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ABSTRACT: CONTEXT: Postoperative paralytic ileus (POI) has profound clinical consequences because it represents a substantial burden on both patients and health care resources. OBJECTIVE: To determine the knowledge base regarding POI in the radical cystectomy (RC) population with an emphasis on preventive measures and risk factors. EVIDENCE ACQUISITION: A systematic literature search of Medline (1966 to February 2011) and a study review were conducted. Eligible studies explicitly reported the incidence of POI and/or at least two quantitative measures of gastrointestinal recovery. EVIDENCE SYNTHESIS: The search identified 727 relevant articles; 77 met eligibility criteria, comprising 13 793 patients. Of these, 21 used explicit definitions of POI, and they varied widely. Across studies, the incidence of POI ranged from 1.58% to 23.5%. Possible risk factors for POI included increasing age and body mass index. Seventeen studies reported effects of an intervention on POI: 3 randomized controlled studies, 11 observational cohort studies with concurrent comparison, and 3 observational cohort studies with nonconcurrent comparison. Gum chewing was associated with shortened times to flatus (2.4 vs 2.9 d; p<0.0001) and bowel movement (BM) (3.2 vs 3.9 d; p<0.001) in one observational cohort study (n=102); omission of a postoperative nasogastric tube (NGT) was associated with shorter time to flatus (4.21 vs 5.33 d; p=0.0001) and shorter length of stay (14.4 vs 19.1 d; p=0.001) in one observational cohort study (n=430); and the routine use of bowel preparation was associated with an increased incidence of POI (5% vs 19%) in another series (n=86). Additionally, readaptation of the dorsolateral peritoneal layer was shown to shorten times to flatus (p=0.016) and times to BM (p=0.011) in one randomized controlled study (n=200). CONCLUSIONS: The incidence/definition of POI after RC is highly variable. An improved reporting strategy is needed to identify true incidence and risk factors, and to guide future research for both potential preventive and therapeutic interventions.
European urology 12/2012; · 7.67 Impact Factor
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ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: No cost-effectiveness studies exist in patients after radical cystectomy for the routine use of alvimopan for the prevention of postoperative ileus. The present study provides a reasonable estimate of the cost-effectiveness of alvimopan for the prevention of postoperative ileus in the patient after radical cystectomy. OBJECTIVE: To determine if the cost of administering alvimopan, to help restore bowel function after abdominal surgery, to all patients undergoing radical cystectomy (RC) is cost prohibitive. PATIENTS AND METHODS: A cost-effective analysis was conducted from a healthcare payer perspective using a decision-tree model that incorporated direct healthcare costs and probabilities associated with the possible events and outcomes. Sensitivity analyses were conducted on the influence of the cost and effectiveness of the drug, the probability of POI in RC patients, and the extended length of stay (LOS) as a result of POI. Precision in estimates was determined using probabilistic sensitivity analyses with 5000 Monte-Carlo simulations. RESULTS: Under the base case assumption, the additional cost of a patient's LOS related to POI was $10 246 per person. Under the assumption that 15.6% of patients will have POI, the mean cost associated with POI in a cohort of patients not treated with alvimopan was $1597 (90% confidence interval [CI] $1335-1875) per patient. Conversely, the routine use of alvimopan for all patients undergoing RC was associated with a mean POI-associated cost of $1495(90% CI $1312-1696) per person, which represents the cost of alvimopan ($700 per hospitalisation) and a 50% reduction in the rate of POI. Sensitivity analyses revealed that there is a cost savings with the routine use of alvimopan under the following conditions: the POI results in extending LOS by ≥3.5 days, POI occurs in ≥14% of patients undergoing RC, or the drug results in a relative risk reduction of ≥44%. CONCLUSIONS: Routine use of perioperative alvimopan may not be cost prohibitive because of its influence on POI rate and associated costs. The cost-effectiveness of alvimopan is influenced by the POI incidence and the degree to which the drug can decrease the LOS.
BJU International 11/2012; · 2.84 Impact Factor
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Evanguelos Xylinas,
Michael Rink,
Giacomo Novara,
David A Green,
Thomas Clozel,
Hans-Martin Fritsche,
Bertrand Guillonneau,
Yair Lotan,
Wassim Kassouf,
Derya Tilki,
Marek Babjuk,
Pierre I Karakiewicz,
Francesco Montorsi,
Joual Abdennabi,
Quoc D Trinh, Robert S Svatek,
Douglas S Scherr,
Marc Zerbib,
Shahrokh F Shariat
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ABSTRACT: BACKGROUND: The presence of positive soft tissue surgical margins (STSM) at radical cystectomy (RC) is rare. Although some patients with STSM experience disease recurrence rapidly, some have long-term local disease control. We sought to describe the oncologic outcomes, identify predictors, and assess the impact of location and multifocality in patients with positive STSMs at RC. METHODS: We retrospectively collected the data of 4,335 patients treated with RC and pelvic lymphadenectomy at 11 academic centers from 1981 to 2008. STSM was defined as the presence of tumor at inked areas of soft tissue on the RC specimen. Univariate and multivariate Cox regression models addressed recurrence-free survival and cancer-specific survival after surgery. RESULTS: STSM were identified in 231 patients (5 %). Actuarial recurrence-free survival estimates at 2 and 5 years after RC were 26 ± 3 and 21 ± 3 %, respectively. Actuarial cancer-specific survival estimates at 2 and 5 years after RC were 33 ± 3 and 25 ± 4 %, respectively. Higher body mass index (p = 0.050), higher tumor stage (p = 0.017), presence of grade 3 disease (p = 0.046), lymphovascular invasion (p = 0.003), and lymph node involvement (p = 0.003) were all independently associated with disease recurrence. Furthermore, higher tumor stage (p = 0.015), lymphovascular invasion (p = 0.006), and lymph node involvement (p = 0.006) were independently associated with cancer specific mortality. Location and multifocality of STSM were not associated with outcomes. CONCLUSIONS: Although most patients with STSM at RC had poor outcomes, more than one-fifth had durable cancer control. Pathologic features associated with disease recurrence in the general RC population also stratify patients with STSM into differential risk groups.
Annals of Surgical Oncology 10/2012; · 4.17 Impact Factor
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Ashish M Kamat,
Paul K Hegarty,
Jason R Gee,
Peter E Clark, Robert S Svatek,
Nicholas Hegarty,
Shahrokh F Shariat,
Evanguelos Xylinas,
Bernd J Schmitz-Dräger,
Yair Lotan,
Lawrence C Jenkins,
Michael Droller,
Bas W van Rhijn,
Pierre I Karakiewicz
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ABSTRACT: CONTEXT AND OBJECTIVE: To present a summary of the 2nd International Consultation on Bladder Cancer recommendations on the screening, diagnosis, and markers of bladder cancer using an evidence-based strategy. EVIDENCE ACQUISITION: A detailed Medline analysis was performed for original articles addressing bladder cancer with regard to screening, diagnosis, markers, and pathology. Proceedings from the last 5 yr of major conferences were also searched. EVIDENCE SYNTHESIS: The major findings are presented in an evidence-based fashion. Large retrospective and prospective data were analyzed. CONCLUSIONS: Cystoscopy alone is the most cost-effective method to detect recurrence of bladder cancer. White-light cystoscopy is the gold standard for evaluation of the lower urinary tract; however, technology like fluorescence-aided cystoscopy and narrow-band imaging can aid in improving evaluations. Urine cytology is useful for the diagnosis of high-grade tumor recurrence. Molecular medicine holds the promise that clinical outcomes will be improved by directing therapy toward the mechanisms and targets associated with the growth of an individual patient's tumor. The challenge remains to optimize measurement of these targets, evaluate the impact of such targets for therapeutic drug development, and translate molecular markers into the improved clinical management of bladder cancer patients. Physicians and researchers eventually will have a robust set of molecular markers to guide prevention, diagnosis, and treatment decisions for bladder cancer.
European urology 10/2012; · 7.67 Impact Factor
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Michael Rink,
Shahrokh F Shariat,
Evanguelos Xylinas,
John P Fitzgerald,
Jens Hansen,
David A Green,
Ashish M Kamat,
Giacomo Novara,
Siamak Daneshmand,
Yves Fradet, [......],
Pierre I Karakiewicz,
Hans-Martin Fritsche,
Derya Tilki,
Felix K Chun,
Bjoern G Volkmer,
Marko Babjuk,
Axel S Merseburger,
Douglas S Scherr,
Yair Lotan, Robert S Svatek
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ABSTRACT: PURPOSE: To determine whether the number of lymph nodes (LNs) examined is associated with outcomes in patients without nodal metastasis after radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analyzed data from 4,188 patients treated at 12 centers with RC and pelvic lymphadenectomy without neo-adjuvant chemotherapy for urothelial carcinoma of the bladder (UCB). Outcomes of patients without LN metastasis (n = 3,088) were examined according to the LN yield analyzed as continuous variable, tertiles, and using the cutoffs of ≥9 and ≥20. RESULTS: The median nodal yield was 18 (range 1-123; IQR:20). A total of 2591 (84 %) and 1445 (47 %) patients had a LN yield ≥9 and ≥20, respectively. Median follow-up was 47 months (IQR:70). In multivariable analyses that adjusted for the standard clinicopathologic factors, higher LN yield was associated with a decreased risk of disease recurrence (continuous: HR = 0.996, p = 0.05; 3rd vs 1st tertile: HR = 0.853, p = 0.048; cutoff ≥20: HR = 0.851, p = 0.032). In the subgroups of patients with muscle-invasive UCB or those with ≥9 LN removed, LN yield was not associated with outcomes (p values >0.05). CONCLUSIONS: In this large multicenter cohort of patients with node-negative UCB, higher nodal yield improved recurrence-free survival when all patients were analyzed. Patients with a high LN yield (≥20 LN removed or 3rd tertile) had the largest benefit. The lack of prognostic significance of LN yield in patients with muscle-invasive UCB or those stratified by 9 LNs removed suggests that this effect is weak. Further prospective studies are needed to help identify preoperatively the optimal template for each patient.
World Journal of Urology 07/2012; · 2.41 Impact Factor
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Harun Fajkovic,
Eugene K Cha,
Claudio Jeldres,
Brian D Robinson,
Michael Rink,
Evanguelos Xylinas,
Thomas F Chromecki,
Eckart Breinl, Robert S Svatek,
Gerhard Donner, [......],
Pierre I Karakiewicz,
Bjoern G Volkmer,
Giacomo Novara,
Abdennabi Joual,
Talia Faison,
Guru Sonpavde,
Siamak Daneshmand,
Yair Lotan,
Douglas S Scherr,
Shahrokh F Shariat
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ABSTRACT: 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.
European urology 07/2012; · 7.67 Impact Factor
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Michael Rink,
Jens Hansen,
Eugene K Cha,
David A Green,
Marko Babjuk, Robert S Svatek,
Evanguelos Xylinas,
Scott T Tagawa,
Talia Faison,
Giacomo Novara, [......],
Wassim Kassouf,
Hans-Martin Fritsche,
Armin Pycha,
Evi Comploj,
Derya Tilki,
Patrick J Bastian,
Felix K Chun,
Roland Dahlem,
Douglas S Scherr,
Shahrokh F Shariat
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ABSTRACT: Study Type - Therapy (outcomes) Level of Evidence 2b 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.
BJU International 07/2012; · 2.84 Impact Factor
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Thomas F Chromecki,
Eugene K Cha,
Harun Fajkovic,
Michael Rink,
Behfar Ehdaie, Robert S Svatek,
Pierre I Karakiewicz,
Yair Lotan,
Derya Tilki,
Patrick J Bastian, [......],
Wassim Kassouf,
Matthieu Durand,
Giacomo Novara,
Hans-Martin Fritsche,
Maximilian Burger,
Jonathan I Izawa,
Antonin Brisuda,
Marek Babjuk,
Karl Pummer,
Shahrokh F Shariat
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ABSTRACT: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Little is known on the association between obesity and urothelial carcinoma of the bladder (UCB). Most studies have shown that higher body mass index (BMI) is associated with higher rates of perioperative complications. Only one study specifically investigated obesity and bladder cancer-specific outcomes and reported no significant association between higher BMI and disease-specific survival in patients with UCB treated with radical cystectomy. However, that study was limited by its small sample size and a high rate of preoperative therapies. In contrast to the only previous study evaluating the association of BMI with oncological outcomes in UCB, we found that obesity (BMI ≥30 kg/m(2) ) was associated with features of biologically aggressive UCB and clinical outcomes after radical cystectomy and, even when adjusting for the effects of standard clinicopathological features, obesity remained an independent predictor of cancer recurrence, cancer-specific mortality and overall mortality. OBJECTIVE: • To investigate the association between body mass index (BMI) and oncological outcomes in patients after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) in a large multi-institutional series. PATIENTS AND METHODS: • Data were collected from 4118 patients treated with RC and pelvic lymphadenectomy for UCB. Patients receiving preoperative chemotherapy or radiotherapy were excluded. • Univariable and multivariable models tested the effect of BMI on disease recurrence, cancer-specific mortality and overall mortality. • BMI was analysed as a continuous and categorical variable (<25 vs 25-29 vs ≥30 kg/m(2) ). RESULTS: • Median BMI was 28.8 kg/m(2) (interquartile range 7.9); 25.3% had a BMI <25 kg/m(2) , 32.5% had a BMI between 25 and 29.9 kg/m(2) , and 42.2% had a BMI ≥30 kg/m(2) . • Patients with a higher BMI were older (P < 0.001), had higher tumour grade (P < 0.001), and were more likely to have positive soft tissue surgical margins (P = 0.006) compared with patients with lower BMI. • In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI >30 was associated with higher risk of disease recurrence (hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.46-1.91, P < 0.001), cancer-specific mortality (HR 1.43, 95% CI 1.24-1.66, P < 0.001), and overall mortality (HR 1.81, CI 1.60-2.05, P < 0.001). The main limitation is the retrospective design of the study. CONCLUSIONS: • Obesity is associated with worse cancer-specific outcomes in patients treated with RC for UCB. • Focusing on patient-modifiable factors such as BMI may have significant individual and public health implications in patients with invasive UCB.
BJU International 06/2012; · 2.84 Impact Factor
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Shahrokh F Shariat,
Michael Rink,
Behfar Ehdaie,
Evanguelos Xylinas,
Marek Babjuk,
Axel S Merseburger, Robert S Svatek,
Eugene K Cha,
Scott T Tagawa,
Harun Fajkovic, [......],
Quoc-Dien Trinh,
Siamak Daneshmand,
Yair Lotan,
Wassim Kassouf,
Hans-Martin Fritsche,
Felix K Chun,
Guru Sonpavde,
Abdennabi Joual,
Douglas S Scherr,
Mithat Gonen
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ABSTRACT: BACKGROUND: Radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the standard of care for high-risk non-muscle-invasive and muscle-invasive bladder cancer (BCa). OBJECTIVE: To develop a model that allows quantification of the likelihood that a pathologically node-negative patient has, indeed, no positive nodes. DESIGN, SETTING, AND PARTICIPANTS: We analyzed data from 4335 patients treated with RC and PLND without neoadjuvant chemotherapy at 12 international academic centers. INTERVENTIONS: Patients underwent RC and PLND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed a pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative as a function of the number of examined nodes. RESULTS AND LIMITATIONS: Overall, the probability of missing a positive node decreases with the increasing number of nodes examined (52% if 3 nodes are examined, 40% if 5 are examined, and 26% if 10 are examined). The proportion of having a positive node increased proportionally with advancing pathologic T stage and lymphovascular invasion (LVI). Patients with LVI who had 25 examined nodes would have a pNSS of 80% (pT1), 88% (pT2), and 66% (pT3-T4), whereas 10 examined nodes were sufficient for pNSS exceeding 90% in patients without LVI and pT0-T2 tumors. This study is limited because of its retrospective design and multicenter nature. CONCLUSIONS: We developed a tool that estimates the likelihood of lymph node (LN) metastasis in BCa patients treated with RC by evaluating the number of examined nodes, the pathologic T stage, and LVI. The pNSS indicates the adequacy of nodal staging in LN-negative patients. This tool could help to refine clinical decision making regarding adjuvant chemotherapy, follow-up scheduling, and inclusion in clinical trials.
European urology 06/2012; · 7.67 Impact Factor
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European urology 05/2012; 61(5):1062-3. · 7.67 Impact Factor
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Michael Rink,
Behfar Ehdaie,
Eugene K Cha,
David A Green,
Pierre I Karakiewicz,
Marko Babjuk,
Vitaly Margulis,
Jay D Raman, Robert S Svatek,
Harun Fajkovic, [......],
Giacomo Novara,
Jens Hansen,
Siamak Daneshmand,
Yair Lotan,
Wassim Kassouf,
Hans-Martin Fritsche,
Armin Pycha,
Margit Fisch,
Douglas S Scherr,
Shahrokh F Shariat
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ABSTRACT: Dissimilarities in management and outcomes exist between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB).
The aim of this study was to analyze the stage-specific impact of upper or lower urinary tract tumor location on oncologic outcomes.
Data were collected from 4335 patients with UCB treated with radical cystectomy (RC) and bilateral pelvic lymphadenectomy (PLND), 877 patients with ureteral UTUC, and 1615 with pelvicalyceal UTUC treated with radical nephroureterectomy (RNU). No patient received preoperative chemotherapy or radiation therapy.
Patients were treated with RC and bilateral PLND or RNU.
Outcomes were assessed according to primary tumor location.
Compared to UTUC patients, UCB patients had more advanced tumor stage and higher grade, and they were more likely to harbor lymphovascular invasion (LVI) and lymph node metastasis (p<0.001). In non-muscle-invasive tumor stages, UCB patients were more likely to experience disease recurrence and mortality compared to renal pelvicalyceal tumor patients (p<0.002) but not ureteral tumors (p>0.05). In pT2 and pT3 tumors, there was no difference in outcomes between the three tumor locations. In pT4 tumors, patients with ureteral and pelvicalyceal tumors were more likely to experience disease recurrence and mortality compared to UCB patients (p<0.004). These stage-specific findings were unchanged after adjustment for the effects of age, gender, tumor grade, LVI, lymph node status, and adjuvant chemotherapy. This study is limited by its retrospective and multicenter nature.
Stage-specific differences in outcomes exist between UCB and UTUC. The differentially worse outcomes by stage between UCB and UTUC patients underline the differences between both cancer entities and the need for individualized stage-specific management for each patient.
European urology 02/2012; 62(4):677-84. · 7.67 Impact Factor
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Shahrokh F Shariat,
Behfar Ehdaie,
Michael Rink,
Eugene K Cha, Robert S Svatek,
Thomas F Chromecki,
Harun Fajkovic,
Giacomo Novara,
Scott G David,
Siamak Daneshmand, [......],
Hans-Martin Fritsche,
Maximilian Burger,
Jonathan I Izawa,
Derya Tilki,
Firas Abdollah,
Felix K Chun,
Guru Sonpavde,
Pierre I Karakiewicz,
Douglas S Scherr,
Mithat Gonen
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ABSTRACT: Radical cystectomy (RC) with pelvic lymph node dissection (LND) is the standard of care for refractory non-muscle-invasive and muscle-invasive bladder cancer. Although consensus exists on the need for LND, its extent is still debated.
To develop a model that allows preoperative determination of the minimum number of lymph nodes (LNs) needed to be removed at RC to ensure true nodal status.
We analyzed data from 4335 patients treated with RC and pelvic LND without neoadjuvant chemotherapy at 12 academic centers located in the United States, Canada, and Europe.
We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed clinical (preoperative) nodal staging scores (cNSS), which represent the probability that a patient has LN metastasis as a function of the number of examined nodes.
The probability of missing a positive LN decreased with an increasing number of nodes examined (52% if 3 nodes were examined, 40% if 5 were examined, and 26% if 10 were examined). A cNSS of 90% was achieved by examining 6 nodes for clinical Ta-Tis tumors, 9 nodes for cT1 tumors, and 25 nodes for cT2 tumors. In contrast, examination of 25 nodes provided only 77% cNSS for cT3-T4 tumors. The study is limited due to its retrospective design, its multicenter nature, and a lack of preoperative staging parameters.
Every patient treated with RC for bladder cancer needs an LND to ensure accurate nodal staging. The minimum number of examined LNs for adequate staging depends preoperatively on the clinical T stage. Predictive tools can give a preoperative estimation of the likelihood of nodal metastasis and thereby allow tailored decision-making regarding the extent of LND at RC.
European urology 02/2012; 61(2):237-42. · 7.67 Impact Factor
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Robert S Svatek,
Jonathan E Rosenberg,
Matthew D Galsky,
Cheryl T Lee,
David M Latini,
Bernard H Bochner,
Alon Z Weizer,
Andrea B Apolo,
Srikala S Sridhar,
Ashish M Kamat,
Donna Hansel,
Thomas W Flaig,
Norm D Smith,
Yair Lotan
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ABSTRACT: The 6th Annual Bladder Cancer Think Tank brought together a multidisciplinary group of clinicians, researchers, and representatives from the National Cancer Institute and Industry in an effort to advance bladder cancer research efforts. This year's meeting comprised panel discussions and research involving 5 separate working groups, including the Survivorship, Clinical Trials, Standardization of Care, Data Mining, and Translational Science working groups. In this manuscript, the accomplishments and objectives of the working groups are summarized. Notable efforts include: (1) the development of a survivorship care plan for early and late-stage bladder cancer; (2) the development of consensus criteria for eligibility and endpoints for bladder cancer clinical trials; (3) an improved understanding of current practice patterns regarding the use of perioperative chemotherapy in an effort to standardize care; (4) creation of a comprehensive handbook to assist researchers with developing bladder cancer databases; and (5) identification of response to therapy of high-grade non muscle invasive disease through a collaborative exchange of expertise and resources.
Urologic Oncology 01/2012; · 3.22 Impact Factor
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Yair Lotan,
Gilad Amiel,
Stephen A Boorjian,
Peter E Clark,
Michael Droller,
Jeffrey R Gingrich,
Thomas J Guzzo,
Brant A Inman,
Ashish M Kamat,
Larry Karsh,
Matthew E Nielsen,
Norm D Smith,
Shahrokh F Shariat, Robert S Svatek,
Jennifer M Taylor
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ABSTRACT: OBJECTIVE: In an effort to standardize data collection for research regarding bladder cancer, the Bladder Cancer Working Group sought to provide a handbook that can be used as a guide for prospective or retrospective data collection. METHODS: Expert opinions for various data groups were compiled through a team of researchers at the BCAN. Peer review of each data group was performed from within the group. RESULTS: Essential and comprehensive data elements are provided for 9 groups of data elements, including demographics, comorbidities, staging, laboratory data, operative details, pathology, complications, outcomes, and quality of life measurements. CONCLUSIONS: Establishment of a comprehensive bladder cancer database is important in initiating multicenter collaborations. While not every data point is critical, this review may be useful in serving as a reference in initiating projects and providing a framework for collaborations.
Urologic Oncology 11/2011; · 3.22 Impact Factor
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Thomas F Chromecki,
Julian Mauermann,
Eugene K Cha, Robert S Svatek,
Harun Fajkovic,
Pierre I Karakiewicz,
Yair Lotan,
Derya Tilki,
Patrick J Bastian,
Bjoern G Volkmer, [......],
Wassim Kassouf,
Giacomo Novara,
Hans-Martin Fritsche,
Vincenzo Ficarra,
Christian G Stief,
Colin P Dinney,
Eila Skinner,
Karl Pummer,
Yves Fradet,
Shahrokh F Shariat
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ABSTRACT: PURPOSE: Small studies have suggested that older patients have worse outcomes following radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). We evaluated the association of patient age with clinical outcomes in a large multi-institutional RC series. METHODS: Data were collected from 4,429 patients treated with RC and lymphadenectomy for UCB without neoadjuvant chemotherapy. Age at RC was analyzed both as a continuous and categorical variable. RESULTS: Higher age at RC, analyzed as a continuous or categorical variable, was associated with advanced pathologic stage (P < 0.001), higher tumor grade (P = 0.045), presence of lymphovascular invasion (P = 0.018), and positive soft-tissue surgical margin status (P = 0.004). Elderly patients were less likely to receive postoperative chemotherapy (P < 0.001). In multivariable analyses, higher age was associated with disease recurrence, cancer-specific, and overall mortality (P < 0.001). Patients ≥80 years had a significantly greater risk of cancer-specific mortality than patients <50 years (HR 1.763, P < 0.001). Age minimally improved the accuracy of a base model that included standard pathologic features for prediction of disease recurrence (+0.2-0.3%) and cancer-specific survival (+0.3%). Conversely, age improved the predictive accuracy for overall survival by a sizeable margin (+4.2-4.5%). CONCLUSIONS: This large external validation study confirms that advanced patient age is minimally but significantly associated with worse prognosis after RC. Nevertheless, a large proportion of elderly patients benefitted from RC with curative intent. We need to improve our understanding of the reasons for the worse UCB outcomes in this growing segment of the population and to develop strategies to improve cancer care in the elderly.
World Journal of Urology 10/2011; · 2.41 Impact Factor
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Christopher E Barbieri,
Eugene K Cha,
Thomas F Chromecki,
Allison Dunning,
Yair Lotan, Robert S Svatek,
Douglas S Scherr,
Pierre I Karakiewicz,
Maxine Sun,
Madhu Mazumdar,
Shahrokh F Shariat
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ABSTRACT: • To employ decision curve analysis to determine the impact of nuclear matrix protein 22 (NMP22) on clinical decision making in the detection of bladder cancer using data from a prospective trial.
• The study included 1303 patients at risk for bladder cancer who underwent cystoscopy, urine cytology and measurement of urinary NMP22 levels. • We constructed several prediction models to estimate risk of bladder cancer. The base model was generated using patient characteristics (age, gender, race, smoking and haematuria); cytology and NMP22 were added to the base model to determine effects on predictive accuracy. • Clinical net benefit was calculated by summing the benefits and subtracting the harms and weighting these by the threshold probability at which a patient or clinician would opt for cystoscopy.
• In all, 72 patients were found to have bladder cancer (5.5%). In univariate analyses, NMP22 was the strongest predictor of bladder cancer presence (predictive accuracy 71.3%), followed by age (67.5%) and cytology (64.3%). • In multivariable prediction models, NMP22 improved the predictive accuracy of the base model by 8.2% (area under the curve 70.2-78.4%) and of the base model plus cytology by 4.2% (area under the curve 75.9-80.1%). • Decision curve analysis revealed that adding NMP22 to other models increased clinical benefit, particularly at higher threshold probabilities.
• NMP22 is a strong, independent predictor of bladder cancer. • Addition of NMP22 improves the accuracy of standard predictors by a statistically and clinically significant margin. • Decision curve analysis suggests that integration of NMP22 into clinical decision making helps avoid unnecessary cystoscopies, with minimal increased risk of missing a cancer.
BJU International 08/2011; 109(5):685-90. · 2.84 Impact Factor
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Philipp Nuhn,
Patrick J Bastian,
Giacomo Novara, Robert S Svatek,
Pierre I Karakiewicz,
Eila Skinner,
Yves Fradet,
Jonathan I Izawa,
Wassim Kassouf,
Francesco Montorsi,
Stefan C Müller,
Hans-Martin Fritsche,
Guru Sonpavde,
Derya Tilki,
Hendrik Isbarn,
Vincenzo Ficarra,
Colin P Dinney,
Shahrokh F Shariat
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ABSTRACT: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients.
The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC.
1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups.
We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making.
Urologia Internationalis 06/2011; 87(1):42-8. · 0.99 Impact Factor
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ABSTRACT: Intravesical immunotherapy using attenuated bacillus Calmette-Guérin (BCG) strains and intravesical chemotherapy are the modalities most commonly used to treat intermediate- or high-risk patients with non-muscle invasive bladder cancer. BCG has been shown to decrease recurrence rates by up to 67% compared with tumor resection alone, but intensive BCG maintenance regimens are poorly tolerated in a large proportion of patients. Intravesical chemotherapy also decreases the risk of recurrence for these patients, but has diminished efficacy compared with BCG. If BCG dose reduction can be achieved with combined intravesical immunotherapy and chemotherapy, this regimen may improve compliance and thus optimize treatment for these patients by limiting side effects from BCG monotherapy, while at the same time improving oncologic efficacy via the separate anti-tumor mechanisms of these agents. The authors discuss the most recent data regarding combining these agents in an alternating or sequential regimen.
Expert Review of Anti-infective Therapy 06/2011; 11(6):949-57. · 2.65 Impact Factor
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Wassim Kassouf, Robert S Svatek,
Shahrokh F Shariat,
Giacomo Novara,
Seth P Lerner,
Yves Fradet,
Patrick J Bastian,
Armen Aprikian,
Pierre I Karakiewicz,
Hans Martin Fritsche,
Colin P N Dinney,
Derya Tilki,
Ashish M Kamat,
Jonathan I Izawa,
Vincenzo Ficarra,
Yair Lotan,
Arthur I Sagalowsky,
Mark P Schoenberg,
Eila C Skinner
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ABSTRACT: OBJECTIVE: To validate the prognostic relevance of lymph node density (LND) and identify its optimal cut-points in a large international multicenter series of patients treated with radical cystectomy (RC) for invasive bladder cancer. METHODS: From 1993 to 2005, 4,430 bladder cancer patients who underwent RC without neoadjuvant chemotherapy were reviewed; of these, 1,038 were pN+M0 disease and form the basis of this report. RESULTS: Median age of patients was 67 years with median follow-up in survivors of 33 months. Overall, 5-year DSS estimate was 36%. Median number of lymph nodes removed was 18 (IQR, 11-32), median number of positive lymph nodes was 2 (IQR, 1-5), and median LND was 14.3% (IQR, 6.67-33.3%). LND as continuous variable was a stronger prognostic factor for DSS in patients that underwent a more extensive PLND (P < 0.001). HR for inverse association of LND with DSS increased incrementally with increasing LND cut-points. Categorizing LND into quintiles revealed strong tertiary distribution of risk based on LND <6%, 6%-41%, or >41% with cumulative 5-year DSS of 47%, 36%, and 21%, respectively (P < 0.001). When patients were stratified by adjuvant chemotherapy, LND remains independently prognostic in patients who received adjuvant chemotherapy as well as those who did not. CONCLUSION: Lymph node density is prognostic in bladder cancer patients who undergo a more extensive PLND and remains prognostic even when adjuvant chemotherapy is used. Prognostic value of LND is best represented as a continuum of risk and LND <6% represents the best possible outcome in patients with nodal disease.
Urologic Oncology 04/2011; · 3.22 Impact Factor
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Urology 04/2011; 77(4):876-7. · 2.43 Impact Factor
