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Objective: To estimate the effect of radiation therapy (RT) administered for uterine cancer (UtC) on bladder cancer (BC) incidence, tumour characteristics at presentation, and mortality., Patients and Methods: In this retrospective cohort study, records of 56 681 patients diagnosed with UtC as their first primary malignancy during 1980-2005 were obtained from the Surveillance, Epidemiology and End-Results (SEER) database. Follow-up for incident BC ended on 31 December 2008. Occurrences of BC diagnoses and BC deaths in patients with UtC managed with or without RT were summarised with counts and person-time incidence rates (counts divided by person-years of observation). Age adjustment of rates was performed by direct standardisation. Incident BC cases were described in terms of histological types, grades and stages., Results: With a mean follow-up of 15 years, BC was diagnosed in 146 (0.93%) of 15 726 patients with UtC managed with RT, and in 197 (0.48%) of 40 955 patients with UtC managed without RT, with an age-adjusted rate ratio of 2.0 (95% confidence interval [CI] 1.6-2.5). Fatal BC occurred in 39 (0.25%) and 36 (0.09%) of patients with UtC managed with vs without RT, respectively, with an age-adjusted rate ratio of 2.9 (95% CI 1.8-4.6). Incident BC cases diagnosed in patients with UtC managed with vs without RT had similar distributions of histological types, grades, and stages., Conclusions: Use of RT for UtC is associated with increased BC incidence and mortality later in life. Heightened awareness should help identify women with new voiding symptoms or haematuria, all of which should be fully evaluated., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objectives: In the United States, among patients diagnosed with bladder cancer (BC), women have increased disease-specific mortality compared with men. The main objective of this study was to determine whether this pattern is also present in other countries. For comparison, similar analyses were performed for kidney cancer (KC)., Methods and Materials: Data for this study were obtained from the GLOBOCAN 2008 database. A total of 49 countries with available information on BC and KC incidence and mortality were included in the analysis, representing all major geographic regions except Africa. For each country, we computed the sex-specific ratio of the total number of deaths from a given cancer to the total number of diagnoses in the year 2008 (the mortality-to-incidence ratio [MIR]). The relative MIR was computed for each country as a ratio of MIR in women to MIR in men. A relative MIR of more than 1 would indicate that the number of cancer-specific deaths relative to the number of cancer-specific diagnoses is greater in women than in men., Results: For BC, the relative MIRs were significantly more than 1 in 26 countries (53%), significantly less than 1 in 2 countries (4%), and not significantly different from 1 in 21 countries (43%). The median relative MIR was 1.21 (interquartile range: 1.04-1.41). For KC, the relative MIRs were significantly more than 1 in 4 countries (8%), significantly less than 1 in 3 countries (6%), and not significantly different from 1 in 42 countries (86%). The median relative MIR was 1.00 (interquartile range: 0.94-1.06)., Conclusion: Among BC patients, increased disease-specific mortality in women compared with men appears to be a common (although not a universal) phenomenon. This pattern may potentially be explained by differences between the sexes in the biology of disease, time to diagnosis, treatment decisions, and other factors. In contrast, among KC patients, no significant differences in disease-specific mortality were seen between the 2 sexes in the overwhelming majority of the countries., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Because bladder cancer (BC) patients often have comorbidities that adversely affect their health, we wanted to determine whether grade and stage of BC at diagnosis are associated with the hazard of death from causes other than BC., Materials and Methods: Cancer records for 93,033 patients diagnosed with urothelial BC during 1988-2002 were obtained from the Surveillance Epidemiology and End Results (SEER) database. The grade-stage categories were defined as follows: (1) low grade, stage 0/I (Ta/T1, N0/Nx), (2) high grade, stage 0/I (Ta/Tis/T1, N0/Nx), (3) any grade, stage II (T2, N0/Nx), (4) any grade, stage III (T3-T4a, N0/Nx), (5) any grade, stage IV (T4b and/or N+). Patients with known distant metastases at presentation were excluded. Other covariates were age, gender, and race. The outcome measures were defined as the hazard of death from all causes, from BC, and from non-BC causes. Cox regression model was used to estimate the effect of grade-stage categories on over-all and cause-specific hazards with adjustment for covariates., Results: The 5-year mortality proportions by grade-stage category were as follows: low grade, stage 0/I: all-causes 25%, BC 3%, non-BC 22%; high grade stage 0/I: all-causes 38%, BC 13%, non-BC 25%; stage II: all-causes 63%, BC 36%, non-BC 27%; stage III: all-causes 69%, BC 45%, non-BC 24%; stage IV: all-causes 83%, BC 68%, non-BC 15%. Using low grade, stage 0/I as a reference category, the hazard ratios for increasing grade-stage categories (high grade 0/I, II, III, IV) were as follows: all-cause mortality 1.30, 2.37, 3.07, 6.14; BC-related hazard 3.31, 10.02, 14.65, 32.04; non-BC-related hazard: 1.05, 1.37, 1.49, 1.65 (all P < 0.001)., Conclusion: Grade-stage categories were associated with the hazard of death from non-BC causes. However, their influence on BC-related hazard was much greater in magnitude. Because BC (rather than co-morbidities) is the main cause of death in patients with muscle-invasive disease, aggressive BC-directed therapies in these patients, when feasible, are justified., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to investigate the effect of neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) on pathologic down-staging of patients with locally advanced urothelial cancer (UC) of the bladder., Methods: This was a retrospective cohort study of patients treated with radical cystectomy (RC) for clinical stage cT2-T4, N any, M0 bladder UC at Strong Memorial Hospital from 1999 to 2009. The primary exposure variable was use of neoadjuvant chemotherapy (GC vs none). The primary outcome was stage pT0 at RC. Secondary outcomes included other down-staging end points in the bladder (

Objective: To estimate the average loss in life expectancy (LE) due to bladder cancer (BC) in men and women in the USA., Patients and Methods: 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)., Results: 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)., Conclusion: Compared with men, women loose more years of life and a greater fraction of their life expectancy to BC., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: • To determine whether the effect of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) on the survival of patients with locally advanced urothelial carcinoma (UC) of the bladder treated with radical cystectomy varies with the presence of non-urothelial components in the tumour., Patients and Methods: • This is a secondary analysis of the Southwest Oncology Group-directed intergroup randomized trial S8710 of neoadjuvant MVAC followed by cystectomy versus cystectomy alone for treatment of locally advanced UC of the bladder. • For the purpose of these analyses, tumours were classified based on the presence of non-urothelial components as either pure UC (n= 236) or mixed tumours (n= 59). Non-urothelial components included squamous and glandular differentiation. • Cox regression models were used to estimate the effect of neoadjuvant MVAC on all-cause mortality for patients with pure UC and for patients with mixed tumours, with adjustment for age and clinical stage., Results: • There was evidence of a survival benefit from chemotherapy in patients with mixed tumours (hazard ratio 0.46; 95% CI 0.25-0.87; P= 0.02). Patients with pure UC had improved survival on the chemotherapy arm but the survival benefit was not statistically significant (hazard ratio 0.90; 95% CI 0.67-1.21; P= 0.48). • There was marginal evidence that the survival benefit of chemotherapy in patients with mixed tumours was greater than it was for patients with pure UC (interaction P= 0.09)., Conclusion: • Presence of squamous or glandular differentiation in locally advanced UC of the bladder does not confer resistance to MVAC and in fact may be an indication for the use of neoadjuvant chemotherapy before radical cystectomy., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: To determine whether microscopic invasion of perivesical fat by urothelial carcinoma (stage pT3a) confers a different prognosis relative to deep muscle invasion (pT2b) and/or gross extravesical extension (pT3b) among patients with a given nodal status treated by cystectomy., Methods: Cancer records for patients diagnosed with stage pT2b-pT3b bladder cancer from 1998-2006 were obtained from the SEER database (n = 2388). Pathologic substage (pT3a vs pT2b vs pT3b) was the primary covariate of interest. Other covariates included age, sex, race, grade, number of nodes examined, number of positive nodes, nodal stages, and radiotherapy. Cox regression model was used to estimate the covariate-adjusted effect of tumor substages on all-cause mortality., Results: The risk of nodal metastases increased with increasing substage (pT2b = 20%, pT3a = 36%, pT3b = 48%, trend P <.001). Among patients with node-negative tumors, the adjusted hazard ratios for all-cause mortality were 1.68 (P <.001) for pT3a vs pT2b and 1.03 (P = .78) for pT3b vs pT3a tumors, whereas for node-positive disease, they were 1.42 (P = .009) for pT3a vs pT2b and 1.44 (P = .001) for pT3b vs pT3a tumors., Conclusions: Microscopic invasion of perivesical fat was associated with significantly inferior survival relative to pT2b disease of the same nodal status. For node-positive pT3 tumors, more advanced pathologic substage (pT3b vs pT3a) was also associated with decreased survival. Our findings support the current practice of pathologic distinction between pT2b and pT3a disease and substaging of extravesical tumors based on microscopic versus gross extravesical extension., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose of Review: Women are generally less likely to develop bladder cancer compared with men; however, once they acquire this disease, they have a less favorable prognosis. In this review, we describe our current understanding of the relationship between sex and bladder cancer incidence and outcomes and discuss the most recent developments in this area of research., Recent Findings: Despite some evidence suggesting involvement of hormonal factors in bladder cancer carcinogenesis, the exact mechanisms responsible for increased bladder cancer incidence in men are still incompletely understood. The causes of increased mortality in women are also unclear. It has been hypothesized that women present with more advanced stages (and thus have inferior survival) than men because early signs of bladder cancer in women are often attributed to more common benign conditions. However, recent studies have shown that excess mortality in women persists after adjustment for stage and other tumor characteristics. Women also do not appear to be significantly undertreated for bladder cancer., Summary: Despite considerable research efforts, both increased incidence in men and decreased survival in women remain somewhat of a mystery. The causes of these phenomena may include poorly understood biological factors or environmental influences, which may become a subject of future research.

Objectives: To determine whether the survival of patients with squamous cell carcinoma (SCC) is different from that of patients with urothelial carcinoma, after adjusting for stage, grade, demographic factors, and the initial treatment., Methods: Information on bladder cancer cases diagnosed from 1988 to 2003 was obtained from the Surveillance, Epidemiology, and End Results database. The tumors were classified by histologic type, grade, and American Joint Committee on Cancer (AJCC) stage. Other covariates included age, sex, race, and information on the initial treatment (cystectomy and radiotherapy). The outcome variables examined were all-cause and bladder cancer-specific mortality within 2 years of diagnosis. Covariate-adjusted mortality differences were computed within each stage using the modified least squares model., Results: SCC histologic features were an independent predictor of all-cause and bladder cancer-specific mortality among patients with AJCC Stage I and II tumors who did not undergo cystectomy as a part of their initial treatment and among patients with AJCC Stage III and IV regardless of whether cystectomy was performed. SCC histologic features were not associated with increased mortality among patients with AJCC Stage I and II tumors treated with cystectomy., Conclusions: SCC appears to be more aggressive than urothelial carcinoma after adjusting for stage and other prognostic factors, except for cases in which the tumor was confined to the bladder wall and the bladder was removed as a part of the initial treatment.

Background: Sex, race, and age at diagnosis have a significant impact on mortality from bladder cancer (BC). Women, African Americans of both sexes, and the elderly, all experience higher mortality rates. Tumor grade, stage, and histologic type at presentation also affect outcome. To determine whether age and tumor characteristics alone explain the excess hazard of death from BC observed in some demographic groups, the authors queried the Surveillance, Epidemiology, and End Results (SEER) limited-use database for the presentations and outcomes from BC between 1990 and 2005., Methods: Tumors were characterized by grade, stage, and histologic type. Hazards rates for BC-specific mortality were compared by race and sex using a piecewise Cox regression model, adjusting for factors (age, stage, grade, and histologic type) that differed significantly between the groups that were compared., Results: Excess hazard of death from BC was present during the first 2 to 3 years of follow-up among women and during the first 4 years of follow-up among African Americans. Adjustment for age and tumor characteristics eliminated approximately 30% of this excess hazard in sex comparison among whites. In sex comparison among blacks and in racial comparisons within each sex, approximately 50% to 70% of excess hazard could be eliminated by adjustment., Conclusions: Significant differences in tumor characteristics and age at presentation did not fully account for the excess hazard of death from BC among women and African Americans. Other factors, such as choice and efficacy of therapies, differences within a given tumor characteristic group, and/or host factors also may play important roles., (Copyright (c) 2008 American Cancer Society.)