Selenium and Vitamin E for Prevention of Non-Muscle-Invasive Bladder Cancer Recurrence and Progression: A Randomized Clinical Trial.

Importance: Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer. Objective: To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC. Design, Setting, and Participants: This multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK. A total of 755 patients were screened for inclusion; 484 did not meet the inclusion criteria, and 1 declined to participate. A total of 270 patients were randomly assigned to 4 groups (selenium plus placebo, vitamin E plus placebo, selenium plus vitamin E, and placebo plus placebo) in a double-blind fashion between July 17, 2007, and October 10, 2011. Eligibility included initial diagnosis of NMIBC (stages Ta, T1, or Tis); randomization within 12 months of first transurethral resection was required. Interventions: Oral selenium (200 µg/d of high-selenium yeast) and matched vitamin E placebo, vitamin E (200 IU/d of d-alfa-tocopherol) and matched selenium placebo, selenium and vitamin E, or placebo and placebo. Main Outcome and Measures: Recurrence-free interval (RFI) on an intention-to-treat basis (analyses completed on November 28, 2022). Results: The study randomized 270 patients (mean [SD] age, 68.9 [10.4] years; median [IQR] age, 69 [63-77] years; 202 male [75%]), with 65 receiving selenium and vitamin E placebo, 71 receiving vitamin E and selenium placebo, 69 receiving selenium and vitamin E, and 65 receiving both placebos. Median overall follow-up was 5.5 years (IQR, 5.1-6.1 years); 228 patients (84%) were followed up for more than 5 years. Median treatment duration was 1.5 years (IQR, 0.9-2.5 years). The study was halted because of slow accrual. For selenium (n = 134) vs no selenium (n = 136), there was no difference in RFI (hazard ratio, 0.92; 95% CI, 0.65-1.31; P = .65). For vitamin E (n = 140) vs no vitamin E (n = 130), there was a statistically significant detriment to RFI (hazard ratio, 1.46; 95% CI, 1.02-2.09; P = .04). No significant differences were observed for progression-free interval or overall survival time with either supplement. Results were unchanged after Cox proportional hazards regression modeling to adjust for known prognostic factors. In total, 1957 adverse events were reported; 85 were serious adverse events, and all were considered unrelated to trial treatment. Conclusions and Relevance: In this randomized clinical trial of selenium and vitamin E, selenium supplementation did not reduce the risk of recurrence in patients with NMIBC, but vitamin E supplementation was associated with an increased risk of recurrence. Neither selenium nor vitamin E influenced progression or overall survival. Vitamin E supplementation may be harmful to patients with NMIBC, and elucidation of the underlying biology is required. Trial Registration: isrctn.org Identifier: ISRCTN13889738.

Centralization and prospective audit of cystectomy are necessary: a commentary on the case for centralization, supported by a contemporary series utilizing the ANZUP cystectomy database.

Bladder cancer (BC) outcomes are unacceptably poor. In Australia, BC survival is actually deteriorating. There is an urgent need to improve outcomes in BC patients, which requires a multipronged approach. One area deserving closer scrutiny is radical cystectomy. Audit is necessary to identify areas for improvement and without it, outcomes remain unknown. Evidence convincingly shows high-volume surgeons and centers improve cystectomy outcomes including overall survival, yet centralization has still not occurred. The Australia and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group cystectomy database has been established to facilitate cystectomy audit in Australia and New Zealand. We present initial data from the ANZUP cystectomy database from a single high-volume center, discuss the benefits of centralization and its challenges in the Asia-Pacific context.

Fluid intake and clinicopathological characteristics of bladder cancer: the West Midlands Bladder Cancer Prognosis Programme.

OBJECTIVE: Between 10 and 20% of bladder cancer patients who are diagnosed with nonmuscle-invasive bladder cancer will progress to muscle-invasive disease. Risk of progression depends on several factors at diagnosis including age, tumour stage, grade, size and number, and the presence or absence of carcinoma in situ. Fluid intake may be related to these factors. METHODS: Data of 1123 participants from the West Midlands Bladder Cancer Prognosis Programme were used. Data collection was via a semistructured questionnaire, and case report forms were used to collect clinicopathological data. Fluid intake was measured for six main categories: alcoholic fluids, hot fluids, fruit fluids, milk, fizzy drinks, and water, and converted into quintile variables. Multilevel mixed-effects linear regression was performed for every beverage category per clinicopathological variable and corrected for age, gender, and smoking status. RESULTS: Age at diagnosis was distributed differently amongst those in different total fluid intake quintiles (predicted means 71.5, 70.9, 71.5, 69.9, and 67.4, respectively) and showed a significant inverse linear trend in alcohol (P < 0.01), hot fluids (P < 0.01), and total fluids intake (P < 0.01), in nonmuscle-invasive bladder cancer patients. CONCLUSION: Our results suggest an inverse association for alcohol intake and total fluid intake with age at diagnosis. These results should be confirmed by future studies, alongside a possible (biological) mechanism that could influence tumour growth, and the effect of micturition frequency.

Tar, nicotine and carbon monoxide yield of UK cigarettes and the risk of non-muscle-invasive and muscle-invasive bladder cancer.

Cigarette smoking is a major risk factor for bladder cancer (BC); however, the impact of cigarette content remains unclear. This study aims to investigate tar, nicotine and carbon monoxide (TNCO) yields of different filtered cigarettes in relation to BC risk. From the Bladder Cancer Prognosis Programme 575 non-muscle-invasive bladder cancer (NMIBC) cases, 139 muscle-invasive bladder cancer (MIBC) cases and 130 BC-free controls with retrospective data on smoking behaviour and cigarette brand were identified. Independently measured TNCO yields of cigarettes sold in the UK were obtained through the UK Department of Health and merged with the Bladder Cancer Prognosis Programme dataset to estimate the daily intake of TNCO. BC risk increased by TNCO intake category for NMIBC cases (P <0.050 in all multivariate models), but only for the daily intake of tar for MIBC cases (P=0.046) in multivariate models. No difference in risk was observed between smokers of low-tar/low-nicotine and high-tar/high-nicotine cigarettes compared with never smokers, either for NMIBC (P=0.544) or MIBC (P=0.449). High daily intake of TNCO additionally increases the risk of both NMIBC and MIBC compared with low daily intake. However, as there is no difference in BC risk between low-tar/low-nicotine and high-tar/high-nicotine cigarette smokers, it remains unclear whether smoking behaviour or TNCO yield of cigarettes explains this association.

Total Fluid Intake and the Risk of Recurrence in Patients With Non-Muscle Invasive Bladder Cancer: A Prospective Cohort Study.

OBJECTIVES: To investigate the role of fluid intake from beverages before and after a diagnosis of bladder cancer in relation to the risk of developing bladder cancer recurrence. STUDY DESIGN: Prospective cohort study. METHODS: 716 patients with non-muscle invasive bladder cancer (NMIBC), who received transurethral resection of a primary bladder tumour (TURBT) and completed self-administrated questionnaires on usual fluid intake from beverages at time of diagnosis (over the year before diagnosis) and during follow-up (over the year after diagnosis), were included. Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals of developing recurrent bladder cancer in relation to the intake of total fluid, total alcohol, and individual beverages. RESULTS: During 2,025 person-years of follow-up, 238 (33%) of the included 716 NMIBC patients developed one or more recurrences of bladder cancer. Total fluid intake before diagnosis was not associated with a first recurrence of bladder cancer when comparing the highest and lowest intake group (HR = 0.98, 95% C.I. 0.70-1.38, p = 0.91). Comparable results were obtained for total fluid intake pre-diagnosis and the risk of developing multiple recurrences of bladder cancer (HR = 1.01, 95% C.I. 0.87-1.19, p = 0.85). A total of 379 of the 716 patients reported on usual fluid intake within 1 year of diagnosis. No significant associations between total fluid intake 1 year after diagnosis and a first recurrence of bladder cancer were found when comparing the highest and lowest intake group (HR = 0.91; 95% C.I. 0.60-1.37, p = 0.65) or with multiple recurrences of bladder cancer (HR = 1.06; 95% C.I. 0.89-1.26, p = 0.54). In addition, total alcohol intake and individual beverages were not associated with bladder cancer recurrence. CONCLUSIONS: The results indicate that an individual's fluid intake from beverages is unlikely to have an important role in bladder cancer recurrence.

The association between smoking cessation before and after diagnosis and non-muscle-invasive bladder cancer recurrence: a prospective cohort study.

BACKGROUND: Smoking is a major risk factor for bladder cancer, but the relationship between smoking cessation after initial treatment and bladder cancer recurrence has been investigated less frequently and not prospectively yet. METHODS: 722 non-muscle-invasive bladder cancer (NMIBC) patients (pTa, pT1, and CIS) from the prospective Bladder Cancer Prognosis Programme (BCPP) cohort, selected in the UK between 2005 and 2011, provided complete data on smoking behavior before and up to 5 years after diagnosis. The impact of smoking behavior on NMIBC recurrence was explored by multivariable Cox regression models investigating time-to-first NMIBC recurrence. RESULTS: Over a median follow-up period of 4.21 years, 403 pathologically confirmed NMIBC recurrences occurred in 210 patients. Only 25 current smokers at diagnosis quit smoking (14%) during follow-up and smoking cessation after diagnosis did not decrease risk of recurrence compared to continuing smokers (p = 0.352). CONCLUSIONS: Although quitting smoking after diagnosis might reduce the risk of recurrence based on retrospective evidence, this is not confirmed in this prospective study because the number of NMIBC patients quitting smoking before their first recurrence was too low. Nevertheless, this indicates an important role for urologists and other health care professionals in promoting smoking cessation in NMIBC.

Fruit and vegetable intake and the risk of recurrence in patients with non-muscle invasive bladder cancer: a prospective cohort study.

INTRODUCTION: There is some evidence that greater consumption of fruit and vegetables decreases the risk of bladder cancer. The role of fruit and vegetables in bladder cancer recurrence is still unknown. OBJECTIVE: The role of total fruit and vegetable intake in relation to the risk of developing bladder cancer recurrence in a prospective cohort study. METHODS: 728 patients with non-muscle invasive bladder cancer (NMIBC), who completed self-administrated questionnaires on fruit and vegetable intake at time of diagnosis (over the year before diagnosis) and 1 year after diagnosis, were included. Hazard ratios and 95% confidence intervals were calculated by multivariable Cox regression for developing recurrent bladder cancer in relation to fruit and vegetable intake. RESULTS: During 2,051 person-years of follow-up [mean (SD) follow-up 3.7 (1.5) years], 241 (33.1%) of the included 728 NMIBC patients developed a recurrence of bladder cancer. The sum of total fruit and vegetables before diagnosis was not related to a first bladder cancer recurrence (HR 1.07; 95% CI 0.78-1.47, p = 0.66). No association was found between greater consumption of fruit and vegetables over the year before diagnosis and the risk of developing multiple recurrences of bladder cancer (HR 1.02; 95% CI 0.90-1.15, p = 0.78). Among the remaining 389 NMIBC patients who reported on fruit and vegetable intake 1 year after diagnosis, no association was found between greater consumption of fruit and vegetables and a first recurrence of bladder cancer (HR 0.65; 95% CI 0.42-1.01, p = 0.06) nor with multiple recurrences of bladder cancer (HR 1.00, 95% CI 0.85-1.18, p = 1.00). Similar results were obtained when investigating the association between total intakes of fruit and vegetables separately and bladder cancer recurrence. CONCLUSION: Results from this study did not indicate a protective role for total fruit and vegetables in the development of a recurrence of NMIBC.

A Comparative Analysis of the Influence of Gender, Pathway Delays, and Risk Factor Exposures on the Long-term Outcomes of Bladder Cancer.

BACKGROUND: The relationship between pathway delays and bladder cancer-specific survival is complex because of the influence of tumour- and patient-specific factors. OBJECTIVE: To investigate the influence of tumour factors, patient factors, carcinogen exposure, and pathway delays on the long-term outcome of urothelial bladder cancer (UBC). DESIGN, SETTING, AND PARTICIPANTS: A cohort of 1537 UBC patients were enrolled between January 1, 1991 and June 30, 1992 and followed up for 17.7 yr. The period from the onset of symptoms to first treatment (transurethral resection of bladder tumour, TURBT) was divided into three components of potential delay. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between patient factors, tumour factors, and delay times were analysed using the Pearson χ2 test and the Mann-Whitney U test. Survival was calculated from date of TURBT to date of death or censor date (December 31, 2010). Competing risks of death were assessed with the cumulative incidence function (CIF); CIF comparisons were performed using the Gray test. RESULTS AND LIMITATIONS: At censor, reliable data were available for 1478 patients, of whom 75% had died. Females presented more commonly with muscle-invasive bladder cancer (MIBC; 30% vs 26%) and less frequently with pT1 disease (18% vs 24%; p=0.06) and had a longer total delay time (median 120 d vs 106 d, p=0.02), and those with MIBC had a significantly higher cumulative incidence of death due to UBC (80% vs 67% at 17 yr; p<0.02). Cox regression identified age, smoking status, and tumour stage, grade, and size as the most significant determinants of poor outcome. We did not capture downstream delays associated with cystectomy or radiotherapy. CONCLUSIONS: Female UBC patients present later than males, and our data suggest that delay in referral may be contributory. The relationship between gender, outcomes, delays, and UBC aetiology is complex. PATIENT SUMMARY: We followed a large group of bladder cancer patients for more than 17 yr. The relationship between pathway delays and survival is complex. However, female patients present later than male patients, and our data suggest that delay in referral from general practice may be contributory.

The conservative management of renal trauma: a literature review and practical clinical guideline from Australia and New Zealand.

OBJECTIVE: To review the literature and make practical recommendations regarding the conservative management of renal trauma. PATIENTS AND METHODS: Relevant articles and guidelines published between 1980 and 2014 were reviewed. Graded recommendations were constructed by a multi-disciplinary panel consisting of urologists, radiologists, and infectious disease physicians. These recommendations underwent formal review and debate at the Western Australian USANZ 2013 state conference, and were presented at the USANZ 2014 annual scientific meeting. RESULTS: The literature on the conservative management of renal trauma is reviewed within the framework of the American Association for the Surgery of Trauma (AAST) kidney injury severity scale. Graded recommendations are made regarding several key topics including: imaging, inpatient management, antibiotics, return to activity, and follow-up. Grade IV injuries and intraoperative consults are examined separately in view of the difficulties these groups cause in making appropriate treatment decisions. CONCLUSION: A practical clinical guideline is provided regarding the conservative management of renal trauma.

A comparison of patient and tumour characteristics in two UK bladder cancer cohorts separated by 20 years.

OBJECTIVES: To compare patient and tumour characteristics at presentation from two large bladder cancer cohorts, with recruitment separated by 15-20 years To identify significant differences in the West Midlands' urothelial cancer of the bladder (UCB) population during this period. PATIENTS AND METHODS: Data were collected prospectively from 1478 patients newly diagnosed with UCB in the West Midlands from January 1991 to June 1992 (Cohort 1), and from 1168 patients newly diagnosed with UBC within the same region from December 2005 to April 2011 (Cohort 2). Gender, age, smoking history, and tumour grade, stage, type, multiplicity and size at presentation were compared using a Pearson chi-square test or Cochran-Armitage trend test, as appropriate. RESULT: Cohort 2 had a higher proportion of male patients (P = 0.021), elderly patients (P < 0.001), grade 3 tumours (P < 0.001), Ta/T1 tumours (P = 0.008), multiple tumours (P < 0.001), and tumours of ≤2 cm in diameter (P < 0.001). CONCLUSIONS: There were significant differences between the cohorts. These differences are potentially explained by an ageing population, changes in grading practices, improved awareness of important symptoms, improved cystoscopic technology, and reductions in treatment delays. Regional cohorts remain important for identifying changes in tumour and patient characteristics that may influence disease management in the UK and beyond.

Expression of Engrailed-2 (EN2) protein in bladder cancer and its potential utility as a urinary diagnostic biomarker.

Despite significant advances in our understanding of the molecular pathology of bladder cancer, it remains a significant health problem with high morbidity and mortality associated with muscle-invasive bladder cancer (stages T2+), and high costs associated with the surveillance of non-muscle-invasive bladder cancer (NMIBC, stages Ta/T1/Tis). Moreover, current diagnostic biomarkers are suboptimal and of poor utility for low grade disease and surveillance. In this study, we show that the Engrailed-2 (EN2) transcription factor is expressed in, and secreted by, bladder cancer cell lines and patient tumour specimens, justifying an evaluation of urinary EN2 as a diagnostic biomarker in bladder cancer using archived samples from an established biospecimen collection. In patients with NMIBC, urinary EN2 was detected in most cases with an overall sensitivity of 82% and specificity of 75%. The sensitivity for stage Ta and T1 tumours was 71% and 76%, respectively, and 94% for stage T2+ tumours. This compares favourably with existing markers. The sensitivity for tumour grades 1, 2 and 3 was 69%, 78% and 87%, respectively. Thus urinary EN2 has the potential to be a more sensitive and specific protein biomarker for NMIBC than currently available tests.

Smoking is associated with lower age, higher grade, higher stage, and larger size of malignant bladder tumors at diagnosis.

Smoking is a strong risk factor of bladder cancer (BC), but it is currently unclear whether smoking is also associated with severity of BC at diagnosis. We performed a large hospital-based case-comparison study, examining the relation between smoking and clinical characteristics of BC at diagnosis. A total of 1,544 cases from participating hospitals in the West Midlands were recruited between 19 December 2005 and 21 April 2011. Eligible cases were adult BC patients without a previous history of this disease. At time of diagnosis, semi-structured face-to-face interviews were conducted by trained research nurses to collect smoking information. Clinical characteristics were obtained from medical records. Linear mixed models were performed to calculate predicted means in clinical outcomes for a variety of smoking behaviors. A p < 0.05 was considered statistically significant. After adjustment for age and gender, current smokers were on average 4.0 years younger at diagnosis (95% CI: -5.9 to -2.0), had larger tumors (mean difference: 0.48 cm, 95% CI: 0.04-0.91), a higher T stage (mean difference: 0.25, 95% CI: 0.08-0.41), and a borderline significantly higher grade than never smokers (mean difference: 0.15, 95% CI: 0.00-0.30). Our results suggest that smoking could be associated with a more malignant phenotype of BC at diagnosis. More research is needed on the relation between smoking and prognosis, but our results could strengthen the message about the potential risks of smoking to these patients.

T lymphocyte recruitment into renal cell carcinoma tissue: a role for chemokine receptors CXCR3, CXCR6, CCR5, and CCR6.

BACKGROUND: Evidence suggests that some patients with renal cell carcinoma (RCC) respond to immunomodulatory therapies that activate T lymphocytes. A prerequisite for effective T cell therapy is efficient targeting of effector T cells to the tumour site, yet the molecular basis of T cell recruitment to RCC is unknown. Furthermore, some T cells that naturally infiltrate this cancer are regulatory T cells (Tregs) that may suppress antitumour immune responses. OBJECTIVE: Determine the mechanisms of effector and regulatory T cell recruitment to RCC to allow targeted therapy that promotes local anti-tumour immunity. DESIGN, SETTING, AND PARTICIPANTS: Tumour-infiltrating and peripheral blood T cells were collected from 70 patients undergoing nephrectomy for RCC. MEASUREMENTS: T cells were analysed by multicolour flow cytometry for expression of 19 chemokine receptors and 7 adhesion molecules. Receptors that were expressed at higher levels on tumour-infiltrating lymphocytes (TILs) compared with matched peripheral blood lymphocytes (PBLs) were analysed further for their ability to mediate migration responses in TILs and for expression of corresponding ligands in tumour tissue. RESULTS AND LIMITATIONS: Three chemokine receptors-CCR5, CXCR3, and CXCR6-were significantly overexpressed on TILs compared with matched PBLs (n=16 cases) and were capable of promoting migration in vitro. Their corresponding ligands CCL4-5, CXCL9-11, and CXCL16 were all detected in RCC tissue. However, since they were present in all cases studied, it was not possible to correlate ligand expression with levels of T cell infiltration. Foxp3(+) Tregs were enriched within TILs compared with matched PBLs and expressed high levels of CCR5, CXCR3, and CXCR6, as well as CCR6, the ligand for which (CCL20) was detectable in RCC tissue. CONCLUSIONS: Our data support a role for CCR5, CXCR3, and CXCR6 in the selective recruitment of T cells into RCC tissue and, together with CCR6, in the recruitment of Tregs.

'One stop' haematuria clinic in Fremantle Hospital, Western Australia: a report of the first 500 patients.

UNLABELLED: What's known on the subject? and What does the study add? Haematuria is a symptom of urologic cancer particularly bladder cancer and timely diagnosis can prevent disease from progression to a more advanced or incurable stage. The 'One Stop' Haematuria clinic is the first rapid assessment clinic for haematuria in a public hospital in Western Australia. The results from this study have confirmed that it is an efficient and effective model in the streamlined care of patients with haematuria and provides evidence to support a more widespread adoption of this model of care. OBJECTIVE: • To report the prospective outcomes and clinic process for the first 500 patients at a new 'one stop' Haematuria Clinic (OSHC) in a Western Australian public hospital. PATIENTS AND METHODS: • The first 500 patients who attended the weekly OSHC between May 2008 and February 2011 were included in this paper. • Patients with haematuria were referred by various specialties. Gender, age, outcomes following OSHC attendance, diagnoses and wait times were recorded. RESULTS: • In all, 311 males and 189 females presented to the clinic with visible haematuria (296 cases) and microscopic haematuria (204 cases). • Sixty-six new cancers (13.2%) were diagnosed, 63 urological and three non-urological. • Fifty-one patients (10.2%) were diagnosed with transitional cell carcinoma of the bladder. Further breakdown of staging for bladder transitional cell carcinoma diagnoses were stage Ta (23 patients), stage T1 (21 patients) and stage 2-4 (seven patients). • Sixty-nine patients (13.8%) were diagnosed with urological pathologies requiring surgery. Thirty-four patients (6.8%) were followed up by the nurse practitioner or continence advisors. In all, 61.2% of patients were discharged after a single visit to the OSHC. • Excluding those requiring surgery only 3.4% patients required further urologist follow-up. CONCLUSION: • The results have demonstrated that the first OSHC in a public Western Australian hospital is an efficient and effective model for the streamlined care of patients with haematuria. • We encourage that similar models are adopted in other public hospitals in the region.

Assessment of high-throughput high-resolution MALDI-TOF-MS of urinary peptides for the detection of muscle-invasive bladder cancer.

PURPOSE: There is a need for better biomarkers to both detect bladder cancer and distinguish muscle-invasive (stage T2+) from non-invasive (stage Ta/T1) disease. We assess whether MALDI-TOF-MS of the urine peptidome can achieve this. EXPERIMENTAL DESIGN: We analysed urine from 751 patients with bladder cancer and 127 patients without bladder cancer. Endogenous peptide profiling was performed using a Bruker Ultraflextreme MALDI-TOF-MS. RESULTS: Significant differences were seen between the spectra of urine from patients with and without T2+ disease. Albumin, total protein and haematuria were also elevated in T2+ patients. Haematuria was detected in 39% of patients with Ta/T1 disease and in 77% of patients with T2+ disease. Class prediction models based on MALDI data produced areas under receiver-operator characteristic curves of up to 0.76 but did not significantly outperform a model based on total protein alone. Many peptides significantly associated with invasive disease are fragments of abundant blood proteins and are also associated with haematuria. CONCLUSIONS AND CLINICAL RELEVANCE: Microscopic haematuria is strongly associated with invasive disease; even traces of blood/plasma strongly influence the urinary peptidome. This needs to be taken into consideration when using 'omic' methods to search for urinary biomarkers as blood proteins may give false-positive results.

Emerging endoscopic and photodynamic techniques for bladder cancer detection and surveillance.

This review provides an overview of emerging techniques, namely, photodynamic diagnosis (PDD), narrow band imaging (NBI), Raman spectroscopy, optical coherence tomography, virtual cystoscopy, and endoscopic microscopy for its use in the diagnosis and surveillance of bladder cancer. The technology, clinical evidence and future applications of these approaches are discussed with particular emphasis on PDD and NBI. These approaches show promise to optimise cystoscopy and transurethral resection of bladder tumours.

Narrow-band imaging flexible cystoscopy: a new user's experience.

BACKGROUND AND PURPOSE: We and others have demonstrated previously an improved detection rate for bladder cancer recurrences with narrow-band imaging (NBI) flexible cystoscopy when compared with conventional white-light imaging (WLI) flexible cystoscopy. We investigated whether a "new user" of NBI flexible cystoscopy, previously unfamiliar with this technique, could reproduce these results. PATIENTS AND METHODS: The same protocol from our previous study was used by a new user (ZHS) for this second study at The Queen Elizabeth Hospital, Birmingham, United Kingdom. NBI flexible cystoscopy was performed on 23 patients with known recurrences of urothelial cancer (UC) of the bladder after initial conventional WLI flexible cystoscopy with the same switchable Olympus Lucera sequential red/green/blue instrument. RESULTS: NBI detected 15 additional UCs in 8 of the 23 (35%) patients: Six of these patients had one additional UC, one had four additional UCs, and one had five additional UCs when compared with WLI, with a mean of 0.65 additional UCs per patient (standard deviation 1.30; Wilcoxon P = 0.01). When this second series is compared with our first published series, there is no statistical evidence that the excess number of UCs detected by NBI is different (Wilcoxon [unpaired] signed-rank test P = 0.74), which suggests that there is no difference between a new user and an experienced user in the application of NBI. CONCLUSIONS: We and others continue to demonstrate a significantly improved detection rate of bladder UCs with NBI cystoscopy when compared with conventional WLI cystoscopy, even for new users previously unfamiliar with this technology.

Mechanisms of recurrence of Ta/T1 bladder cancer.

INTRODUCTION: Bladder cancer recurrence occurs via four mechanisms - incomplete resection, tumour cell re-implantation, growth of microscopic tumours, and new tumour formation. The first two mechanisms are influenced by clinicians before and immediately after resection; the remaining mechanisms have the potential to be influenced by chemopreventive agents. However, the relative importance and timing of these mechanisms is currently unknown. Our objective was to postulate the incidence and timing of these mechanisms by investigating the location of bladder cancer recurrences over time. PATIENTS AND METHODS: The topographical locations of tumours and their recurrences were analysed retrospectively for 169 patients newly-diagnosed with Ta/T1 bladder cancer, with median follow-up of 33.8 months. Tumours were assigned to one or more of six bladder sectors, and time to recurrence and location of recurrences were recorded. RESULTS: Median time to first tumour recurrence was 40 months. Median times between subsequent recurrences were 6.6, 7.9, 8.0 and 6.6 months for recurrences 1 to 2, 2 to 3, 3 to 4, and 4 to 5, respectively. The risk of first tumour recurrence in any given bladder sector increased by nearly 4-fold if the primary tumour was resected from that sector (P < 0.001); this association was not significant for subsequent recurrences. The proportion of tumour recurrences in multiple bladder sectors increased from 13% for the first recurrence to 100% for recurrence seven onwards. CONCLUSIONS: First tumour recurrence appears different to subsequent recurrences; incomplete resection and tumour cell reimplantation may dominate at this time-point. Only later does genuine new tumour formation appear to increase in importance. This has important implications for clinical trials, especially those involving chemopreventive agents.

The West Midlands Bladder Cancer Prognosis Programme: rationale and design.

OBJECTIVE To describe the rationale and design of the Bladder Cancer Prognosis Programme (BCPP), and to demonstrate the capability of this design. METHODS There is a need to understand the determinants of bladder cancer to help reduce recurrence, progression, morbidity, mortality and related costs. We previously showed that lifestyle factors are important for determining the risk of bladder cancer, but little is known about their importance in determining the risk of recurrence or progression after diagnosis. Also, histopathological factors alone provide only crude prognostication; the analysis of molecular markers represents a method for refinement but research in this area has not been useful in informing therapeutic decisions or prognostication. The BCPP is a prospective longitudinal cohort study of all patients with newly diagnosed bladder cancer within the West Midlands (UK), investigating the influence of lifestyle factors on recurrence and progression, health-related quality of life, the predictive effect of a panel of molecular markers on recurrence or progression, and the establishment of Europe's largest comprehensive bladder cancer bio-repository. It also incorporates the first randomized clinical trial on the efficacy of selenium and vitamin E on bladder cancer. The numbers and proportions of eligible patients recruited, questionnaires completed and specimens obtained were all recorded. RESULTS Since December 2005, 771 patients have been recruited (68% of eligible patients) and of these, 331 are currently being followed up by questionnaires. We have obtained blood, urine and tumour tissues from 92%, 80% and 80% of patients, respectively. CONCLUSIONS The design of the BCPP has allowed this study to be incorporated into routine clinical work throughout the West Midlands, achieving high levels of recruitment, and data and specimen collection. This might represent a model for the future investigation of urological and other malignancies.

Biomarkers in bladder cancer.

Detailed molecular insights into bladder cancer biology might allow more detailed prognostication and optimization of treatment with the objective of improving patient outcome and quality of life. However, in bladder cancer research the search for biomarkers has been called into question and has even obtained notoriety. It is unlikely that any single marker will be able to improve prognostication for patients with bladder cancer above and beyond grade and stage, but a combination of multiple independent markers might more precisely predict the outcome. From a previous review, we identified seven biomarkers to study within the setting of the Bladder Cancer Prognosis Programme (BCPP), a 5-year multicentre programme of research based at the University of Birmingham and funded by Cancer Research UK, investigating their effectiveness in predicting recurrence and progression. As part of the ongoing quality-assurance process for BCPP we present an updated review of our selected biomarkers, as well as highlighting other recent important developments in bladder cancer research.