Cystectomy For Transitional Cell Carcinoma Research Articles

Effect of age and gender on expression levels of markers of immune cell infiltration and immune checkpoint pathways in patients with muscle-invasive transitional cell carcinoma of the bladder: A retrospective study of 50 patients treated with radical cystectomy.

65 Background: Older age and female gender have been associated with worse outcomes in patients with muscle invasive bladder cancer undergoing radical cystectomy. Reduced immune response has been implicated in disease metastasis and worse survival. The objective of our study was to determine the expression patterns of various cellular proteins active in immune pathways in bladder cancer patients, and assess the correlation between age, gender, and expression of these immune markers. Methods: Tissue samples were obtained from equally distributed male/female patients with/without lymph node metastasis on final pathology after undergoing radical cystectomy for transitional cell carcinoma (TCC) of the bladder from 2009-2011 (n = 50). Immunohistochemistry (IHC) for CD3, CD4, CD8, LAG3, CD56, TIM3, PD-1 and PD-L1 were performed and scored by a single pathologist (scoring was on 0 to 100% scale). Statistical analyses investigated association between age, gender, lymph node metastasis, and IHC results. Results: Mean age at surgery was 67 yrs (range 50 to 78 yrs); all patients were Caucasians. Statistical analyses showed no association between patients' age, gender, and the expression of any of the immune markers (p > 0.05). Similarly, the staining scores for the immune markers were not noted to be correlated with LN metastasis. Correlation between stains showed a negative correlation between CD56 and PD-L1 (-0.286, p = 0.047) and between PD-1 and PD-L1 (-0.381, p = 0.007). Conclusions: Although age and female gender have been associated with worse outcomes in bladder cancer, this association may be independent of the immune pathways active in the disease. Increased expression of PD-L1 is associated significantly with suppression of anti-tumor natural killer cells in the transitional cell carcinoma of the bladder.

Clinical outcome of partial cystectomy for transitional cell carcinoma of the canine bladder.

Canine transitional cell carcinoma (TCC) of the bladder has historically been treated with a combination of chemotherapy, cyclooxygenase inhibitors and radiation therapy. While surgery has been used to treat TCC of the bladder, its efficacy has yet to be established. Thirty-seven client owned dogs that underwent partial cystectomy +/- various nonsurgical treatments for TCC were retrospectively evaluated. The overall median progression-free interval (PFI) was 235 days and the median survival time (ST) was 348 days. Prognostic factors identified on univariate analysis significant for ST were age, tumor location, full thickness excision and frequency of piroxicam administration. Prognostic factors significant for PFI were full thickness excision and frequency of piroxicam administration. The median ST with partial cystectomy and daily piroxicam therapy, with or without chemotherapy, was 772 days. Dogs with non-trigonal bladder TCC treated with full thickness partial cystectomy and daily piroxicam (+/- chemotherapy) may have improved outcome compared to dogs treated with medical therapy.

Lymph node yield in node-negative patients predicts cancer specific survival following radical cystectomy for transitional cell carcinoma.

PurposeTo determine the oncological implications of increased nodal dissection in node-negative bladder cancer during radical cystectomy in a contemporary Australian series.Materials and MethodsWe performed a multicenter retrospective study, including more than 40 surgeons across 5 sites over a 10-year period. We identified 353 patients with primary bladder cancer undergoing radical cystectomy. Extent of lymphadenectomy was defined as follows; limited pelvic lymph node dissection (PLND) (perivesical, pelvic, and obturator), standard PLND (internal and external iliac) and extended PLND (common iliac). Multivariable cox proportional hazards and logistic regression models were used to determine LNY effect on cancer-specific survival.ResultsOver the study period, the extent of dissection and lymph node yield increased considerably. In node-negative patients, lymph node yield (LNY) conferred a significantly improved cancer-specific survival. Compared to cases where LNY of 1 to 5 nodes were taken, the hazard ratio (HR) for 6 to 15 nodes harvested was 0.78 (95% confidence interval [CI], 0.43–1.39) and for greater than 15 nodes the HR was 0.31 (95% CI, 0.17–0.57), adjusted for age, sex, T stage, margin status, and year of surgery. The predicted probability of cancer-specific death within 2 years of cystectomy was 16% (95% CI, 13%–19%) with 10 nodes harvested, falling to 5.5% (95% CI, 0%–12%) with 30 nodes taken. Increasing harvest in all PLND templates conferred a survival benefit.ConclusionsThe findings of the current study highlight the improved oncological outcomes with increased LNY, irrespective of the dissection template. Further prospective research is needed to aid LND data interpretation.

Variations in renal arterial supply in North Indian population: A CT study

Between 1950 and 1974, 35 men and 10 women underwent partial cystectomy for transitional cell carcinoma of the bladder. Indications, contraindications and the principles of technique for partial cystectomy as therapy for transitional cell tumors of the bladder are discussed. All patients were evaluated postoperatively, with cystoscopic examination every 3 months for 1 year, every 6 months for 3 years and then at yearly intervals if no tumors had been detected. None of the patients received preoperative irradiation. Eight ureters were re-implanted and 6 prostate glands were enucleated at the time of partial cystectomy. There was 1 death in the immediate postoperative period. Complications developed in 13 patients, 3 of which were considered major. When recurrences were noted appropriate therapy was performed as indicated. Irradiation was the most commonly used method to treat distant metastases. The over-all 5-year survival rate is 57.7 per cent (26 patients). Thirty-four patients were followed for 10 years. The survival rate for this group of patients was 32.4 per cent (11 patients). The results of this study correlate well with other published reports.

Do African American Patients Treated with Radical Cystectomy for Bladder Cancer have Worse Overall Survival? Accounting for Pathologic Staging and Patient Demographics Beyond Race Makes a Difference.

Background: It is estimated that 74,000 men and women in the United States will be diagnosed with bladder cancer and 16,000 will die from the disease in 2015. The incidence of bladder cancer in Caucasian males is double that of African American males, but African American men and women have worse survival. Although factors contributing to this disparity have been analyzed, there is still great uncertainty as to why this disparity exists.Objective: To evaluate whether the disparities in bladder cancer survival after radical cystectomy for transitional cell carcinoma (TCC) of the bladder amongst African American (AA) and Caucasian patients is attributable to patient demographics, year of diagnosis, and/or tumor characteristics.Methods: Using Surveillance, Epidemiology, and End Results Program (SEER) data from 1973–2011, African American and Caucasian patients treated with a radical cystectomy for TCC of the bladder were identified. Primary outcomes were all-cause and cancer-specific mortality. Differences in survival between African Americans and Caucasian patients were assessed using chi-square tests for categorical variables and Student’s t-tests for continuous variables. Cox proportional hazards regression was used to measure the hazard ratio for African Americans compared to Caucasians for all-cause and cancer-specific mortality. In addition, coarsened matching techniques within narrow ranges, were used to match African American and Caucasian patients on the basis of age, sex, and cancer stage. Following matching, differences in all-cause and cancer-specific mortality were again assessed using a stratified Cox proportional hazards model, using the matching strata for the regression strata.Results: The study cohort consisted of 21,406 African American and Caucasian patients treated with radical cystectomy for bladder urothelial cancer, with 6.2% being African American and 73.9% male. African American patients had worse all-cause and cancer-specific mortality in the univariable analysis (all-cause: HR: 1.23; 95% CI 1.15–1.32, p < 0.001); bladder-cancer specific: HR 1.21; 95% CI 1.11–1.33; p < 0.001). However, after accounting for sex, age, year of diagnosis, marital status, region of treatment, and stage at cystectomy, all-cause mortality was significant (HR 1.20; 95% CI 1.12–1.29; p < 0.0001), but not bladder-cancer specific mortality (HR 1.09; 95% CI 1.00–1.20; p < 0.053). Predictors of bladder cancer specific mortality were age, sex, stage of disease, and marital status. The matched analysis yielded a roughly 1 : 15 match, with 22,511 Caucasians being matched to 1,509 African American patients. In the matched analysis, African Americans had increased all-cause mortality (HR 1.17; 95% CI 1.09–1.26; p < 0.0001), but bladder-cancer specific mortality was no longer significant (HR 1.08; 95% CI 0.99–1.18; p < 0.102).Conclusions: African Americans who undergo a cystectomy are more likely to die, but not necessarily solely because of bladder cancer. Although African American patients have worse all-cause and cancer-specific mortality in univariable models, after controlling for sex, age, year of diagnosis, marital status, region of treatment, and stage at cystectomy, African American patients still have worse overall survival, but equivalent bladder-cancer specific survival. Differences in age, sex, and stage at diagnosis explain some, but not all of the differences in survival.

Impact of preoperative hemoglobin and CRP levels on cancer-specific survival in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder: results of a single-center study

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). 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 70years (35-97). Median follow-up time was 24months (max. 108). Outcome was analyzed using Kaplan-Meier method, log-rank test, and Cox regression models. Median CRP level was 0.5mg/dl (0.1-28.3), and median Hb level was 13.4g/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. 70months; 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. 78months; 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). 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.

Preoperative lymphocyte-to-monocyte ratio predicts clinical outcome in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder: a retrospective analysis.

BackgroundInflammation is a critical component of tumorigenesis, and many cancers arise from sites of infection, chronic irritation, and inflammation. Inflammatory cytokines triggered by tumors alter hematologic components, including neutrophil, lymphocyte, and monocyte counts. The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios have been shown to be valuable prognostic markers in various types of cancers, including bladder cancer. Risk stratification based on clinicopathologic data is insufficient to support treatment-related choices in patients with bladder cancer. Novel prognostic markers are therefore needed. An elevated pretreatment lymphocyte-to-monocyte ratio (LMR) is reportedly associated with improved overall survival (OS) and a longer time to treatment recurrence (TTR) in some types of cancers. However, these data are lacking in patients with bladder cancer. The aim of the present study was to investigate the effect of the preoperative LMR on OS and TTR in a cohort of patients with bladder cancer.MethodsSixty-eight patients with transitional cell carcinoma of the bladder were included in this retrospective analysis. The associations between a high and low LMR with OS and TTR were analyzed using Kaplan–Meier curves and compared by the log-rank test.ResultsIn our study cohort, an elevated preoperative LMR was significantly associated with an increased TTR (P = 0.001) and OS (P = 0.020). Patients with an LMR of ≤2.87 showed a median TTR of 2.0 years (95% CI, 0.27–3.73), whereas patients with an LMR of >2.87 had a median TTR of 11.1 years (95% CI, 2.31–19.88) (P = 0.001). Patients with an LMR of ≤2.81 showed a median OS of 2.7 years (95% CI, 0.63–4.70), whereas patients with an LMR of >2.81 had a median OS of 6.0 years (95% CI, 3.60–8.40) (P = 0.020). The clinical stage at diagnosis was the only clinicopathologic feature associated with the LMR, while tumor invasion depth showed borderline significance.ConclusionsThe LMR is an easily measured and inexpensive prognostic marker that was significantly correlated with OS and TTR in the present retrospective analysis. However, because of the small sample size in this study, larger multicenter, prospective studies are needed.

Technique Selection of Bricker or Wallace Ureteroileal Anastomosis in Ileal Conduit Urinary Diversion: A Strategy Based on Patient Characteristics

This study was designed to establish an individualized selection strategy for the two most common types of ureteroenteric anastomotic techniques (Bricker and Wallace anastomosis) used in ileal conduit (IC) diversion. Patients who underwent IC diversion after radical cystectomy for transitional cell carcinoma between January 2009 and December 2011 were prospectively collected. The choice of anastomosis type (Bricker vs. Wallace) was successively based on tumor characteristics, ureteral anomalies, and ureteral length after retrosigmoidal tunneling. Ninety-nine patients were enrolled in the final study. Fifty-three patients underwent Bricker anastomosis, and 46 underwent Wallace anastomosis. Ureteral stricture developed in 6 (6.1%) patients and the overall stricture rate for all ureters was 3.1% (6/196). Strictures occurred at an average of 13.3 months after surgery and were predominately located in the left ureter (66.7%, 4/6). The difference in the ureter stricture rates between the two groups was not statistically significant: 3.8% (4/104) and 2.2% (2/92) for Bricker and Wallace, respectively (p=0.686). There were no significant differences in age, sex, body mass index (BMI), prevalence of pelvic radiation therapy, length of stay, follow-up time, or time to stricture between the two techniques. Patients in whom stricture developed had a significantly higher mean BMI compared with those without stricture (25.2 vs. 23.3 kg/m(2), respectively; p=0.008). Our preliminary outcomes demonstrate that this selection strategy of Bricker vs. Wallace anastomosis seems to be clinically reliable, providing an acceptable low ureteral stricture rate of 3.1%. However, the potential advantage for oncologic control of this strategy is needed to further confirm.

The SPARC Score: A Multifactorial Outcome Prediction Model for Patients Undergoing Radical Cystectomy for Bladder Cancer

While multiple independent clinicopathological variables are associated with the outcome of radical cystectomy for bladder cancer, limited prediction tools exist to facilitate individualized risk assessment. We developed the SPARC (Survival Prediction After Radical Cystectomy) score, a prediction model for bladder cancer specific survival after radical cystectomy. We evaluated 2,403 patients who underwent radical cystectomy without neoadjuvant therapy at our institution between 1980 and 2008 with pathological re-review of all specimens. Of these patients 1,776 with nonmetastatic urothelial carcinoma were identified for analysis. A multivariate model was developed using stepwise selection to determine variables associated with cancer specific survival. We created a scoring system based on the β coefficients of this model. Median followup after radical cystectomy in patients alive at last followup was 10.5 years (IQR 7.3, 15.3), during which time 610 had died of bladder cancer. In addition to pathological tumor stage, nodal status, multifocality and lymphovascular invasion, the patient specific factors of Charlson comorbidity index, Eastern Cooperative Oncology Group (ECOG) performance status, current smoking, preoperative hydronephrosis and receipt of adjuvant chemotherapy were significantly associated with the risk of bladder cancer death. We used cumulative scores of these variables to stratify patients into risk groups with 95%, 80%, 60%, 38% and 23% 5-year cancer specific survival from the lowest to the highest risk group, respectively (p<0.0001). The concordance index of this model was 0.75. We present a model to individualize the estimation of cancer specific survival after radical cystectomy. Pending external validation, these data may be used for patient counseling, specifically in regard to recommendations for adjuvant therapy and surveillance frequency, as well as for clinical trial development.

Survival Impact of Followup Care after Radical Cystectomy for Bladder Cancer

Due to substantial variation in patient followup after radical cystectomy for bladder cancer, we sought to understand the effect of urine and laboratory tests, physician visits and imaging on overall survival. We analyzed a cohort of patients treated in the fee for service Medicare population from 1992 through 2007 using Surveillance Epidemiology and End Results (SEER)-Medicare data. Using propensity score analysis, we assessed the relationship between time and geography standardized expenditures on followup care and overall survival during 3 postoperative periods, including perioperative (0 to 3 months), early followup (4 to 6 months) and later followup (7 to 24 months). Using instrumental variable analysis, we assessed the overall survival impact of the quantity of followup care by category, including physician visits, imaging, and laboratory and urine tests. We found no improvement in survival due to followup care in the perioperative and early followup periods. Receiving followup care during later followup was associated with improved survival in the low, middle and high expenditure tertiles (HR 0.23, 95% CI 0.15-0.35, HR 0.27, 95% CI 0.18-0.40 and HR 0.47, 95% CI 0.31-0.71, respectively). Instrumental variable analysis suggested that only physician visits and urine testing improved survival (HR 0.96, 0.93-0.99 and 0.95, 0.91-0.99, respectively). Followup care after radical cystectomy in the later followup period was associated with improved survival. Physician visits and urine tests were associated with this improved survival. Our results suggest that aspects of followup care significantly improve patient outcomes but imaging could be done more judiciously after cystectomy.

External Validation of a Risk Model to Predict Recurrence-Free Survival After Radical Cystectomy in Patients With Pathological Tumor Stage T3N0 Urothelial Carcinoma of the Bladder

Patients with stage pT3N0 urothelial bladder cancer vary in outcome after radical cystectomy. To improve prognosis estimation a model was recently developed that defines 3 risk groups for recurrence-free survival based on pT substaging, lymphovascular invasion and positive surgical margin. We present what is to our knowledge the first external validation of this risk model. Analogous to the risk model derivation cohort our study group comprised 472 patients with stage pT3, pN0, cM0 disease without perioperative chemotherapy and with a median followup of 42 months (IQR 20-75). The primary end point was recurrence-free survival. The effect of variables was determined by univariate and multivariate Cox regression analysis, and predictive accuracy was determined by ROC analysis. Stage pT3aN0 and pT3bN0 cases showed significantly different recurrence-free survival after 5 years (51% vs 29%, p<0.001). In the multivariate Cox model pT3 substage (HR 1.86, p<0.001), lymphovascular invasion (HR 1.48, p=0.002), positive surgical margins (HR 1.90, p=0.030) and patient age with a dichotomy at 70 years (HR 1.51, p=0.001) had an independent effect on recurrence-free survival. In the low (221 patients or 47%), intermediate (184 or 39%) and high (67 or 14%) risk groups the 5-year recurrence-free survival rate was 55%, 45% and 13%, respectively (p<0.001). The concordance index of the risk model to predict recurrence-free survival was 0.64 (95% CI 0.59-0.69). This user friendly risk model can be recommended to estimate prognosis in patients with stage pT3N0 after radical cystectomy. Patients at high risk showed clearly compromised recurrence-free survival and should be included in adjuvant therapy studies.

Potential Years of Life Lost Due to Urogenital Cancer in the United States: Trends From 1972 to 2006 Based on Data From the SEER Database

Urogenital cancer is a major health problem in the United States. We assessed potential years of life lost secondary to genitourinary cancer in the United States from 1972 to 2006 using the SEER (Surveillance, Epidemiology and End Results) database. We report trends in potential years of life lost during the same period. Potential years of life lost were calculated to assess premature mortality trends for ureter, bladder, kidney and renal pelvis, penis, testis and prostate cancers. Calculations were based on SEER cancer mortality data. Potential years of life lost up to and including age 75 years were calculated by and across genders in 5-year increments between 1972 and 2006. A total of 7,733,235 potential years of life were lost in men and women. In each gender the greatest potential loss was for kidney and renal pelvis cancer related mortality. In each gender no improvement in the potential loss due to ureteral and bladder cancer related mortality was observed during 3 decades. In males the greatest decrease in potential years of life lost was for testicular cancer, followed by prostate cancer. There has been an increasing trend in potential years of life lost related to urogenital cancer during the last 35 years for males and females. This trend is mainly due to an increase in kidney cancer. The continued increase in potential years of life lost due to renal cancer and the lack of a decrease in the loss in those with bladder cancer should alert urologists and health care policy makers to deficient areas that most need to be addressed.

Complications and Long-Term Results of Salvage Cystectomy After Failed Bladder Sparing Therapy for Muscle Invasive Bladder Cancer

Radical cystectomy has been the standard treatment for muscle invasive bladder cancer. Combined modality therapy involving transurethral bladder tumor resection, external beam radiation and chemotherapy is an effective alternative to cystectomy in selected patients. Salvage cystectomy is reserved for those in whom combined modality therapy fails. We characterized complications associated with salvage cystectomy. From 1986 to 2007 of 348 patients undergoing bladder sparing therapy 102 (29%) underwent salvage cystectomy, 91 of whom were treated at Massachusetts General Hospital after receiving combined modality therapy for T2-T4aNxM0 bladder cancer. Patients underwent transurethral bladder tumor resection followed by chemoradiation (40 Gy). Early assessment was performed by cystoscopy/re-biopsy. Patients with complete response continued with consolidation chemoradiation (total dose 64 Gy). Immediate salvage cystectomy (50 of 91) was performed for persistent disease, while delayed salvage cystectomy (41 of 91) was performed for an invasive recurrence. Complications were classified using the Clavien system. Median patient age was 69.4 years (range 27.5 to 88.9) and median living patient followup was 12 years (range 0 to 23). Of the patients 99% (90 of 91) underwent ileal diversion. Complications of any grade within 90 days occurred in 69% (63 of 91) of patients and 16% (15 of 91) experienced major complications within 90 days. Of the patients 21% (19 of 91) required hospital readmission within 90 days. The 90-day mortality rate was 2.2% (2 of 91). Significant cardiovascular/hematological complications (pulmonary embolism, myocardial infarction, deep vein thrombosis, transfusion) within 90 days were more common in the immediate than in the delayed cystectomy group (37% vs 15%, p = 0.02). Tissue healing complications (fascial dehiscence, wound infection, ureteral stricture, anastomotic stricture, stoma/loop revisions) were more common in the delayed than in the immediate cystectomy group (35% vs 12%, p = 0.05). Salvage cystectomy is associated with acceptable morbidity, although complication rates are slightly higher than for other cystectomy series. Immediate cystectomies have more cardiovascular/hematological complications while delayed cystectomies have more tissue healing complications.

Metastatic bladder transitional cell carcinoma presenting as a vascularised cutaneous right arm lesion

A 65-year-old man presented to the emergency department with a 3-week history of a fast-growing and painful mass in his right antecubital fossa. He felt otherwise well. Four months earlier, he had undergone a radical cystectomy for transitional-cell carcinoma (TCC) of the bladder (grade 3, stage pT1). Two months after the cystectomy, at another hospital, he was diagnosed with, and treated for, a pseudoaneurysm in his right antecubital fossa. Duplex ultrasonography of the presenting lesion revealed a highly vascularised mass with no pseudoaneurysm. Histological and immunohistochemical analysis preceded a diagnosis of cutaneous metastatic TCC. Whole-body CT revealed widespread metastases. This is the first reported case of a highly vascularised cutaneous lesion being the presenting feature of metastatic bladder TCC.

Prognostic Risk Stratification of Pathological Stage T3N0 Bladder Cancer After Radical Cystectomy

Patients with pathological T3N0 stage urothelial carcinoma of the bladder show a range of outcomes after radical cystectomy. Given that nomograms have included heterogeneous groups of patients, we focused on and stratified patients with pT3N0 urothelial carcinoma of the bladder after radical cystectomy into prognostically different risk groups to facilitate the development of adjuvant therapy trials for those at high risk. The study comprised a total of 578 patients from 9 centers worldwide with pT3N0 urothelial carcinoma of the bladder who underwent radical cystectomy without perioperative chemotherapy. We evaluated the effect of pT3 substage at radical cystectomy, age, grade, lymphovascular invasion, margin status and number of lymph nodes removed on recurrence-free survival using Cox regression analysis. A weighted prognostic model was devised. Median followup was 39.4 months (IQR 64). On multivariate analysis pT3 substage at radical cystectomy (pT3b vs pT3a HR 2.056, p <0.0001), lymphovascular invasion (positive vs negative HR 2.004, p <0.0001) and margin status (positive vs negative HR 2.503, p = 0.002) were associated with recurrence-free survival (concordance index 0.66) in the context of generally adequate lymph node dissection, that is with a median of 17 removed. Three risk groups were devised based on weighted variables with a 5-year recurrence-free survival rate of 79% (95% CI 70-84), 57% (95% CI 50-64) and 37% (95% CI 26-48) in the low, intermediate and high risk groups, respectively. We constructed a user friendly prognostic risk model for patients with pT3N0 urothelial carcinoma of the bladder treated with radical cystectomy based on pT3 substage at radical cystectomy, lymphovascular invasion and margin status. These data warrant validation and may enable tailored monitoring and selection of appropriate patients for adjuvant therapy trials.

Disease-Free Survival at 2 or 3 Years Correlates With 5-Year Overall Survival of Patients Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer

The conventional primary end point in trials of perioperative systemic therapy for muscle invasive bladder cancer is 5-year overall survival. We identified an association between disease-free survival at 2 to 3 years and 5-year overall survival. We retrospectively analyzed a multicenter database containing records of 2,724 patients treated with radical cystectomy for muscle invasive bladder cancer with negative margins. Of these patients 844 had received adjuvant chemotherapy. We evaluated the association of disease-free survival at 2 and 3 years with overall survival at 5 years using Cox proportional hazards modeling and the kappa statistic. Overall 2-year/3-year disease-free survival was 0.63/0.57 and 5-year overall survival was 0.47. The overall agreement between 2-year disease-free survival and 5-year overall survival was 79%, and between 3-year disease-free survival and 5-year overall survival was 81%. Agreements were similar when analyzed within pathological substages, radical cystectomy decades and adjuvant chemotherapy subgroups. The kappa statistic was 0.57 (95% CI 0.53-0.60) for 2-year disease-free survival/5-year overall survival and 0.61 (95% CI 0.58-0.64) for 3-year disease-free survival/5-year overall survival, indicating moderate agreement. The hazard ratio for disease-free survival as a time dependent variable was 12.7 (95% CI 11.60-13.90), indicating a strong relationship between disease-free and overall survival. Disease-free survival rates at 2 and 3 years correlate with and are potential intermediate surrogates for 5-year overall survival in patients treated with radical cystectomy for muscle invasive bladder cancer regardless of adjuvant chemotherapy. These data warrant external validation and may expedite the development of adjuvant systemic therapy. In addition, they may be applicable to the neoadjuvant setting.

Effect of Preoperative Nutritional Deficiency on Mortality After Radical Cystectomy for Bladder Cancer

Poor preoperative nutritional status is a risk factor for adverse outcomes after major surgery. We evaluated the effect of preoperative nutritional deficiency on perioperative mortality and overall survival in patients undergoing radical cystectomy for bladder cancer. A total of 538 patients underwent radical cystectomy for urothelial carcinoma between January 2000 and June 2008, and had nutritional parameters documented. Patients with preoperative albumin less than 3.5 gm/dl, body mass index less than 18.5 kg/m(2) or preoperative weight loss greater than 5% of body weight were considered to have nutritional deficiency. Primary outcomes were 90-day mortality and overall survival. Survival was estimated using Kaplan-Meier analysis and compared using the log rank test. Cox proportional hazards models were used for multivariate survival analysis. Of 538 patients 103 (19%) met the criteria for nutritional deficiency. The 90-day mortality rate was 7.3% overall (39 deaths), with 16.5% in patients with nutritional deficiency and 5.1% in the others (p < 0.01). Nutritional deficiency was a strong predictor of death within 90 days on multivariate analysis (HR 2.91; 95% CI 1.36, 6.23; p < 0.01). Overall survival at 3 years was 44.5% (33.5, 54.9) for nutritionally deficient patients and 67.6% (62.4, 72.2) for those who were nutritionally normal (p < 0.01). On multivariate analysis nutritional deficiency cases had a significantly higher risk of all cause mortality (HR 1.82; 95% CI 1.25, 2.65; p < 0.01). Nutritional deficiency, as measured by preoperative weight loss, body mass index and serum albumin, is a strong predictor of 90-day mortality and poor overall survival. Prospective studies are needed to demonstrate the best indices of preoperative nutritional status and whether nutritional intervention can alter the poor prognosis for patients treated with radical cystectomy who have nutritional deficiencies.

Stage pT0 at Radical Cystectomy Confers Improved Survival: An International Study of 4,430 Patients

We describe the cancer related outcome in patients with pT0 bladder urothelial carcinoma at radical cystectomy who did not receive preoperative chemotherapy in a large multicenter series. We also compared outcomes in patients with pT0 bladder urothelial carcinoma to those in patients with other stages and assessed the effect of clinical stage on outcome. We reviewed the records of 4,430 patients treated with radical cystectomy for bladder urothelial carcinoma without neoadjuvant chemotherapy at 12 centers in the United States, Canada and Europe. Of the patients 228 (5.1%) had pT0 disease at radical cystectomy. Clinical stage was cTa or cTis in 13.6% and cT1 in 29.8% of these patients, and disease was muscle invasive (cT2-4a) in 56.2%. Metastasis developed to regional lymph nodes in 17 cases (7.5%). At a median 48.2-month followup 15 patients (6.6%) had died of bladder cancer. Five-year recurrence-free and cancer specific survival estimates were 89.7% (95% CI 85.3-93.1) and 93.1% (95% CI 88.9-95.6), respectively. Disease-free and cancer specific survival in pT0 cases was similar to that in pTa/pTis cases but significantly better than in pT1 or pT2 cases. On multivariate analysis increased disease recurrence and cancer specific mortality risks were significantly associated with lymph node metastasis (each p <0.001) and female gender (p <0.001 and 0.013, respectively). Although stage pT0 at radical cystectomy confers a benefit in survival, some patients experience disease recurrence and eventual death. Identifying these patients may help tailor postoperative decision making in patients with pT0.

1834 DO ROUTINE FOLLOW-UP INVESTIGATIONS FOR DETECTING RECURRENCES AFTER RADICAL CYSTECTOMY BENEFIT THE PATIENT?

You have accessJournal of UrologyBladder Cancer: Invasive/Metastatic Disease III1 Apr 20101834 DO ROUTINE FOLLOW-UP INVESTIGATIONS FOR DETECTING RECURRENCES AFTER RADICAL CYSTECTOMY BENEFIT THE PATIENT? Gianluca Giannarini, Thomas M. Kessler, Harriet C. Thoeny, Claudia Meissner, and Urs E. Studer Gianluca GiannariniGianluca Giannarini More articles by this author , Thomas M. KesslerThomas M. Kessler More articles by this author , Harriet C. ThoenyHarriet C. Thoeny More articles by this author , Claudia MeissnerClaudia Meissner More articles by this author , and Urs E. StuderUrs E. Studer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1772AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The need for follow-up (FU) and the intensity to detect disease recurrence after radical cystectomy for transitional cell carcinoma (TCC) is a matter of debate. We determined whether the diagnosis of asymptomatic recurrence by routine FU exams is associated with a survival benefit compared to that of symptomatic recurrence after radical cystectomy. METHODS A consecutive series of 418 patients with bladder TCC who underwent extended pelvic lymph node dissection and radical cystectomy with ileal orthotopic bladder substitution were analyzed retrospectively. All patients were prospectively followed up with a standardized institutional protocol. Recurrence patterns were categorized as pelvic, distant and concomitant pelvic/distant recurrences, and secondary urothelial tumors. Cancer-specific and overall survival were assessed for asymptomatic and symptomatic recurrent patients. The effect of age, nerve sparing surgery, tumor stage, lymph node status, adjuvant chemotherapy, mode of recurrence diagnosis and recurrence site on survival was explored with multivariate Cox regression models. RESULTS After a median FU of 44 months (range 3-220), 153/418 (37%) patients were diagnosed with recurrence. Of the 153 recurrent patients, 75 (49%) were diagnosed by routine FU exams and 78 (51%) by symptoms (p=0.99). Routine FU investigations mostly detected lung metastases and urethral recurrences, while symptoms were predominantly due to bone metastases and concomitant pelvic/distant recurrences. Of 18 men with urethral recurrences, 7 are still disease-free after urethra-sparing treatment. Among the other long-term survivors with recurrence, there were patients with lymph node and lung metastases. In multivariate analysis, mode of recurrence diagnosis and site of initial recurrence were the only independent predictors of both cancer-specific and overall survival. Patients with recurrences detected by routine FU investigations and patients with secondary urothelial tumors as recurrence site had a slightly, but significantly higher survival probability. CONCLUSIONS Patients diagnosed during our routine FU with asymptomatic recurrences after radical cystectomy for bladder TCC had a slightly better survival than patients with symptomatic recurrences. Regular surveillance appears to be particularly effective in early detection of urethral recurrences, which can be treated conservatively. In addition, the predominance of lymph node and lung metastases in long-term survivors may justify the use of routine CT scan. Bern, Switzerland© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e712 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gianluca Giannarini More articles by this author Thomas M. Kessler More articles by this author Harriet C. Thoeny More articles by this author Claudia Meissner More articles by this author Urs E. Studer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Survival after cystectomy for invasive bladder cancer

Aim To determine the difference in survival after cystectomy between patients presenting with primary muscle infiltrating bladder cancer and patients with progression to muscle infiltration after treatment for initial non-muscle-invasive bladder cancer (NMIBC). Patients and Methods We retrospectively analyzed the files of 188 patients who underwent cystectomy for transitional cell carcinoma between 1987 and 2005. Two groups were defined: patients presenting with muscle-invasive tumours and those progressing to muscle invasion after initial treatment. This second group was further divided into low-intermediate and high risk according to the EAU grouping for NMIBC. Results The 5-year disease specific survival (95% confidence intervals) for all patients was 50%(42–59%); 49%(40–60%) in the primary muscle infiltrating group and 52%(37–74%) in the progressive group ( p = ns). The 5-year disease specific survival in the progressive group according to EAU risk groups was 75%(58–97%) for the initially diagnosed low-intermediate risk tumours and 35%(17–71%) for the initially diagnosed high-risk tumours ( p = 0.015). The percentage of patients with non-locally confined tumours (pT3/4-N0//any pT-N+) was 31%//45% and 24%//46% in the primary muscle infiltrating and progressive group, respectively. Conclusions Despite close observation of patients treated for non-muscle-invasive bladder cancer, the survival of patients who progress to muscle invasion is not better than survival of patients presenting with primary muscle infiltrating cancer. Patients with high-risk non-invasive tumours (EAU risk-categories) who progress to muscle-invasive disease have a worse prognosis compared to patients with low or intermediate risk tumours.