomies were performed using robotics, with substantial growth from 2003 (9.3%) to 2007 (43%) . The trend toward robot-assisted surgery for PCa is obvious, but the benefits for patients are not as clear cut.

Death Certificates Are Valid for the Determination of Cause of Death in Patients With Upper and Lower Tract Urothelial Carcinoma - Corrected Proof

2012-01-06

Accurate appraisal of cause of death (COD) is critically important for determining correct cause-specific survival in cancer patients. Death certificates are used for assessment of COD in case control , cohort outcomes , and occupational mortality studies . Likewise, large data sets, such as the Surveillance Epidemiology and End Results program, and tumor registries rely on death certificates to assign COD . However, this method may become inaccurate (1) when patients get older, (2) when patients have serious comorbidities associated with a risk of dying of other causes , or (3) when cancer patients are long-term survivors.

Botulinum Toxin A Versus Placebo for Refractory Detrusor Overactivity in Women: A Randomised Blinded Placebo-Controlled Trial of 240 Women (the RELAX Study) - Corrected Proof

2012-01-06

Abstract: Background: Emerging data suggest botulinum toxin is an effective treatment for detrusor overactivity (DO), but large studies confirming efficacy and safety are lacking.Objective: Study the efficacy and safety of onabotulinumtoxinA (onaBoNTA) for the treatment of DO.Design, setting, and participants: A double-blind placebo-controlled randomised trial in eight UK urogynaecology centres was conducted between 2006 and 2009. A total of 240 women with refractory DO were randomised to active or placebo treatment and followed up for 6 mo.Intervention: Treatment consisted of 200 IU onaBoNTA or placebo injected into the bladder wall (20 sites; 10 IU per site in 1ml saline).Measurements: Primary outcome was voiding frequency per 24h at 6 mo. Secondary outcomes included urgency and incontinence episodes and quality-of-life data. Intention-to-treat analysis was used with imputation of missing data.Results and limitations: A total of 122 women received onaBoNTA and 118 received the placebo. Median (interquartile range) voiding frequency was lower after onaBoNTA compared with placebo (8.3 [6.83–10.0] vs 9.67 [8.37–11.67]; difference: 1.34; 95% confidence interval [CI], 1.00–2.33; p=0.0001). Similar differences were seen in urgency episodes (3.83 [1.17–6.67] vs 6.33 [4.0–8.67]; difference: 2.50; 95% CI, 1.33–3.33; p<0.0001) and leakage episodes (1.67 [0–5.33] vs 6.0 [1.33–8.33]; difference: 4.33; 95% CI, 3.33–5.67; p<0.0001). Continence was more common after botulinum toxin type A (BoNTA; 31% vs 12%; odds ratio [OR]: 3.12; 95% CI, 1.49–6.52; p=0.002). Urinary tract infection (UTI; 31% vs 11%; OR: 3.68; 95% CI, 1.72–8.25; p=0.0003) and voiding difficulty requiring self-catheterisation (16% vs 4%; OR: 4.87; 95% CI, 1.52–20.33; p=0.003) were more common after onaBoNTA.Conclusions: This randomised controlled trial of BoNTA for refractory DO, the largest to date, confirms efficacy and safety of the compound. UTI (31%) and self-catheterisation (16%) are common. A third of women achieved continence.Trial registration: The study received ethical committee approval from the Scottish Multicentre Research Ethics Committee (reference: 04/MRE10/67). The trial has a EudraCT number (2004-002981-39), a clinical trial authorisation from the UK Medicines and Healthcare Regulatory Agency, and it was registered on Current Controlled Trials (ISRCTN26091555) on May 26, 2005.Take Home Message: This randomised controlled trial on botulinum toxin, the largest to date, confirms effectiveness and safety of onabotulinumtoxinA for detrusor overactivity in women. Urgency and incontinence appear more responsive than frequency. Voiding difficulty occurs in up to 16% of women.

Efficacy and Safety of Everolimus in Elderly Patients With Metastatic Renal Cell Carcinoma: An Exploratory Analysis of the Outcomes of Elderly Patients in the RECORD-1 Trial - Corrected Proof

2012-01-06

Abstract: Background: Elderly patients with metastatic renal cell carcinoma (mRCC) may require special treatment considerations, particularly when comorbidities are present. An understanding of the efficacy and safety of targeted agents in elderly patients with mRCC is essential to provide individualized therapy.Objective: To evaluate the efficacy and safety of everolimus in elderly patients (those ≥65 and ≥70 yr of age) enrolled in RECORD-1.Design, setting, and participants: The multicenter randomized RECORD-1 phase 3 trial (Clinicaltrials.gov identifier, NCT00410124; http://www.clinicaltrials.gov) enrolled patients with mRCC who progressed during or within 6 mo of stopping sunitinib and/or sorafenib treatment (n=416).Intervention: Everolimus 10mg once daily (n=277) or placebo (n=139) plus best supportive care. Treatment was continued until disease progression or unacceptable toxicity.Measurements: Median progression-free survival (PFS), median overall survival (OS), and time to deterioration in Karnofsky performance status (TTD-KPS) were assessed using the Kaplan-Meier method; the log-rank test was used to compare treatment arms. Other outcomes evaluated included reduction in tumor burden, overall response rate (ORR), and safety.Results and limitations: In RECORD-1, 36.8% of patients were ≥65 yr and 17.5% were ≥70 yr of age. PFS, OS, TTD-KPS, reduction in tumor burden, and ORR were similar in the elderly and the overall RECORD-1 population. Everolimus was generally well tolerated in elderly patients, and most adverse events were grade 1 or 2 in severity. The toxicity profile of everolimus was generally similar in older patients and the overall population; however, peripheral edema, cough, rash, and diarrhea were reported more frequently in the elderly regardless of treatment. The retrospective nature of the analyses was the major limitation.Conclusions: Everolimus is effective and tolerable in elderly patients with mRCC. When selecting targeted therapies in these patients, the specific toxicity profile of each agent and any patient comorbidities should be considered.Take Home Message: In the RECORD-1 study, everolimus provided significant clinical benefit in elderly patients with metastatic renal carcinoma, with an acceptable safety profile. Efficacy in elderly patients was consistent with that of the overall population, and no increase in everolimus-related adverse events was observed.

Infectious Complications and Hospital Admissions After Prostate Biopsy in a European Randomized Trial - Corrected Proof

2012-01-06

Abstract: Background: The complications of prostate needle biopsy (PNB) are important when considering the benefits and harms of prostate cancer screening. Studies from the United States and Canada have recently reported increasing numbers of hospitalizations for infectious complications after PNB.Objective: Examine the risk of infectious complications and hospital admissions after PNB in a European screening trial.Design, setting, and participants: From 1993 to 2011, 10 474 PNBs were performed in the European Randomized Study of Screening for Prostate Cancer (Rotterdam section). Prophylaxis originally consisted of trimethoprim-sulfamethoxazole. Beginning in 2008, it was changed to ciprofloxacin.Measurements: Febrile complications and hospital admissions were assessed by questionnaires 2 wk after PNB. Logistic regression was used to identify risk factors for biopsy-related fever and hospital admission.Results and limitations: Fever and hospital admission were reported on 392 of 9241 questionnaires (4.2%) and 78 of 9198 questionnaires (0.8%), respectively. Although most fevers were managed on an outpatient basis, 81% of hospital admissions were for infection. Of the 56 available blood cultures, 34 were positive with Escherichia coli as the predominant organism. On multivariable analysis, prostate enlargement and diabetes were significantly associated with an increased risk of fever after PNB, whereas later year of biopsy was the only factor significantly associated with an increased risk of hospital admission.Conclusions: In a European screening trial, <5% PNBs resulted in febrile complications. Significant risk factors included diabetes and prostatic enlargement. Although most fevers were managed on an outpatient basis, infection remained the leading cause of hospital admission after PNB. Consistent with prior international reports, the frequency of hospital admissions after PNB significantly increased over time. Nevertheless, the absolute frequency of hospital admissions related to PNB was low and should not dissuade healthy men who would benefit from early prostate cancer diagnosis from undergoing biopsy when clinically indicated.Take Home Message: In a European screening trial, fever and hospital admission were reported after 4.2% and 0.8% of prostate needle biopsies (PNBs), respectively. Although hospital admissions significantly increased over time, the low absolute frequency should not dissuade healthy men from undergoing PNB.

Anatomic Grading of Nerve Sparing During Robot-Assisted Radical Prostatectomy - Corrected Proof

2012-01-05

Abstract: Background: Because of the lack of intraoperative visual cues, the amount of nerve sparing (NS) intended by the surgeon does not always correspond to what is actually performed during surgery.Objective: Describe a standardized NS grading system based on intraoperative visual cues.Design, setting, and participants: A total of 133 consecutive patients who underwent robot-assisted radical prostatectomy (RARP) by a single surgeon were evaluated. The surgeon intraoperatively graded the NS independently for either side as follows: 1=no NS; 2=<50% NS; 3=50% NS; 4=75% NS; 5=≥95% NS.Surgical procedure: RARP; detailed description of a five-point NS grading system.Measurements: The area of residual nerve tissue on prostatectomy specimens was compared with the intraoperative NS score (NSS). The rate of positive surgical margins (PSMs) according to the NSS is also reported.Results and limitations: In all, 52.6% of operated sides (140 of 266 sides) had NSS 5, 30.1% (80 of 266) had NSS 4, 2.3% (6 of 266) had NSS 3, 13.2% (35 of 266) had NSS 2, and 1.9% (5 of 266) had NSS 1. The area of residual nerve tissue was significantly different among the different NSSs: median area (interquartile range) for NSS 5: 0.5 (0–2) mm2; for NSS 4: 3 (0–8) mm2; for NSS 3: 13 (7–23) mm2; for NSS 2: 14 (8–24) mm2; and for NSS 1: 57 (56–165) mm2 (p<0.001). Overall, 9.02% of the patients (12 of 133 patients) had a PSM, with 8.3% (9 of 108) for pT2 and 12% (3 of 25) for pT3. Side-specific PSMs according to NSS were 3.6% (5 of 140) for NSS 5, 7.5% (6 of 80) for NSS 4, 16.7% (1 of 6) for NSS 3, 5.7% (2 of 35) for NSS 2, and 0% (0 of 5) for NSS 1. A limitation of our study is that the key anatomic landmarks are not recognizable in every case, and this technique might not be easy to perform during the early learning curve.Conclusions: We believe that the visual cues exposed in this article will help surgeons achieve more consistent NS during RARP.Take Home Message: The advantages for visualization, magnification, and dexterity provided by the robotic platform allow identification of key anatomic landmarks that can be used to perform more tailored and consistent nerve sparing during radical prostatectomy.

Reply from Authors re: William D. Steers. Remarks about Remarkable Surgical Outcomes. Eur Urol. In Press. DOI:10.1016/j.eururo.2011.12.035 - Corrected Proof

Robert P. Myers, R. Jeffrey Karnes — 2012-01-05

We appreciate the opportunity to respond to Dr. Steers’ commentary concerning our prospective radical prostatectomy (RP) study , which was conceived to see how well open retropubic RP (ORRP) could be accomplished in a contemporary setting. Robot-assisted RP (RARP) is not as widely available worldwide as in the United States, and open surgeons everywhere might benefit from appreciating the technical methods that were used to produce our results. We can only set the stage for others in terms of our methods being generalized. That “open surgeons need not be deterred by the sweeping popularity of RARP” was carefully predicated on their ability, adopting what they perceive to be important elements of our described technique, to reproduce our results.

Open Versus Laparoscopic Nephroureterectomy: Is There Really a Debate? - Corrected Proof

Brant A. Inman — 2012-01-05

On March 17, 1987, Phillippe Mouret performed the first laparoscopic cholecystectomy in Lyon, France . Despite the initial absence of any trials demonstrating superiority, within 5 yr of its inception, laparoscopic cholecystectomy became the standard of care worldwide . Why did smart and normally highly critical general surgeons accept such an unproven operation so rapidly? Because it was clearly better. There were lots of doubters, lots of naysayers, and even talk of severe biliary strictures and unusual patient deaths. Eventually, there were large case series, multicenter comparative studies, and even a few randomized trials. But the results did not matter. The “horse was already out of the barn,” and laparoscopic cholecystectomy was going to stay. It was just a better operation.

Personalized Treatment of Prostate Cancer Based on Inherited Variations of Steroid Pathway–Related Genes - Corrected Proof

Tilman Todenhöfer, Christian Schwentner, Arnulf Stenzl — 2012-01-05

There is increasing evidence that genetic differences of genes involved in the synthesis and biotransformation of steroid hormones are independent predictors of outcome in prostate cancer (PCa). In this issue, Audet-Walsh and colleagues report that specific single nucleotide polymorphisms (SNPs) in the family of hydroxysteroid (17-beta) dehydrogenase (HSD17B) genes are associated with increased risk for biochemical recurrence in localized PCa . Furthermore, they demonstrate that various SNPs predict decreased progression-free and overall survival in advanced PCa.

Reply from Authors re: Alexander Kutikov, Marc C. Smaldone, Brian L. Egleston, Robert G. Uzzo. Should Partial Nephrectomy Be Offered to All Patients Whenever Technically Feasible? Eur Urol. In press. DOI:10.1016/j.eururo.2011.12.014 - Corrected Proof

Maxine Sun, Quoc-Dien Trinh, Pierre I. Karakiewicz — 2012-01-05

We read with great interest the editorial comment by Kutikov and colleagues regarding our recent publication demonstrating a non-cancer-related survival benefit in patients diagnosed with small renal masses treated with partial nephrectomy (PN) relative to radical nephrectomy (RN) . Despite the nonrandomized and retrospective observational nature of our report, it corroborates several previous publications that examined the same topic . In addition, a stringent methodology was used within our report, namely, propensity-based matching, which allows valid comparison of cases and controls when inherent group differences exist, and competing-risks regression, which focuses on a more specific end point than overall survival.

Reply to Pascal Mouracade's Letter to the Editor re: Rustom P. Manecksha, Ivor M. Cullen, Sarfraz Ahmad, et al. Prospective Randomised Controlled Trial Comparing Trigone-Sparing versus Trigone-Including Intradetrusor Injection of AbobotulinumtoxinA for Refractory Idiopathic Detrusor Overactivity. Eur Urol. In press. DOI:10.1016/j.eururo.2011.10.043 - Corrected Proof

2011-12-30

The authors thank Dr. Mouracade for his interest and comments on our paper evaluating trigone-sparing versus trigone-including intradetrusor injections of abobotulinumtoxinA in patients with refractory idiopathic detrusor overactivity . The overactive bladder symptom score (OABSS) questionnaire was chosen as the instrument to measure response to treatment in our study because it is validated , is concise (comprises seven questions on a single page), and quantifies lower urinary tract symptoms that predominate in patients with idiopathic detrusor overactivity. Our study was designed to detect a mean difference in the OABSS total score of 4 points, with a standard deviation of 4 points. To our knowledge, there is currently no validated minimum important difference value for the OABSS total score. Because the difference in OABSS total score that would be expected to be clinically significant is unknown, a 4-point difference was assigned arbitrarily.

Re: Rustom P. Manecksha, Ivor M. Cullen, Sarfraz Ahmad, et al. Prospective Randomised Controlled Trial Comparing Trigone-Sparing versus Trigone-Including Intradetrusor Injection of AbobotulinumtoxinA for Refractory Idiopathic Detrusor Overactivity. Eur Urol. In press. DOI:10.1016/j.eururo.2011.10.043 - Corrected Proof

Pascal Mouracade — 2011-12-30

In this paper , Manecksha et al. evaluate the efficacy and safety of trigone-including versus trigone-sparing intradetrusor injections of abobotulinumtoxinA in patients with idiopathic detrusor overactivity. The authors conducted a prospective randomized controlled study. The study was designed to have 80% power to detect a mean difference in total overactive bladder symptom score (OABSS) of 4 points between trigone-including and trigone-sparing groups, assuming the standard deviation (SD) is 4 points using a two-sided type I error of 5%. The authors assumed that a sample size of 18 patients (9 per group) was required.