Urothelial Carcinoma Of The Bladder Patients Research Articles

Metastatic Urothelial Carcinoma of the Bladder with Lymph Node-only Metastasis Treated with M-VAC (Methotrexate, Vinblastine, Doxorubicin and Cisplatin) has a Better Survival than GC (Gemcitabine and Cisplatin)

BackgroundPrevious studies demonstrated that GC (gemcitabine and cisplatin) provided a similar survival advantage as M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for urothelial carcinoma of the bladder (UCB), and had a better safety profile and improved tolerability. However, no clinical clues in selection of first-line chemotherapy regimen were suggested. This study aims to determine whether different sites of metastasis and chemotherapy regimens affected the prognosis of patients with metastatic UCB. MethodsPatients with metastatic UCB were retrospectively reviewed. Data on clinical characteristics, progression free survival (PFS), overall survival (OS), overall response rate (ORR) and complete response (CR) rate were analyzed. ResultsBetween 2000 and 2012, a total of 76 patients with metastatic UCB were enrolled. The median age was 64.5 years and the median follow-up period was 13.6 months. Of these patients, 37 had lymph node-only metastasis (LOM) and 39 had non-LOM. The median survival was significantly longer for UCB patients with LOM. The median PFS was 10.0 months for LOM and 4.3 months for non-LOM (P = < 0.01), while the median OS was 16.9 months for LOM and 10.5 months for non-LOM (P = < 0.01). The ORR and CR rate were both significantly higher in patients with LOM than in those with non-LOM. Subgroup analysis suggested that UCB patients with LOM treated with M-VAC had a better survival. The median PFS was 16.4 months in the M-VAC group and 8.7 months in the GC group (P = 0.08), while the median OS was 23.1 months in the M-VAC group and 16.0 months in the GC group (P = 0.03). The CR rate remained significant. ConclusionsUCB patients with LOM, especially those treated with M-VAC, had better survival outcomes and greater CR rate than those with non-LOM. However, the sample size of this study was quite small and analyzed on a retrospective basis. Further prospective randomized studies are warranted.

MP49-07 THE RISK OF POSTOPERATIVE VENOUS THROMBOEMBOLISM ACCORDING TO THE CIRCULATING TUMOR CELL STATUS IN PATIENTS WITH UROTHELIAL CARCINOMA OF THE BLADDER TREATED WITH RADICAL CYSTECTOMY

You have accessJournal of UrologyBladder Cancer: Invasive III1 Apr 2016MP49-07 THE RISK OF POSTOPERATIVE VENOUS THROMBOEMBOLISM ACCORDING TO THE CIRCULATING TUMOR CELL STATUS IN PATIENTS WITH UROTHELIAL CARCINOMA OF THE BLADDER TREATED WITH RADICAL CYSTECTOMY Armin Soave, Sabine Riethdorf, Roland Dahlem, Lars Weisbach, Valentin Maurer, Oliver Engel, Sarah Minner, Klaus Pantel, Margit Fisch, and Michael Rink Armin SoaveArmin Soave More articles by this author , Sabine RiethdorfSabine Riethdorf More articles by this author , Roland DahlemRoland Dahlem More articles by this author , Lars WeisbachLars Weisbach More articles by this author , Valentin MaurerValentin Maurer More articles by this author , Oliver EngelOliver Engel More articles by this author , Sarah MinnerSarah Minner More articles by this author , Klaus PantelKlaus Pantel More articles by this author , Margit FischMargit Fisch More articles by this author , and Michael RinkMichael Rink More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.420AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urothelial carcinoma of the bladder (UCB) patients are at a relevant risk for venous thromboembolism (VTE) following radical cystectomy (RC). In other cancer entities, circulating tumor cells (CTC) are associated with an increased risk of VTE. To evaluate whether the presence of CTC is associated with an increased postoperative risk of VTE and surgical complications in UCB patients treated with RC. METHODS We included 201 UCB patients treated with RC with bilateral pelvic lymphadenectomy without neoadjuvant chemotherapy at an academic center between 2007 and 2014. Preoperatively collected blood samples (7.5 ml) were analyzed for CTC using the CellSearch® system (Janssen, USA). Postoperative VTE was defined as clinically apparent venous thrombosis and/or pulmonary embolism following RC, and was confirmed by diagnostic imaging studies. Data on postoperative VTE and complications were collected retrospectively by patients' chart review. Postoperative complications were classified according to the Clavien-Dindo classification of surgical complications. Clinico-pathologic features were correlated with the VTE status and the CTC status. RESULTS Prior to RC, 54 patients (26.9%) had presence of CTC (mean CTC number: 4.9±31.3 (standard deviation (SD); median: 0; range: 0-372). Within 30 days postoperatively, 6 patients (3.0%) had VTE, and 136 patients (67.7%) had any surgical complication. The most frequent complications were Clavien-Dindo grade 1 and 2 complications in 95 patients (47.3%), followed by grade 3 complications in 25 patients (12.4%) and grade 4 complications in 15 patients (7.5%), respectively. The presence of VTE was not associated with the CTC status or any other clinico-pathologic characteristics. There was no difference in the number of CTC in patients with VTE (mean CTC number: 1.0±1.5 SD) and without VTE (mean CTC number: 5.0±31.7 SD), respectively. The VTE status and the CTC status were not associated with surgical complications. The presence of CTC was associated with a positive soft tissue surgical margin, the presence of lymphovascular and micro-vessel invasion, and the administration of adjuvant chemotherapy (all p-values≤0.045). CONCLUSIONS While complications occur frequently within 30 days after RC, VTE are relatively rare events. Following RC, UCB patients with presence of CTC do not seem to be at an increased risk of VTE. In addition, the presence of CTC is not associated with surgical complications. However, a longer follow-up is urgently warranted. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e666-e667 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Armin Soave More articles by this author Sabine Riethdorf More articles by this author Roland Dahlem More articles by this author Lars Weisbach More articles by this author Valentin Maurer More articles by this author Oliver Engel More articles by this author Sarah Minner More articles by this author Klaus Pantel More articles by this author Margit Fisch More articles by this author Michael Rink More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Overexpression of RNF2 Is an Independent Predictor of Outcome in Patients with Urothelial Carcinoma of the Bladder Undergoing Radical Cystectomy.

RNF2 (ring finger protein 2) is frequently overexpressed in several types of human cancer, but the status of RNF2 amplification and expression in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance is unclear. In this study, immunohistochemical analysis and fluorescence in situ hybridization (FISH) were used to examine the expression and amplification of RNF2 in 184 UCB patients after radical cystectomy. Overexpression of RNF2 was observed in 44.0% of UCBs and was found to significantly associate with shortened overall and cancer-specific survival (P < 0.001). In different subsets of UCBs, RNF2 overexpression was also identified as a prognostic indicator in patients with pT1, pT2, pN(−), and/or negative surgical margins (P < 0.05). Importantly, RNF2 overexpression together with pT status and surgical margin status provided significant independent prognostic parameters in multivariate analysis (P < 0.01). FISH results showed amplification of RNF2 in 8/79 (10.1%) of informative UCB cases. Additionally, RNF2 overexpression was significantly associated with RNF2 gene amplification (P = 0.004) and cell proliferation (P = 0.003). These findings suggested that overexpression of RNF2, as examined by immunohistochemical analysis, might serve as a novel prognostic biomarker and potential therapeutic target for UCB patients who undergo radical cystectomy.

Metabolic syndrome and the risk of urothelial carcinoma of the bladder: a case-control study.

BackgroundThe Metabolic syndrome (MetS) is an emerging condition worldwide, consistently associated with an increased risk of several cancers. Some information exists on urothelial carcinoma of the bladder (UCB) and MetS. This study aims at further evaluating the association between the MetS and UCB.MethodsBetween 2003 and 2014 in Italy, we conducted a hospital-based case-control study, enrolling 690 incident UCB patients and 665 cancer-free matched patients. The MetS was defined as the presence of at least three of the four selected indicators: abdominal obesity, hypercholesterolemia, hypertension, and diabetes. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) for MetS and its components were estimated through multiple logistic regression models, adjusting for potential confounders.ResultsPatients with MetS were at a 2-fold higher risk of UCB (95 % CI:1.38–3.19), compared to those without the MetS. In particular, ORs for bladder cancer were 2.20 (95 % CI:1.42–3.38) for diabetes, 0.88 (95 % CI: 0.66-1.17) for hypertension, 1.16 (95 % CI: 0.80-1.67) for hypercholesterolemia, and 1.63 (95 % CI:1.22–2.19) for abdominal obesity. No heterogeneity in risks emerged across strata of sex, age, education, geographical area, and smoking habits. Overall, 8.1 % (95 % CI: 3.9-12.4 %) of UCB cases were attributable to the MetS.ConclusionsThis study supports a positive association between the MetS and bladder cancer risk.

Impact of reduced levels of APE1 transcripts on the survival of patients with urothelial carcinoma of the bladder.

Molecular evidence indicates that alterations in genes involved in the maintenance of genome stability may be related to susceptibility to bladder carcinoma. Our goal was to evaluate the prognostic role of base excision repair (BER) genes in a cohort of patients diagnosed with primary urothelial carcinoma of the bladder (UCB). The levels of all APE1, XRCC1 and POLB transcripts were detected by quantitative real-time PCR (qPCR) technique in tumor samples from 52 patients undergoing transurethral resection (TUR) for primary UCB at the Department of Urology, Brazilian National Cancer Institute, Rio de Janeiro. Increased levels of APE1, XRCC1 and POLB transcripts were significantly associated with high-grade tumors when compared to these levels in low-grade tumors (p<0.01) and could be attributed to different mechanisms of transcriptional regulation as a response to tumorigenesis and oxidative stress. By analyzing the collected data in the present study, regardless of pathological grade or stage, univariate analysis revealed that the reduced levels of APE1 transcripts were significantly associated with cancer-specific mortality (p=0.032). Furthermore, the variant genotype (TG/GG) of the APE1 T1349G polymorphism was observed in 75% of a subset of patients who concomitantly experienced reduced levels of the APE1 transcript and death and/or recurrence events. Taken together, our data reinforce the idea that human DNA repair mechanisms must be finely regulated in order to avoid instability leading to tumorigenesis and poor clinical outcomes in UCB patients.

Do circulating tumor cells have a role in deciding on adjuvant chemotherapy after radical cystectomy?

Radical cystectomy (RC) with bilateral pelvic lymphadenectomy with or without perioperative chemotherapy is the golden standard treatment in muscle invasive and recurrent high-grade non-muscle invasive urothelial carcinoma of the bladder (UCB). Despite treatment with curative intent, up to 50% of patients develop metastasis and die from UCB due to micro-metastatic disease undetectable for current staging techniques prior to definitive therapy. Tumor cell dissemination is a crucial step in the natural history of the metastatic cascade. Circulating tumor cells (CTC) are malignant epithelial cells detectable in the peripheral blood of patients with various malignancies. In UCB, CTC are detectable in a significant number of patients prior to RC and associated with inferior outcomes. In this review, we summarize the current literature regarding CTC in UCB, discussing their potential on clinical decision-making regarding multimodal treatment and implications on the application of novel targeted therapies in the future. There is reliable evidence that presence of CTC in clinically non-metastatic UCB patients treated with RC are a powerful predictor for unfavorable outcomes and may be useful for adjuvant chemotherapy decision-making and monitoring. However, currently, the evidence is limited, and thus, integration of CTC in future UCB clinical trials is strongly recommended to shed more light on the potential of this promising biomarker.

The impact of the AB0 and the Rhesus blood group system on outcomes in bladder cancer patients treated with radical cystectomy.

To investigate the impact of the AB0 and the Rhesus blood group system on outcomes of urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). We included 511 UCB patients treated with RC without neoadjuvant chemotherapy from 1996 to 2011 at our institution. Cox and logistic regression models assessed the association of the AB0 blood group antigen and Rhesus factor expression with tumor biologic features and outcomes, respectively. In total, 216 patients (42.3 %) had the blood group antigen A0, 73 patients (14.3 %) the antigen B0, 33 patients (6.4 %) the antigen AB and 189 patients (37.0 %) the antigen 00. In addition, 414 patients (81.0 %) were Rhesus factor positive. The AB0 blood group antigen expression was associated with a higher tumor grade (p = 0.003). In contrast, the Rhesus factor was not associated with any clinicopathologic characteristics. Neither the AB0 blood group antigens nor the Rhesus factor was associated with survival. In a sensitivity analysis of patients receiving adjuvant chemotherapy, however, the blood group antigen AB expression was associated with reduced cancer-specific and overall survival. The AB0 blood group antigens and the Rhesus factor are not associated with survival. Although the AB0 blood groups and the Rhesus factor are analyzed in every patient treated with RC, they do not represent appropriate biomarkers for UCB outcome prognostication. The association of the AB0 blood group antigens with response to adjuvant chemotherapy requires further validation.

Prospective validation of DACH2 as a novel biomarker for prediction of metastasis and prognosis in muscle-invasive urothelial carcinoma of the bladder

Metastasis is the main cause of death from muscle-invasive urothelial carcinoma of the bladder (UCB), and the metastatic potential of tumors is often unpredictable. The role of Dachshund homolog 2 gene (DACH2) in tumorigenesis remains unexplored. We aimed to investigate whether DACH2 can be used as a biomarker to predict metastasis and prognosis of muscle-invasive UCB in a sequential training and validation fashion. For the training set (n = 40), compared with UCB patients without lymph node (LN) metastasis, both DACH2 protein and mRNA expression were greatly increased in case-matched patients with LN metastasis. For the independent validation set (n = 243), patients with primary UCB that did not express DACH2 had a longer metastasis-free survival (MFS) and overall survival (OS) than did those with tumors expressing DACH2 (5-year MFS: 88% [95% CI 80–96] versus 19% [95% CI 7–31], p < 0.001; 5-year OS: 93% [95% CI 87–99] versus 37% [95% CI 23–51], p < 0.001). Multivariable analysis of DACH2 status showed hazard ratios of 7.34 (95% CI 3.15-11.87, p < 0.001) for MFS and 3.96 (95% CI 2.04-7.16, p < 0.001) for OS which were much higher than hazard ratios associated with other independent risk factors. Collectively, DACH2 is an independent prognostic marker that can be used at initial diagnosis of UCB to identify patients who have a high potential to develop metastasis.

Detection of lymphovascular invasion in urothelial carcinoma of the bladder through D2-40 immunostaining

Lymphovascular invasion (LVI) represents a surrogate marker for micrometastatic urothelial carcinoma of the bladder (UCB). We evaluated whether D2-40 immunhistochemistry (IHC) alters detection of LVI when compared to conventional HE (hematoxylin-eosin) staining of UCB specimens in a blinded fashion. HE- and D2-40-IHC-stained representative sections of 80 patients after radical cystectomy (RC) were re-reviewed. LVI detection rates were recorded and compared after blinded evaluation. LVI was present in 53 patients (66.3%) in HE-stained sections and in 44 patients (55%) in D2-40 stainings. In 13 patients, LVI (16.3%) was found in HE stained sections but not confirmed when IHC was applied (false positive when using IHC as a reference standard). D2-40 IHC identified LVI in 4 additional patients (5%) who were classified as LVI negative in conventional HE staining (false negative). 52 patients (65%) were lymph node negative (pN0), 21 of whom (40.4%) were LVI positive in conventional HE sections and 16 of whom (30.8%) were LVI positive in IHC. In 9 pN0 patients (17.3%), LVI was diagnosed in HE sections but not confirmed by IHC (false positive). D2-40 IHC identified LVI in 4 additional patients (7.7%) who were node negative and classified as LVI negative in conventional HE staining (false negative). In patients who experienced recurrence (n=35) and who were classified as pN0 at the time of RC, HE staining resulted both in false-positive (n=2; 5.7%) and false-negative (n=3; 8.6%) findings. Different detection rates of LVI were observed when using IHC with D2-40 in UCB patients compared to conventional HE staining. The routine use of D2-40 IHC should be considered in clinical trial design to improve risk stratification of pN0 patients after RC.

Outcome of Patients with Pathological Tumor Stage T3 Urothelial Carcinoma of the Bladder following Radical Cystectomy in a Single-Center Series with 116 Patients

Objective: Outcome prediction of pT3 urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) remains challenging. The objective of our study was to determine high-risk patients with poor survival outcome in a heterogeneous group substaged pT3 who might profit from early adjuvant chemotherapy. Materials and Methods: We compiled clinicopathological and immunohistochemical data of E-cadherin (E-cad) expression in 116 patients with pT3 UCB after RC in our single-center series. Multivariable Cox regression models including substaged pT3 established clinicopathological features, and the expression of the predictive immunohistochemical feature E-cad was used to identify independent predictors on progression-free (PFS), cancer-specific (CSS) and overall survival (OS), respectively. Results: No significant differences were found addressing clinicopathological data and substaged pT3. In multivariable Cox regression models, lymph node involvement was an independent predictor for PFS (p < 0.001), CSS (p < 0.001) and OS (p = 0.002), respectively. Lymphovascular invasion (LVI) significantly influenced PFS (p = 0.016). ASA score 3/4 independently predicted CSS (p = 0.049) and OS (p = 0.032). Neither pT3 substages nor E-cad expression were significant prognosticators for survival. Conclusions: In pT3 UCB patients with ASA 3/4, positive lymph node status and/or presence of LVI, administration of chemotherapy should be considered due to the high risk of poor oncological outcome. The immunohistochemical marker E-cad was not an independent predictor.

Genomic Predictors of Survival in Patients with High-grade Urothelial Carcinoma of the Bladder

Urothelial carcinoma of the bladder (UCB) is genomically heterogeneous, with frequent alterations in genes regulating chromatin state, cell cycle control, and receptor kinase signaling. To identify prognostic genomic markers in high-grade UCB, we used capture-based massively parallel sequencing to analyze 109 tumors. Mutations were detected in 240 genes, with 23 genes mutated in ≥5% of cases. The presence of a recurrent phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation was associated with improved recurrence-free survival (RFS) (hazard ratio [HR]: 0.35; p=0.014) and improved cancer-specific survival (CSS) (HR: 0.35; p=0.040) in patients treated with radical cystectomy (RC). In multivariable analyses controlling for pT and pN stages, PIK3CA mutation remained associated with RFS (HR: 0.39; p=0.032). The most frequent alteration, TP53 mutation (57%), was more common in extravesical disease (69% vs 32%, p=0.005) and lymph node–positive disease (77% vs 56%, p=0.025). Patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)–altered tumors experienced worse RFS (HR: 5.76; p<0.001) and worse CSS (HR: 2.94; p=0.029) in multivariable analyses. Mutations in chromatin-modifying genes were highly prevalent but not associated with outcomes. In UCB patients treated with RC, PIK3CA mutations are associated with favorable outcomes, whereas TP53 and CDKN2A alterations are associated with poor outcomes. Genomic profiling may aid in the identification of UCB patients at highest risk following RC. Patient summaryUsing next-generation sequencing, we identified genomic subsets of high-grade urothelial bladder cancer associated with favorable and unfavorable outcomes. These findings may aid in the selection of patients most likely to benefit from novel combined modality approaches.

Cell-free urinary microRNA-99a and microRNA-125b are diagnostic markers for the non-invasive screening of bladder cancer.

BackgroundEvidence implicated the diagnostic significance of microRNAs in whole urine/urine sediments in urothelial carcinoma of the bladder (UCB). However, the contaminated blood cells in patients with haematouria significantly altered the expression profiles of urinary microRNA, influencing the test accuracy.MethodsMicroRNA profiles of the urine supernatants of UCB patients and controls without any malignancy and profiles of malignant and corresponding normal mucosa tissues from the patients were determined by microRNA microarray and compared to identify differentially expressed microRNAs. The differential expression was verified in the tissues of an independent patient cohort by RT-qPCR. The diagnostic significance of selected microRNAs as biomarkers in the urine supernatant was investigated in the expanded cohorts.ResultsMicroRNA-99a and microRNA-125b were down-regulated in the urine supernatants of UCB patients. The degree of down-regulation was associated with the tumor grade. A diagnostic model was developed using a combined index of the levels of microRNA-99a and microRNA-125b in the urine supernatant with a sensitivity of 86.7%, a specificity of 81.1% and a positive predicted value (PPV) of 91.8%. Discriminating between high- and low-grade UCB, the model using the level of microRNA-125b alone exhibited a sensitivity of 81.4%, a specificity of 87.0% and a PPV of 93.4%.ConclusionsThe results revealed a unique microRNA expression signature in the urine supernatants of UCB patients for the development of molecular diagnostic tests. An effective cell-free urinary microRNA-based model was developed using a combined index of the levels of microRNA-99a and microRNA-125b to detect UCB with good discriminating power, high sensitivity and high specificity.

Prognostic Significance of Lactate/Proton Symporters MCT1, MCT4, and Their Chaperone CD147 Expressions in Urothelial Carcinoma of the Bladder

To investigate the prognostic significance of lactate/proton monocarboxylate transporters MCT1, MCT4, and their chaperone CD147 expressions in urothelial carcinoma of the bladder (UCB). We examined the expressions of MCT1, MCT4, and CD147 proteins in a total of 360 cases of UCB by immunohistochemistry. The immunohistochemical expressions were quantified using an ImageJ-based analysis program. MCT1, MCT4, and CD147 expressions were increased in 130 (36.1%), 168 (46.7%), and 228 (63.3%) UCB cases, respectively. Most tumor cells showed diffuse membranous staining, whereas normal urothelial cells showed negative or weak staining. High levels of MCT1 expression correlated with high World Health Organization grade (P<.001), advanced tumor node metastasis (TNM) stage (P<.001), nonpapillary growth type (P<.001), and lymphatic tumor invasion (P=.010), whereas high levels of MCT4 expression did not significantly correlate with any of these variables. High CD147 expression was associated with high World Health Organization grade (P<.001), advanced tumor node metastatis stage (P<.001), and nonpapillary growth type (P=.003). Univariate analyses revealed that high MCT1 (P<.001) and CD147 (P=.029) expressions were associated with poor overall survival and that high MCT4 expression was correlated with poor recurrence-free survival (P=.036). Multivariate analyses revealed that high MCT1 and MCT4 expressions were independent prognostic factors for poor overall survival and poor recurrence-free survival, respectively, in UCB patients. Our results indicate that increased MCT1, MCT4, and CD147 expressions have prognostic implications in UCB and suggest their roles in urothelial cancer metabolism.

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.

MP55-02 DO CIRCULATING TUMOR CELLS HELP IN DECISION-MAKING REGARDING ADJUVANT CHEMOTHERAPY IN PATIENTS WITH UROTHELIAL CARCINOMA OF THE BLADDER TREATED WITH RADICAL CYSTECTOMY?

You have accessJournal of UrologyBladder Cancer: Invasive II1 Apr 2014MP55-02 DO CIRCULATING TUMOR CELLS HELP IN DECISION-MAKING REGARDING ADJUVANT CHEMOTHERAPY IN PATIENTS WITH UROTHELIAL CARCINOMA OF THE BLADDER TREATED WITH RADICAL CYSTECTOMY? Armin Soave, Sabine Riethdorf, Lars Weisbach, Sarah Minner, Oliver Engel, Jens Hansen, Felix K. Chun, Roland Dahlem, Klaus Pantel, Margit Fisch, and Michael Rink Armin SoaveArmin Soave More articles by this author , Sabine RiethdorfSabine Riethdorf More articles by this author , Lars WeisbachLars Weisbach More articles by this author , Sarah MinnerSarah Minner More articles by this author , Oliver EngelOliver Engel More articles by this author , Jens HansenJens Hansen More articles by this author , Felix K. ChunFelix K. Chun More articles by this author , Roland DahlemRoland Dahlem More articles by this author , Klaus PantelKlaus Pantel More articles by this author , Margit FischMargit Fisch More articles by this author , and Michael RinkMichael Rink More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1550AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Circulating tumor cells (CTC) in urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC) are predictors for unfavorable outcomes. Administration of adjuvant chemotherapy is associated with improved survival in some UCB patients. To evaluate if determination of CTC may help in patient counseling regarding administration of adjuvant chemotherapy. Methods We prospectively collected data of 181 UCB patients treated with RC without neoadjuvant chemotherapy at an academic center between 2007 and 2012. Preoperatively collected blood samples (7.5ml) were analyzed for CTC using the CellSearch® system (Veridex, USA). We correlated clinico-pathologic parameters and outcomes with administration of adjuvant chemotherapy and according to the CTC status. Cox regression models evaluated the association with disease recurrence and cancer-specific survival, respectively. Results In total, 40 patients (22.1%) had presence of CTC (mean number: 11±34; median: 1) prior to RC. Adjuvant chemotherapy (86.9% Cisplatin-based) was administered to 46 patients (25.4%) with a median number of 4 cycles (range: 1-6). Administration of adjuvant chemotherapy was significantly associated with younger age, advanced pT-stage, higher grade, lymph node metastasis, presence of LVI and positive soft tissue margin status (p-values ≤0.039). Patients with presence of CTC received more often adjuvant chemotherapy (CTC pos vs. neg: 35% vs. 18%; p=0.023). At a mean follow-up of 30 months, CTC presence was associated with disease recurrence and cancer-specific mortality (both p<0.001), respectively, in patients without adjuvant chemotherapy. In contrast, in patients who received adjuvant chemotherapy CTC status was not associated with outcomes. In multivariable analysis that adjusted for age, pT-stage, tumor grade, lymph node metastasis, LVI and margin status, presence of CTC was an independent predictor for disease recurrence (HR 3.94; 95%CI 1.77-8.77; p=0.001) and cancer specific mortality (HR 3.83; 95%CI 1.56-9.38; p=0.003), respectively, in patients without adjuvant chemotherapy administration. Conclusions Presence of CTC is a strong predictor for outcomes in UCB patients treated with RC without adjuvant chemotherapy. Thus, CTC status may be used for patient counseling and decision- making regarding further therapies in patients who otherwise would not be counseled regarding adjuvant therapies. In addition, adjuvant chemotherapy may abrogate the impact of CTC on survival. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e555 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Armin Soave More articles by this author Sabine Riethdorf More articles by this author Lars Weisbach More articles by this author Sarah Minner More articles by this author Oliver Engel More articles by this author Jens Hansen More articles by this author Felix K. Chun More articles by this author Roland Dahlem More articles by this author Klaus Pantel More articles by this author Margit Fisch More articles by this author Michael Rink More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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.

Gender-specific outcomes of bladder cancer patients: A stage-specific analysis in a contemporary, homogenous radical cystectomy cohort

IntroductionControversial findings regarding gender-specific oncological outcomes of urothelial carcinoma of the bladder (UCB) have recently been reported. The aim of this study was to analyze gender-specific outcomes using a stage-adjusted approach in a homogenous, contemporary radical cystectomy (RC) cohort. Material and methodsWe prospectively collected data of 517 UCB patients treated with RC and pelvic lymphadenectomy without neoadjuvant chemotherapy at our institution between 1996 and 2010. Stage-adjusted uni- and multivariable Cox regression models analyzed the association of gender with disease recurrence, cancer-specific mortality and overall survival. ResultsIn total, 398 (77%) patients were male and 119 (23%) were female. Compared to men, women were more likely to have advanced tumor stages (p = 0.017), nodal metastasis (p = 0.047) and received more frequently adjuvant chemotherapy (p = 0.009). At a median follow-up of 44 months, there was no statistical difference in disease recurrence, cancer-specific mortality and overall survival between both genders when analyzed as a group. In stage-adjusted analyses, only women with non-invasive UCB were more likely to die of UCB compared to the male counterparts (p = 0.013). In gender-specific multivariable analyses that adjusted for standard clinico-pathologic features, pathologic tumor stage was an independent predictor for disease recurrence (p-values ≤0.047) and cancer-specific mortality (p-values ≤0.049), respectively. ConclusionWomen present with more aggressive tumor biologic features at RC, however this did not translate into inferior outcomes compared to men in stage-specific analyses in our cohort. Tumor stage is the most important factor influencing the course of disease in both genders. Validation of our findings is warranted in a larger cohort.

The effect of intra- and postoperative allogenic blood transfusion on patients’ survival undergoing radical cystectomy for urothelial carcinoma of the bladder

Radical cystectomy (RC) can be associated with significant blood loss. Allogenic blood transfusion (ABT) may alter disease outcome because of a theoretical immunomodulatory effect. We evaluated the effects of ABT on overall survival (OS) and progression-free survival (PFS) of patients undergoing RC for urothelial carcinoma of the bladder (UCB). This is a retrospective single-center study of 350 consecutive patients of a university health center with a median follow-up of 70.1 month. All patients underwent RC and pelvic lymph node dissection. The effect of ABT on OS and PFS was analyzed using univariable and multivariable Cox proportional hazards models. The overall ABT rate was 63 % (n = 219), with intraoperative blood transfusion and postoperative blood transfusion being performed in 183 patients (52 %) and 99 patients (28 %), respectively. Preoperative anemia was detected in 156 patients (45 %) with median estimated blood loss of 800 ml (IQR: 500-1,200). ABT was associated with significant decrease of OS and PFS in multivariable analyses (p < 0.001), whereas patients' prognosis worsened the more packed red blood cells (PRBC) were transfused (p < 0.001). The study is limited in part due to its retrospective design. We found that ABT and the number of PRBC transfused are associated with poor prognosis for UCB patients undergoing RC, whereas preoperative anemia had no influence on survival. This emphasizes the importance of surgeon's awareness for a strict indication for ABT. A prospective study will be necessary to evaluate the independent risks associated with ABT during surgical treatments.

Comparison of oncologic outcomes following systemic neoadjuvant chemotherapy and radical cystectomy in patients with mixed histologic variants and pure urothelial carcinoma of the bladder.

333 Background: Neoadjuvant chemotherapy (CT) is recommended prior to radical cystectomy (RC) in patients with muscle invasive urothelial carcinoma of the bladder (UCB), and has been shown to have modest survival benefit in clinical trials. The purpose of our study was to investigate the response and survival rates in patients with histologic variants (HV) and compare oncologic outcomes to patients with pure UCB. Methods: We performed a retrospective review of 163 patients treated with neoadjuvant CT prior to RC. Twenty-four patients with HV and 139 with pure UCB were identified. Numerous patient demographics, clinical and pathologic characteristics were evaluated including; clinical and pathologic stage, HV, lymphovascular invasion (LVI), margin status, node counts, concomitant carcinoma in situ (CIS), previous intravesical treatments, prior pelvic radiation, completeness of bladder tumor resection (TURBT), and CT regimens. Results: Patients with HV were younger (66.5 versus 71 years, p=0.04) but otherwise there were no significant differences noted between the two groups comparing previous treatments, clinical staging, margin status, node counts, CT regimens, # of neoadjuvant CT cycles, or rates of adjuvant CT administration. Of the 24 HV patients, 11 (47.8%) were downstaged to &lt; pT2 compared to 50 (64.1%) of 139 patients with pure UCB (P=0.37). pT0 rates for HV and pure UCB were 16.7% and 23%, respectively (p=0.60). Twelve (50%) of the HV group compared to 65 (46.8%) of the pure UCB patients (p=0.83), had no evidence of disease at a mean follow up after RC of 19.5 (HV) and 22 (UCB) months. Eight (33.3%) patients with HV died of disease compared to 44 (31.7%) in the UCB group, (p=1.0). There was no significant difference noted in CSS and OS between the 2 groups, although there was a trend towards higher rates of node positive disease (p=0.086) and inferior CSS (p=0.09) in patients with HV compared to patients with pure UCB. Conclusions: Our results indicate that patients with HV experience similar oncologic outcomes from neoadjuvant systemic CT compared to patients with pure UCB.

Clinical Significance of Survivin Expression in Patients with Urothelial Carcinoma

Background. Survivin is a member of the inhibitors of apoptosis protein family that plays an important role in carcinogenesis. Here, we examined the association between survivin expression and clinical outcome in urothelial carcinoma of the bladder (UCB). Methods. A total of 56 histopathologically confirmed UCB patients were recruited from the Department of Urology of Chiayi Christian Hospital from August 2007 to May 2009. Immunohistochemistry (IHC) was used to detect the survivin expression in tumor tissues. The –31 C/G polymorphism in survivin promoter region was determined by polymerase chain reaction-restricted fragment length polymorphism. Results. The frequency of high survivin expression was significantly higher in muscle-invasive tumors (66.6%) than in non-muscle-invasive tumors (34.2%) (P = 0.042) and in poorly differentiated (85.7%) tumors than in moderately differentiated tumors (30.8%) (P = 0.0014). The higher frequency of risk genotypes (C/C and C/G) was found in the median (72.7%) and high (68.0%) survivin expression groups. The multivariate analysis showed that a high survivin expression level was a potential predictive biomarker of poor overall survival (P = 0.02). Conclusion. Our results suggest that the high survivin expression was associated with tumor stage and grade and may present a predictive marker of overall survival in UCB.