Radical Cystectomy For Urothelial Carcinoma Of The Bladder Research Articles

MP23-01 URETHRECTOMY AT THE TIME OF RADICAL CYSTECTOMY FOR NON-METASTATIC UROTHELIAL CARCINOMA OF THE BLADDER: A COLLABORATIVE MULTICENTER STUDY

MP23-01 URETHRECTOMY AT THE TIME OF RADICAL CYSTECTOMY FOR NON-METASTATIC UROTHELIAL CARCINOMA OF THE BLADDER: A COLLABORATIVE MULTICENTER STUDY

Preoperative plasma level of endoglin as a predictor for disease outcomes after radical cystectomy for nonmetastatic urothelial carcinoma of the bladder.

Elevated preoperative plasma level of endoglin has been associated with worse oncologic outcomes in various malignancies. The present large‐scale study aimed to determine the predictive and prognostic values of preoperative endoglin with regard to clinicopathologic and survival outcomes in patients treated with radical cystectomy (RC) for nonmetastatic urothelial carcinoma of the bladder (UCB). We prospectively collected preoperative blood samples from 1036 consecutive patients treated with RC for UCB. Logistic and Cox regression analyses were undertaken to assess the correlation of endoglin levels with pathologic and survival outcomes, respectively. The AUC and C‐index were used to assess the discrimination. Patients with adverse pathologic features had significantly higher median preoperative endoglin plasma levels than their counterparts. Higher preoperative endoglin level was independently associated with an increased risk for lymph node metastasis, ≥pT3 disease, and nonorgan confined disease (NOCD; all p < 0.001). Plasma endoglin level was also independently associated with cancer‐specific and overall survival in both pre‐ and postoperative models (all p < 0.05), as well as with recurrence‐free survival (RFS) in the preoperative model (p < 0.001). The addition of endoglin to the preoperative standard model improved its discrimination for prediction of lymph node metastasis, ≥pT3 disease, NOCD, and RFS (differential increases in C‐indices: 10%, 5%, 5.8%, and 4%, respectively). Preoperative plasma endoglin is associated with features of biologically and clinically aggressive UCB as well as survival outcomes. Therefore, it seems to hold the potential of identifying UCB patients who may benefit from intensified therapy in addition to RC such as extended lymphadenectomy or/and preoperative systemic therapy.

Prognostic Impact of Preoperative Plasma Levels of Urokinase Plasminogen Activator Proteins on Disease Outcomes after Radical Cystectomy.

We sought to validate the association of plasma levels of urokinase-type plasminogen activator (uPA), its soluble receptor (SuPAR) and its inhibitor (PAI-one) with oncologic outcomes in a large cohort of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). We collected preoperative blood samples from 1,036 consecutive patients treated with RC for UCB. Plasma specimens were assessed for levels of uPA, SuPAR and PAI-one. Retrospective logistic and Cox regression analyses were performed to assess their correlation with clinical outcomes. The additional clinical net benefit provided by the biomarkers was evaluated using decision curve analysis. Preoperative plasma uPA, SuPAR and PAI-one levels were significantly elevated in patients harboring adverse pathological features. Higher levels of all biomarkers were independently associated with an increased risk of lymph node metastasis; uPA levels were also independently associated with ≥pT3 disease. Preoperative uPA and SuPAR were independently associated with recurrence-free and cancer-specific survival. The addition of these biomarkers to standard pre-treatment and post-treatment models improved the discriminatory power for prediction of lymph node metastasis, ≥pT3 disease, and recurrence-free and cancer-specific survival by a prognostically significant margin. We confirmed that elevated preoperative plasma levels of uPA, SuPAR and PAI-one are associated with features of aggressive disease and worse survival outcomes in patients treated with RC for UCB. These biomarkers hold potential in identifying patients who are likely to benefit from intensified/multimodal therapy. They also demonstrated the ability to improve the discriminatory power of predictive/prognostic models, thus refining personalized clinical decision-making.

Impact of preoperative plasma levels of interleukin 6 and interleukin 6 soluble receptor on disease outcomes after radical cystectomy for bladder cancer

BackgroundPreoperative plasma levels of Interleukin 6 (IL6) and its soluble receptor (IL6sR) have previously been associated with oncologic outcomes in urothelial carcinoma of the bladder (UCB); however, external validation in patients treated with radical cystectomy (RC) for UCB is missing.Patients/methodsWe prospectively collected preoperative plasma from 1,036 consecutive patients at two institutes. These plasma specimens were assessed for levels of IL6 and IL6sR. Logistic and Cox regression analyses were used to assess the correlation of plasma levels with pathologic and survival outcomes. The additional clinical net benefits of preoperative IL6 and IL6sR were evaluated using decision curve analysis (DCA).ResultsMedian IL6 and IL6sR plasma levels were significantly higher in patients with adverse pathologic features. Elevated biomarker levels were independently associated with an increased risk for lymph node metastasis and ≥ pT3 disease. Both biomarkers were independently associated with recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The addition to, respectively, fitted pre- and postoperative prognostic models improved the predictive accuracy for lymph node metastasis, ≥ pT3 disease, RFS and CSS on DCA.InterpretationWe confirmed that elevated preoperative plasma levels of IL6 and IL6sR levels are associated with worse oncological disease survival in patients treated with RC for UCB in a large multicenter study. Both biomarkers hold potential in identifying patients with adverse pathological features that may benefit from intensified/multimodal therapy and warrant inclusion into predictive/prognostic models. They demonstrated the ability to improve the discriminatory power of such models and thus guide clinical decision making.

Benefit of Adjuvant Chemotherapy After Radical Cystectomy for Treatment of Urothelial Carcinoma of the Bladder in the Elderly –An International Multicenter Study

BACKGROUND: Radical cystectomy (RC) is the standard treatment for muscle invasive bladder cancer, but approximately half of all patients will ultimately succumb to disease progression despite apparent cure with extirpative surgery. Elderly patients are at especially high risk of advanced disease and may benefit from perioperative systemic therapy. OBJECTIVE: To assess the real-world benefit of adjuvant chemotherapy (AC) in patients ≥75 years old. METHODS: We retrospectively reviewed patients who underwent RC for non-metastatic urothelial carcinoma of the bladder (UCB) from 12 participating international medical institutions. Kaplan-Meier survival curves and Cox regression models were used to assess the association between age groups, administration of AC and oncological outcome parameters such as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: 4,335 patients were included in the analyses, of which 820 (18.9%) were ≥75 years old. These elderly patients had a higher rate of adverse pathologic features. In an univariable subgroup analysis in patients ≥75 years with lymph node metastasis, 5-year OS was significantly higher in patients who had received AC (41% vs. 30.9%, p = 0.02). In a multivariable Cox model that was adjusted for several established outcome predictors, there was a significant favorable association between the administration of AC in elderly patients and OS, but no RFS or CSS. CONCLUSIONS: In this large observational study, the administration of AC was associated with improved OS, but not RFS or CSS, in elderly patients treated with RC for UCB. This is of clinical importance, as elderly patients are more likely to have adverse pathologic features and experience worse survival outcomes. Treatment of UCB should include both a multidisciplinary approach and a geriatric evaluation to identify patients who are most likely to tolerate and benefit from AC.

Impact of preoperative serum albumin-globulin ratio on disease outcome after radical cystectomy for urothelial carcinoma of the bladder

IntroductionThe Albumin-Globulin Ratio (AGR; albumin/total protein − albumin) has been associated with oncological outcome in various malignancies. However, its role in urothelial carcinoma of the bladder (UCB) has not been clearly established. In this study, we assessed the association of preoperative AGR (pAGR) with survival in patients who underwent radical cystectomy (RC) for UCB. Material and MethodsWe conducted a retrospective analysis of an established multicenter database of 4.335 patients who were treated with RC for UCB. The cohort was divided into 2 groups according to the pAGR status. Binominal logistic regression as well as uni- and multivariable Cox regression analyses were used. The predictive value of the models was assessed by calculating receiver operating characteristics curves and concordance-indices (C-Index). The additional clinical value was assessed using the decision curve analysis (DCA). ResultsOverall, 1.670 patients (38.5%) had a low pAGR. On multivariable logistic regression analyses, low pAGR was associated with an increased risk of ≥pT3 disease at RC (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01–1.31, P= 0.04). On multivariable Cox regression analyses, low pAGR remained associated with worse recurrence-free survival (RFS, HR 1.24, 95% CI 1.1–1.37, P< 0.001), cancer-specific survival (CSS, HR 1.23, 95% CI 1.1–1.38, P< 0.001) and overall survival (OS, HR 1.17, 95% CI 1.07–1.28, P< 0.001). The addition of pAGR to multiple prognostic models that were respectively fitted for clinical and postoperative variables did not improve the predictive accuracy. ConclusionpAGR status is an independent predictor of ≥pT3 disease, therefore it could help identify patients who have a higher likelihood to benefit from neoadjuvant systemic therapy. While pAGR was independently associated with RFS, CSS, and OS, it did not improve the predictive accuracy and clinical value beyond obtained by information already available. The predictive value of this biomarker in the age of immunotherapy needs further evaluation.

The association of cigarette smoking and pathological response to neoadjuvant platinum-based chemotherapy in patients undergoing treatment for urinary bladder cancer - A prospective European multicenter observational study of the EAU Young Academic Urologists (YAU) urothelial carcinoma working group

ObjectiveTo prospectively study the impact of smoking on pathological response to neoadjuvant chemotherapy (NAC) in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). Materials & methodsWe collected standard clinicopathological variables, including smoking status (never, former, current) in patients undergoing NAC and RC for UCB at 12 European tertiary care centers between 12/2013-12/2015. Clinicopathological variables were compared according to smoking status. Multivariable logistic regression models were built to assess the association of smoking status and a) complete (no residual disease), b) partial (residual, non-muscle invasive disease), c) no pathological response (residual muscle invasive or lymph node positive disease). Kaplan-Meier and Cox regression analyses were employed to study the impact of response to NAC on survival. Results and limitationsOur final cohort consisted of 167 NAC patients with a median follow-up of 15 months (interquartile range (IQR) 9–26 months) of whom 48 (29%), 69 (41%), and 50 (30%) where never, former, and current smokers, respectively. Smoking was significantly associated with advanced age (p = 0.013), worse ECOG performance status (p = 0.049), and decreased pathological response to NAC (p = 0.045). On multivariable logistic regression analyses, former and current smoking status was significantly associated with lower odds of complete pathological response (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.16–0.87, p = 0.023, and OR 0.34, 95% CI 0.13–0.85, p = 0.021), while current smoking status was significantly associated with a greater likelihood of no pathological response (OR 2.49, 95% CI 1.02–6.06, p = 0.045). Response to NAC was confirmed as powerful predictor of survival. ConclusionsSmoking status is adversely associated with pathological response to NAC. Smokers should be informed about these adverse effects, counseled regarding smoking cessation, and possibly be considered for immunotherpeutics as they may be more effective in smokers.

PD60-08 ONCOLOGICAL OUTCOMES FOLLOWING RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA OF THE BLADDER WITH POSITIVE LYMPH NODES

You have accessJournal of UrologyBladder Cancer: Invasive VI (PD60)1 Apr 2020PD60-08 ONCOLOGICAL OUTCOMES FOLLOWING RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA OF THE BLADDER WITH POSITIVE LYMPH NODES Seyedeh-Sanam Ladi Seyedian*, Zhoobin Bateni, Shane Pearce, Saum Ghodoussipour, Azadeh Nazemi, Jie Cai, Gus Miranda, Sumeet Bhanvadia, Hooman Djaladat, Anne Schuckman, and Siamak Daneshmand Seyedeh-Sanam Ladi Seyedian*Seyedeh-Sanam Ladi Seyedian* More articles by this author , Zhoobin BateniZhoobin Bateni More articles by this author , Shane PearceShane Pearce More articles by this author , Saum GhodoussipourSaum Ghodoussipour More articles by this author , Azadeh NazemiAzadeh Nazemi More articles by this author , Jie CaiJie Cai More articles by this author , Gus MirandaGus Miranda More articles by this author , Sumeet BhanvadiaSumeet Bhanvadia More articles by this author , Hooman DjaladatHooman Djaladat More articles by this author , Anne SchuckmanAnne Schuckman More articles by this author , and Siamak DaneshmandSiamak Daneshmand More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000977.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We sought to determine oncological outcomes among patients who underwent radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder with positive lymph nodes (LN). METHODS: On a retrospective review of 4093 patients from our institutional IRB approved cystectomy database from Jan 1971 to Dec 2017, we identified 3284 patients who underwent RC for UC of the bladder. We included patients with positive LNs at the final pathology. The data was stratified into three groups based on number of positive LNs: 1, 2-9, and more than 10 positive LNs. Multivariable analysis was performed to identify prognostic factors for overall survival (OS) and recurrence-free survival (RFS). A subgroup analysis was performed to assess the oncological outcomes in cases that did not receive any chemotherapy (adjuvant or neoadjuvant). RESULTS: 712 patients (22%) had positive LN after RC. Median age was 68 years and 76% of patients were male. 105 (15%) patients had clinical evidence of LN involvement on pre-operative imaging. Patient characteristics are provided in Table 1. Five-year (5-y) RFS for 1, 2-9 and 10+ positive LNs was 39%, 36% and 16%, respectively (p<0.001) and 5-y OS were 45%, 33% and 14%, respectively (p<0.001). On multivariable analysis, more than 10 positive LNs, pathologic tumor stage >pT2, and neoadjuvant chemotherapy were associated with increased risk of recurrence and worse overall survival after radical cystectomy. Adjuvant chemotherapy was associated with decreased risk of recurrence and better overall survival after radical cystectomy. On subgroup analysis of patients with positive LNs without peri-operative chemotherapy, 5-y RFS for 1, 2-9 and 10+ positive LNs was 25%, 32% and 5%, respectively (p<0.001) and 5-y OS was 31%, 20% and 4%, respectively (p<0.001). CONCLUSIONS: Only 15% of patients with positive LNs have clinical evidence of LN involvement prior to cystectomy. Oncological outcomes after radical cystectomy are associated with the number of involved LNs. Surgery alone can be curative in 20-30% of patients with less than 10+ LN. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1277-e1277 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Seyedeh-Sanam Ladi Seyedian* More articles by this author Zhoobin Bateni More articles by this author Shane Pearce More articles by this author Saum Ghodoussipour More articles by this author Azadeh Nazemi More articles by this author Jie Cai More articles by this author Gus Miranda More articles by this author Sumeet Bhanvadia More articles by this author Hooman Djaladat More articles by this author Anne Schuckman More articles by this author Siamak Daneshmand More articles by this author Expand All Advertisement PDF downloadLoading ...

Oncological outcomes following radical cystectomy for urothelial carcinoma of the bladder with positive lymph nodes.

584 Background: To determine oncological outcomes among patients who underwent radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder with positive lymph nodes (LN). Methods: On a retrospective review of 4093 patients from our institutional IRB approved cystectomy database from Jan 1971 to Dec 2017, we identified 3284 patients who underwent RC for UC of the bladder. We included patients with positive LNs at the final pathology. The data was stratified into three groups based on number of positive LNs: 1, 2-9, and more than 10 positive LNs. Multivariable analysis was performed to identify prognostic factors for overall survival (OS) and recurrence-free survival (RFS). A subgroup analysis was performed to assess the oncological outcomes in cases that did not receive any chemotherapy (adjuvant or neoadjuvant). Results: 712 patients (22%) had positive LN after RC. Median age was 68 years and 76% of patients were male. 105 (15%) patients had clinical evidence of LN involvement on pre-operative imaging. Patient characteristics are provided in Table. Five-year (5-y) RFS for 1, 2-9 and 10+ positive LNs was 39%, 36% and 16%, respectively (p&lt;0.001). 5-y OS were 45%, 33% and 14%, respectively (p&lt;0.001). On multivariable analysis, more than 10 positive LNs pathologic tumor stage &gt;pT2, and neoadjuvant chemotherapy were associated with increased risk of recurrence and worse overall survival after radical cystectomy. Adjuvant chemotherapy was associated with decreased risk of recurrence and better overall survival after radical cystectomy. On subgroup analysis of patients with positive LNs without peri-operative chemotherapy, 5-y RFS for 1, 2-9 and 10+ positive LNs was 25%, 32% and 5%, respectively (p&lt;0.001). 5-y OS was 31%, 20% and 4%, respectively (p&lt;0.001). Conclusions: Only 15% of patients with positive LNs have clinical evidence of LN involvement prior to cystectomy. Oncological outcomes after radical cystectomy are associated with the number of involved LNs. Surgery alone can be curative in 20-30% of patients with less than 10+ LN.

MP58-12 CLINICAL DESTINY OF INDETERMINATE PULMONARY NODULES IN PATIENTS UNDERGOING RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA OF THE BLADDER

You have accessJournal of UrologyBladder Cancer: Invasive V1 Apr 2017MP58-12 CLINICAL DESTINY OF INDETERMINATE PULMONARY NODULES IN PATIENTS UNDERGOING RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA OF THE BLADDER David Cahn, Brian McGreen, Albert Lee, Karen Ruth, Elizabeth Plimack, Daniel Geynisman, Matthew Zibelman, Benjamin Ristau, Marc Smaldone, Richard Greenberg, Rosalia Viterbo, David Chen, Robert Uzzo, and Alexander Kutikov David CahnDavid Cahn More articles by this author , Brian McGreenBrian McGreen More articles by this author , Albert LeeAlbert Lee More articles by this author , Karen RuthKaren Ruth More articles by this author , Elizabeth PlimackElizabeth Plimack More articles by this author , Daniel GeynismanDaniel Geynisman More articles by this author , Matthew ZibelmanMatthew Zibelman More articles by this author , Benjamin RistauBenjamin Ristau More articles by this author , Marc SmaldoneMarc Smaldone More articles by this author , Richard GreenbergRichard Greenberg More articles by this author , Rosalia ViterboRosalia Viterbo More articles by this author , David ChenDavid Chen More articles by this author , Robert UzzoRobert Uzzo More articles by this author , and Alexander KutikovAlexander Kutikov More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1807AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Perioperative risks and significant quality of life concerns following radical cystectomy (RC) render accurate pre-operative staging paramount. Incidental indeterminate pulmonary nodules (IPNs) are a common pre-operative finding in clinical practice, thus representing a significant management challenge since metastatic patients are unlikely to benefit from extirpation. Thus, we sought to evaluate the natural history of IPNs in a large institutional cohort that underwent RC. METHODS We reviewed our institutional database for patients who underwent RC from 2000-2014 for urothelial carcinoma (UCC) of the bladder & had ≥1 identifiable pulmonary lesion on preoperative staging imaging measuring <2cm in any axis. Patients who were M1 at surgery or had non urothelial histology were excluded. Cumulative incidence of any lung metastasis was estimated, adjusting for competing risk of death; overall survival (OS) was estimating using Kaplan Meier methods. We sought to determine the natural history of these pulmonary lesions and evaluated predictors of metastatic etiology. RESULTS During the study period, 681 RC were performed at our institution. Of which, 73 patients with an identifiable preoperative IPN met inclusion criteria & underwent RC. In this subset, 23% were female, 22% were active smokers & 55% former smokers. The median age at surgery was 70 yrs (range 43-88). 51% received neoadjuvant chemotherapy & 62% of RC were performed using the traditional open approach (vs 38% robotically). Final pathologic staging included 16% pT0N0Mx, 19% pTa/Tis/T1N0Mx, 43% pT2-4N0Mx, & 22% pTanyN+Mx. Median IPN size was 0.7±0.3cm. At median follow up of 23.5 months, the IPNs in 92% (67/73) of patients were clinically benign, with metastatic urothelial cancer confirmed in only 5 patients, & a primary lung malignancy diagnosed in 1 patient. In the IPN cohort, lung metastasis at non-IPN sites were detected in 2 additional patients. Cumulative incidence of any lung metastasis at 12, 24 & 36 months was 5.9% (95%CI 1.9-13.3%), 7.6% (95%CI 2.8-15.7%), & 10.3% (95%CI 3.9-20.2%), respectively. OS at 12, 24 & 36 months was 75.3% (95%CI 62.3-83.9%), 65.8% (95%CI 53-1-75.9%), & 54.0% (95%CI 39.7-66.2%), respectively. CONCLUSIONS The majority of IPNs in patients who proceeded to RC for UCC of the bladder were stable upon follow-up & rarely represented malignancy. Patients with IPNs have OS consistent with previously published literature. As such, in appropriately screened UCC patients, IPNs should not be a barrier to proceeding with extirpative surgical therapy. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e776-e777 Advertisement Copyright & Permissions© 2017MetricsAuthor Information David Cahn More articles by this author Brian McGreen More articles by this author Albert Lee More articles by this author Karen Ruth More articles by this author Elizabeth Plimack More articles by this author Daniel Geynisman More articles by this author Matthew Zibelman More articles by this author Benjamin Ristau More articles by this author Marc Smaldone More articles by this author Richard Greenberg More articles by this author Rosalia Viterbo More articles by this author David Chen More articles by this author Robert Uzzo More articles by this author Alexander Kutikov More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Clinical destiny of indeterminate pulmonary nodules in patients undergoing radical cystectomy for urothelial carcinoma of the bladder.

297 Background: Perioperative risks and significant quality of life concerns following radical cystectomy (RC) render accurate pre-operative staging paramount, since metastatic patients are unlikely to benefit from extirpation. Yet, incidental indeterminate pulmonary nodules (IPNs) are a common pre-operative finding in clinical practice, thus representing a significant management challenge. As such, we sought to evaluate the natural history of IPNs in a large institutional cohort that underwent RC. Methods: We reviewed our institutional database for patients who underwent RC from 2000 through 2014 for urothelial carcinoma (UCC) of the bladder and had at least 1 identifiable pulmonary lesion on preoperative staging imaging measuring &lt;2cm in any axis. Patients who were M1 at surgery, had gynecologic, colorectal, or missing pathology, or non-urothelial histology were excluded. We sought to determine the natural history of these pulmonary lesions and evaluated predictors of metastatic etiology. Results: During the study period, 681 RC were performed at our institution. We identified 73 patients with an identifiable preoperative IPN who met inclusion criteria and underwent RC. In this subset, 23.3% were female, 21.9% were active smokers, and 54.8% former smokers. The median age at surgery was 70±8.6 years. Nearly half (49.3%) received neoadjuvant chemotherapy. 61.6% of RC were performed using the traditional open approach, while 38.4% were performed robotically. Final pathologic staging included 16.4% pT0N0Mx, 19.2% pTa/Tis/T1N0Mx, 42.5% pT2-4N0Mx, and 21.9% pTanyN+Mx. Median IPN size was 0.7±0.3cm. At median follow up of 23.5±21.9 months, 93% (68/73) of IPNs in our cohort were clinically benign, with metastatic urothelial cancer confirmed in only 4 patients, and a primary lung malignancy diagnosed in 1 patient. Conclusions: The majority of IPNs in patients who proceeded to RC for UCC of the bladder were stable upon follow-up and rarely represented malignancy. As such, in appropriately screened UCC patients, IPNs should not be a barrier to proceeding with extirpative surgical therapy.

Disease-Free Survival at 2 and 3 Years is a Significant Early Surrogate Marker Predicting the 5-Year Overall Survival in Patients Treated with Radical Cystectomy for Urothelial Carcinoma of the Bladder: External Evaluation and Validation in a Cohort of Korean Patients.

We aimed to externally validate the association of 2- and 3-year disease-free survival (DFS) with 5-year overall survival (OS) in patients treated with radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder. We reviewed the clinical data of 422 patients who underwent RC for UC of the bladder in our institution between 1991 and 2012. Survival curves were plotted with the Kaplan-Meier method. The Kappa statistic and Kendall tau-b test were used to assess the agreements between 2- and 3-year DFS and 5-year OS. In the entire study population, 2- and 3-year DFS and 5-year OS rates were 76.4, 71.5, and 67.4%, respectively. All Kappa and Kendall's tau-b test values for agreements between 2- and 3-year DFS and 5-year OS were more than 0.40, indicating moderate agreement for all patients and in each patient subgroup selected according to specific variables (all p-values <0.05). Kaplan-Meier analysis for DFS and Cox-proportional hazard models for landmark analysis at each time point indicated that most recurrences occurred within 3 years after surgery. The 5-year OS rates of patients who were recurrence-free at each time point gradually increased to more than 95% in an extended recurrence-free interval of 12-36 months. Our external validation results support the existing finding that 2- and 3-year DFS can be a valid early surrogate end point to predict 5-year OS after RC in patients with UC of the bladder.

Prognostic Model for Predicting Survival in Patients with Disease Recurrence Following Radical Cystectomy

BackgroundAlthough the natural history of urothelial carcinoma of the bladder (UCB) from radical cystectomy (RC) to disease recurrence (DR) has been investigated intensively, the course of patients who have experienced DR after RC for UCB remains poorly understood. ObjectiveTo evaluate the prognostic value of the Bajorin criteria that consists of two risk factors: Karnofsky performance status (KPS) and the presence of visceral metastases (VMs) in patients with DR after RC for UCB. Furthermore, to identify additional factors associated with cancer-specific mortality (CSM) and thus build a multivariable model to predict survival after DR. Design, setting, and participantsWe identified 967 patients with UCB who underwent RC at 17 centers between 1979 and 2012 and experienced DR. Of these, 372 patients had complete data we used for analysis. Outcomes measurements and statistical analysisUnivariable Cox regressions analysis was performed. We used a forward stepwise selection process for our final multivariable model. Results and limitationsWithin a median follow-up of 18 mo, 266 patients died of disease. Cancer-specific survival at 1 yr was 79%, 76%, and 47% for patients with no (n=105), one (n=180), and two (n=87) risk factors (p<0.001; c-index: 0.604). On multivariable analyses, we found that KPS <80%, higher American Society of Anesthesiologists score, anemia, leukocytosis, and shorter time to DR (all p values <0.034) were independently associated with increased CSM. The combination of time to DR and KPS resulted in improved discrimination (c-index: 0.694). ConclusionsWe confirmed the prognostic value of KPS and VMs in patients with DR following RC for UCB. We also found several other clinical variables to be associated with worse CSM. We developed a model for predicting survival after DR inclusive of time to DR and KPS assessed at DR. If validated, this model could help clinical trial design. Patient summaryWe developed a model to predict survival following disease recurrence after radical cystectomy for urothelial carcinoma of the bladder, based on time to disease recurrence and Karnofsky performance status.

Optimizing outcome reporting after radical cystectomy for organ-confined urothelial carcinoma of the bladder using oncological trifecta and pentafecta.

Radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) is associated with heterogeneous functional and oncological outcomes. The aim of this study was to generate trifecta and pentafecta criteria to optimize outcome reporting after RC. We interviewed 50 experts to consider a virtual group of patients (age ≤ 75 years, ASA score ≤ 3) undergoing RC for a cT2 UCB and a final histology of ≤pT3pN0M0. A ranking was generated for the three and five criteria with the highest sum score. The criteria were applied to the Prospective Multicenter Radical Cystectomy Series 2011. Multivariable binary logistic regression analyses were used to evaluate the impact of clinical and histopathological parameters on meeting the top selected criteria. The criteria with the highest sum score were negative soft tissue surgical margin, lymph node (LN) dissection of at least 16 LNs, no complications according to Clavien-Dindo grade 3-5 within 90 days after RC, treatment-free time between TUR-BT with detection of muscle-invasive UCB and RC <3 months and the absence of local UCB-recurrence in the pelvis ≤12 months. The first three criteria formed trifecta, and all five criteria pentafecta. A total of 334 patients qualified for final analysis, whereas 35.3 and 29 % met trifecta and pentafecta criteria, respectively. Multivariable analyses showed that the relative probability of meeting trifecta and pentafecta decreases with higher age (3.2 %, p = 0.043 and 3.3 %, p = 0.042) per year, respectively. Trifecta and pentafecta incorporate essential criteria in terms of outcome reporting and might be considered for the improvement of standardized quality assessment after RC for UCB.

MP58-20 PREDICTION OF LOCOREGIONAL RECURRENCE AFTER RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA OF THE BLADDER

INTRODUCTION AND OBJECTIVES: Data on locoregional recurrence (LR) after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) is scarce. An accurate stratification of patients potentially experiencing LR could help in patient counseling regarding adjuvant therapy and in clinical trial design-setting. We therefore externally validated Christodouleas’ risk-model (RM) incorporating pathological tumor stage, lymph node count and soft-tissue surgical margin and stratifying patients who develop LR after RC for UCB. In addition, we generated a new model including established clinicopathological features that were absent in Christodouleas’ RM based on the data of the Prospective Multicenter Radical Cystectomy Series 2011 (PROMETRICS 2011). METHODS: Prospectively assessed multicenter data from 565 patients undergoing RC in 2011 qualified for final analysis. For the purpose of external validation, risk-group stratification according to Christodouleas was performed. Competing-risk models were calculated to compare the cumulative incidences of LR after RC. RESULTS: After a median follow-up of 25 months, the LR rate was in 11.5%. Christodouleas’ RM showed a predictive accuracy of 83.2% in our cohort. In multivariable competing-risks analysis, tumor stage pT3 (HR4.32, p<0.001), positive soft-tissue surgical margin (HR2.93, p1⁄40.005), the presence of lymphovascular invasion (HR3.41, p<0.001), the number of removed lymph nodes <10 (HR2.62, p<0.001) and the administration of adjuvant chemotherapy (HR0.40, p1⁄40.008) independently predicted the LR rate. The resulting risk-groups revealed significant differences in LR rates after 24 months with 4.8% for low-risk patients, 14.7% for intermediate-risk patients and 38.9% for high-risk patients (p<0.001 for all), respectively, with a predictive accuracy of 85.6%. CONCLUSIONS: Christodouleas’ RM for prediction of LR after RC for UCB could be externally validated with a good discrimination within our cohort. In contrast, we incorporated besides the established clinico-pathological features pathological tumor stage, lymph node count, soft tissue surgical margin also lymphovascular invasion and adjuvant chemotherapy which have been missed to include in Christodouleas’ RM. Furthermore, our bely developed RM allows stratifying patients individually for their risk of LR with a good predictive accuracy and can serve as a tool for identifying eligible patients who can be administered adjuvant chemotherapy and included in clinical trials setting.

MP59-01 IMPACT OF BLOOD TRANSFUSIONS ON ONCOLOGICAL OUTCOMES OF SURGICALLY TREATED LOCALIZED RENAL CELL CARCINOMA

INTRODUCTION AND OBJECTIVES: Data on locoregional recurrence (LR) after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) is scarce. An accurate stratification of patients potentially experiencing LR could help in patient counseling regarding adjuvant therapy and in clinical trial design-setting. We therefore externally validated Christodouleas’ risk-model (RM) incorporating pathological tumor stage, lymph node count and soft-tissue surgical margin and stratifying patients who develop LR after RC for UCB. In addition, we generated a new model including established clinicopathological features that were absent in Christodouleas’ RM based on the data of the Prospective Multicenter Radical Cystectomy Series 2011 (PROMETRICS 2011). METHODS: Prospectively assessed multicenter data from 565 patients undergoing RC in 2011 qualified for final analysis. For the purpose of external validation, risk-group stratification according to Christodouleas was performed. Competing-risk models were calculated to compare the cumulative incidences of LR after RC. RESULTS: After a median follow-up of 25 months, the LR rate was in 11.5%. Christodouleas’ RM showed a predictive accuracy of 83.2% in our cohort. In multivariable competing-risks analysis, tumor stage pT3 (HR4.32, p<0.001), positive soft-tissue surgical margin (HR2.93, p1⁄40.005), the presence of lymphovascular invasion (HR3.41, p<0.001), the number of removed lymph nodes <10 (HR2.62, p<0.001) and the administration of adjuvant chemotherapy (HR0.40, p1⁄40.008) independently predicted the LR rate. The resulting risk-groups revealed significant differences in LR rates after 24 months with 4.8% for low-risk patients, 14.7% for intermediate-risk patients and 38.9% for high-risk patients (p<0.001 for all), respectively, with a predictive accuracy of 85.6%. CONCLUSIONS: Christodouleas’ RM for prediction of LR after RC for UCB could be externally validated with a good discrimination within our cohort. In contrast, we incorporated besides the established clinico-pathological features pathological tumor stage, lymph node count, soft tissue surgical margin also lymphovascular invasion and adjuvant chemotherapy which have been missed to include in Christodouleas’ RM. Furthermore, our bely developed RM allows stratifying patients individually for their risk of LR with a good predictive accuracy and can serve as a tool for identifying eligible patients who can be administered adjuvant chemotherapy and included in clinical trials setting.

Effect of African-American Race on Tumor Recurrence After Radical Cystectomy for Urothelial Carcinoma of the Bladder

BackgroundAfrican-American race appears to be associated with higher stages of urothelial carcinoma of the bladder (UCB) at presentation and poorer survival. However, the independent effect of African-American race on objective tumor recurrence after radical cystectomy (RC) after controlling for clinical and pathologic variables is unknown. Patients and MethodsThe data from consecutive patients with UCB who underwent RC with curative intent at a single institution (University of Alabama, Birmingham) from 2001 to 2012 with or without perioperative chemotherapy or chemoradiation were reviewed. The patient demographics, risk factors, clinical course, pathologic characteristics, and long-term outcomes were collected. Descriptive statistics were performed. Cox regression analysis was performed for key clinical, demographic, and pathologic variables, including race, stratified as African American versus white. ResultsA total of 215 patients, 163 men (76%) and 52 women (24%), with a mean age at RC of 65.6 years, were identified and reviewed. A total of 186 patients (87%) were white and 28 (13%) were African American. The median follow-up period after RC was 17.6 months. On conventional multivariate analysis, African-American race nearly attained statistical significance (hazard ratio [HR], 2.48; 95% confidence interval [CI], 0.98-6.29; P = .055). In a stepwise regression model, race was significantly associated with tumor recurrence (HR, 3.11; 95% CI, 1.2-7.4; P < .011). ConclusionAfrican-American race appears to be independently associated with a greater risk of tumor recurrence after RC for UCB. The effect of host genetics on tumor biology needs to be characterized at the genomic level to develop precision medicine.

221 Prostate sparing cystectomy: 20 years single center experience

INTRODUCTION AND OBJECTIVES: Patients who experience disease recurrence after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) have a very poor prognosis. Most recurrences occur during the first two years following RC. The incidence, patterns, and prognosis of late recurrences (LRs) following RC have not been well described. METHODS: We queried our prospectively maintained institutional database and identified 1953 consecutive patients who underwent RC for UCB from 1995-2010. We identified patients who experienced disease recurrence following RC and analyzed both nonurothelial tract disease recurrence and urothelial recurrence. Late recurrence was defined as a non-urothelial tract recurrence occurring three or more years following RC. RESULTS: Of 648 UCB patients who experienced non-urothelial tract disease recurrence following RC, 93 (14%) occurred greater than 3 years following RC, and 42 (6%) occurred after 5 years (range 3.01 e 12.89 years). Of these 93 LRs, 22 (24%) were local, 54 (58%) were distant, and 17 (18%) were both local and distant. Sites of metastasis in patients with LRs included 21 (23%) lung, 20 (22%) bone, 47 (51%) lymphatic, 18 (19%) liver, 20 (22%) pelvis, and 5 (5%) other. Urothelial tract recurrences were identified in 44 of 93 patients with LR, 30 upper tract and 18 urethral. After excluding 17 patients in whom the LR could be ascribed to an invasive upper tract second primary tumor, 76 LR patients were left for analysis. The stage distribution at RC for LR patients was pT0 (7%), pTa (5%), pTis (18%), pT1 (12%), pT2 (26%), pT3 (21%), and pT4 (8%). Twelve LR patients (16%) had LN-positive disease. Eleven LR patients had received pre-operative cisplatin-based chemotherapy and 8 received adjuvant chemotherapy. LR patients were more likely to have organ-confined disease at RC (62% vs. 21%, p<0.001) and concomitant CIS (78% vs. 61%, p1⁄40.02) than patients experiencing recurrence within 3 years. However, the prognosis following recurrence was similarly poor for patients experiencing LR as it was for early recurrence, although LR patients had a slightly longer time from recurrence to death (p1⁄40.002). CONCLUSIONS: Bladder cancer patients treated with RC remain at risk for disease recurrence for many years, although the majority of patients who will recur do so within the first two years. Patients who experience late recurrence have different disease characteristics than those who experience early recurrence. Continued surveillance for detection of local, distant, and urothelial recurrences following RC may be beneficial.

MP55-05 LATE RECURRENCE FOLLOWING RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA OF THE BLADDER

INTRODUCTION AND OBJECTIVES: Patients who experience disease recurrence after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) have a very poor prognosis. Most recurrences occur during the first two years following RC. The incidence, patterns, and prognosis of late recurrences (LRs) following RC have not been well described. METHODS: We queried our prospectively maintained institutional database and identified 1953 consecutive patients who underwent RC for UCB from 1995-2010. We identified patients who experienced disease recurrence following RC and analyzed both nonurothelial tract disease recurrence and urothelial recurrence. Late recurrence was defined as a non-urothelial tract recurrence occurring three or more years following RC. RESULTS: Of 648 UCB patients who experienced non-urothelial tract disease recurrence following RC, 93 (14%) occurred greater than 3 years following RC, and 42 (6%) occurred after 5 years (range 3.01 e 12.89 years). Of these 93 LRs, 22 (24%) were local, 54 (58%) were distant, and 17 (18%) were both local and distant. Sites of metastasis in patients with LRs included 21 (23%) lung, 20 (22%) bone, 47 (51%) lymphatic, 18 (19%) liver, 20 (22%) pelvis, and 5 (5%) other. Urothelial tract recurrences were identified in 44 of 93 patients with LR, 30 upper tract and 18 urethral. After excluding 17 patients in whom the LR could be ascribed to an invasive upper tract second primary tumor, 76 LR patients were left for analysis. The stage distribution at RC for LR patients was pT0 (7%), pTa (5%), pTis (18%), pT1 (12%), pT2 (26%), pT3 (21%), and pT4 (8%). Twelve LR patients (16%) had LN-positive disease. Eleven LR patients had received pre-operative cisplatin-based chemotherapy and 8 received adjuvant chemotherapy. LR patients were more likely to have organ-confined disease at RC (62% vs. 21%, p<0.001) and concomitant CIS (78% vs. 61%, p1⁄40.02) than patients experiencing recurrence within 3 years. However, the prognosis following recurrence was similarly poor for patients experiencing LR as it was for early recurrence, although LR patients had a slightly longer time from recurrence to death (p1⁄40.002). CONCLUSIONS: Bladder cancer patients treated with RC remain at risk for disease recurrence for many years, although the majority of patients who will recur do so within the first two years. Patients who experience late recurrence have different disease characteristics than those who experience early recurrence. Continued surveillance for detection of local, distant, and urothelial recurrences following RC may be beneficial.

MP55-17 PRE-TREATMENT NEUTROPHIL-TO-LYMPHOCYTE RATIO AS PREDICTOR OF ADVERSE OUTCOMES IN PATIENTS UNDERGOING RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA OF THE BLADDER

Division of Medical Oncology, Department of Medicine, Princess Margaret Cancer Centre, 610 University Avenue, Toronto,Ontario, Canada M5G 2M9Background: An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor outcome in various tumours. Its prognosticutility in patients with urothelial carcinoma of the bladder (UCB) undergoing radical cystectomy (RC) is yet to be fully elucidated.Methods: A cohort of patients undergoing RC for UCB in a tertiary referral centre between 1992 and 2012 was analysed.Neutrophil-to-lymphocyte ratio was computed using complete blood counts performed pre-RC, or before neo-adjuvantchemotherapy where applicable. Time-dependent receiver operating characteristic curves were used to determine the optimalcutoff point for predicting recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The predictiveability of NLR was assessed using Kaplan–Meier analyses and multivariable Cox proportional hazards models. The likelihood-ratiotest was used to determine whether multivariable models were improved by including NLR.Results: The cohort included 424 patients followed for a median of 58.4 months. An NLR of 3 was determined as the optimal cutoffvalue. Patients with an NLRX3.0 had significantly worse survival outcomes (5y-RFS: 53% vs 64%, log-rank P¼0.013; 5y-CSS: 57% vs75%, log-rank Po0.001; 5y-OS: 43% vs 64%, log-rank Po0.001). After adjusting for disease-specific predictors, an NLR X3.0 wassignificantly associated with worse RFS (HR¼1.49; 95% CI¼1.12–2.0, P¼0.007), CSS (HR¼1.88; 95% CI¼1.39–2.54, Po0.001) andOS (average HR¼1.67; 95% CI¼1.17–2.39, P¼0.005). The likelihood-ratio test confirmed that prognostic models were improvedby including NLR.Conclusions: Neutrophil-to-lymphocyte ratio is an inexpensive prognostic biomarker for patients undergoing RC for UCB. It offerspre-treatment prognostic value in addition to established prognosticators and may be helpful in guiding treatment decisions.Radical cystectomy (RC) with pelvic lymph node dissectionis the standard treatment for muscle-invasive (MI) urothelialcarcinoma of the bladder (UCB) and is recommended for patientswith non-muscle-invasive (NMI) UCB with high risk ofprogression (Clark et al,2013).Despitecurativeintent,diseaserecurs in a significant proportion of patients and 5-year survival