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Introduction and Objectives: We examined the impact of preoperative plasma potassium levels (PPLs) on outcomes in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB), hypothesizing that potassium imbalances might influence outcomes., Patients and Methods: In this retrospective study, 501 UCB patients undergoing RC from 2009 to 2017 at a tertiary center were analyzed. Blood samples collected a week prior to surgery defined normal and abnormal PPL based on institutional standards. We assessed overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), postoperative complications, 30-day mortality, and non-organ confined disease. Kaplan-Meier estimates, Cox proportional hazards, logistic regression, and decision curve analyses (DCA) were employed., Results: 63 (13%) patients had abnormal preoperative PPLs, with 50 (10%) elevated and 13 (2.5%) decreased. In a 59 months median follow-up, 152 (31%) had disease recurrence, 197 (39%) died from any cause, and 119 (24%) from UCB. Multivariable cox regression analyses adjusting for perioperative parameters demonstrated abnormal PPL was associated with worse OS (HR=1.9, P=0.009), CSS (HR=2.8, P<0.001) and RFS (HR=2.1; P=0.007). Elevated preoperative PPLs also demonstrated significant associations with adverse outcomes in OS, CSS, and RFS (all P<0.05). In multivariable logistic regression analyses, abnormal and elevated PPLs were not associated with 30-day mortality, major 30-day postoperative complications, positive nodal disease, pT3/4 stage, and non-organ confined disease (all P>0.05)., Conclusion: Abnormal and elevated preoperative PPLs correlate with adverse oncologic outcomes in UCB patients treated with RC. Pending external validation, preoperative PPLs might be a cost-effective, easily obtainable supplemental biomarker for enriching accuracy of outcome prediction in this highly variable maladie., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: 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)., Materials and Methods: 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., Results: 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., Conclusions: 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.

Background: To evaluate whether the preoperative serum albumin level can predict the survival outcome in patients with bladder urothelial carcinoma (BUC) undergoing transurethral resection of bladder tumor (TURBT)., Methods: Four hundred fifty six newly diagnosed patients with BUC who underwent TURBT between January 2014 and December 2017 were retrospectively enrolled. Patients were categorized into low albumin (<40 g/L) and high albumin (≥40 g/L) groups. Survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional analyses were used to determine the hazard ratios (HRs) for overall survival (OS). Of patients with available data, 108 (24%) and 348 (76%) patients were classified into the low albumin (<40 g/L) and high albumin (≥40 g/L) groups, respectively., Results: The results of the Kaplan-Meier analysis and log-rank test showed a significantly worse 5-year OS (P = .003) in the low albumin group than in the high albumin group. In the multivariate Cox regression analysis, after adjusting for confounding variables, the preoperative albumin level remained an independent predictor for 5-year OS (HR: 0.434, 95% confidence interval: 0.221-0.852; P = .015)., Conclusion: Our study determined that a low preoperative albumin level predicted poor OS in patients with BUC who underwent TURBT. Preoperative serum albumin is an inexpensive and easily available marker that has the potential to be a good prognostic factor for predicting mortality in patients with BUC treated with TURBT., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To investigate differences in standard preoperative inflammatory markers in patients with urothelial carcinoma (UC) and variant histologies undergoing radical cystectomy (RC) and determine its impact on survival., Methods: Patients undergoing RC at an academic high-volume center were retrospectively analyzed. Preoperatively taken CRP, leukocytes, hemoglobin (Hb), and thrombocytes were analyzed as routine inflammatory biomarkers. Log-rank tests and Kruskal-Wallis analysis were used to calculate for differences in survival and in blood levels of biomarkers., Results: 886 patients with complete follow-up and UC or variant histology underwent RC at our institution between 2004 and 2019. Although variant histology presents with significantly higher t stage than UC, cancer-specific survival (CSS) of UC (1-year-CSS: 93%) is not significantly different to variant histology of UC with squamous differentiation (UCSD, 1-year-CSS: 81%), squamous cell carcinoma (SCC, 1-year-CSS: 82%), and adenocarcinoma (AC, 1-year-CSS: 81%). In UC, alterations in all biomarkers except leukocytes beyond routine cut-off values were associated with poor survival (p < 0.01), whereas Hb beyond cut-off values are associated with poor prognosis in SCC (p < 0.05). CRP levels are significantly elevated in UCSD and SCC at time of surgery compared to UC (p < 0.05)., Conclusion: Inflammatory biomarkers reveal distinctive patterns across UC and variant histologies of bladder cancer. As inflammation might play an important role in cancer progression, further research is warranted to understand those molecular mechanisms and their potential therapeutic impact in variant histology of bladder cancer., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The 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 Methods: We 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)., Results: Overall, 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., Conclusion: pAGR 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., Competing Interests: Conflicts of interest All authors have no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aims to evaluate whether preoperative serum albumin-to-globulin ratio (AGR) could predict the prognosis of patients with urothelial bladder cancer (UBC) after radical cystectomy (RC)., Materials and Methods: A total of 176 patients with UBC who underwent RC in a tertiary hospital between 2008 and 2019 were retrospectively analyzed. The AGR was calculated as albumin/(total protein - albumin). In addition, the AGR was divided into two groups for the time-dependent receiver operating characteristic curve (ROC) analysis. Survival was estimated using the Kaplan-Meier analysis and compared using the log-rank test. Cox proportional- hazards models were used for multivariate survival analysis., Results: The best cutoff AGR value for metastasis prediction was 1.32 based on the ROC curve analysis. Patients who had lower pretreatment AGR (<1.32) values composed the low-AGR group (n = 57; 32.4%). On the other hand, the remaining patients (n = 119; 67.6%) composed the high-AGR group. The patients in the low-AGR group had more advanced stage tumors compared with the patients in the high-AGR group. The Kaplan-Meier curves revealed that the patients in the low-AGR group had significantly lower rates of metastasis-free survival (MFS) and cancer-specific survival (CSS). The multivariate Cox regression analysis showed that preoperative AGR was an independent prognostic factor for MFS and CSS., Conclusion: In this single-institution retrospective study, lower preoperative AGR values demonstrated a poor prognostic effect on MFS and CSS in patients with UBC who underwent RC.

Background: A routine blood examination is one of the most rapid, convenient and inexpensive clinical examinations that can reflect a patient's inflammatory status and other blood conditions, and the prognostic value of routine preoperative blood parameters in MIBC patients is still unclear, so we evaluated the prognostic value of routine preoperative blood parameters in muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC)., Methods: Data on 202 patients with MIBC who underwent RC at our institution were retrospectively collected between October 2007 and August 2018. The median preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and hemoglobin (HGB) values were used as cutoffs to form the low and high NLR, low and high PLR, and low and high HGB groups, respectively. The clinicopathologic characteristics of each group were compared by chi-square and t tests. Kaplan-Meier survival and multivariate Cox regression analyses were used to analyze prognosis., Results: The median NLR, PLR and HGB values were 2.42, 112 and 125 g/L, respectively. Kaplan-Meier results showed that the low HGB group had poor progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). A high NLR and high PLR groups correlated only with poor OS. Multivariate Cox analyses showed that pathological T3/4 stage, positive lymph node status and low HGB were independent risk factors for PFS, CSS and OS, and age was the only independent risk factor for OS., Conclusion: Preoperative peripheral blood HGB is an independent risk factor for the prognosis of MIBC patients. These data suggest that HGB may be a useful prognostic marker for MIBC patients undergoing RC.

Objectives: Patients' oncological outcome after radical cystectomy (RC) due to urothelial carcinoma of the urinary bladder (UCB) is always up for debate. There is accumulating evidence on the influence of routine blood parameters. We aimed to identify reasonable and easy-to-detect biomarkers, such as preoperative C-reactive protein (CRP) and hemoglobin (Hb) levels, as predictors of overall survival (OS) and cancer-specific survival (CSS) in patients undergoing RC for UCB., Materials and Methods: This is a large single-center study in which both preoperative CRP and Hb levels were available in 1,043 patients undergoing RC for UCB from 2004 to 2018 with a median follow-up time of 22 months (mean 38, max. 170). We used the Kaplan-Meier method, log-rank test, and Cox regression models for assessment of OS and CSS. Using our data, we validated an existing outcome prediction score (TNR-C)., Results: Median CRP level was 0.5 mg/dL (IQR 0.2-1.4), and median Hb level was 13.4 g/dL (IQR 11.9-14.7). We found that patients with CRP values above the median reached a significantly lower median survival than those with CRP values below the median (23 vs. 83 months, p < 0.001). The TNR-C score was successfully validated, and we discriminated between 3 risk groups (5-year CSS: 76, 40, and 16% for low, intermediate, and high risk, respectively). We observed a similar outcome for patients with a Hb level below the median: CSS was significantly poorer than with Hb levels above the median (median CSS 27 vs. 91 months, p < 0.001). Multivariant analysis showed CRP and Hb levels to be independent prognostic parameters for CSS and OS., Conclusions: We found elevated preoperative CRP levels and decreased Hb levels to be independent prognostic factors indicating an unfavorable outcome in patients undergoing RC for UCB and were able to validate the TNR-C score in a large patient cohort. We propose using these routine biomarkers for individual risk stratification and optimization of therapeutic strategies in patients undergoing RC for UCB., (© 2020 S. Karger AG, Basel.)

Objective: To date, only a few studies have demonstrated the prognostic value of pretreatment serum albumin in bladder urothelial carcinoma (BUC). The aim of this study was to evaluate the association between the pretreatment albumin/globulin ratio (AGR) and the survival of patients with BUC treated with radical cystectomy (RC)., Materials and Methods: Data from 296 patients with BUC who underwent RC between June 2000 and June 2013 were analyzed. The AGR was calculated as follows: albumin/(total protein-albumin). The AGR was divided into 2 groups for receiver operating characteristics curve analysis. Survival was estimated using Kaplan-Meier analysis and compared using the log rank test. Cox proportional hazards models were used for univariate and multivariate survival analyses., Results: Patients in the high AGR group (AGR≥1.60) had a lower 5-year recurrence-free mortality rate compared with those in the low AGR group (AGR<1.60) (87.0% vs. 48.0%, P<0.001). The median cancer-specific survival (CSS) time was 71.1 months for low AGR patients and 156.0 months for the high AGR patients (P<0.001). After adjusting for confounding variables, the AGR remained an independent predictor of recurrence-free survival (RFS) (hazard rate = 0.356; 95% CI: 0.170-0.748; P = 0.006) and CSS (hazard rate = 0.280; 95% CI: 0.115-0.683; P = 0.005). Moreover, in the subset of 167 patients with normal serum albumin (albumin of≥40.0g/l), serum AGR continues to be an independent predictor of RFS (P = 0.012) and CSS (P = 0.008)., Conclusions: High AGR is a strong independent predictor of long-term RFS and CSS in patients with BUC undergoing RC. Additionally, among patients with normal albumin (≥40g/l) levels, patients with higher globulin, but lower AGR have worse survival. The pretreatment AGR is an easily accessible and cheap to use for predicting mortality in patients with BUC treated by RC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To develop a preoperative multivariable decision-making tool to predict nonorgan-confined urothelial carcinoma of the bladder (NOC-UCB) using standard clinical and pathological factors as well as biomarkers of systemic inflammatory response., Materials and Methods: We retrospectively analyzed a prospectively maintained single-institutional database comprising 310 patients with clinically N0 M0 UCB who underwent radical cystectomy (RC) with pelvic lymph node dissection without neoadjuvant cisplatin-based chemotherapy (NAC). NOC-UCB was defined as pT3-4/Nany or pTany/N + disease. A predictive nomogram was built based on significant variables in a bootstrap-corrected multivariable logistic regression model. The accuracy was measured by the area under the curve. Decision-curve analysis was used to evaluate the clinical net benefit., Results: NOC-UCB was found in 147 (47%) of the 310 patients. On multivariable analysis, T stage at transurethral resection of the bladder, lymphovascular invasion, abnormal imaging, and Glasgow prognostic score (GPS) were all independent predictors of NOC-UCB and formed the basis of the nomogram. By adding the GPS, the accuracy of the nomogram improved by 4.7% to 81.7%. The decision curve analysis showed a net benefit of this model compared with the Green model and the strategies of treating all patients or no patient with NAC. Limitations include the retrospective design and the lack of a validation cohort., Conclusion: NOC-UCB at radical cystectomy can be accurately predicted. The accuracy of preoperative models can be improved by adding biomarkers of systemic inflammatory response, such as the GPS. The use of this nomogram may help physicians to accurately identify patients with NOC-UCB who may benefit from NAC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Various systemic inflammatory response biomarkers are associated with oncological outcome. We evaluated the superiority of prognostic predictive accuracy between neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR), and the prognostic significance of their perioperative change in patients with bladder cancer undergoing radical cystectomy (RC). We retrospectively analyzed 302 patients who had undergone RC in four institutions. Comparison of predictive accuracy between NLR and LMR was performed using receiver operating characteristic curve analysis. Overall survival (OS) and cancer-specific survival (CSS) were assessed with the Kaplan-Meier method and Cox regression analysis. Preoperative and postoperative LMR showed higher predictive accuracy for OS than NLR did (p = 0.034). Applying a cutoff of 3.41, change in perioperative LMR stratified patients into three groups (low, intermediate, and high risk), showing a significant difference in OS and CSS (p < 0.001, each), and pathological outcomes. Multivariable analyses for OS and CSS showed that poor changes in LMR (high risk) were an independent prognostic factor (hazard ratio 5.70, 95 % confidence interval 3.49-9.32, p < 0.001; hazard ratio 4.53, 95 % confidence interval 2.63-7.82, p < 0.001; respectively). Perioperative LMR is significantly associated with survival in patients with bladder cancer after RC, and it is possibly superior to NLR as a prognostic factor.

Purpose: Different blood parameters have shown to be associated with patient's oncological outcome. There is only limited knowledge about the prognostic relevance of routine blood parameters in patients undergoing radical cystectomy for transitional cell carcinoma (TCC). Therefore, we retrospectively analyzed the influence of preoperative C-reactive protein (CRP) and hemoglobin (Hb) levels on overall survival (OS) and cancer-specific survival (CSS)., Materials and Methods: Preoperative CRP and Hb levels were available in 664 patients who underwent RC due to TCC from 2004 to 2013 at our institution. More men than women (77 vs. 23 %) underwent surgery with a median age of 70 years (35-97). Median follow-up time was 24 months (max. 108). Outcome was analyzed using Kaplan-Meier method, log-rank test, and Cox regression models., Results: Median CRP level was 0.5 mg/dl (0.1-28.3), and median Hb level was 13.4 g/dl (6.7-17.9). Patients with CRP value above the median died significantly earlier due to their disease than those with CRP below the median (median CSS 19 vs. 70 months; p < 0.001). Patients with preoperative Hb level below the median had significantly worse outcome than those with Hb level above the median (median CSS 25 vs. 78 months; p < 0.001). In multivariate analysis, CRP and Hb levels were independent prognostic parameters regarding CSS/OS (CRP p = 0.016/p = 0.004; Hb p = 0.006/p = 0.004, respectively)., Conclusions: In our single-center study, preoperative CRP and Hb levels were found to be independent prognostic factors, indicating impaired outcome in patients undergoing RC for TCC. These findings could be used for individual risk stratification and optimization of therapeutic strategies.

Background: We sought to determine which parsimonious combination of complete blood count (CBC)-based biomarkers most efficiently predicts oncologic outcomes in patients undergoing radical cystectomy (RC) for bladder cancer (BC)., Methods: Using our institutional RC database (1992-2012), nine CBC-based markers (including both absolute cell counts and ratios) were evaluated based on pre-treatment measurements. The outcome measures were recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Time-dependent receiver-operating characteristics curves were used to characterise each biomarker. The CBC-based biomarkers, along with several clinical predictors, were then considered for inclusion in predictive multivariable Cox models based on the Akaike Information Criterion., Results: Our cohort included 418 patients. Neutrophil-lymphocyte ratio (NLR) was the only biomarker satisfying criteria for inclusion into all models, independently predicting RFS (HR per 1-log unit=1.52, 95% CI=1.17-1.98, P=0.002), CSS (HR=1.47, 95% CI=1.20-1.80, P<0.001), and OS (HR=1.56, 95% CI=1.16-2.10, P=0.004). Haemoglobin was also independently predictive of CSS (HR per 1 g/dl=0.91, 95% CI=0.86-0.95, P<0.001) and OS (HR=0.90, 95% CI=0.88-0.93, P<0.001), but not RFS., Conclusions: Among CBC biomarkers studied, NLR was the most efficient marker for predicting RFS, whereas NLR and haemoglobin were most efficient in predicting CSS and OS. NLR and haemoglobin are promising, cost-effective, independent biomarkers for predicting oncologic BC outcomes following RC., Condensed Abstract: Various CBC-based biomarkers have separately been shown to be predictive of oncologic outcomes in patients undergoing cystectomy for BC. Our study evaluated these biomarkers, and determined that NLR is the best CBC-based biomarker for predicting RFS, whereas NLR and haemoglobin are most efficient for predicting CSS and OS.

Purpose: 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)., Methods: 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., Results: 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., Conclusion: 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.

Objective: To evaluate the impact of the preoperative American Society of Anesthesiologists (ASA) score and serum albumin level on complications, recurrences and survival rates of patients who underwent radical cystectomy (RC) for urothelial bladder cancer (UBC)., Patients and Methods: In all, 1964 patients underwent RC for UBC at our institution between 1971 and 2008. Preoperative serum albumin and ASA score were available in 1471 and 1140 patients, respectively. A complication was defined as any surgery related/unrelated event leading to lengthening hospital stay or re-admission. Endpoints were 90-day complication (90dC) rate, recurrence-free survival (RFS) and overall survival (OS)., Results: The median (range) follow-up was 12.4 (0.2-27.3) years. In all, 197 patients (13.4%) had a low albumin level (<3.5 g/dL) and 740 (64.8%) had a high ASA score (3 or 4). Low serum albumin and a high ASA score were associated with higher 90dC rate (42% vs 34%, P = 0.03 and 40% vs 28%, P < 0.001, respectively). On multiple logistic regression analysis, a high ASA score remained independently associated with increased 90dC rate (hazard ratio [HR] 1.52, P = 0.005) and decreased OS (HR 1.45, 95% confidence interval [CI] 1.13-1.86). A low serum albumin level was also independently associated with RFS (HR 1.68, 95% CI 1.16-2.43) and OS (HR 1.93, 95% CI 1.43-2.63)., Conclusion: A low serum albumin level was independently associated with cancer recurrence and decreased OS after RC. A high ASA score was also independently associated with decreased OS. These parameters potentially could be used as prognosticators after RC., (© 2013 The Authors. BJU International © 2013 BJU International.)

Bladder cancer is a heterogeneous disease that offers a unique challenge for the patient and the physician as treatment paradigms are continually evolving. There are multiple factors that can influence how each individual is treated, including lymphovascular invasion, micropapillary histology, and p53 nuclear accumulation which have demonstrated a worse prognosis in patients with bladder cancer. They can influence the use of neoadjuvant and adjuvant chemotherapy, which in itself can affect the timing of extirpative surgery. This review will focus on the contemporary management and treatment of bladder cancer focusing on areas of clinical decision making.

Objective: Despite having an organ confined tumor stage at the time of radical cystectomy, a certain number of bladder cancer patients will develop local or distant metastases over time. Currently there are no reliable serum markers for monitoring and evaluating risk profiles of urothelial cancers. Several studies suggest that detection of Circulating Tumor Cells (CTC) may correlate with disease status and prognosis at baseline and early in the treatment of cancers. The presence of CTCs in whole blood before and during radical cystectomy could provide further information on disease status, and could be used as an indicator to determine the need for adjuvant or even perioperative chemotherapy., Methods: From 03/2009 to 05/2009, five patients with histologically proven transitional cell carcinoma of the urinary bladder participated in this study. All patients were admitted to the hospital for radical cystectomy (rCx). A standard or extended lymph node dissection was performed in all cases. Preoperative CT or MRI scans revealed no distant or local metastases. Median age was 66.8 years (55-81 yrs). After obtaining informed consent from each patient, approximately 30 mL of peripheral blood was taken immediately before rCx and again during surgical removal of the urinary bladder from the patients ' body. As additional parameters, operation time (OR) for surgical removal of the bladder and the amount of blood volume that was used for the detection of CTCs were recorded. Obtained blood samples were processed using the Cell-Search System (Veridex) within 48 hours of collection. CTCs were identified and quantitated using the Cell-Search System, followed by re-evaluation of the provided results by specially trained and experienced personal (CS, SH)., Results: CTCs were detected before and during surgical removal of the urinary bladder in one of five patients (20%). In the one patient positive for CTC, two CTCs were detected in the blood sample that was obtained before surgery (analyzed blood volume was 25 mL). There was one CTC detected in the blood sample that was obtained during surgical removal of the urinary bladder (analyzed blood volume was 27 mL).There was no rise in the amount of CTCs during surgical procedure. The final pathological report of this patient showed an advanced tumor stage (T3b, N0, R1). In the other patients, no CTCs were detected at all, neither before rCX nor right after surgical removal of the bladder. Pathological stage for these patients ranged from pT1m G3 - pT2b G3. None of these patients showed lymph node involvement. An average of 14.6 lymph nodes (5-40 LNs) were obtained. OR time to surgical removal of the urinary bladder ranged from 60 minutes to 150 minutes (mean 82 min.)., Conclusions: Although only a very small group of patients was analyzed in this study, the presence of CTCs seems to be correlated with an advanced tumor stage. Therefore the detection of CTCs could be used for an optimized assessment of a patient's disease status in urothelial cancer. A further aim of this study was to assess whether surgical manipulation during radical cystectomy is associated with a release of CTCs into the vascular system. None of the patients who were negative for CTCs before surgery showed CTCs during surgical removal of the bladder, suggesting that there was no release of CTCs during surgery. However, further study is needed to prove these findings and evaluate the significance of CTCs as an indicator for therapeutic decisions.

Background: Radical cystoprostatectomy and radical prostatectomy are the two major operations where prostate is totally and radically removed. Radical cystoprostatectomy is usually performed in patients with invasive bladder cancer. The aim of the study was to examine Total PSA, Free PSA, and Free/Total Ratio elimination kinetics after radical cystoprostatectomy., Methods: Serum PSA, Free PSA, and Free/Total Ratio were determined preoperatively, at the time of cystoprostatectomy specimen removal and then at 3, 6, 12, 24, 48, 72, and 168 hr, from seven patients with muscle invasive bladder cancer, who underwent radical cystoprostatectomy. Free and Total PSA concentrations were measured with non-competitive immunological procedures. The elimination rates and half-lives of Total, Free PSA and Free/Total Ratio were studied using a nonlinear regression analysis., Results: Surgical manipulations caused about 1.5-fold increase of PSA, 5-fold increase in Free PSA and 3-fold increase in Free/Total Ratio. PSA and Free PSA followed a biphasic elimination pattern of a rapid exponential (a) phase with a half-life of 4.27 and 2.14 hr and a terminal, nonexponential (b) phase with a half-life of 63 and 173.2 hr, respectively. Free/Total PSA Ratio followed, also, a biphasic kinetic pattern of a rapid exponential decline with a half-life of 3.34 and a terminal non-exponential increase with a doubling time of 43 hr., Conclusions: Comparing PSA kinetics after radical cystoprostatectomy with those of radical prostatectomy, it appears that PSA follows the same elimination pattern in both models. In contrast, Free PSA and Free/Total Ratio elimination kinetics' patterns differ between the two surgical models., ((c) 2008 Wiley-Liss, Inc.)

Purpose: We evaluated the role of CA 125 as a prognostic marker in patients with transitional cell carcinoma (TCC) of the bladder undergoing uniform radical cystectomy with bilateral pelvic iliac lymphadenectomy., Materials and Methods: From April 1996 to March 2001, 287 patients with a median age of 68 years (range 34 to 89) had preoperative CA 125 serum assays performed. All patients had high grade or invasive TCC and were scheduled to undergo radical cystectomy. Preoperative CA 125 was evaluated according to tumor grade and pathological subgroups (organ confined, extravesical and lymph node positive) as well as recurrence-free and overall survival., Results: Of the 287 patients 31 (10.8%) demonstrated increased serum CA 125 (greater than 35 U/ml). No significant association was found between increased CA 125 and recurrence-free survival or tumor grade. However, a statistically significant association was found among pathological tumor subgroups, namely 4.9% for organ confined, 11.3% for extravesical and 21.6% for lymph node positive disease (p <0.001). Furthermore, patients with lymph node positive disease or high grade tumors (grades III/IV and IV/IV) and increased CA 125 assays demonstrated significantly worse overall survival (p <0.001)., Conclusions: Increased CA 125 was seen in approximately 11% of patients with high grade or invasive TCC preoperatively. It was more commonly found in patients with locally advanced and lymph node positive disease, and it was associated with overall survival. However, recurrence-free survival was not associated with CA 125. Further studies are required to define the exact role of CA 125 in bladder cancer.

Objectives: To test the hypothesis that plasma insulin growth factor (IGF)-I or IGF binding protein (BP)-3 levels would differ between patients with bladder cancer and healthy controls and whether preoperative plasma IGF-I or IGFBP-3 could predict the pathologic characteristics and clinical outcome of patients with bladder cancer undergoing radical cystectomy. The IGFs are mitogens that have been shown to play a significant role in regulating proliferation and differentiation of bladder cancer cells., Methods: The study group consisted of 51 patients who underwent radical cystectomy (median follow-up 45.7 months). The preoperative plasma levels of IGF-I and IGFBP-3 were measured using DSL-enzyme-linked immunosorbent assays. The IGF-I and IGFBP-3 levels were also measured in 44 healthy men., Results: The plasma IGF-I and IGFBP-3 levels in patients with bladder cancer were not significantly different from those in healthy subjects (P >or=0.339). In a preoperative model that included clinical grade, clinical stage, and either IGF-I or IGFBP-3, none of the parameters was associated with either metastases to lymph nodes or clinical outcome. However, in an alternative model that included both IGF-I and IGFBP-3 in addition to clinical stage and grade, only a lower preoperative plasma IGFBP-3 level was associated with metastases to regional lymph nodes, bladder cancer progression, and survival (P = 0.047, 0.050, and 0.040, respectively)., Conclusions: We found no association between preoperative plasma IGF-I and bladder cancer characteristics or outcome, limiting the clinical utility of IGF-I. In contrast, a lower preoperative plasma level of IGFBP-3 was associated with lymph node metastasis and poorer clinical outcome after radical cystectomy when adjusted for IGF-I level.

This study was undertaken to evaluate the risk of haematogenous dissemination of epithelial cells induced by endoscopic resection and/or cystoprostatectomy for transitional cell carcinoma of the bladder. Thirty-three patients were studied. Thirty-one had different stages and grades of bladder cancer and two patients had benign bladder conditions. Twenty-five cancer patients required transurethral resection of their bladder tumour. Of those, 20 had superficial disease (pTaG1-G2: n = 19; pT1G2: n = 1) and five had muscle invasive tumours (pT2G3: n = 2; pT3aG3: n = 1; pT4G3: n = 2). Five patients underwent radical cystoprostatectomy for muscle invasive cancers (pT2G3: n = 3; pT3bG3: n = 1; pT4G3: n = 1) and one man received chemotherapy for metastatic disease. Venous blood (10 ml) was obtained from the antecubital fossa in each patient, before and 1-2 h after completion of surgery, and prior to treatment in the metastatic patient. An indirect immunocytochemical technique was used to detect circulating epithelial cells after centrifugation on Ficoll gradient and fixation of mononuclear cells on slides, using a monoclonal antibody directed against three cytokeratins: CK8, CK18 and CK19. Circulating epithelial cells were detected only in the patient with metastatic disease. None of the other patients had evidence of epithelial circulating cells before or after surgery. The results suggest that irrespective of disease stage and grade, neither endoscopic nor open bladder surgery leads to detectable dissemination of urothelial cells in the peripheral circulation. These procedures are therefore unlikely to increase the risk of progression and metastasis in transitional cell carcinoma of the bladder.