Outcomes In Nonmuscle Invasive Bladder Cancer Research Articles

Predicting non-muscle invasive bladder cancer outcomes using artificial intelligence: a systematic review using APPRAISE-AI.

Accurate prediction of recurrence and progression in non-muscle invasive bladder cancer (NMIBC) is essential to inform management and eligibility for clinical trials. Despite substantial interest in developing artificial intelligence (AI) applications in NMIBC, their clinical readiness remains unclear. This systematic review aimed to critically appraise AI studies predicting NMIBC outcomes, and to identify common methodological and reporting pitfalls. MEDLINE, EMBASE, Web of Science, and Scopus were searched from inception to February 5th, 2024 for AI studies predicting NMIBC recurrence or progression. APPRAISE-AI was used to assess methodological and reporting quality of these studies. Performance between AI and non-AI approaches included within these studies were compared. A total of 15 studies (five on recurrence, four on progression, and six on both) were included. All studies were retrospective, with a median follow-up of 71 months (IQR 32-93) and median cohort size of 125 (IQR 93-309). Most studies were low quality, with only one classified as high quality. While AI models generally outperformed non-AI approaches with respect to accuracy, c-index, sensitivity, and specificity, this margin of benefit varied with study quality (median absolute performance difference was 10 for low, 22 for moderate, and 4 for high quality studies). Common pitfalls included dataset limitations, heterogeneous outcome definitions, methodological flaws, suboptimal model evaluation, and reproducibility issues. Recommendations to address these challenges are proposed. These findings emphasise the need for collaborative efforts between urological and AI communities paired with rigorous methodologies to develop higher quality models, enabling AI to reach its potential in enhancing NMIBC care.

Impact of Agent Orange Exposure on Non-muscle Invasive Bladder Cancer Outcomes

To explore the effect of Agent Orange (AO) exposure on bladder cancer (BCa) outcomes in patients receiving Bacillus Calmette-Guérin (BCG) for non-muscle invasive BCa (NMIBC). We retrospectively examined the association between AO exposure in patients with NMIBC in national veterans affairs databases who were being treated with BCG. Patients were diagnosed with NMIBC from 2000 to 2010 with follow-up through 2018. Clinical, pathological, and demographic variables were compared by AO exposure. Associations of AO exposure with recurrence, progression, and cancer-specific survival were performed using Cox proportional hazard models after inverse propensity score weighting and competing risks adjustments. We also assessed the association of AO exposure on grade and stage via multivariable logistic regression models. A total of 7651 patients were identified of which 753 (9.8%) were exposed to AO. The median follow-up time was 130months. The AO-exposed patients were younger (age 61 vs 71years, P<.001), but had similar Charlson comorbidity scores and stage/grade distribution as the non-AO exposed patients. AO exposure was not associated with higher grade or stage. In our Cox multivariable analyses, AO exposure was not associated with worse recurrence (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.72-1.10, P=.29), progression (HR 1.08, 95% CI 0.86-1.36, P=.51), or cancer-specific survival (HR 1.31, 95% CI 0.92-1.87, P=.13). AO exposure was not associated with worse oncologic outcomes in patients receiving BCG for NMIBC. While this is reassuring, additional research is needed in other patient populations and disease states to determine if the effect is consistent.

Predicting Recurrence of Non-Muscle-Invasive Bladder Cancer: Current Techniques and Future Trends.

Simple SummaryNon-muscle-invasive bladder cancer is associated with its high rates of progression and recurrence, the proper diagnosis and management can save lives. Bladder cancer is the tenth most common type of cancer in the world. This review discusses the current markers used in the recurrence prediction of non-muscle-invasive bladder cancer and future trends, published in the last decade, in addition to the limitations and future prospects in the field of AI-based prediction systems.Bladder cancer (BC) is the 10th most common cancer globally and has a high mortality rate if not detected early and treated promptly. Non-muscle-invasive BC (NMIBC) is a subclassification of BC associated with high rates of recurrence and progression. Current tools for predicting recurrence and progression on NMIBC use scoring systems based on clinical and histopathological markers. These exclude other potentially useful biomarkers which could provide a more accurate personalized risk assessment. Future trends are likely to use artificial intelligence (AI) to enhance the prediction of recurrence in patients with NMIBC and decrease the use of standard clinical protocols such as cystoscopy and cytology. Here, we provide a comprehensive survey of the most recent studies from the last decade (N = 70 studies), focused on the prediction of patient outcomes in NMIBC, particularly recurrence, using biomarkers such as radiomics, histopathology, clinical, and genomics. The value of individual and combined biomarkers is discussed in detail with the goal of identifying future trends that will lead to the personalized management of NMIBC.

Bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer outcomes in patients without radical cystectomy.

Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) is a newly defined subtype that is unlikely to benefit from BCG rechallenge. Radical cystectomy is currently recommended for BCG-unresponsive NMIBC; however, a certain proportion of these patients can be managed with treatments other than that. Herein, we conducted a multicenter retrospective study to analyze the clinical outcomes of BCG-unresponsive NMIBC patients who did not receive radical cystectomy. Of the 141 BCG-unresponsive NMIBC patients, 94 (66.7%) received treatment except radical cystectomy. Survival outcomes were calculated from the date of diagnosis using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were identified using the multivariate Cox regression model. This group was further classified into three groups according to the number of risk factors, and survival outcomes were compared. Multivariate analyses identified low estimated glomerular filtration rate (< 45ml/min/1.73 m2) and large tumor size (≥ 30mm) before BCG induction as independent poor prognostic factors for progression-free survival and overall survival, while the latter was also an independent factor for cancer-specific survival. The presence of variant histology was an independent poor prognostic factor for overall survival. The high-risk non-cystectomy group showed a significantly poor prognosis for progression-free survival (hazard ratio: 7.61, 95% confidence interval: 2.11-27.5), cancer-specific survival (10.4, 0.54-70.02), and overall survival (8.28, 1.82-37.7). Our findings suggest that patients with renal impairment and large tumors should undergo radical cystectomy if the complications and intentions of the patients allow so.

Lifestyle and Non-muscle Invasive Bladder Cancer Recurrence, Progression, and Mortality: Available Research and Future Directions.

BACKGROUND:A broad, comprehensive review of studies exploring associations between lifestyle factors and non-muscle invasive bladder cancer (NMIBC) outcomes is warranted to consolidate recommendations and identify gaps in research.OBJECTIVE:To summarize the literature on associations between lifestyle factors and clinical outcomes among patients with NMIBC.METHODS:PubMed was systematically queried for articles published through March 2019 regarding lifestyle factors and recurrence, progression, cancer-specific mortality, and all-cause mortality among patients with NMIBC.RESULTS:Notwithstanding many ambiguities, there is good-quality evidence suggesting a benefit of smoking avoidance/cessation, healthy body mass index (BMI), and type II diabetes mellitus prevention and treatment. Lactobacillus casei probiotic supplementation may reduce recurrence. There have been individual studies suggesting a benefit for uncooked broccoli and supplemental vitamin E as well as avoidance of supplemental vitamin B9, areca nut chewing, and a “Western diet” pattern high in fried foods and red meat. Additional studies do not suggest associations between NMIBC outcomes and use of fibrin clot inhibitors; insulin and other oral hypoglycemics; statins; supplemental selenium, vitamin A, vitamin C, and vitamin B6; fluid intake and intake of specific beverages (e.g., alcohol, coffee, green tea, cola); various dietary patterns (e.g., Tex-Mex, high fruit and vegetable, low-fat); and occupational and chemical exposures.CONCLUSIONS:Despite a myriad of publications on lifestyle factors and NMIBC, a need remains for research on unexplored associations (e.g., physical activity) and further studies that can elucidate causal effects. This would inform future implementation strategies for healthy lifestyle change in NMIBC patients.

Intravesical bacillus Calmette-Guérin for bladder cancer: are all the strains equal?

Intravesical immunotherapy with bacillus Calmette-Guérin (BCG) is the standard of care for high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Several BCG strains are available. Despite originating all from subcultures of the same Mycobacterium, strains are genetically different which may lead to differences in treatment efficacy and adverse events. Identification of a more efficient strain and assessing its optimal administration schedule may improve oncological outcomes in NMIBC, specifically because of the worldwide shortage in BCG availability. This review focused on the antitumor effect of different BCG strains with a particular emphasis on the evidence underlying BCG dose and treatment schedules.

Comparison of the EORTC and CUETO prognostic models in non-muscle-invasive bladder cancer

Bladder cancer is one of the most common malignant diseases involving the urinary system. Accurate prediction of the disease course and outcome is crucial for choosing an appropriate treatment strategy in these patients. Currently, there are several prognostic models for predicting non-muscle invasive bladder cancer outcomes. The scoring systems developed by the European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Urological Club for Oncological Treatment (CUETO) are the most widely used prognostic models for bladder cancer. Despite the undeniable merits of these scales, they need to be supplemented. Since the prognostic score has a direct impact on the treatment strategy, intensity and costs of postoperative follow-up, and outcome, its accuracy should be higher than it is now. Identifying the additional parameters that would increase the robustness of these models is one of the major challenges for researchers.The molecular and genetic characteristics of the tumor, that can be estimated after the first surgery, are probably the best candidates for this role. The main limitation of these prognostic models lies in the fact that they assess only morphological properties of the tumor, while the most important molecular characteristics are neglected. These scoring systems do not evaluate clinical factors, concomitant diseases, and iatrogenic complications occurring during the treatment of relapses. The assessment of molecular mechanisms and clinical characteristics underlying the development of non-muscle-invasive bladder cancer as well as identification of key molecular markers, that could complement the currently existing risk assessment models, are the most important goals for researchers dealing with bladder cancer. It will significantly improve predictive capabilities of these models, ensuring the choice of an optimal treatment strategy.

Dose, duration and strain of bacillus Calmette-Guerin in the treatment of nonmuscle invasive bladder cancer: Meta-analysis of randomized clinical trials.

Intravesical bacillus Calmette-Guerin (BCG) instillation is widely used as an adjuvant therapy after transurethral resection of bladder tumor (TURBT) in patients with intermediate- and high-risk nonmuscle invasive bladder cancer (NMIBC). However, the effective dose, duration, and strain of BCG have not yet been clearly determined. We aimed to elucidate the relationship between dose, duration, and strain of BCG and clinical outcomes in NMIBC patients treated with TURBT. We conducted a literature search in Embase, Scopus, and PubMed databases for all relevant articles published up to October 2016 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The relative risks of clinical outcomes, including recurrence, progression, cancer-specific mortality, and all-cause mortality according to dose (standard vs low), duration (induction vs maintenance), and strain of BCG were presented as the pooled risk ratio (RR) and 95% confidence interval (CI). Nineteen studies meeting the inclusion criteria were finally selected in this meta-analysis. The risk of recurrence was significantly highly observed in case of low-dose BCG (RR, 1.17; 95% CI 1.06-1.30) and induction BCG (RR, 1.33; 95% CI 1.17-1.50) only group without heterogeneity among the included studies. Although there were no significant differences between dose or duration and other clinical outcomes. On direct comparison in each study comparing BCG strains, the Tice stain showed a relatively high probability of recurrence compared with the Connaught (RR, 1.29; 95% CI 1.01-1.64) and RIVM (RR, 2.04, 95% CI 1.28-3.25) strains. Funnel plot testing revealed no significant publication bias. The use of standard dose and maintenance BCG instillation may be effective to reduce recurrence rate after TURBT for NMIBC. Further large scale, well-designed, and prospective studies, with stratification of the patients into risk group at randomization, will be required to determine the optimal guideline of BCG use to improve clinical outcomes in NMIBC.

Incidence, Clinicopathological Risk Factors, Management and Outcomes of Nonmuscle Invasive Recurrence after Complete Response to Trimodality Therapy for Muscle Invasive Bladder Cancer

We describe the incidence, clinicopathological risk factors, management and outcomes of recurrent nonmuscle invasive bladder cancer after a complete response to trimodality therapy of muscle invasive bladder cancer. We retrospectively reviewed the records of 342 patients with cT2-4aN0M0 muscle invasive bladder cancer and a complete response after trimodality therapy from 1986 to 2013. Using competing risks analyses we examined the association between baseline clinicopathological variables and nonmuscle invasive bladder cancer outcomes. Kaplan-Meier and the generalized Fleming-Harrington test were used to compare disease specific and overall survival. At a median followup of 9 years nonmuscle invasive bladder cancer recurred in 85 patients (25%) who had had a complete response. On Kaplan-Meier analysis baseline carcinoma in situ was associated with recurrent nonmuscle invasive bladder cancer (p = 0.02). However, on multivariate analysis carcinoma in situ and other baseline clinicopathological characteristics did not predict such recurrence. Patients with recurrent nonmuscle invasive bladder cancer had worse 10-year disease specific survival than those without recurrence (72.1% vs 78.4%, p = 0.002), although overall survival was similar (p = 0.66). Of the 39 patients (46%) who received adjuvant intravesical bacillus Calmette-Guérin 29 (74%) completed induction therapy and 19 (49%) reported bacillus Calmette-Guérin toxicity. Three-year recurrence-free and progression-free survival after induction bacillus Calmette-Guérin was 59% and 63%, respectively. After a complete response to trimodality therapy nonmuscle invasive bladder cancer recurred in 25% of patients, developing in some of them more than a decade after trimodality therapy. No baseline clinicopathological characteristics were associated with such recurrence after a complete response. Patients with nonmuscle invasive bladder cancer recurrence had worse disease specific survival than those without such recurrence but similar overall survival. Adjuvant intravesical bacillus Calmette-Guérin had a reasonable toxicity profile and efficacy in this population. Properly selected patients with recurrent nonmuscle invasive bladder cancer after a complete response may avoid immediate salvage cystectomy.

Impact of variant histology on disease-specific mortality and survival in patients with non-muscle invasive bladder cancer (NMIBC): A population-based analysis.

332 Background: Prior studies have reported that variant histology is associated with poor outcomes in NMIBC. We utilized the Surveillance, Epidemiology and End Results (SEER) database to compare disease specific survival (DSS) and mortality (DSM) among the different variant histologies and urothelial carcinoma (UC). Methods: Patients diagnosed with NMIBC (Ta, Tis, T1) between 2004 and 2012 were eligible for analysis. Patients were separated into cohorts based on histology: UC and variant histology which included micro-papillary variant (MPV), neuroendocrine (NEC), squamous (SCC), adenocarcinoma (AC) and other variants (e.g., lymphoepithelial, giant cell, undifferentiated/anaplastic, sarcomatoid). Univariate and multivariable Cox proportional hazard analysis was used to evaluate the impact of variant histology on DSM after adjusting for other covariates. DSS was estimated amongst the different histologic and treatment groups using the Kaplan-Meier method and compared using Log-rank test. Results: We identified 111,756 patients, who were predominantly Caucasian (90%) and older than 70 years (57.5%; n=64,314). Variant histology accounted for 1.2% (n=1354) of cases. AC and SCC were the most common variant subtypes (26.4%; n=357 and 25.6%; n=347 respectively) followed by NEC (11.2%; n=151) and MPV (7.1%; n=96). On multivariable analysis adjusting for age, sex, race, T-stage, histologic grade and number of primary tumors, all variant subgroups except MPV were associated with increased DSM compared to UC (p&lt;0.001). SCC had the worst 5-year DSS (53.8%; P&lt;0.001) followed by NEC (65.1%) and AC (77.8%). Compared to treatment with TURBT or intravesical BCG, cystectomy was associated with improved DSS for variant histology patients with T1 tumors (75.8% vs. 66.3%; P&lt;0.001). Conclusions: Variant histology, specifically SCC and NEC, was associated with significantly worse 5-year DSS in NMIBC. MPV, which is generally thought to be aggressive, had outcomes comparable to UC. Cystectomy was associated with improved DSS in patients with T1 disease and should be considered for NMIBC with variant histology.

The Preoperative Neutrophil-to-lymphocyte Ratio is a Novel Biomarker for Predicting Worse Clinical Outcomes in Non-muscle Invasive Bladder Cancer Patients with a Previous History of Smoking.

We speculated that a heterogeneous population of non-muscle invasive bladder cancer (NMIBC) patients with a previous history of smoking may be more precisely stratified by a biomarker associated with tumor aggressiveness and then focused on the preoperative neutrophil-to-lymphocyte ratio (pre-NLR), which is a simple index of systemic inflammation. Our study population comprised 605 patients initially diagnosed with NMIBC at our 3 institutions between 1995 and 2013. We analyzed the relationships between pre-NLR levels and clinical outcomes in NMIBC. A pre-NLR level of ≥2.2 was defined as elevated according to a calculation by a receiver-operating curve analysis. In overall, a total of 296 patients (48.9%) had pre-NLR≥2.2, and the pre-NLR level was one of independent risk factors for tumor recurrence and stage progression. Among 344 patients with a previous history of smoking, 184 (53.5%) had pre-NLR≥2.2 and the pre-NLR level was one of independent risk factors for tumor recurrence and stage progression. The 5-year recurrence-free survival and progression-free survival rates in patients with pre-NLR<2.2 were 66.3 and 97.5%, respectively, which were significantly higher than those in their counterparts (31.7 and 90.4%, p<0.001). In either subgroup of patients who were current smokers (N=175) or former smokers (N=169), the pre-NLR level was the only independent risk factor for tumor recurrence. The pre-NLR level was not associated with tumor recurrence or stage progression in 261 nonsmoking patients. Pre-NLR levels may be a useful marker for identifying worse clinical outcomes in NMIBC patients, particularly those with a previous history of smoking.

Prediction of non-muscle invasive bladder cancer outcomes assessed by innovative multimarker prognostic models.

BackgroundWe adapted Bayesian statistical learning strategies to the prognosis field to investigate if genome-wide common SNP improve the prediction ability of clinico-pathological prognosticators and applied it to non-muscle invasive bladder cancer (NMIBC) patients.MethodsAdapted Bayesian sequential threshold models in combination with LASSO were applied to consider the time-to-event and the censoring nature of data. We studied 822 NMIBC patients followed-up >10 years. The study outcomes were time-to-first-recurrence and time-to-progression. The predictive ability of the models including up to 171,304 SNP and/or 6 clinico-pathological prognosticators was evaluated using AUC-ROC and determination coefficient.ResultsClinico-pathological prognosticators explained a larger proportion of the time-to-first-recurrence (3.1 %) and time-to-progression (5.4 %) phenotypic variances than SNPs (1 and 0.01 %, respectively). Adding SNPs to the clinico-pathological-parameters model slightly improved the prediction of time-to-first-recurrence (up to 4 %). The prediction of time-to-progression using both clinico-pathological prognosticators and SNP did not improve. Heritability (ĥ2) of both outcomes was <1 % in NMIBC.ConclusionsWe adapted a Bayesian statistical learning method to deal with a large number of parameters in prognostic studies. Common SNPs showed a limited role in predicting NMIBC outcomes yielding a very low heritability for both outcomes. We report for the first time a heritability estimate for a disease outcome. Our method can be extended to other disease models.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2361-7) contains supplementary material, which is available to authorized users.

Diagnostics techniques in nonmuscle invasive bladder cancer.

Introduction:Nonmuscle invasive bladder cancer (NMIBC) is the most common presentation of bladder cancer and is often treatable with endoscopic resection and intravesical therapies. Cystoscopy and urine cytology are the gold standard in diagnosis and surveillance but are limited by their sensitivity in some situations. We seek to provide an overview of recent additions to the diagnostic armamentarium for urologists treating this disease.Methods:Articles were identified through a literature review of articles obtained through PubMed searches including the terms “bladder cancer” and various diagnostic techniques described in the article.Results:A variety of urinary biomarkers are available to assist the diagnosis and management of patients with NMIBC. Many have improved sensitivity over urine cytology, but less specificity. There are certain situations in which this has proved valuable, but as yet these are not part of the standard guidelines for NMIBC. Fluorescence cystoscopy has level 1 evidence demonstrating increased rates of tumor detection and prolonged recurrence-free survival when utilized for transurethral resection. Other technologies seeking to enhance cystoscopy, such as narrow band imaging, confocal laser endomicroscopy, and optical coherence tomography are still under evaluation.Conclusions:A variety of urine biomarker and adjunctive endoscopic technologies have been developed to assist the management of NMIBC. While some, such as fluorescence cystoscopy, have demonstrated a definite benefit in this disease, others are still finding their place in the diagnosis and treatment of this disease. Future studies should shed light on how these can be incorporated to improve outcomes in NMIBC.

The clinical course of non-muscle invasive bladder cancer after transurethral resection of the tumor with or without subsequent intravesical application of bacillus Calmette-Guérin: The influence of patients gender and age.

BACGROUND/AIM: The therapy with intravesical instillation of bacillus Calmette-Guérin (BCG) after transurethral resection (TUR) of tumor is the gold standard of treatment of non-muscle invasive bladder cancer (NMIBC). The role and importance of BCG intravesical therapy in various shape of tumors, were confirmed by our previous investigation. The aim of this study was to examine whether incidence of recurrence and tumor regression differs depending on sex and age of patients. This study included a total of 899 patients suffering from NIMBC, treated at our institution from January 1, 2007 to March 1, 2013. Two groups of patients were formed: patients underwent TUR + BCG therapy (the group I) and the group II with patients in whom TUR was performed as only therapy. These two groups of patients were divided into subgroups of respondents male and female, age 60 years or younger and older than 60 years. Statistical analysis was performed using χ2 test and the Kolmogorov-Smirnov test. This research suggests that if the frequency of recurrence is seen as the only parameter, considering all the subjects, the lowest recurrence rate was determined in the male subjects, aged 60 years and younger who had received BCG after TUR. A high statistical significance was found in the incidence of recurrence in patients younger than 60 years, depending on the response to the therapy, while in those older than 60 years, the difference was at the level of statistical significance. This can be attributed to a certain degree of infravesical obstruction in older men. Sex and age of patients may have a significant influence on the course and outcome of NMIBC. The disease has the most malignant and most aggressive behavior when present in males older than 60 years.

Smoking and smoking cessation effects on oncological outcomes in nonmuscle invasive bladder cancer.

Cigarette smoking is the best established risk factor for the development of bladder cancer. Nevertheless, the impact of smoking and smoking cessation on the outcomes of patients with nonmuscle invasive bladder cancer (NMIBC) remains poorly investigated. Currently, there are no prospective studies analyzing the impact of smoking on NMIBC outcomes. The majority of retrospective studies found an association between smoking status as well as cumulative lifetime exposure and disease recurrence. A recently published study demonstrated a significant impact of smoking on disease progression; however, the evidence regarding this end point is weak. There are insufficient data investigating the impact on cancer-specific and overall survival in patients with NMIBC. Assessment of the impact of smoking on particular subsets of patients with NMIBC including T1 or high-risk disease, patients receiving intravesical therapies, or sex-specific differences is limited because of a lack of data and controversial findings. Smoking cessation seems to mitigate the detrimental effects on outcomes. Although there are limited data, the growing body of evidence indicates that smoking increases the risk of disease recurrence and potentially disease progression in patients with NMIBC. Current and heavy long-term smokers seem to be at the greatest risk for both end points. Smoking cessation may limit these effects thereby improving prognosis. To improve our understanding of the associations of this important, modifiable risk factor with outcomes in patients with NMIBC, smoking should be incorporated into clinical trial design and analysis. It is the duty of each urologist to raise awareness regarding the greatest preventable cause of the development of bladder cancer, morbidity, and mortality.

1152 THE COMBINED INVESTIGATION OF MOLECULAR PROTEINS PREDICTS CANCER-SPECIFIC SURVIVAL IN PATIENTS WITH HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 20101152 THE COMBINED INVESTIGATION OF MOLECULAR PROTEINS PREDICTS CANCER-SPECIFIC SURVIVAL IN PATIENTS WITH HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER Kazumasa Matsumoto, Takefumi Satoh, Ken-ichi Tabata, Tetsuo Fujita, Yuichi Satoh, Masatsugu Iwamura, Kazunari Yoshida, and Shiro Baba Kazumasa MatsumotoKazumasa Matsumoto More articles by this author , Takefumi SatohTakefumi Satoh More articles by this author , Ken-ichi TabataKen-ichi Tabata More articles by this author , Tetsuo FujitaTetsuo Fujita More articles by this author , Yuichi SatohYuichi Satoh More articles by this author , Masatsugu IwamuraMasatsugu Iwamura More articles by this author , Kazunari YoshidaKazunari Yoshida More articles by this author , and Shiro BabaShiro Baba More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.651AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES High grade bladder cancer comprises approximately 10% of non-muscle invasive diseases. Despite the presence of only superficial lesions, it is clinically invasive. Treatment to successfully preserve the bladder potentially requires radical cystectomy that can reveal distant metastases. We sought to determine whether the molecular markers E-cadherin, uroplakin III, coxsackie-adenovirus receptor (CAR), p53, S100A2 and S100A4 are associated with clinicopathological outcomes and prognosis in high grade (grade 3) non-muscle invasive bladder cancer. METHODS Immunohistochemical staining was carried out on serial sections from archival specimens of 84 patients who underwent transurethral resection of bladder tumors (TURBT). Altered expression of these proteins was stratified further into simple (one or fewer) and multiple altered (two or more) for the purpose of analyses. Clinicopathological outcomes included gender, tumor stage (Ta, T1), tumor size (<1 cm, >1 cm), number of tumors (single, multiple), concomitant CIS and intravesical instillation of bacille Calmette-Guerin (BCG). Median follow-up time was 52 months. RESULTS E-cadherin, uroplakin III, CAR, p53, S100A2 and S100A4 expression were altered in 13 (16%), 49 (58%), 13 (16%), 51 (61%), 16 (19%) and 23 (27%) tumors, respectively. Seventy-five patients (89%) had at least one protein altered and four (25%) had five altered. There were no patients with altered expression of all six proteins. Multivariate models that included clinicopathologic outcomes and categorized molecular markers found multiple altered molecular markers and lack of BCG instillation to be predictors of cancer-specific death (p<0.03), while lack of BCG instillation was the sole predictor of disease-recurrence (p=0.02). However, no individual altered protein was associated with any clinicopathological outcomes or prognosis. CONCLUSIONS While the altered expression of an individual molecular protein is not associated with non-muscle invasive bladder cancer outcomes in patients undergoing TURBT, multiple alteration of molecular markers is a strong predictor of mortality, suggesting that high-grade non-muscle invasive cancer is heterogeneous and has a variety of biologically aggressive behaviors. A combination of molecular markers plays a more pivotal role in bladder cancer progression. Sagamihara, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e446 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazumasa Matsumoto More articles by this author Takefumi Satoh More articles by this author Ken-ichi Tabata More articles by this author Tetsuo Fujita More articles by this author Yuichi Satoh More articles by this author Masatsugu Iwamura More articles by this author Kazunari Yoshida More articles by this author Shiro Baba More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Stopping smoking might reduce tumour recurrence in nonmuscle‐invasive bladder cancer

To evaluate effects of stopping smoking on the outcome of nonmuscle-invasive bladder cancer, as cigarette smoking is a risk factor for bladder cancer and little is known about whether stopping smoking reduces the risk of recurrence or progression. Between January 1997 and July 2005, 297 men with primary nonmuscle-invasive bladder cancer were treated with transurethral resection (TUR); their smoking status before and after the diagnosis of bladder cancer was obtained by a post hoc questionnaire and interview. 'Quitters' were those who ceased smoking within a year before and 3 months after the diagnosis. Ex-smokers were those who ceased smoking more than a year before diagnosis. Several pathological and clinical variables were compared, with all statistical comparisons being two-sided. In all, 265 patients completed the questionnaire, including 64 non-smokers, 64 ex-smokers, 59 quitters, and 78 continued smokers. The median follow-up was 38 months. There were no significant differences in the strata of stage, grade, tumour multiplicity, intravesical therapy, or median follow-up duration between the four patient groups. The respective 3-year recurrence-free survival of continued smokers, non-smokers, ex-smokers and quitters was 45%, 57%, 62% and 70%. By multivariate analysis, high-grade, T1-stage, multiple tumours and continued smoking were significant independent predictors for a shorter recurrence-free survival. Quitters had a lower risk of recurrence than did either continued smokers or non-smokers, but had a similar risk to ex-smokers. Stopping smoking might be associated with a lower recurrence rate for patients with nonmuscle-invasive bladder cancer.