You have accessJournal of UrologyBladder Cancer: Superficial1 Apr 2014MP56-07 COMPARISON OF THE EORTC TABLES AND THE NEWLY INTRODUCED EAU CATEGORIES FOR RISK STRATIFICATION OF PATIENTS WITH NON-MUSCLE-INVASIVE BLADDER CANCER Malte Rieken, Shahrokh Shariat, Bashir Al Hussein Al Awamlh, Luis Kluth, Joseph Crivelli, James Chrystal, Talia Faison, Yair Lotan, Pierre Karakiewicz, Marek Babjuk, Harun Fajkovic, Christian Seitz, Tobias Klatte, Armin Pycha, Alexander Bachmann, Mithat Gönen, and Evanguelos Xylinas Malte RiekenMalte Rieken More articles by this author , Shahrokh ShariatShahrokh Shariat More articles by this author , Bashir Al Hussein Al AwamlhBashir Al Hussein Al Awamlh More articles by this author , Luis KluthLuis Kluth More articles by this author , Joseph CrivelliJoseph Crivelli More articles by this author , James ChrystalJames Chrystal More articles by this author , Talia FaisonTalia Faison More articles by this author , Yair LotanYair Lotan More articles by this author , Pierre KarakiewiczPierre Karakiewicz More articles by this author , Marek BabjukMarek Babjuk More articles by this author , Harun FajkovicHarun Fajkovic More articles by this author , Christian SeitzChristian Seitz More articles by this author , Tobias KlatteTobias Klatte More articles by this author , Armin PychaArmin Pycha More articles by this author , Alexander BachmannAlexander Bachmann More articles by this author , Mithat GönenMithat Gönen More articles by this author , and Evanguelos XylinasEvanguelos Xylinas More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1575AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives The EORTC scoring is used to stratify patients with TaT1 urothelial carcinoma of the bladder (UCB) into risk groups of disease recurrence and progression. In 2013, the European Association of Urology (EAU) Non-muscle invasive UCB guidelines introduced a simplified risk-group stratification. We aimed to characterize outcomes of TaT1 UCB patients stratified by the EAU categories and compared them to the EORTC risk-groups to assess the rate and effect of reclassification. Methods Multi-institutional database of 5122 patients with TaT1 UCB who underwent TURB with or without adjuvant therapy between 1996 and 2007. Multivariable Cox regression analyses addressed factors associated with disease recurrence and progression. The net reclassification index was used to compare the performance of the EAU categories with the EORTC scoring system. Results Of 5122 patients, 632 (12.3%), 2302 (45.0%) and 2188 (42.7%) were assigned to the low-, intermediate-, and high-risk EAU category, respectively. Within a median follow-up of 62 months (Interquartile range 27-97), 2365 (46.2%) and 516 (10.1%) patients experienced disease recurrence and progression, respectively. In multivariable Cox regression analyses adjusted for type of intravesical treatment, EAU intermediate- and high-risk categories were associated with a higher risk of disease recurrence (intermediate-risk: HR: 1.92, 95% CI 1.64-2.23, p<0.001; high-risk: HR: 2.09, 95% CI 1.79-2.45, p<0.001) and progression (intermediate-risk: HR: 3.84, 95% CI 2.09-7.08, p<0.001; high-risk: HR: 10.22, 95% CI 5.59-18.66, p<0.001) compared to low-risk patients, respectively. Comparison of the EORTC tables and the EAU categories revealed that the EAU categories reclassified 1940 (37.9%) patients into a higher risk group for recurrence. Likewise, 602 (11.8%) patients were reclassified to a higher and 278 (5.4%) patients were reclassified into a lower risk group for progression. The net reclassification index of the EAU risk stratification was 0.1% (95% CI -3.1% - 3.2%) for recurrence and 10.1% (95% CI -8.0% - 12.0%) for progression, respectively. Conclusions The novel risk stratification of the EAU for Non-muscle invasive UCB seems to represents a valid prognostic alternative to the EORTC tables for progression but not for recurrence. Despite this, it reclassifies many patients into higher risk-groups leading to a potential Will Rogers phenomenon. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e566 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Malte Rieken More articles by this author Shahrokh Shariat More articles by this author Bashir Al Hussein Al Awamlh More articles by this author Luis Kluth More articles by this author Joseph Crivelli More articles by this author James Chrystal More articles by this author Talia Faison More articles by this author Yair Lotan More articles by this author Pierre Karakiewicz More articles by this author Marek Babjuk More articles by this author Harun Fajkovic More articles by this author Christian Seitz More articles by this author Tobias Klatte More articles by this author Armin Pycha More articles by this author Alexander Bachmann More articles by this author Mithat Gönen More articles by this author Evanguelos Xylinas More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

OBJECTIVE:To assess the association between diabetes mellitus (DM) and metformin use with prognosis and outcomes of non-muscle-invasive bladder cancer (NMIBC) PATIENTS AND METHODS: We retrospectively evaluated 1117 patients with NMIBC treated at four institutions between 1996 and 2007. Cox regression models were used to analyse the association of DM and metformin use with disease recurrence, disease progression, cancer-specific mortality and any-cause mortality.RESULTS:Of the 1117 patients, 125 (11.1%) had DM and 43 (3.8%) used metformin. Within a median (interquartile range) follow-up of 64 (22-106) months, 469 (42.0%) patients experienced disease recurrence, 103 (9.2%) experienced disease progression, 50 (4.5%) died from bladder cancer and 249 (22.3%) died from other causes. In multivariable Cox regression analyses, patients with DM who did not take metformin had a greater risk of disease recurrence (hazard ratio [HR]: 1.45, 95% confidence interval [CI] 1.09-1.94, P = 0.01) and progression (HR: 2.38, 95% CI 1.40-4.06, P = 0.001) but not any-cause mortality than patients without DM. DM with metformin use was independently associated with a lower risk of disease recurrence (HR: 0.50, 95% CI 0.27-0.94, P = 0.03).CONCLUSION:Patients with DM and NMIBC who do not take metformin seem to be at an increased risk of disease recurrence and progression; metformin use seems to exert a protective effect with regard to disease recurrence. The mechanisms behind the impact of DM on patients with NMIBC and the potential protective effect of metformin need further elucidation.

Background: Few studies have investigated the natural history of TaG1 urothelial carcinoma of the bladder (UCB).Objective: To assess the long-term outcomes of patients with TaG1 UCB and the impact of immediate postoperative instillation of chemotherapy (IPIC).Design, setting, and participants: A retrospective analysis of 1447 patients with TaG1 UCB treated between 1996 and 2007 at eight centers. Median follow-up was 67.2 mo (interquartile range: 67.9). Patients were stratified into three European Association of Urology (EAU) guidelines risk categories; high-risk patients (n = 11) were excluded.Intervention: Transurethral resection of the bladder with or without IPIC.Outcome measurements and statistical analysis: Univariable and multivariable Cox regression models addressed factors associated with disease recurrence, disease progression, death of disease, and any-cause death.Results and limitations: Of the 1436 patients, 601 (41.9%) and 835 (58.1%) were assigned to low-and intermediate-risk categories, respectively. The actuarial estimate of 5-yr recurrence-free survival was 56% (standard error: +/- 1). Advancing age (p = 0.04), tumor > 3 cm (p = 0.001), multiple tumors (p < 0.001), and recurrent tumors (p < 0.001) were independently associated with increased risk of disease recurrence, whereas IPIC was associated with decreased risk (p = 0.001). The actuarial estimate of 5-yr progression-free survival was 95% +/- 1. Advancing age (p < 0.001) and multiple tumors (p = 0.01) were independent risk factors for disease progression. Five-year cancer-specific survival was 98% +/- 1. Advancing age (p = 0.001) and previous recurrence (p = 0.04) were associated with increased risk, whereas female gender (p = 0.02) was associated with decreased risk of cancer-specific mortality. Compared with low-risk patients, intermediate-risk patients were at significantly higher risk of disease recurrence, disease progression, and cancer-specific mortality (all p < 0.01). Limitations include the retrospective design of the study and the lack of a central pathology review.Conclusions: TaG1 UCB patients experience heterogeneous risks of disease recurrence. We validated the EAU guidelines risk stratification in TaG1 UCB patients. IPIC was associated with a reduced risk of disease recurrence in patients with low-and intermediate-risk TaG1 UCB. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Objectives: Evidence suggests a positive effect of metfoimin on cancer incidence and outcome. To date, the effect of metfoimin use on prognosis in urothelial carcinoma of the bladder (UCB) remains uninvestigated. We tested the hypothesis that metformin use affects oncologic outcomes of patients treated with radical cystectomy for UCB.Methods and materials: We retrospectively evaluated 1,502 patients treated at 4 institutions with radical cystectomy and pelvic lymphadenectomy without neoadjuvant therapy. Cox regression models addressed the association of diabetes mellitus (DM) and metformin use with disease recurrence, cancer-specific mortality, and any-cause mortality.Results: A total of 200 patients (13.3%) had DM, 80 patients (5.3%) used metformin. Within a median follow-up of 34 months, 509 patients (33.9%) experienced disease recurrence, 402 patients (26.8%) died of UCB, and 551 patients (36.7%) died from any cause. In univariable Cox regression analyses, DM without metfonnin use was associated with increased risk of disease recurrence (hazard ratio RIR]: 1.40, 95% confidence interval ICII 1.05 1.87, P = 0.02), cancer-specilic mortality (HR: 1.60, 95% CI 1.17 2.17, P = 0.003), and any-cause mortality (HR: 1.55, 95% CI 1.18 2.03, P = 0.002), whereas mettOrmin use was associated with decreased risk of disease recurrence (IIR: 0.61. 95% CI 0.37 0.98, P = 0.04), cancer-specific mortality (11R: 0.56, 95% CI 0.33 0.97, P = 0.04), and any-cause mortality (IIR: 0.54, 95% CI 0.33 0.88, P = 0.01). In multivariable Cox regression analyses, DM treated without metformin use remained associated with worse cancer-specific mortality (HR: 1.53, 95% CI 1.12-2.09, P = 0.007) and any-cause mortality (HR: 1.52, 95% CI 1.16-2.00, P = 0.003) but not disease recurrence.Conclusions: Diabetic patients who do not use metformin appear to be at higher risk of cancer-specific and any-cause mortality than patients without DM. It remains unclear, whether the severity of DM in this group of patients or the use of metformin itself affects outcomes of UCB. The mechanisms behind the effect of DM on patients with UCB and the potential protective effect of metformin need further elucidation. (C) 2014 Elsevier Inc. All rights reserved.

The impact of diabetes mellitus (DM) and metformin use on biochemical recurrence (BCR) in patients treated with radical prostatectomy (RP) remains controversial.

OBJECTIVE:To investigate the impact of variant histologies of urothelial carcinoma of the bladder (UCB) on oncologic outcomes after radical cystectomy (RC).MATERIALS AND METHODS:Data from 1984 UCB patients treated by RC without preoperative chemo- or radiotherapy were reviewed for histological differentiation and variants. We analysed the differences between pure UCB and UCB with variant histology, and those between the different histological variants using various stratifications.RESULTS:Overall, 488 (24.6%) patients had UCB variants with squamous cell (11.4%) and glandular differentiation (3.8%) being the most common. Histological UCB variants were associated with advanced tumour stage, lymphovascular invasion and lymph node metastasis (all p-values<0.01) when compared to pure UCB. In univariable analyses, patients with non-squamous UCB variants were at significantly higher risk for disease recurrence and cancer-specific mortality than those with pure UCB patients (p-values=0.001) and those with squamous cell differentiated UCB (p-values=0.04); the latter two had the same risk. In multivariable analyses that adjusted for the effects of standard clinicopathologic characteristics, variant UCB histology was not associated with both survival end-points. In patients treated with adjuvant chemotherapy (n=492) there was no difference in cancer-specific survival between pure UCB, squamous cell differentiated UCB and other histological UCB variants.CONCLUSIONS:A quarter of UCB patients treated with RC harboured histological UCB variants. Variant UCB histologies were associated with features of biologically aggressive disease. While variant UCB histology was associated with worse outcomes in univariable analyses, this effect did not remain significant in multivariable analyses.

Purpose: The role of lymph node dissection is still controversial in patients treated with radical nephroureterectomy for upper tract urothelial cancer. We developed a pathological nodal staging model that allows quantification of the likelihood that a patient with pathologically node negative disease has, indeed, no lymph node metastasis.Materials and Methods: We analyzed data on 814 patients treated with radical nephroureterectomy and lymph node dissection, and estimated the sensitivity of pathological nodal staging using a beta-binomial model. We developed a pathological nodal staging score that represents the probability that a case is correctly staged as node negative.Results: A median of 5 lymph nodes (range 1 to 46) was removed and 593 patients (73%) had pN0 disease. The probability of missing lymph node metastasis decreased as the number of nodes examined increased. If only a single node was examined, 44% of patients would have been misclassified as having pN0 disease while harboring lymph node metastasis. Even when 5 nodes were examined, 12% of patients would have been misclassified. The proportion of those with a positive node increased with advancing pathological T stage and lymphovascular invasion. Patients with pT0-Ta-Tis-T1/lynaphovascular invasion had more than a 95% chance of correct pathological nodal staging with 2 examined nodes. However, if a patient had pT3-T4 and positive lymphovascular invasion, even 20 examined lymph nodes did not attain 95% accuracy.Conclusions: Lymph node dissection provides more accurate staging and prediction of survival. The number of examined nodes needed for adequate staging depends on pT stage and lymphovascular invasion. We developed a tool to estimate the likelihood of false-negative lymph node metastasis, which could help refine clinical decision making regarding the administration of adjuvant chemotherapy.

What's known on the subject? and What does the study add? Lymph node (LN) metastasis is a critical predictor for disease recurrence and cancer‐specific survival in patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy. Patients with a low LN disease burden (pN1) might be cured by surgery alone, while patients with a high LN disease burden (stage ≥ pN2) might benefit most from adjuvant chemotherapy. We found that outcomes of patients with pN1 UCB are significantly affected by pathological stage and soft tissue surgical margin status. Our nomogram may help to improve outcomes prediction in patients with pN1 UCB. An accurate prediction of the individual risk of outcomes may help risk stratifying patients with pN1 UCB to help improve clinical decision‐making. Objectives To identify clinicopathological factors that predict outcomes in patients with a single lymph node (LN) metastasis (pN1) treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). LN metastasis is an established predictor of clinical outcomes in patients. While most patients with large LN burden experience disease recurrence, lymphadenectomy can be curative in patients with pN1 disease. Patients and Methods We analysed 381 patients with pN1 UCB from a multi‐institutional cohort of 4335 patients with UCB treated with RC and lymphadenectomy without preoperative chemo‐ or radiotherapy. Subgroup analyses were performed for patients with ≥9 LNs removed and according to adjuvant chemotherapy administration (n = 215). Results The median (interquartile range, IQR) LN number was 15 (19) and the median (IQR) LN density was 6.7 (7.5)%. Within a median follow‐up of 41 months, the mean (+/− sd) 2‐ and 5‐year cancer‐specific survival (CSS) rates were 55 (3)% and 46 (3)%, respectively. On multivariable analysis that adjusted for the effects of standard clinicopathological features, female gender (hazard ratio [HR] 1.48, P = 0.023), higher tumour stage (HR 1.68, P = 0.007), positive soft tissue surgical margin (STSM; HR 2.06, P = 0.004), higher LN density (HR 2.99, P = 0.025) and absence of adjuvant chemotherapy (HR 0.70, P = 0.026) were independently associated with CSS. In subgroup analyses of patients with ≥9 LNs removed, tumour stage and STSM status remained independent predictors for CSS (P = 0.009 and P < 0.001, respectively). Conclusions About half of the patients with pN1 UCB died from UCB within 5 years of RC. Pathological stage and STSM status are strong predictors for outcomes. Accurate prediction of the individual risk of CSS may help risk stratifying pN1 UCB in order to help improve clinical‐decision making. Patients with pN1 UCB presenting with additional unfavourable risk factors need a closer follow‐up scheduling and might receive adjuvant therapy.

Background: Lymph node metastasis (LNM) is the most powerful pathologic predictor of disease recurrence after radical cystectomy (RC). However, the outcomes of patients with LNM are highly variable.Objective: To assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters.Design, setting, and participants: A retrospective analysis of 748 patients with urothelial carcinoma of the bladder and LNM treated with RC and lymphadenectomy without neoadjuvant therapy at 10 European and North American centers (median follow-up: 27 mo).Intervention: All subjects underwent RC and bilateral pelvic lymphadenectomy.Outcome measurements and statistical analysis: Each LNM was microscopically evaluated for the presence of ENE. The number of LNs removed, number of positive LNs, and LN density were recorded and calculated. Univariable and multivariable analyses addressed time to disease recurrence and cancer-specific mortality after RC.Results and limitations: A total of 375 patients (50.1%) had ENE. The median number of LNs removed, number of positive LNs, and LN density were 15, 2, and 15, respectively. The rate of ENE increased with advancing pT stage (p < 0.001). In multivariable Cox regression analyses that adjusted for the effects of established clinicopathologic features and LN parameters, ENE was associated with disease recurrence (hazard ratio [HR]: 1.89; 95% confidence interval [CI], 1.55-2.31; p < 0.001) and cancer-specific mortality (HR: 1.90; 95% CI, 1.52-2.37; p < 0.001). The addition of ENE to a multivariable model that included pT stage, tumor grade, age, gender, lymphovascular invasion, surgical margin status, LN density, number of LNs removed, number of positive LNs, and adjuvant chemotherapy improved predictive accuracy for disease recurrence and cancer-specific mortality from 70.3% to 77.8% ( p < 0.001) and from 71.8% to 77.8% ( p = 0.007), respectively. The main limitation of the study is its retrospective nature.Conclusions: ENE is an independent predictor of both cancer recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of ENE status could help with patient counseling, clinical decision making regarding inclusion in clinical trials of adjuvant therapy, and tailored follow-up scheduling after RC. (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.