Diagnosis Of Non-muscle Invasive Bladder Cancer Research Articles

Early recurrence and the need for re-resection following Photodynamic diagnosis–assisted Transurethral Resection of Bladder Tumours: Multi-centre real-world experience of the UK PDD Users Group

Objective: This study aimed to investigate the association between Photodynamic Diagnosis (PDD) with hexaminolevulinate (HAL) and the rate of complete resection and disease persistence at first follow-up cystoscopy for non-muscle-invasive bladder cancer (NMIBC) in UK real-world practice. Methods: Audit data were pooled from six UK centres where HAL PDD was used in patients with a new NMIBC diagnosis undergoing transurethral resection of bladder tumours (TURBT) since 2008. Patients received adjunctive intra-vesical therapy and surveillance in line with European and UK guidelines, including early re-resection in high-grade NMIBC. Results: PDD-assisted TURBT was done in 837 patients with new NMIBC. The detrusor muscle was present in 69.4% of cases. At early re-TURBT in 207 high-risk patients, 13.0% had residual disease. Multifocal disease was the most significant factor in increasing the rate of residual disease (odds ratio excluding cases of CIS=4.1; 95% confidence interval 1.5–11.3). The recurrence rate at first follow-up cystoscopy (RRFFC) was 10.6% (8.9% in patients with complete initial TURBT). In the historical cohort undergoing good-quality white-light TURBT, RRFFC was 31%; 40.5% of high-risk patients had residual disease at early re-TURBT. Conclusion: HAL PDD may increase the rates of complete resection, reducing the risk of early recurrence and the need for routine re-resection in high-grade NMIBC. Level of evidence: 2b.

Factors affecting guideline adherence in the initial treatment of non-muscle invasive bladder cancer: Retrospective study in a French peripheral hospital

To assess whether the initial treatment of non-muscle invasive bladder cancer (NMIBC) was performed according to the guidelines, and to determine the reasons why initial treatment was not provided in nonadherence cases. We retrospectively reviewed all patients with NMIBC who underwent their first transurethral resection of bladder tumor (TURBT) at a peripheral hospital, between 2007 and 2016. The treatment offered to the patient was compared to the European Association of Urology guidelines according to risk stratification. For each patient who did not receive the treatment according to the guidelines, one of the following reasons was identified: poor patient compliance, poor patient general health status, urologist's decision, lack of resources. One hundred fifty-nine patients were included with a mean age of 72.2 years at the time of NMIBC diagnosis. The low-risk patients were strictly treated according to the guidelines. Among the intermediate-risk patients, 14% received mitomycin C. Among the high-risk patients, 39% received intravesical Bacillus Calmette-Guerin. In the nonadherence cases (61%), the reasons were related to the patient in 44% of cases (poor compliance, 21%; poor patient general health status, 23%), urologist's decision in 54% of cases, and lack of resources in 2% of cases. Thirty-seven percent of the high-risk patients underwent re-resection. Overall, adherence to NMIBC guidelines was low in all treatment types (intravesical therapy, re-resection, or cystectomy for very high-risk patients), but this finding was similar to that in previous studies. Reasons were mainly related to the urologist's decision or to the patient condition (poor compliance or poor general health status). 3.

Bladder cancer mortality after a diagnosis of nonmuscle-invasive bladder carcinoma.

Aim: To assess mortality from bladder cancer following a diagnosis of nonmuscle-invasive bladder cancer. Materials & methods: This is a SEER registry-based study. The risk of death from bladder cancer was compared with that of the general population. Cox proportional model was performed to calculate the hazard ratio (HR) for death according to baseline characteristics. Results: The bladder cancer-specific mortality at 20 years was 11%; and it was higher for black patients compared with white patients (adjusted HR: 1.711 [95% CI: 1.564-1.872]; p < 0.0001); additionally, it was higher for patients older than 70 years old compared with younger patients (adjusted HR: 2.005 [95% CI: 1.916-2.099]; p < 0 .0001). The risk of bladder cancer mortality increased after diagnosis of a recurrent bladder cancer (both nonmuscle-invasive and muscle-invasive; adjusted HR: 6.97 [95% CI: 6.56-7.40]; p < 0 .0001). Conclusion: Important predictors for death from bladder cancer following a diagnosis of nonmuscle-invasive bladder cancer include older age at diagnosis and black race.

Recurrence Rate and Cost Consequence of the Shortage of Bacillus Calmette-Guérin Connaught Strain for Bladder Cancer Patients

BackgroundBetween 2013 and 2016, global production of bacillus Calmette-Guérin (BCG) was dramatically reduced due to the collapse of the factory producing BCG Connaught. ObjectiveTo evaluate the clinical and economic impact of BCG shortage on a cohort of non–muscle-invasive bladder cancer (NMIBC) patients treated during the period of restricted supply. Design, setting and participantsThis retrospective, before and after, cost-consequence study included patients with intermediate- and high-risk NMIBC. Those resected between November 2011 and September 2013 (control group) were compared with those resected between October 2013 and December 2016 (study group). Outcome measurements and statistical analysisThe primary endpoint was the rate of tumor recurrence from 30 d after transurethral resection to the end of follow-up at 24 mo; the secondary endpoints included the average cost of primary treatment, average cost of treatment of recurrence, and excess cost due to BCG shortage per patient. Results and limitationsA total of 402 patients were included: 191 in the control group and 211 in the study group. The rate of recurrence at 24 mo was significantly higher in the study group than in the control group (46.9% vs 16.2%; relative risk: 0.7, 95% confidence interval [0.60; 0.82]; p < 0.001). The increased cost due to the decrease in BCG production was estimated to be €783 per patient with a new diagnosis of NMIBC during the period of restricted supply. This is a retrospective analysis at the level of our unit. A more precise evaluation would require a study of a larger cohort of patients. ConclusionsThe shortage of BCG between October 2013 and December 2016 had a significant medical and economic impact; there was an increased rate of bladder cancer recurrence, and the total cost of care for intermediate- and high-risk NMIBC was higher. Patient summaryIn this report, we analyzed the medical and economic impact of bacillus Calmette-Guérin (BCG) shortage that occurred between 2013 and 2016. We found a significant increase of bladder cancer recurrence and progression, and an increase in the number of patients who had to be treated by cystectomy. BCG shortage also had a significant impact on the total cost. Since there are no alternatives to BCG for high-risk non–muscle-invasive bladder cancer patients, BCG production has to be maintained by any means.

Current concept of transurethral resection of bladder cancer: from re-transurethral resection of bladder cancer to en-bloc resection.

Transurethral resection of bladder cancer (TURB) is the critical step in the management of nonmuscle invasive bladder cancer (NMIBC). This review presents new improvements in the strategy and technique of TURB as well as in technological developments used for tumour visualization and removal. The goal of TURB is to perform complete resection of NMIBC. Tumor visualization during procedure can be improved by enhanced optical technologies. Fluorescence-guided photodynamic diagnosis (PDD) and narrow-band imaging (NBI) used during TURB can improve tumour detection and potentially reduce recurrence rate, their influence on progression, however, remains controversial. TURB can be performed using monopolar or bipolar electrocautery without significant differences in results or safety. To overcome limitations of traditional TURB, the technique of en-bloc resection was introduced to improve the quality of tumour removal. In selected cases, an early re-resection (re-TURB) within 2-6 weeks after initial procedure is recommended. TURB is a fundamental step in diagnosis and treatment of NMIBC. Urologists should be aware of promising innovations including new imaging and surgical techniques and their potential benefits. Hopefully, new technologies and performance of TURB bring improved outcomes, which can alter the indication criteria for re-TURB.

39 - Does preoperative neutrophil-to-lymphocyte ratio has a value in predicting recurrence in bladder tumor after intravesical BCG treatment?

The purpose of this study was to evaluate the prognostic value of the ratio of preoperative neutrophil to lymphocyte after intravesical BCG treatment in non-muscle invasive bladder cancer (NMIBC). The data of 89 patients, operated for urothelial carcinoma and treated with BCG after the diagnosis of NMIBC between 2007 and 2014, were reviewed retrospectively. Preoperative complete blood counts and first cystoscopic examination findings of the patients were examined. Median follow-up was 28.7 months. Tumour recurrence was detected in 33 patients (Group 2) of 89 patients. There was no tumour recurrence in 56 patients (Group 1). Neutrophil/lymphocyte ratio, MPV and CIS incidence were significantly increased in Group 2. This study showed that, preoperative high neutrophil/lymphocyte ratio, MPV and CIS occurrence can be used as independent criteria to predict tumour recurrence after intravesical BCG treatment in NMIBC.

PMD65 - ECONOMIC VALUE OF NARROW BAND IMAGING VERSUS WHITE LIGHT ENDOSCOPY FOR THE MANAGEMENT OF NON-MUSCLE INVASIVE BLADDER CANCER: COST-CONSEQUENCE MODEL

Narrow band imaging (NBI) is a technology used for endoscopic diagnosis and support during the treatment of lesions in non-muscle invasive bladder cancer (NMIBC). NBI has demonstrated improved sensitivity and specificity compared with white-light imaging (WLI), and is associated with lower cancer recurrence. Through these clinical benefits, NBI has the potential to provide cost-savings vs. WLI due to the associated reductions in healthcare resource utilisation. This analysis quantifies the economic benefit of NBI in NMIBC. A cost-consequence analysis was conducted adopting the UK hospital perspective. A cohort of N=100 NMIBC-suspected patients enter the model and receive diagnosis with NBI or WLI cystoscopy. Based on diagnostic accuracy, patients are classified as: true positive (TP), true negative (TN), false positive (FP), or false negative (FN). Patients with a NMIBC diagnosis undergo transurethral resection of bladder tumor (TURBT), while patients diagnosed as cancer-free receive standard monitoring. After one year of observation, patients are stratified into three states: i) cancer-free; ii) recurrence; iii) non-diagnosed NMIBC. Patients with recurrence or non-diagnosed NMIBC can progress from non-invasive to invasive bladder cancer. The model considers hospital costs related to equipment, reprocessing, maintenance, consumables / medication, staff, TURBT, recurrence management and disease progression. A micro-costing approach was adopted to calculate cystoscopy costs. NBI reduced the recurrence rate vs. WLI (16.9% vs. 37.4%, respectively), and resulted in cost-savings of £9,046 (overall costs: £170,577 vs. £179,623, respectively). More NIMBC cases were detected with NBI vs. WLI (81 vs. 69 TP cases, respectively), resulting in increased TURBT costs (£19,309; £127,614 vs. £108,305, respectively). However, increased TURBT costs were offset by the reduction of recurrences, which determined cost-savings of £28,355 (£23,282 with NBI; £51,637 with WLI). This analysis suggests that NBI is dominant vs. WLI for detection and support during the treatment of NMIBC in UK hospitals.

Can routine outpatient follow-up of patients with bladder cancer be improved? A multicenter prospective observational assessment of blue light flexible cystoscopy and fulguration.

BackgroundThe aim of this prospective cohort study was to determine the feasibility of incorporating blue light flexible cystoscopy (BLFC) and biopsy/fulguration into routine outpatient follow-up of non-muscle invasive bladder cancer patients.MethodsThe study included patients with non-muscle-invasive bladder cancer (NMIBC) who were scheduled for routine follow-up. Hexaminolevulinate was instilled in the outpatient department, and the bladder was examined under white light and then with BLFC. Biopsies were taken from all suspicious lesions. Small tumors and suspicious lesions were fulgurated on site; patients with larger lesions were referred to the operating room for resection.ResultsThe study included 69 patients, with a mean age of 70 years (range 33–89 years) and a mean duration since NMIBC diagnosis of 8 years. Most patients had high-grade cancer at initial diagnosis (52/69) and were at high risk of recurrence (48/69). Two patients per hour could be assessed using outpatient BLFC. Preparation and instillation of hexaminolevulinate took less than 10 minutes per patient, and patients had an additional waiting time of 45–60 minutes following instillation, while the hexaminolevulinate solution was retained in the bladder before examination. Eleven patients had histologically confirmed tumors that were identified using both white light flexible cystoscopy and BLFC. An additional three patients had tumors that were identified by BLFC only: two with Ta tumors and one with carcinoma in situ. Of the 14 patients with confirmed tumors, 11 could be managed on site with fulguration, whereas three were referred to the operating room. No adverse events attributable to BLFC were reported.ConclusionRoutine outpatient management of patients with NMIBC using BLFC and on-site biopsy/fulguration is feasible, despite the additional time required for hexaminolevulinate instillation, and appears to allow early detection of recurrent lesions, which can be fulgurated without the need for hospitalization.

ICUD-SIU International Consultation on Bladder Cancer 2017: management of non-muscle invasive bladder cancer.

To provide a summary of the Third International Consultation on Bladder Cancer recommendations for the management of non-muscle invasive bladder cancer (NMIBC). A detailed review of the literature was performed focusing on original articles for the management of NMIBC. An international committee assessed and graded the articles based on the Oxford Centre for Evidence-based Medicine system. The entire spectrum of NMIBC was covered such as prognostic factors of recurrence and progression, risk stratification, staging, management of positive urine cytology with negative white light cystoscopy, indications of bladder and prostatic urethral biopsies, management of Ta low grade (LG) and high risk tumors (Ta high grade [HG], T1, carcinoma in situ [CIS]), impact of BCG strain and host on outcomes, management of complications of intravesical therapy, role of alternative therapies, indications for early cystectomy, surveillance strategies, and new treatments. The working group provides several recommendations on the management of NMIBC. Recommendations were summarized with regard to staging; management of primary and recurrent LG Ta and high risk disease, positive urine cytology with negative white light cystoscopy and prostatic urethral involvement; indications for timely cystectomy; and surveillance strategies. NMIBC remains a common and challenging malignancy to manage. Accurate staging, grading, and risk stratification are critical determinants of the management and outcomes of these patients. Current tools for risk stratification are limited but informative, and should be used in clinical practice when determining diagnosis, surveillance, and treatment of NMIBC.

Evaluating cell cycle progression score as a prognostic marker for non-muscle invasive bladder cancer (NMIBC).

476 Background: Accurate grading and staging from transurethral resection of bladder tumors (TURBT) is vital for appropriate clinical management. Non-muscle-invasive bladder cancer (NMIBC) can recur progress with higher grade and or stage progression to MIBC, requiring radical intervention with poorer prognosis. Further, grade and stage may change in 20-50% of TURBTs following re-review by expert GU pathologists Objective measures of stage and grade might offer additional and/or improved risk stratification; therefore we evaluated a molecular RNA signature as a prognostic marker for NMIBC. Methods: Patients were diagnosed with NMIBC at the University of Minnesota (UM)or Spectrum Health System(SHS) from 2005-2012. A Cell Cycle Progression (CCP) score was determined from the average expression of 36 CCP genes for patients with available FFPE diagnostic TURBT. The combined cohort consisted of 293 patients (UM n = 152, SHS n = 141). Study outcome was time from NMIBC diagnosis to progression to MIBC. Median follow-up for patients who did not experience an event was 4.4 years for UM and 6.9 for SHS. Association with outcomes was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. All analyses were stratified by cohort. Results: CCP score was associated with progression to MIBC in univariable analysis [hazard ratio 1.42 (95% CI 1.19, 1.68), p = 4.3x10-5]. Tumor grade and stage were also highly prognostic. CCP score was strongly associated with stage (T1 vs Ta, p &lt; 10-6) and grade (high vs low, p &lt; 10-14) in both cohorts. As a result, CCP score did not provide independent prognostic information in multivariable analysis after adjusting for stage and grade (p = 0.32). There was a significant interaction between stage and CCP score (p = 0.0017), justifying an exploratory analysis of CCP score in Ta disease. In this subset, CCP score trended toward (p = 0.056) after adjusting for grade. Conclusions: In NMIBC, CCP score was highly correlated with tumor stage and grade and could serve as a quantitative measure of clinical parameters. The score may also provide prognostic information regarding risk of progression to MIBC, particularly in patients with Ta disease, but requires additional validation.

Impact of oral hypoglycemic agents on mortality among diabetic patients with non-muscle-invasive bladder cancer: A populationbased analysis.

Non-muscle-invasive bladder cancer (NMIBC) accounts for 75-85% of all urothelial bladder cancers (UBC). Many UBC patients are also afflicted by diabetes mellitus (DM). It has been postulated that several oral hypoglycemic agents could impact disease-specific survival (DSS), but the data are sparse among NMIBC patients. Our primary objective was to evaluate the impact of metformin on DSS and overall survival (OS) in NMIBC patients. This is a retrospective, population-based study that used linked administrative databases to identify diabetic patients ≥66 years who were subsequently diagnosed with NMIBC in Ontario between 1992 and 2012. Cumulative use of metformin and other hypoglycemic agent were calculated before and after NMIBC diagnosis. DSS and OS were estimated using multivariable competing risk and Cox proportional hazards models, respectively. A total of 1742 subjects were included in the study. After a median followup of 5.2 years, 1122 (64%) had died, including 247 (15%) deaths as a result of UBC. On multivariable analysis, cumulative duration of metformin use after NMIBC diagnosis did not appear to impact DSS (hazard ratio [HR] 1.1; 95% confidence interval [CI] 0.92-1.2), whereas glyburide use appeared to have a detrimental effect (HR 1.17; 95% CI 1.02-1.3). None of the other hypoglycemic agents had an impact on OS. In this large, population-based study, we have provided further evidence that metformin use does not significantly impact DSS among diabetic patients diagnosed with NMIBC. However, our findings demonstrate that glyburide use inversely affects DSS. The detrimental effect of glyburide on DSS will require further validation.

A Second-Look at the Repeat Resections of Bladder Tumors

Background: Research looking at the effects of repeat transurethral resection of bladder tumor (TURBT) on long-term survival and recurrence of bladder cancer has mixed results, with some studies showing improvement and others showing unclear benefit. The purpose of this current study is to evaluate the differences in recurrence rates, progression, and survival for patients with non-muscle invasive bladder cancer (NMIBC) who underwent a second TURBT 2 - 6 weeks after an initial TURBT, as compared to patients who only had an initial TURBT. Methods: We performed a retrospective analysis of patients who received a TURBT at our institution over a 12-year period (2005 - 2017). Patients 18 years or older with high-grade pT1 or pTis pathology on initial TURBT were included. Patients with low-grade, pTa, or stage pT2 or greater on initial TURBT and patients with variant histology other than urothelial carcinoma were excluded from the study. Differences in overall survival, recurrence rates, and cancer progression were analyzed using Cox regression to event and Poisson regression to number of occurrences in patients who had repeat TURBT vs. those who did not. Cancer progression was measured as time to cystectomy. Results: One hundred fifty-three patients with a diagnosis of high-grade NMIBC were included in the study. Forty-six patients (30.1%) had a repeat TURBT. There was no significant difference in baseline characteristics including age, stage, or gender between the two groups. After a median follow-up of 67.5 months (range 7.5 - 200 months), there was no significant difference in overall survival (OS) (P = 0.63), cancer progression (P = 0.51) or recurrence rates (P = 0.60) for patients who underwent second-look TURBT compared to those who did not. Of those patients who underwent repeat TURBT, 32 (69.6%) had residual tumor and 13 (28.2%) had a change in stage. Of the patients that had a change in stage, five were upstaged to muscle invasive (pT2) disease. Conclusions: Our analysis did not show an association between second-look TURBT with overall survival, progression, or recurrence rate of bladder cancer as compared to no second-look TURBT. However, there was a small rate of upstaging to pT2 disease on repeat TURBT. Even though there was no change in OS, repeat TURBT has an important role in finding T2 disease, and this is so critical that continuing with this conservative approach of a second TURBT is still recommended. World J Nephrol Urol. 2018;7(3-4):63-66 doi: https://doi.org/10.14740/wjnu361w

Role of second transurethral resection in determining residual tumor in nonmuscle-invasive bladder cancer

Introduction: Presence of residual tumors is not an uncommon event after transurethral resection of bladder tumor, and no studies from Nepal so far has addressed this issue. We conducted this study to determine the rate of residual tumors after first transurethral resection of nonmuscle-invasive bladder cancer, and to determine the factors associated with the presence of residual tumors and upstaging of nonmuscle-invasive bladder cancer.&#x0D; Methods: This was a prospective observational study of 43 patients of bladder cancer who had a diagnosis of nonmuscle-invasive bladder cancer following an initial transurethral resection. Demographic data and data on tumor characteristics were obtained. Patients underwent a second transurethral resection within 2 to 8 weeks. Histopathological findings at first and second resection were compared.&#x0D; Results: There were 20 patients with Ta tumor and 23 patiens with T1 tumor at initial resection. Residual tumor was detected in 18 (41.86%) patients overall, 2 in patients with Ta tumor (10%) and 16 in patients with T1 tumor (69.5%). Tumors with T1 stage, high grade, size more than 3 centimeters and sessile growth pattern were seen to have significant association with the presence of residual tumors. Six patients with T1 disease upstaged to T2 disease after second resection (26%), while there were no upstaging with Ta tumors. Tumors with T1 stage, sessile configuration and size more than 3 centimeters were found to be significantly associated with upstaging.&#x0D; Conclusion: A second transurethral resection for nonmuscle-invasive bladder cancer should be considered if the initial tumor is T1 stage, high grade, more than 3 centimeters in size and has sessile growth pattern.

Predictors of quality of life in non-muscle-invasive bladder cancer survivors.

193 Background: Non-muscle-invasive bladder cancer (NMIBC) survivors face frequent invasive surveillance cystoscopies, repeated treatment, and the highest recurrence rates and medical cost among all cancer survivors for the remainder of their lifespan. Despite the burdens of survivorship for this group, very little is known about the quality of life (QOL) impact of NMIBC diagnosis. We identified factors associated with QOL in NMIBC survivors. Methods: 2000 patients were randomly selected from the 5979 NMIBC population diagnosed between 2010-2014 in North Carolina. These patients received a mailed survey including cancer-specific (EORTC QLQ-C30) and NMIBC-specific (QLQ-NMIBC24) measures of QOL. QOL in this population was described, and hierarchical multiple linear regression was used to determine which patient and disease characteristics are associated with QOL. Results: 376 survivors were included in the analyses (response rate 22%). The mean QOL scores for the following domains include (range 0- 100, higher score is better in all domains but symptoms): global health 73.6±21.7, function 84.8±18.5, symptoms 15.5±17.2, NMIBC-specific sexual function 31.5±27.1 and NMIBC-specific sexual enjoyment 48.1±38.1. Survivors reporting significantly lower global health status were more likely to be male (p &lt; .01), lower income (p = .02), stage Tis at diagnosis (p &lt; .01), and have lower cognitive abilities (p &lt; .01). Lower function (p &lt; .01) and higher symptoms (p = .01) were seen in survivors who were not cured or unsure whether were cured (vs. cured). Lower global health status (p &lt; .01) and higher symptoms (p &lt; .01) were found in survivors who had not received intravesical immunotherapy. Lower social support was associated with lower global health status (p &lt; .01) and lower function (p &lt; .01). A higher number of comorbidities and more cognitive general concerns were associated with poorer QOL in all domains (all p &lt; .01). Conclusions: We identified correlates of QOL in NMIBC survivors. Special attention should be given to those with high risk of lower QOL, including patients with more comorbidities, more cognitive general concerns, or lower social support.

Observational Studies Requested by European Health Authorities: Governmental Interference or an Enhancement of Everyday Urological Practice? The Hexvix® Observational Patients Evaluation Study as an Example of What to Expect

Objective: The Hexvix® Observational Patients Evaluation (HOPE) study was designed to determine the extent of distribution of the use of hexaminolevulinate in the diagnosis of non-muscle invasive bladder cancer (NMIBC) and assess patient and treatment characteristics associated with different endoscopic modalities and to address the French authorities' request for information on routine practices for NMIBC diagnosis and surveillance. Patients and Methods: A prospective, observational study in 30 centres in France with fluorescence endoscopy equipment available. All candidates for endoscopy with transurethral resection who gave their consent were eligible. The primary endpoint was the proportion of patients with an NMIBC diagnosis performed with hexaminolevulinate. Results: 506 patients were included: 252 (49.8%) diagnosed with hexaminolevulinate and 254 (50.2%) with white-light endoscopy alone. There were more patients with tumour recurrence, multiple lesions, lesions with a diameter <3 cm, stage Ta disease, and grade 1 lesions in the hexaminolevulinate group. The first quartile median recurrence-free survival time was 310 days in the hexaminolevulinate group and 144 days in the standard-endoscopy group (p = 0.0015). Conclusion: Hexaminolevulinate was in frequent use in France with specific patient and disease characteristics associated with its use. HOPE illustrates the type of data that can be gained in post-authorisation studies to address requests from European health authorities.

The long-term prognostic value of survivin expressing circulating tumor cells in patients with high-risk non-muscle invasive bladder cancer (NMIBC).

Long-term follow-up study to evaluate the impact on disease-free survival and cancer-specific survival of survivin expression in tissue and CTCs from T1G3 bladder cancer patients. The study was conducted using tumor tissue and blood samples from 54 patients with a primary diagnosis of T1G3 NMIBC. Survivin was evaluated by reverse transcription-polymerase chain reaction in tumor tissues. CTCs were isolated from blood by CELLection™ Dynabeads (Invitrogen, Carlsbad, CA, USA). Cells were lysed and cDNA was synthesized and analysed for the expression of CD45, CK8 and survivin. The endpoints of this long-termanalysis were disease-free survival, DFS and cancer-specific survival, CSS. Here, we report that, at 9years of median follow-up, disease-free survival and cancer-specific survival are both significantly influenced by the expression of survivin in tumor tissue (p=0.006), by the presence of CTCs (p<0.0001) and by the expression of survivin in CTCs (p<0.0001). The statistically significant impact of survivin expressing CTCs on cancer-specific survival that we observed might be interpreted as the result of the persistence of a subpopulation of highlander cells in the blood of T1G3 bladder patients over time.

Voided urine versus bladder washing cytology for detection of urothelial carcinoma: which is better?

Objective: Cytology is recommended as part of the follow-up of high-grade non-muscle-invasive bladder cancer (NMIBC). However, currently there are no solid guideline recommendations regarding the use of voided urine versus bladder washing for cytology as part of the diagnosis or follow-up of NMIBC. The aim of this study was to investigate whether the cytological outcome was equal regarding the two techniques.Materials and methods: The authors reviewed all outpatient flexible cystoscopies carried out in their department in 2013. Patient records in the registry of pathology were examined and those with simultaneous urine and bladder washing cytology were included. Previous urothelial disease and positive histology within 3 months after the cystoscopy were registered.Results: A total of 1458 patients had both voided urine and bladder washing cytology and were included in the study, of whom 643 (44%) had a history of urothelial disease. An equal outcome of urine and bladder washing cytology was found in 1447 patients (99.2%). For the remaining 11 patients, only four patients underwent further examinations based on cytology findings in addition to what had already been planned after cystoscopy. Of the included patients, 100 (6.9%) had a positive histological outcome within 3 months.Conclusions: In most patients, no relevant difference between voided urine and bladder washing cytology was observed. Therefore, if cytology is indicated, it is recommended to use the test that is most readily available locally. The additional gain in using both urine and bladder wash is minimal, and can therefore be discarded.

A meta-analysis of narrow band imaging for the diagnosis and therapeutic outcome of non-muscle invasive bladder cancer.

ObjectivesTo assess the additional detection rate (ADR) of within-patient comparisons of Narrow band imaging (NBI) and white light cystoscopy (WLC) for non-muscle invasive bladder cancer (NMIBC) detection and compare the impact of NBI and WLC on bladder cancer recurrence risk.MethodsWe searched relevant studies from PubMed, Embase, Medline, Web of Science and the Cochrane Library database for all articles in English published beforeJuly26th, 2016. Pooled ADR, diagnostic accuracy, relative risk (RR) and their 95% confidence intervals (CIs) were calculated.ResultsTwenty-five studies including 17 full texts and eight meeting abstracts were included for analysis. Compared to WLC, pooled ADR of NBI for NMIBC diagnosis was 9.9% (95% CI: 0.05–0.14) and 18.6% (95% CI: 0.15–0.25) in per-patient and per-lesion analysis, respectively. Pooled ADR of NBI for carcinoma in situ (CIS) diagnosis was 25.1% (95% CI: 0.09–0.42) and 31.1% (95% CI: 0.24–0.39) for per-patient and per-lesion analyses, respectively. The pooled sensitivity of NBI was significantly higher than WLC both at the per-patient (95.8% vs. 81.6%) and per-lesion levels (94.8% vs. 72.4%). In addition, NBI significantly reduced the recurrence rate of bladder cancer with a pooled RR value of 0.43 (95% CI: 0.23–0.79) and0.81 (95% CI: 0.69–0.95) at month three and twelve, respectively.ConclusionsNBI is a valid technique that improves the diagnosis of NMIBC and CIS compared to standard WLC either at per-patient or per-lesion level. It can reduce the recurrence rate of bladder cancer accordingly.

Validation of a protein panel for the noninvasive detection of recurrent non-muscle invasive bladder cancer

Context: About 50–70% of patients with non-muscle invasive bladder cancer (NMIBC) experience relapse of disease.Objective: To establish a panel of protein biomarkers incorporated in a multiplexed microarray (BCa chip) and a classifier for diagnosing recurrent NMIBC.Materials and methods: Urine samples from 45 patients were tested. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis.Results: A multi biomarker panel (ECadh, IL8, MMP9, EN2, VEGF, past recurrences, BCG therapies and stage at diagnosis) was identified yielding an area under the curve of 0.96.Discussion and conclusion: This biomarker panel represents a potential diagnostic tool for noninvasive diagnosis of recurrent NMIBC.

The Prognostic Role of Circulating Tumor Cells (CTC) in High-risk Non-muscle-invasive Bladder Cancer.

The purpose of this study was to evaluate the impact of circulating tumor cells (CTCs) as a prognostic marker in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) and assess the efficacy and reliability of 2 different CTC isolation methods. Globally, 155 patients with a pathologically confirmed diagnosis of high-risk NMIBC were included (pT1G3 with or without carcinoma in situ) and underwent transurethral resection of bladder tumor (TURB) after a blood withdrawal for CTC evaluation. A total of 101 patients (Group A) had their samples analyzed with the CellSearch automated system, and 54 (Group B) had their samples analyzed with the CELLection Dynabeads manual system. Patients were followed for 28 months, and during this interval, there were a total of 65 (41.9%) recurrences, 27 (17.4%) disease progressions, and 9 (5.8%) lymph node and/or bone metastasis. In our CTC analysis, there were 20 (19.8%) positive patients in Group A and 24 in Group B (44.4%). In our analysis, we found a strong correlation between CTC presence and time to first recurrence; in Group A, we observed an incidence of recurrence in 75% of CTC-positive patients and in Group B of 83% of CTC-positive patients. The time to progression was also strongly correlated with CTCs: 65% and 29%, respectively, of those patients who progressed in those with CTCs in Group A and B. The study demonstrates the potential role of CTCs as a prognostic marker for risk stratification in patients with NMIBC, to predict both recurrence and progression.