Bladder Cancer Death Research Articles

Bladder Cancer Mortality after Spinal Cord Injury over 4 Decades

We estimate bladder cancer mortality in people with spinal cord injury compared to the general population. Data and statistics were retrieved from the National Spinal Cord Injury Statistical Center and the National Center for Health Statistics. The mortality experience of the 45,486 patients with traumatic spinal cord injury treated at a Spinal Cord Injury Model System or Shriners Hospital was compared to the general population using a standardized mortality ratio. The standardized mortality ratio data were further stratified by age, gender, race, time since injury and injury severity. Our study included 566,532 person-years of followup between 1960 and 2009, identified 10,575 deaths and categorized 99 deaths from bladder cancer. The expected number of deaths from bladder cancer would have been 14.8 if patients with spinal cord injury had the same bladder cancer mortality as the general population. Thus, the standardized mortality ratio is 6.7 (95% CI 5.4-8.1). Increased mortality risk from bladder cancer was observed for various ages, races and genders, as well as for those injured for 10 or more years and with motor complete injuries. Bladder cancer mortality was not significantly increased for ventilator users, those with motor incomplete injuries or those injured less than 10 years. Individuals with a spinal cord injury can potentially live healthier and longer by reducing the incidence and mortality of bladder cancer. Study findings highlight the need to identify at risk groups and contributing factors for bladder cancer death, leading to the development of prevention, screening and management strategies.

Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder-sparing protocol. ERBB 2-targeting treatment may improve the outcomes of such patients.

Investigation of poorer bladder cancer survival in women in NSW, Australia: a data linkage study

To investigate the associations of a range of personal and clinical variables with bladder cancer survival in men and women in NSW to see if we could explain why bladder cancer survival is consistently poorer in women than in men. All 6880 cases of bladder cancers diagnosed in NSW between 2000 and 2008 were linked to hospital separation data and to deaths. Separate Cox proportional hazards regression models of hazard of bladder cancer death were constructed for those who did or did not undergo cystectomy. A total of 16% of patients with bladder cancer underwent cystectomy (16% of men and 15% of women). Women who underwent cystectomy were 26% more likely to die than men (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.00-1.59) after adjustment for age, stage, time from diagnosis to cystectomy, distance from treatment facility and country of birth. None of the above covariates had a material effect on the difference in hazard between women and men; however, when stratified by a history of cystitis, the adjusted hazard was 55% higher in women (HR 1.55, 95% CI 1.15-2.10) than in men with a history of cystitis while, in the absence of this history, there was no difference in the hazard between men and women (HR 0.99, 95% CI 0.57-1.70). This apparent modification of the effect of sex on bladder cancer outcome was not seen in patients treated only by resection: the adjusted HRs in women relative to men were 1.10 (95% CI 0.92-1.31) in those with a history of cystitis and 1.21 (95% CI 0.98-1.50) in those without. A history of haematuria did not modify appreciably the association of sex with bladder cancer outcome. Women's poorer survival from bladder cancer compared with that of men remains unexplained; however, the possibility that some factor associated with a history of cystitis may contribute to or explain the poorer outcome in women merits further investigation.

Quality of transurethral resection in patients with bladder cancer: A process-outcomes link.

292 Background: Detrusor muscle at diagnostic transurethral resection of a bladder tumor (TURBT) is often used as a surrogate of resection quality. We examined whether surgical and pathologic quality at the time of initial resection was associated with improved cancer-specific survival among subjects diagnosed with non-muscle-invasive bladder cancer. Methods: We retrospectively reviewed the operative and pathology reports of all individuals ≥18 years of age within the Los Angeles SEER registry, with an incident diagnosis of urothelial non-muscle-invasive bladder cancer between 2004-2005. We recorded patient age, gender, race, marital status, socioeconomic status, insurance type, institution type, surgeon and pathologist volume, tumor stage and grade, detrusor muscle presence/mention, and vital status. After adjusting for confounding using competing-risks regression analysis, we determined whether surgical and pathologic quality was associated with cancer-specific survival. Results: We identified 1,865 patients, 335 urologists, and 278 pathologists. Muscle was reported as present in 972 (52.1%), reported as absent in 564 (30.2%), and was not mentioned in 329 (17.7%) of the initial pathology reports. The incidence of detrusor muscle sampling did not differ according to grade or stage. However, bladder cancer death was more likely with higher stage disease (Tis: HR=5.00, 95% CI 2.38-10.50; T1: HR=5.44, 95% CI 3.00-9.88) and lower quality staging (muscle absent: HR=1.50, CI 1.00-2.27; muscle not mentioned: HR=2.01, CI 1.14-3.56). This pattern was enhanced among those with high-grade disease. For this group, the 5-year cancer-specific mortality was 8.0%, 13.0%, and 21.5% when muscle was present, absent, or not mentioned, respectively. Conclusions: Nearly half of all diagnostic TURBTs do not include muscle. This omission is associated with increased mortality, particularly in high-grade disease—yet few of these patients undergo treatment to correct this error. Because urologists cannot discern between high- or low-grade disease, we contend that all patients with bladder cancer should undergo endoscopic resection with detrusor muscle sampling (and appropriate pathology reporting) at diagnosis.

Adjuvant chemotherapy is associated with decreased mortality after radical cystectomy for locally advanced bladder cancer

We sought to evaluate the association of adjuvant chemotherapy with the risk of subsequent mortality among patients with locally advanced urothelial carcinoma (UC) of the bladder undergoing radical cystectomy (RC). We identified 675 patients who underwent RC for pT2-4 and/or N+ UC between 1980 and 2005. Adjuvant chemotherapy was defined as treatment within 90 days of RC. Survival was estimated using the Kaplan-Meier method and compared according to receipt of adjuvant chemotherapy with the log-rank test. Multivariate models were used to analyze the impact of adjuvant chemotherapy on disease progression and survival. A total of 80 (12 %) patients received adjuvant chemotherapy. Median age was 69 years [interquartile range (IQR) 63, 76]. Median follow-up was 11 years (IQR 8, 16). Patients receiving adjuvant chemotherapy were more likely to have pT3-4 tumors (71 vs. 61 %; p < 0.001) and pN+ (85 vs. 19 %; p < 0.001). The 5-year cancer-specific survival was 46 % in those receiving adjuvant chemotherapy and 51 % in those that did not (p = 0.63). The 5-year overall survival was 39 % in those receiving adjuvant chemotherapy and 38 % in those that did not (p = 0.24). When controlling for age, sex, stage, and performance status, adjuvant chemotherapy was associated with a 29 % decrease in the risk of bladder cancer death (HR 0.71, p = 0.06) and a 39 % decrease in the risk of all-cause mortality (HR 0.61, p = 0.002). After controlling patient and tumor features, adjuvant chemotherapy was associated with a trend toward reduction in cancer-specific mortality and a statistically significant reduction in all-cause mortality.

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.

519 SPARC (SURVIVAL PREDICTION AFTER RADICAL CYSTECTOMY): A MULTIFACTORIAL OUTCOME PREDICTION MODEL FOR PATIENTS UNDERGOING RADICAL CYSTECTOMY FOR BLADDER CANCER

INTRODUCTION AND OBJECTIVES: While multiple independent clinicopathologic variables associated with outcome following radical cystectomy (RC) for bladder cancer (BC) have been identified, limited prediction tools exist to facilitate an individualized risk assessment based on the relative weight of these various features. Herein, we developed an outcome prediction model based on clinical and pathologic characteristics found to be significantly associated with death from BC after RC. METHODS: We evaluated 1829 patients who underwent RC without neoadjuvant therapy at our institution between 1980–2008. Of these, 1,751 with non-metastatic, non-small cell histology were identified. Univariate analysis evaluating variables associated with BC specific mortality was conducted. A multivariate model was obtained using a stepwise selection process from variables significant at the 0.05 level. A scoring system based on the -coefficients of this model was created, assigning 1 point for each parameter estimate value of 0.20. RESULTS: Median follow-up after RC was 10.7 years (interquartile range 7.7, 15.7), during which time 652 patients experienced death due to BC. On multivariate analysis (Table), race, Charlson comorbidity index, ECOG status, current smoking status, preoperative hydronephrosis, pathologic stage, multifocality, lymphovascular invasion, and concurrent CIS were significantly associated with BC death. Cumulative scores from these variables were used to stratify patients into quintiles according to risk score of BC death as 4, 5-8, 9-12, 13-16, and 17. 5-year cancer specific survival (CSS) from the lowest to highest risk quintile was 95%, 82%, 58%, 35%, and 17%, respectively (p 0.0001). The c-index for this model was 0.76. CONCLUSIONS: We present a model for individualizing estimation of CSS following radical cystectomy. Pending external validation, these data may be used for patient counseling, specifically with regard to recommendations for adjuvant therapy and surveillance frequency, as well as in clinical trial development.

Lymphovascular invasion is independently associated with bladder cancer recurrence and survival in patients with final stage T1 disease and negative lymph nodes after radical cystectomy

To determine the outcomes of patients with final pathological stage T1N0 disease after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) and to determine whether lymphovascular invasion (LVI) is an independent predictor of prognosis in these patients. Records of 958 consecutive patients who underwent RC at three academic centres were reviewed. A total of 101 patients with negative lymph nodes and with final stage (the higher of the pre-RC clinical/transurethral resection [TUR] and post-RC pathological stages) T1 UCB were identified. The median (range) follow-up was 38 (0.4-177) months and the median (range) number of nodes examined was 19 (9-80). Overall, 12/101 (11.9%) patients experienced cancer recurrence and 7/101 (6.9%) died from their cancer. The 3-year recurrence-free survival probability (SD) was 0.89 (0.04) and 3-year cancer-specific survival probability (SD) was 0.96 (0.02). Six of 101 (6%) patients had LVI, of whom four experienced disease recurrence and three died from bladder cancer. All recurrences and deaths occurred in patients who had either LVI and/or concomitant carcinoma in situ. On multivariable analysis, LVI (hazard ratio [HR] 4.9, P = 0.01) and higher pathological stage (HR 8.5, P = 0.04) predicted cancer recurrence and LVI (HR 6.7, P = 0.01) predicted cancer-specific survival. LVI helps identify patients with final pathological T1N0 UCB who are at significantly increased risk of bladder cancer recurrence and death. These patients should be considered for close monitoring after cystectomy.

Identifying Better Practices for Early-stage Bladder Cancer

Practice guidelines for nonmuscle invasive (ie, early stage) bladder cancer are ambiguous, resulting in substantial practice variation without a clear patient benefit. To profile urologist practice styles and empirically derive better patterns of use for common bladder cancer services. Retrospective cohort. Elderly patients diagnosed with early-stage bladder cancer between January 1, 1992 and December 31, 2005 in Surveillance, Epidemiology, and End Results-Medicare linked data. After identifying each patient's treating urologist, we fit multilevel models to obtain reliability-adjusted measures of the urologist's use of surveillance-associated (cytoscopy and urine cytology) and treatment-associated (intravesical therapy) services during the 2 years after diagnosis. We then used the Cox proportional hazards regression to evaluate the association between a patient's risk of bladder cancer death and his urologist's frequency of service use. Regardless of disease severity, no measurable patient benefit was associated with care delivery by a urologist residing in the highest quartile for cystoscopy or intravescial therapy use. However, maximal intensity of cytology use was associated with a lower risk of bladder cancer death for patients with high-grade stage Ta/Tis (highest vs. lowest intensity quartiles: hazard ratio, 0.73; 95% confidence interval, 0.56-0.95) and stage T1 disease (hazard ratio, 0.59; 95% confidence interval, 0.49-0.72). Our analysis supports a more tailored approach to patients with early-stage bladder cancer. Further, it serves as an example for applying observational data to characterize better clinical practices in the absence of experimental studies.

ErbB2 and NFκB Overexpression as Predictors of Chemoradiation Resistance and Putative Targets to Overcome Resistance in Muscle-Invasive Bladder Cancer

Radical cystectomy for muscle-invasive bladder cancer (MIBC) patients frequently impairs their quality of life (QOL) due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR) to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS) were investigated. Of the 35 patients, 11 (31%) achieved pathological CR, while tumors in the remaining 24 patients (69%) were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014), 15.4 (P = 0.024) and 14.3 (P = 0.038). The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001). The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056) along with chemoradiation resistance (P = 0.003) and hydronephrosis (P = 0.018). The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with chemoradiation-resistant disease was 61% (P = 0.018). Thus, erbB2 and NFκB overexpression are relevant to chemoradiation resistance and are putative targets aimed at overcoming chemoradiation resistance in MIBC.

The burden of bladder cancer in men and women: analysis of the years of life lost

To estimate the average loss in life expectancy (LE) due to bladder cancer (BC) in men and women in the USA. Cancer records for 51,528 patients diagnosed with BC during 1988-1997 were obtained from the Surveillance, Epidemiology, and End Results database. Potential follow-up ranged from 10 to 20 years (median 14 years). Loss in median LE at BC diagnosis was computed as the difference between expected median survival and observed median survival. Expected survival was calculated using two methods: method 1 used age, sex, and race-specific LE in the general population, method 2 used the hazard of death from non-BC causes in patients with BC (to account for past exposures and treatment-related toxicities not present in the general population). During the study period, BC death occurred in 17% of men and 23% of women and non-BC death occurred in 53% of men and 47% of women. Using LE in the general population as the reference (method 1), loss in median LE at BC diagnosis was 3.9 years for men (33% of their potential remaining years of life) and 6.5 years for women (47% of their potential remaining years of life). Using non-BC-specific hazard as the reference (method 2), loss in median LE was 2.7 years for men (26% of their potential remaining years of life) and 4.1 years for women (36% of their potential remaining years of life). Compared with men, women loose more years of life and a greater fraction of their life expectancy to BC.

SP4-4 Analysis of knowledge about alcohol and tobacco by students of pharmacy in the university of Barcelona

IntroductionIt is well known that knowledge can change behaviours, thus introducing healthy habits or reducing the prevalence of risky habits. Based on this information, we studied the level of knowledge...

Editorial Comment to Cancer death from non‐muscle invasive bladder cancer: Report of the Japanese Urological Association of data from the 1999–2001 registry in Japan

The authors reported on 1919 clinical T1 (cT1) bladder cancer patients from the Japanese National Bladder Cancer Registry between 1999 and 2001, sponsored by the Japanese Urological Association. All survivors were followedup for at least 3 years (up to 5 years) and the 3-year cancer specific survival rate was 95.5%. The authors analyzed risk factors for bladder cancer death and concluded that large tumor size (>3 cm), positive urine cytology and nonpapillary tumor architecture were significant and independent risk factors. Histological grade is a well-known predictive factor for progression of non-muscle invasive bladder cancer. In the current study, however, the presence of a grade 3 lesion was not identified as an independent risk factor for bladder cancer death. This might be attributed to the lack of central pathology review and/or the relatively short-term follow up of the current study. Interestingly, urine cytology provided prognostic information on cT1 bladder cancer patients. Urine cytology reflects not only cellular atypia, but also the fragility of intercellular attachment of bladder cancer cells. Recent advances in translational research have shown that epithelial to mesenchymal transition (EMT) is critical for the progression of bladder cancer. During EMT of bladder cancer cells, expression of molecules determining epithelial features including E-cadherin and p63 is downregulated, leading to loosened intercellular attachment. At the same time, upregulation of mesenchyme-associated molecules, including Twist, Snail and N-cadherin, activates various oncogenic signaling pathways, increases cell motility and excretion of matrix metalloproteinases, and eventually promotes invasion and metastasis. Given these biological processes during progression of bladder cancer, it is conceivable that urine cytology provides prognostic value by reflecting EMT status. I look forward to further investigations to validate the prognostic value of urine cytology in non-muscle invasive bladder cancer patients.

Understanding bladder cancer death

To the authors' knowledge, the extent to which death from bladder cancer is attributable to tumor biology or physician practice patterns is unknown. For this reason, the relative importance of broadening indications for aggressive therapy has unclear implications. Patients whose deaths were caused directly by bladder cancer were identified using institutional (n = 126 patients) and administrative (n = 6326 patients) data sources. By using implicit review (clinical data, 2001-2005) and explicit algorithms (Surveillance, Epidemiology, and End Results [SEER]-Medicare, 1992-2002), the authors estimated the proportion of potentially avoidable deaths from bladder cancer. After an implicit review of clinical data, 40 of 126 deaths (31.7%) were classified as potentially avoidable. Compared with those patients who were deemed unsalvageable, these patients generally presented with nonmuscle-invasive disease (80% vs 25.6%; P < .001), received multiple courses of intravesical therapy (32.5% vs 1.2%; P < .001), and had a more protracted course from diagnosis to aggressive treatment (median, 23 months vs 2 months; P < .001). An explicit review of claims data indicated that between 31.6% and 46.8% of the 6326 bladder cancer deaths identified in the SEER-Medicare data potentially were avoidable, depending on the survivorship threshold chosen. Patients whose deaths potentially were avoidable more commonly presented with nonmuscle-invasive disease (66.7% vs 24.7%; P < .0001) and lower grade disease (35.1% vs 15.1%; P < .0001). The greatest inroads into reducing death from bladder cancer likely hinge on earlier detection or improvement of systemic therapies. However, changing physician practice may translate into nontrivial reductions in bladder cancer mortality.

Tissue microarray based analysis of prognostic markers in invasive bladder cancer: Much effort to no avail?

Purpose To evaluate altered protein expression with tissue microarray methodology for 15 different markers with potential prognostic significance in invasive bladder cancer. Materials and Methods Invasive tumor was sampled with the tissue-arraying instrument in 133 consecutive patients who underwent radical cystectomy, and at least 3, 0.6-mm tissue cores were obtained. With immunohistochemistry, the expressions of TP53, RB1, CDKN1A (p21), MKI67 (Ki67), PTGS2 (Cox-2), CTNNA1 (α-catenin), CTNNB1 (β-catenin), AKT, PTEN, RHOA, RHOC, STAT1, VEGFC, EGFR, and ERBB2 (HER2) were quantified, and correlations were made with tumor grade, pathologic stage, lymph node status, and disease-specific survival. Results Decreased immunohistochemical expression of CTNNA1 and of PTEN correlated with higher pathologic tumor stages ( P = 0.01 and P = 0.01, respectively), whereas increased AKT1 and ERBB2 correlated with lower pathologic tumor stages ( P = 0.01 and P = 0.03, respectively). Increased RHOA expression was more common in grade 3 than in grade 2 tumors ( P = 0.016). There were no other correlations among the 15 factors studied and pathologic stage, lymph node status, or tumor grade. No association was found between bladder cancer death and altered marker status for any of the markers studied. Conclusions Currently, there are reasons to have a skeptical attitude toward the value of tissue microarray based immunohistochemistry as a method for evaluating prognostic markers in invasive bladder cancer. In this study, 15 antibodies were tested but were found to be of little clinical value. Whether this negative finding is related to the group of patients or factors studied, or the methodology is unclear.

Bladder Cancer in Taiwan: Relationship to Trihalomethane Concentrations Present in Drinking-Water Supplies

The objective of this study was to evaluate whether exposure to disinfection by-products (DBP) is associated with bladder cancer. A matched case-control study was used to investigate the relationship between the risk of death from bladder cancer and exposure to total trihalomethanes (TTHM) in drinking water in 65 municipalities in Taiwan. All bladder cancer deaths of the 65 municipalities from 1996 through 2005 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth,and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water in study municipalities were collected from the Taiwan Environmental Protection Administration. The municipality of residence for cancer cases and controls was assumed to be the source of the subject's TTHM exposure via drinking water. The adjusted odds ratios for bladder cancer death for those with high TTHM concentrations in their drinking water were 1.8 (1.18–2.74) and 2.11 (1.43–3.11) compared to the lowest group. The results of this study show that there was a significant positive correlation between the concentration of TTHM in drinking water and risk of death from bladder cancer.

Nitrate in Drinking Water and Risk of Death from Bladder Cancer: An Ecological Case-Control Study in Taiwan

The relationship between nitrate levels in drinking water and bladder cancer development is controversial. A matched cancer case-control with nitrate ecology study was used to investigate the association between bladder cancer mortality occurrence and nitrate exposure from Taiwan drinking water. All bladder cancer deaths of Taiwan residents from 1999 through 2003 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth,and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on nitrate-nitrogen (NO3-N) levels in drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios for bladder cancer death for those with high nitrate levels in their drinking water were 1.76 (1.28–2.42) and 1.96 (1.41–2.72) as compared to the lowest tertile. The results of the present study show that there was a significant positive relationship between the levels of nitrate in drinking water and risk of death from bladder cancer.

Outcomes of Radical Cystectomy for Transitional Cell Carcinoma of the Bladder: A Contemporary Series From the Bladder Cancer Research Consortium

We present the characteristics and outcomes of a large, contemporary, consecutive series of patients treated with radical cystectomy and pelvic lymphadenectomy for transitional cell carcinoma of the bladder. We developed a multi-institutional database and collected retrospective and prospective data on 888 consecutive patients with bladder transitional cell carcinoma who were treated with radical cystectomy and pelvic lymphadenectomy at 3 academic centers in the United States between 1984 and 2003. Of the patients 25% had extravesical tumor extension with negative lymph nodes and 23% had lymph node metastasis. The rate of lymph node involvement increased with advancing pathological stage. Mean recurrence-free and bladder cancer specific survival +/- SE was 58% +/- 2% and 66% +/- 2% at 5 years, respectively. On preoperative multivariate analysis clinical tumor stage and neoadjuvant systemic chemotherapy were associated with cancer recurrence, while more advanced age, clinical tumor stage and preoperative carcinoma in situ were associated with bladder cancer specific mortality. On postoperative multivariate analysis pathological tumor stage, lymph node metastasis, lymphovascular invasion, adjuvant radiotherapy and adjuvant chemotherapy were associated with cancer recurrence, while higher pathological tumor stage, more advanced age, lymph node metastasis, lymphovascular invasion and adjuvant radiotherapy were associated with disease specific survival. Patients with metastasis to regional lymph nodes (pT any N1-3) were at significantly higher risk for bladder cancer recurrence and death than patients with extravesical tumor extension (pT3N0), who in turn were at significantly higher risk than patients with organ confined disease (pT2 N0 or less). The results of this large, contemporary, multi-institutional series show that radical cystectomy and pelvic lymphadenectomy provide durable local control and disease specific survival in patients with localized invasive transitional cell carcinoma.

Characteristics and outcomes of patients with carcinoma in situ only at radical cystectomy

Objectives To describe the cancer-specific outcomes of patients with pathologic carcinoma in situ (CIS) only at radical cystectomy. Methods The records of 812 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder transitional cell carcinoma at three U.S. academic centers were reviewed. Of the 812 patients, 99 (12%) had CIS only at radical cystectomy. Results The distribution of clinical stage for the 99 patients with CIS only at radical cystectomy was as follows: 47% of patients had CIS only, 8% had cT1, 15% had cT1 plus CIS, 10% had cT2, 13% had cT2 plus CIS, 6% had cTa, and 1% had Ta plus CIS. Two patients had lymphovascular invasion in the radical cystectomy specimen, and three had metastases to the lymph nodes. The actuarial recurrence-free survival estimates were 89.8% (95% confidence interval [CI] 83.0% to 96.6%) at 3 years and 83.0% (95% CI 73.2% to 92.8%) at 5 and 7 years after radical cystectomy. Six patients (6%) had died of bladder cancer at analysis and 13 (13%) had died of other causes without evidence of disease recurrence. The actuarial disease-specific survival estimates were 95.8% (95% CI 91.2% to 99.9%) at 3 years, 90.7% (95% CI 82.4% to 98.9%) at 5 years, and 87.2% (95% CI 76.8% to 97.5%) at 7 years after surgery. On univariate Cox regression analyses, only metastasis to lymph nodes was associated with bladder cancer recurrence and death ( P <0.001). Conclusions Disease control seemed durable for patients with pathologic CIS only at radical cystectomy in the absence of metastases to the lymph nodes, even in the case of failure after intravesical therapy.

Clinical Outcomes Following Radical Cystectomy for Primary Nontransitional Cell Carcinoma of the Bladder Compared to Transitional Cell Carcinoma of the Bladder

The effect of bladder cancer histological subtypes other than transitional cell carcinoma (nonTCC) on clinical outcomes remains uncertain. We conducted a multi-institutional retrospective study of patients with bladder cancer treated with radical cystectomy to assess the impact of nonTCC histology on bladder cancer specific outcomes. A total of 955 consecutive patients underwent radical cystectomy with bilateral pelvic lymphadenectomy for bladder cancer at 3 academic institutions. TCC was present in the radical cystectomy specimen in 888 patients (93%). NonTCC histology was present in 67 patients (7%), including squamous cell carcinoma in 26, adenocarcinoma in 13, small cell carcinoma in 10 and other nonTCC subtypes (ie spindle cell carcinoma, carcinosarcoma and undifferentiated carcinoma) in 18. For patients alive at last followup median followup was 39 and 23 months for patients with TCC and nonTCC histologies, respectively. Bladder cancer specific progression and survival were assessed using Kaplan-Meier and multivariate Cox proportional hazards analyses. Bladder cancer specific progression and mortality did not differ significantly between patients with SCC and TCC histologies. Patients with nonTCC and nonSCC bladder cancer were at significantly increased risk for progression and death compared to patients with TCC or SCC (p <0.001). This association remained statistically significant in patients with organ confined disease (stage pT2 or lower) and patients with nonorgan confined disease (stage pT3 or higher) (p <0.001). In a multivariate analysis nonTCC and nonSCC histology was associated with an increased risk of bladder cancer progression and death (OR 2.272 and 2.585, respectively, p <0.001), even after adjusting for final pathological stage, lymph node status, lymphovascular invasion and neoadjuvant or adjuvant treatments. NonTCC and nonSCC histological subtype is an independent predictor of bladder cancer progression and mortality in patients undergoing radical cystectomy for bladder cancer. Patients with bladder TCC and SCC share similar stage specific clinical outcomes.