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Background: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. Patients: and methods We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201).Results: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type.Conclusions: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting.

BACKGROUNDThere is few data on what constitutes the distribution of metastatic sites in prostate cancer (PCa). The aim of our study was to systematically describe the most common sites of metastases in a contemporary cohort of PCa patients. METHODSPatients with metastatic PCa were abstracted from the Nationwide Inpatient Sample (1998-2010). Most common metastatic sites within the entire population were described. Stratification was performed according to the presence of single or multiple (2 sites) metastases. Additionally, we evaluated the distribution of metastatic sites amongst patients with and without bone metastases. RESULTSOverall, 74,826 patients with metastatic PCa were identified. The most common metastatic sites were bone (84%), distant lymph nodes (10.6%), liver (10.2%), and thorax (9.1%). Overall, 18.4% of patients had multiple metastatic sites involved. When stratifying patients according to the site of metastases, only 19.4% of men with bone metastases had multiple sites involved. Conversely, among patients with lymph nodes, liver, thorax, brain, digestive system, retroperitoneum, and kidney and adrenal gland metastases the proportion of men with multiple sites involved was 43.4%, 76.0%, 76.7%, 73.0%, 52.2%, 60.9%, and 76.4%, respectively. When focusing exclusively on patients with bone metastases, the most common sites of secondary metastases were liver (39.1%), thorax (35.2%), distant lymph nodes (24.6%), and brain (12.4%). CONCLUSIONSAlthough the majority of patients with metastatic PCa experience bone location, the proportion of patients with atypical metastases is not negligible. These findings might be helpful when planning diagnostic imaging procedures in patients with advanced PCa. Prostate 74:210-216, 2014. (c) 2013 Wiley Periodicals, Inc.

Objective To examine whether percentage of tumour volume (%TV) and percentage of high-grade tumour volume (%HGTV) help to better identify men at higher risk of early biochemical recurrence (BCR) after radical prostatectomy (RP) for non-metastatic high-risk prostate cancer, as early BCR after RP might be associated with higher risk of metastases and cancer-specific mortality. Patients and Methods We examined the data of 595 men treated with RP for non-metastatic high-risk prostate cancer between 1992 and 2011 at two European tertiary care centres. Kaplan-Meier analyses were used to graphically depict 2-year BCR-free survival. Multivariable Cox regression models addressed early BCR. We tested whether addition of %TV and %HGTV to a multivariable Cox regression model helps to increase a model's predictive accuracy (PA) for prediction of early BCR. Results In all, 32 men (10%) with specimen-confined prostate cancer (pT2-pT3a, negative surgical margin, pN0) and 67 men (24%) with non-specimen-confined prostate cancer had early BCR. After stratification according to %HGTV (%HGTV threshold: ≤33.33 vs >33.33%), the 2-year BCR-free survival rates were respectively 93 vs 60% (log-rank P < 0.001). In multivariable Cox regression models %HGTV emerged as an independent predictor of early BCR (P < 0.001), whereas %TV did not (P > 0.05). However, adding %HGTV (regardless of its coding) to other covariates in multivariable Cox regression analysis did not increase the model's PA in a meaningful fashion compared with the use of the detailed Gleason grading system (6 vs 7a vs 7b vs 8 vs 9-10). Conclusions In a large cohort of patients with high-risk prostate cancer, %HGTV and %TV did not improve prediction of early BCR after RP substantially, although %HGTV was an independent predictor of early BCR. Therefore, sophisticated TV/HGTV measurements do not seem to have additional benefit for early BCR prediction relative to the use of Gleason grading. However, these results need to be confirmed in larger, prospective studies. © 2013 The Authors. BJU International © 2013 BJU International.

Objective To assess the prognostic role of extranodal extension (ENE) and the size of the largest lymph node (LN) metastasis in predicting early biochemical relapse (eBCR) in patients with LN metastasis after radical prostatectomy (RP). Patients and Methods We evaluated BCR-free survival in men with LN metastases after RP and pelvic LN dissection performed in six high-volume centres. Multivariable Cox regression tested the role of ENE and diameter of largest LN metastasis in predicting eBCR after adjusting for clinicopathological variables. We compared the discrimination of multivariable models including ENE, the size of largest LN metastasis and the number of positive LNs. Results Overall, 484 patients were included. The median (interquartile range, IQR) follow-up was 16.1 (6-27.5) months. The median (IQR) number of removed LNs was 10 (4-14), and the median (IQR) number of positive LNs was 1 (1-2). ENE was present in 280 (58%) patients, and 211 (44%) had their largest metastasis >10 mm. Patients with ENE and/or largest metastasis of >10 mm had significantly worse eBCR-free survival (all P < 0.01). On multivariable analysis, number of positive LNs (≤2 vs >2) and the diameter of LN metastasis (≤10 vs >10 mm), but not ENE, were significant predictors of eBCR (all P < 0.003). ENE and diameter of LN metastasis increased the area under the curve of a baseline multivariable model (0.663) by 0.016 points. Conclusions The diameter of the largest LN metastasis and the number of positive LNs are independent predictors of eBCR. Considered together, ENE and the diameter of the largest LN metastasis have less discrimination than the number of positive LNs.

A recent population-based analysis suggested a potential survival benefit with respect to performing lymph node dissection at nephrectomy in node-positive patients with RCC. The findings of the present study failed to corroborate the association of a survival benefit with the performance of lymph node dissection at nephrectomy. Objective Previous studies showed no survival benefit with respect to performing lymph node dissection (LND) at nephrectomy, whereas a recent population-based analysis suggested otherwise, although the latter relied on imputation. To reconcile the findings of that study by critically evaluating the handling of missing data. Patients and Methods Study participants comprised patients diagnosed with non-metastatic renal cell carcinoma (RCC) of all stages who underwent LND at nephrectomy (n = 10596). Multivariable Cox regression models were performed to predict cancer-specific mortality (CSM), where the primary variable of interest was the extent of LND. To examine differences in approaches with respect to handling missing data, separate analyses were performed: (i) imputed population; (ii) exclusion of patients with missing data; and (iii) inclusion of patients with missing data as a sub-category. Results Overall, 2916 (28%) patients had missing tumour grade. In multivariable analyses, our findings showed that increasing the extent of LND was associated with a significant protective effect on CSM in patients with pN1 after imputation (hazard ratio [HR], 0.82; P = 0.04). By contrast, the extent of LND was no longer significantly associated with a lower risk of CSM after excluding patients with a missing tumour grade (HR, 0.83; P = 0.1) or when including patients with missing tumour grade as a sub-category (HR, 0.82; P = 0.05). Conclusions The findings of the present study failed to corroborate the association of a survival benefit with increasing extent of LND at nephrectomy. The different methodologies employed to account for missing data may introduce important biases. Such considerations are non-negligible with respect to the interpretation of results for investigators who rely on administrative cohorts.

Fragestellung: Arbeiten zur prognostischen Qualität des UICC Tumor-Node-Metastasis Staging Systems (TNM) beim Nierenzellkarzinom (RCC) werden entscheidend vom klarzelligen Subtyp dominiert. Die wenigen Studien mit isolierter Analyse von Patienten mit papillärem RCC (papRCC) liefern widersprüchliche[zum vollständigen Text gelangen Sie über die oben angegebene URL], 42. Gemeinsame Tagung der Bayerischen Urologenvereinigung und der Österreichischen Gesellschaft für Urologie und Andrologie

Fragestellung: Das papilläre Nierenzellkarzinom (papRCC) ist mit ca. 10-15% der Fälle der zweithäufigste RCC-Subtyp. Obwohl Männer einer deutlich höhere Inzidenz für diesen Subtyp aufweisen, wurden bisher weder geschlechtsspezifische Unterschiede bezüglich klinischer[zum vollständigen Text gelangen Sie über die oben angegebene URL], 42. Gemeinsame Tagung der Bayerischen Urologenvereinigung und der Österreichischen Gesellschaft für Urologie und Andrologie

Context: There is uncertainty regarding the oncologic effectiveness of kidney-sparing surgery (KSS) compared with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Objective: To systematically review the current literature comparing oncologic outcomes of KSS versus RNU for UTUC. Evidence acquisition: A computerised bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting comparative oncologic outcomes of KSS versus RNU. Approaches considered for KSS were segmental ureterectomy (SU) and ureteroscopic (URS) or percutaneous (PC) management. Using the methodology recommended by the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, we identified 22 nonrandomised comparative retrospective studies published between 1999 and 2015 that were eligible for inclusion in this systematic review. A narrative review and risk-of-bias (RoB) assessment were performed using cancer-specific survival (CSS) as the primary end point. Evidence synthesis: Seven studies compared KSS overall (n = 547) versus RNU (n = 1376). Information on the comparison of SU (n = 586) versus RNU (n = 3692), URS (n = 162) versus RNU (n = 367), and PC (n = 66) versus RNU (n = 114) was available in 10, 5, and 2 studies, respectively. No significant difference was found between SU and RNU in terms of CSS or any other oncologic outcomes. Only patients with low-grade and noninvasive tumours experienced similar CSS after URS or PC when compared with RNU, despite an increased risk of local recurrence following endoscopic management of UTUC. The RoB assessment revealed, however, that the analyses were subject to a selection bias favouring KSS. Conclusions: Our systematic review suggests similar survival after KSS versus RNU only for low-grade and noninvasive UTUC when using URS or PC. However, selected patients with high-grade and invasive UTUC could safely benefit from SU when feasible. These results should be interpreted with caution due to the risk of selection bias. Patient summary: We reviewed the studies that compared kidney-sparing surgery versus radical nephroureterectomy for upper tract urothelial carcinoma. We found similar oncologic outcomes for favourable tumours when using ureteroscopic or percutaneous management, whereas indications for segmental ureterectomy could be extended to selected cases of aggressive tumours. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Maxine Sun1, Firas Abdollah2, Jan Schmitges1, Claudio Jeldres1, Shahrokh F Shariat3, Paul Perrotte4, Pierre I Karakiewicz1,4 1Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; 2Department of Urology, Vita Salute San Raffaele University, Milan, Italy; 3Department of Urology, Weill Medical College of Cornell University, New York, NY, USA; 4Department of Urology, University of Montreal Health Center, Montreal, CanadaAbstract: The efficacy of sequential everolimus, an orally administered inhibitor of mammalian target of rapamycin (mTOR), was proven in a placebo-controlled phase III study, where median progression-free survival was 4.9 vs 1.9 months for placebo (hazard ratio: 0.33, P < 0.001). Placebo crossovers (80%) contaminated overall survival data. Adverse event discontinuation rate was of only 10% and health-adjusted quality-of-life was sustained. These data represent the first placebo-controlled evidence of efficacy for a seque ntially used targeted agent. Everolimus resulted in the strongest hazard ratio ever recorded for progression-free survival, despite it being tested in a population with the most aggressive natural history ever recorded in all available phase III metastatic renal cell carcinoma trials. Everolimus use after exclusively one prior antivascular endothelial growth factor f ailure resulted in an even longer progression-free survival time (5.4 months) than in the entire population (4.9 months). These benefits should also be considered in the light of sustained and unimpaired health-related quality of life. Use in first line other than second or subsequent lines remains to be validated.Keywords: everolimus, metastatic renal cell carcinoma, targeted therapy, sequential therapy, mTOR

Introduction and Objectives: The impact of prognostic factors in T1G3 patients (pts) is critical for proper treatment decision making, however most available data are from small series of pts. The aim of the current study is to assess prognostic factors in a large group of pts who received BCG as initial treatment of T1G3 tumours and identify a subgroup of high risk pts who should be considered for early cystectomy. Patients and Methods: Individual pt data were collected for 1743 ptsfrom 20 centers who received induction or maintenance BCG between 1990 and 2008. Using Cox regression analysis, the prognostic importance of the following variables were assessed for time to recurrence, progression to muscle invasive disease and overall survival:age (70yrs), gender, primary T1G3 vs. recurrent T1G3 after previous non T1G3 tumour, tumour size (3 cm), multiplicity (single vs. multiple), concomitant CIS (no/yes), and maintenance BCG (no/yes). Results: Median age was 68yrs, 84% were male, 89% were primary T1G3, 50% had multifocal disease, 67% had tumours less than 3 cm, 24% had concomitant CIS, 30% had a restaging TUR, 52% received some sort of maintenance BCG. With a follow up out to 15 years, 801 pts (46%) recurred, 326 (19%) progressed, 291 underwent cystectomy (17%) and 409 (23%) died, 151 (9%) due to bladder cancer. In multivariate analyses, the most important prognostic factors (p70, size >3 cm and presence of CIS. Progression free rates at 10 yrs were 84%, 75%, 66% and 28% for patients with 0, 1, 2 and 3 bad factors while the corresponding overall survival rates were 78%, 56%, 45% and 6%, respectively. Conclusion: T1G3 patients treated with BCG have a heterogeneous prognosis, with overall survival at 10 yrs ranging from 78% to 6%. Although maintenance BCG improves outcome as compared to induction alone, fit pts over 70 yrs of age with tumours greater than 3 cm and concomitant CIS should be considered for an early cystectomy.

Objectives To examine cancer-specific mortality in patients with nodal metastases relative to patients without nodal involvement at nephrectomy for non-metastatic renal cell carcinoma in a population-based cohort. Methods A total of 11374 non-metastatic renal cell carcinoma patients who underwent a lymph node dissection at nephrectomy were identified using the Surveillance, Epidemiology and End Results database (19882008). The 5-year cancer-specific mortality-free survival rates were examined according to the presence or absence of nodal involvement within the entire cohort, and stratified according to pathological tumor stage (pT1vspT2vspT3vspT4) and Fuhrman grade (IvsIIvsIIIvsIV). Cox regression analyses for prediction of cancer-specific mortality were modeled to assess the effect of nodal metastases versus no nodal involvement in the entire population. Finally, separate Cox regression models were fitted within each pathological stage and grade. Results Overall, 1260 (11%) patients had nodal metastases at nephrectomy. The overall 5-year cancer-specific mortality-free survival rates were 38.4 versus 83.8% in patients with nodal metastases and without nodal metastases, respectively. In multivariable analyses, amongst pT1, pT2, pT3 and pT4, patients with nodal metastases were 6.0-, 3.6-, 3.2- and 2.0-fold, respectively, more likely to die after nephrectomy (all P

Objective To quantify the effect of partial nephrectomy (PN) vs radical nephrectomy (RN) on other-cause mortality (OCM) in elderly patients with localized renal cell carcinoma (RCC) and/or multiple comorbidities. Methods Using the Surveillance, Epidemiology, and End Results Medicare-linked database, patients with T1 RCC, aged >= 75 years, or who had >= 2 comorbidities, were identified (1988-2005). To adjust for inherent differences between treatment types, propensity-based matched analyses were performed. Competing-risks regression analyses for prediction of OCM were assessed according to treatment type. The effect of PN and RN on OCM was examined in three sub-groups: patients aged >= 75 years; patients with >= 2 comorbidities; and patients aged >= 75 years with >= 2 comorbidities. Results After propensity-based matched analyses and adjustment for all covariates, PN was found to exert a protective effect relative to RN with respect to OCM in all patients (hazard ratio [HR]: 0.84, P = 0.048). In subanalyses, no difference was recorded between PN and RN in patients who were aged >= 75 years (HR: 0.83, P = 0.2), with >= 2 baseline comorbidities at diagnosis (HR: 0.83, P = 0.1), or in patients who were aged >= 75 years and who had >= 2 baseline comorbidities (HR: 0.77, P = 0.2). Conclusions Some elderly patients and/or those with multiple comorbidities at diagnosis may not benefit from PN with respect to OCM. After rigorous patient selection, alternative treatment options could be considered.

Objective To examine the impact of length of survival on future survival probability, otherwise known as the effect of conditional survival (CS), after nephrectomy (NT) in patients diagnosed with renal cell carcinoma (RCC). Patients and Methods Overall, 42090 patients with RCC who underwent NT were abstracted from the Surveillance, Epidemiology, and End Results database (1988-2008). Based on cumulative survival estimates, CS rates were derived according to patient and disease characteristics. Separate multivariable Cox regression analyses were performed for the prediction of cancer-specific mortality (CSM), according to 1-, 2-, 3-, 4- and 5-year survival postoperatively. Results Immediately after surgery, the 5-year cancer-specific survival rate was 83.5%. Amongst patients who survived 1, 2, 3, 4, and 5 years after NT, the probability rates for surviving an additional 5 years were 87.0, 89.6, 90.9, 92.0 and 92.3%, respectively. Provided that patients survived 1 and 2 years after NT, the probability of being CSM-free for another 5 years increased by +4.1 and 4.3% for stage III and +12.9 and 10.3% for stage IV disease, respectively. Similar observations were recorded for patient age, grade, nodal stage and tumour size, and were confirmed upon multivariable analyses. Conclusion Survival probabilities vary according to length of survival after NT. Specifically, even amongst patients with more advanced disease at surgery, a more favourable prognosis can be achieved after surviving for 1-2 years.

Objectives The 2004 National Comprehensive Cancer Network practice guidelines recommend pelvic lymph node dissection at radical prostatectomy. We sought to examine the adherence to the 2004 National Comprehensive Cancer Network guidelines and to test the their accuracy, as well as the accuracy of the most contemporary National Comprehensive Cancer Network, American Urological Association, and European Association of Urology guidelines to predict lymph node metastases. Methods A total of 33037 radical prostatectomy patients were identified, between 2004 and 2006. Adherence to the 2004 National Comprehensive Cancer Network guidelines was calculated using three clinically plausible cut-offs: 2, 5 and 10%. The accuracy was tested using the area under the curve. Results Overall, 63% of patients underwent pelvic lymph node dissection. Of those, 61, 49 and 45% were managed according to the 2004 National Comprehensive Cancer Network guideline cut-off of 2, 5 and 10%, respectively. The accuracy of all the examined guidelines ranged from 61% to 71%. The highest accuracy was recorded for the European Association of Urology and the 2004 National Comprehensive Cancer Network cut-off 5% guidelines. The lowest accuracy was recorded for the most contemporary National Comprehensive Cancer Network guideline. Conclusions Adherence to the 2004 National Comprehensive Cancer Network guidelines was suboptimal. The accuracy of all the examined guidelines ranged from 61% to 71%. None of the examined guidelines can be regarded as an ideal indication for pelvic lymph node dissection.

Objective To examine the discriminant properties of the most contemporary version of the Tumour-Node-Metastasis (TNM) staging for renal cell carcinoma (RCC) sub-classification of T2 lesions according to a threshold size of 10cm. Other thresholds were also assessed. Patients and Methods Between 1988 and 2006, within the Surveillance, Epidemiology, and End Results database, patients with T2 N0-2 M0-1 RCC treated with a nephrectomy were abstracted. Tumour size was evaluated according to several thresholds: 8, 9, 10, 11, and 12cm. Kaplan-Meier and life tables for cancer-specific mortality (CSM) were computed. Several Cox regression modes were fitted for prediction of CSM, using different thresholds. The predictive accuracy of various thresholds was compared using the area under the curve and methods of calibration. Results In all, 4963 patients were identified. Kaplan-Meier analyses showed statistically significant CSM-free survival differences between all examined thresholds. In multivariable Cox-regression models, all tested tumour size thresholds emerged as independent predictors of CSM. Of all thresholds, the values of 9 (0.55) and 11cm (0.55) achieved the highest discrimination in univariable analysis, followed by 10 (0.539), 12 (0.539), and 8cm (0.531). When the thresholds were combined with all other variables, the 11cm (0.688) achieved the highest discrimination. Conclusion The discriminant properties of all examined thresholds showed very similar discriminant properties, which brings into questioning whether a dichotomization of pT2 tumours is really necessary.

Background: Approximately 10-20% of recurrences in patients treated with nephrectomy for renal cell carcinoma (RCC) develop beyond 5 yr after surgery (late recurrence). Objective: To determine features associated with late recurrence. Design, setting, and participants: A total of 5009 patients from a multicenter database comprising 13 107 RCC patients treated surgically had a minimum recurrence-free survival of 60 mo (median follow-up [FU]: 105 mo [range: 78-135]); at last FU, 4699 were disease free (median FU: 103 mo [range: 78-134]), and 310 patients (6.2%) experienced disease recurrence (median FU: 120 mo [range: 93-149]). Interventions: Patients underwent radical nephrectomy or nephron-sparing surgery. Outcome measurements and statistical analysis: Multivariable regression analyses identified features associated with late recurrence. Cox regression analyses evaluated the association of features with cancer-specific mortality (CSM). Results and limitations: Lymphovascular invasion (LVI) (odds ratio [OR]: 3.07; p < 0.001), Fuhrman grade 3-4 (OR: 1.60; p = 0.001), and pT stage >pT1 (OR: 2.28; p < 0.001) were significantly associated with late recurrence. Based on accordant regression coefficients, these parameters were weighted with point values (LVI: 2 points; Fuhrman grade 3-4: 1 point, pT stage >1: 2 points), and a risk score was developed for the prediction of late recurrences. The calculated values (0 points: Late recurrence risk 3.1%; 1-3 points: 8.4%; 4-5 points: 22.1%) resulted in a good-, intermediate- and poor-prognosis group (area under the curve value for the model: 70%; 95% confidence interval, 67-73). Multivariable Cox regression analysis showed LVI (HR: 2.75; p < 0.001), pT stage (HR: 1.24; p < 0.001), Fuhrman grade (HR: 2.40; p < 0.001), age (HR: 1.01; p < 0.001), and gender (HR: 0.71; p = 0.027) to influence CSM significantly. Limitations are based on the multicenter and retrospective study design. Conclusions: LVI, Fuhrman grade 3/4, and a tumor stage >pT1 are independent predictors of late recurrence after at least 5 yr from surgery in patients with RCC. We developed a risk score that allows for prognostic stratification and individualized aftercare of patients with regard to counseling, follow-up scheduling, and clinical trial design. © 2012 European Association of Urology.

Fragestellung: Patienten mit Urothelkarzinom (UC) entwickeln häufig multifokale metachrone Tumoren im gesamten Harntrakt. In der vorliegenden Studie evaluierten wir die prognostische Bedeutung eines früheren UC der Harnblase (UCB) bei Patienten mit UC des oberen Harntrakts (UTUC) in einer [for full text, please go to the a.m. URL], 61. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie

OBJECTIVE. We tested relationship between pelvic lymph node dissection (PLND) status at the time of radical prostatectomy (RP) and survival in prostate cancer (PCa) patients. METHODS. Overall, 127,824 PCa patients treated with RP between 1988 and 2006 were included. Univariable and multivariable Cox regression analyses were used to evaluate the impact of PLND status (pN0 vs. pNx vs. pN1) on cancer-specific mortality (CSM) and overall mortality (OM) rates. RESULTS. In pT2 patients, the 5-, 10-, and 15-year CSM rates were: 0.4%, 1.7%, and 3.9% for pN0, 0.6%, 2.5%, and 4.7% for pNx, 2.7%, 11.9%, and 20.6% for pN1 patients (all P < 0.001). The 5-, 10-, and 15-year OM rates were: 5.4%, 16.3%, and 34.5% for pN0, 6.1%, 18.2%, and 35.3% for pNx, 11.5%, 32.7%, and 53.4% for pN1 (all P < 0.001). In multivariable analyses, pNx and pN1 stage increased CSM rate, respectively by 1.3- and 3.8-fold (both P < 0.001) relative to pN0. Similarly, pNx and pN1 increased OM rate respectively by 1.1- and 1.6-fold (both P < 0.001) relative to pN0. In pT3 patients, pNx stage did not significantly increase CSM or OM rates relative to pN0 (both P > 0.05). CONCLUSIONS. Patients with localized PCa treated with RP without a PLND (pNx) have less favorable survival rate than their counterparts that do not harbor lymph node invasion at PLND. However, the difference is modest (0.8% at 10 years). In consequence, the related costs and benefits of this procedure should be weighted carefully. In addition, the survival benefit of PLND was not observed in locally advanced PCa patients. Prostate 71: 1587-1594, 2011. (C) 2011 Wiley-Liss, Inc.

OBJECTIVE To assess the 2010 European Association of Urology (EAU) guidelines for prostate cancer, which recommend a pelvic lymph node dissection (PLND) at radical prostatectomy in all individuals with a nomogram-predicted lymph node invasion (LNI) risk of >7%. PATIENTS AND METHODS We focused on 1520 patients treated with radical prostatectomy and PLND, between 2006 and 2010, at a single European institution. We examined the ability of the EAU proposed threshold to correctly predict histologically confirmed LNI. Moreover, we tested the ability of a range of nomogram thresholds between 1 and 14% to correctly predict histologically confirmed LNI. Finally, we externally validated the EAU PLND guideline nomogram. RESULTS Overall, 10.6% of patients had LNI. The use of the 7% limit would have allowed the avoidance of 49% of PLNDs, at the cost of missing 11% of patients with LNI. The use of thresholds of 6% and 8% would have allowed the avoidance of respectively 46% and 52% of PLNDs, at the cost of missing respectively 9% and 11% of patients with LNI. Overall, the accuracy of the EAU guideline nomogram according to the receiver operating characteristics derived area under curve was 81% CONCLUSION Our observations indicate that the EAU guideline nomogram is highly accurate. The recommended threshold of 7%, above which a PLND should be performed, is associated with a favourable compromise between avoidable PLNDs and potentially missed LNI cases. OBJECTIVE To assess the 2010 European Association of Urology (EAU) guidelines for prostate cancer, which recommend a pelvic lymph node dissection (PLND) at radical prostatectomy in all individuals with a nomogram-predicted lymph node invasion (LNI) risk of >7%. PATIENTS AND METHODS We focused on 1520 patients treated with radical prostatectomy and PLND, between 2006 and 2010, at a single European institution. We examined the ability of the EAU proposed threshold to correctly predict histologically confirmed LNI. Moreover, we tested the ability of a range of nomogram thresholds between 1 and 14% to correctly predict histologically confirmed LNI. Finally, we externally validated the EAU PLND guideline nomogram. RESULTS Overall, 10.6% of patients had LNI. The use of the 7% limit would have allowed the avoidance of 49% of PLNDs, at the cost of missing 11% of patients with LNI. The use of thresholds of 6% and 8% would have allowed the avoidance of respectively 46% and 52% of PLNDs, at the cost of missing respectively 9% and 11% of patients with LNI. Overall, the accuracy of the EAU guideline nomogram according to the receiver operating characteristics derived area under curve was 81% CONCLUSION Our observations indicate that the EAU guideline nomogram is highly accurate. The recommended threshold of 7%, above which a PLND should be performed, is associated with a favourable compromise between avoidable PLNDs and potentially missed LNI cases.

Objectives: The contemporary ability of prostate -specific antigen (PSA) to predict pathologic stage in men with localized prostate cancer was recently questioned. Methods: We quantified the added value related to the addition of pretreatment PSA to established pathologic stage predictors (namely clinical stage and biopsy Gleason sum) in 5921 consecutive radical prostatectomy (RP) patients. Univariable and multivariable logistic regression analyses predicting pathologic stage (extracapsular extension [ECE], seminal vesicle invasion [SVI], lymph node invasion [LNI], and organ-confined disease [OC]) were stratified according to four time quartiles. The gain in predictive accuracy (PA) related to the inclusion of PSA to multivariable models was quantified by using the area under the curve method. Results: Temporal analyses showed a decrease in PSA levels over the study years (p < 0.001). Conversely, the rate of nonpalpable disease and the rate of biopsy Gleason sum < 6 increased over time (all p < 0.001). At RP, the rate of OC increased over time, while the rate of ECE and SVI decreased over time (all p < 0.001). The rate of LNI remained stable (p = 0.1). In multivariable models, PSA represented an independent predictor of all pathologic stages over time (all p < 0.03), except for ECE in the first and last time quartiles. The addition of PSA significantly increased the multivariable PA of all models predicting pathologic stages over time (all p < 0.03), except for ECE predictions in the first quartile (p = 0.1). Conclusions: In the new millennium, PSA has not lost its ability to accurately predict the pathologic stage in contemporary patients.

Context: The first European Association of Urology (EAU) guidelines on bladder cancer were published in 2002 [1]. Since then, the guidelines have been continuously updated. Objective: To present the 2013 EAU guidelines on non-muscle-invasive bladder cancer (NMIBC). Evidence acquisition: Literature published between 2010 and 2012 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the levels of evidence and grades of recommendation were assigned. Evidence synthesis: Tumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection (TUR) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TUR is essential for the patient's prognosis. Where the initial resection is incomplete, where there is no muscle in the specimen, or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. The risks of both recurrence and progression may be estimated for individual patients using the EORTC scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups is pivotal to recommending adjuvant treatment. For patients with a low-risk tumour, one immediate instillation of chemotherapy is recommended. Patients with an intermediate-risk tumour should receive one immediate instillation of chemotherapy followed by 1 yr of full-dose bacillus Calmette-Guerin (BCG) intravesical immunotherapy or by further instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. In patients at highest risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is recommended in BCG-refractory tumours. The long version of the guidelines is available from the EAU Web site: http://www.uroweb.org/guidelines/. Conclusions: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. Patient summary: The EAU Panel on Non-muscle Invasive Bladder Cancer released an updated version of their guidelines. Current clinical studies support patient selection into different risk groups; low, intermediate and high risk. These risk groups indicate the likelihood of the development of a new (recurrent) cancer after initial treatment (endoscopic resection) or progression to more aggressive (muscle-invasive) bladder cancer and are most important for the decision to provide chemo-or immunotherapy (bladder installations). Surgical removal of the bladder (radical cystectomy) should only be considered in patients who have failed chemo-or immunotherapy, or who are in the highest risk group for progression. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.