Diagnosis Of NMIBC Research Articles

Selenium and Vitamin E for Prevention of Non–Muscle-Invasive Bladder Cancer Recurrence and Progression

Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer. To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC. 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. 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. Recurrence-free interval (RFI) on an intention-to-treat basis (analyses completed on November 28, 2022). 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. 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. isrctn.org Identifier: ISRCTN13889738.

P144 - Accuracy of novel urinary biomarker tests for diagnosis and surveillance of NMIBC: A systematic review, diagnostic test accuracy and network meta-analyses

P144 - Accuracy of novel urinary biomarker tests for diagnosis and surveillance of NMIBC: A systematic review, diagnostic test accuracy and network meta-analyses

ANALYSIS OF ENDOUROLOGICAL TREATMENT TECHNIQUES OF URINARY BLADDER TUMORS

Transurethral resection is very important not only for diagnosis and treatment of NMIBC, but also for its management. The application field of transurethral resection includes establishing histological diagnosis, determination of prognostic factors including the tumor stage, complete resection of all detected tumors of urinary bladder. Transurethral resection of bladder tumor (TURBT) is the standard technique for the diagnosis and treatment of non-muscle invasive bladder cancer. This method has also some limitations. One of the limitations is the insufficient assessment of the resection depth. It leads to the necessity of intravesical tumor fragmentation, but its disadvantage is that it limits the histopathological evaluation. In order to improve the treatment outcome for patients with non-muscular invasive bladder tumors, several new techniques such as En-bloc resection were proposed.

Impact of UTUC on Outcomes of Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacillus Calmette-Guerin

There is a paucity of information regarding impact of upper tract urothelial carcinoma (UTUC) on the patterns of BCG response in patients with NMIBC treated with BCG. We present the clinicopathological characteristics of patients with a history of NMIBC and UTUC treated with intravesical BCG and evaluate the impact of UTUC on BCG response and progression. An IRB approved review of patients with NMIBC patients treated with at least induction BCG at our institution between 2000 and 2018 was performed. Patients were then stratified by (1) presence of UTUC and (2) time of UTUC onset (prior to NMIBC diagnosis vs synchronous or metachronous disease). Outcomes were calculated from date of index transurethral resection. Of 577 patients who received BCG induction for NMIBC, 63 (11%) patients were diagnosed with UTUC. Of these, 36 patients had a history of UTUC prior to NMIBC (median 344 days prior, IQR 211 – 821 days), while 27 developed UTUC after diagnosis of NMIBC (8 synchronous and 19 metachronous, median 350 days after, IQR 25-833 days). There was no difference between the UTUC and no UTUC groups, except that the UTUC group had more multifocal bladder tumors (71% vs 50%, P=0.002) and prostatic urethral involvement (12% vs 5%, P=0.023). The UTUC group had more non-responders to BCG with respect to recurrence (60% vs. 36%, P=0.0002), any stage/grade progression (25% vs 11%, P=0.005), and progression to muscle invasive or metastatic disease (18% vs 8%, P=0.016). There was no significant difference in rates of recurrence or progression based on timing of UTUC with respect to bladder tumor, albeit this analysis is limited by small numbers. Presence of UTUC – whether prior to or after diagnosis of bladder cancer - was associated with an almost 2-fold increased recurrence and progression rate following BCG. This should be factored in when counselling patients and designing cohorts for clinical trials.

'Çok düşük riskli mesane kanseri' Kas-invaziv olmayan mesane kanserlerinde gerçekten yeni bir alt grup mu?

Introduction: We aimed to evaluate the predictive roles of “very-low-risk” bladder cancer by analyzing the clinical outcomes of low-risk bladder cancer Material and Methods: 32 patients who were treated and followed up between 2013 and December 2019 with the diagnosis of low-risk NMIBC were retrospectively analyzed. Patients were divided into two prognostic groups based on tumor size (≤1.0 cm vs >1.0 cm). Two groups were compared in terms of clinical, pathological findings and recurrence, progression in follow-up. Results: A total of 32 patients were followed up to recurrence time. A total of 14 patients had tumors that were ≤1,0 cm. Using univariate Cox modeling, smoking status and Intravesical Mitomycin C (MMC) were significantly associated with shorter time to recurrence (HR 0.103 95% CI 0.020-0,520, P = 0.006; HR 4.264 95% CI 1.026-17.727, P = 0.046; respectively ) . Tumor size was not significantly associated with any differences in time to recurrence (P = 0,838). Conclusion: Lower tumors (≤1.0 cm) are not significantly associated with shorter time to recurrence compared with larger tumors (>1.0 cm).

Comparative bioinformatics analysis of prognostic and differentially expressed genes in non-muscle and muscle invasive bladder cancer

Bladder cancer (BC) is classified into non-muscle (NMIBC) and muscle invasive (MIBC) diseases. Several molecular alterations were previously associated with NMIBC and MIBC, but few studies have systematically compared the molecular differences between these subtypes. Here, we analyzed prognostic and differentially expressed genes in NMIBC and MIBC, using an integrative bioinformatics approach. These genes were used in functional enrichment and co-expression protein interaction (COPI) network analyses to reveal common and exclusive biological functions involved in NMIBC and MIBC. In NMIBC, the enriched functions were related to oxidative stress response, cell cycle, glutathione metabolism, ubiquitination and protein translation. Conversely, enriched functions in MIBC were extracellular matrix organization, cell migration and actin cytoskeleton. Several genes in NMIBC did not overlap with those reported to MIBC, suggesting these subtypes may have distinct underlying mechanisms. Particularly, MIBC genes were enriched for functions involved in cell migration and invasion, which could help to molecularly differentiate NMIBC and MIBC. The analysis of COPI networks disclosed high centrality nodes that may be essential for NMIBC and MIBC. Further research will determine to which extent NMIBC and MIBC share common biological functions and identify potential candidates for the differential diagnosis, prognosis and treatment of NMIBC and MIBC. SIGNIFICANCE: This study has systematically compared prognostic and differentially expressed genes between non-muscle (NMIBC) and muscle invasive (MIBC) bladder cancer, using an integrative bioinformatics approach. Many genes and biological functions were exclusively associated with either NMIBC or MIBC, suggesting that these disease subtypes could be driven by distinct molecular mechanisms. Particularly, prognostic and differentially expressed genes in MIBC were involved in cell migration and invasion, which can help to molecularly differentiate the NMIBC and MIBC subtypes. Moreover, the analysis of co-expression protein interaction networks identified high centrality nodes that could be potential candidates for the prognosis and treatment of NMIBC and MIBC.

Current and innovative approaches in the treatment of non-muscle invasive bladder cancer: the role of transurethral resection of bladder tumor and organoids.

BackgroundBladder cancer is the 7th most common cancer in men. About 75% of all bladder cancer are non-muscle invasive (NMIBC). The golden standard for definite diagnosis and first-line treatment of NMIBC is transurethral resection of bladder tumour (TURB). Historically, the monopolar current was used first, today bipolar current is preferred by most urologists. Following TURB, depending on the tumour grade, additional intravesical chemo- or/and immunotherapy is indicated, in order to prevent recurrence and need for surgical resection. Development of new technologies, molecular and cell biology, enabled scientists to develop organoids – systems of human cells that are cultivated in the laboratory and have characteristics of the tissue from which they were harvested. In the field of urologic cancers, the organoids are used mainly for studying the course of different diseases, however, in the field of bladder cancer the data are scarce.ConclusionsDifferent currents - monopolar and bipolar, have different effect on urothelium, that is important for oncological results and pathohistological interpretation. Specimens of bladder cancer can be used for preparation of organoids that are further used for studying carcinogenesis. Bladder organoids are step towards personalised medicine, especially for testing effectiveness of chemo-/immunotherapeutics.

PD03-05 DIAGNOSTIC PERFORMANCE OF MCM5 IN THE DIAGNOSIS OF RECURRENT BLADDER CANCER: RESULTS FROM A LARGE PROSPECTIVE, BLINDED, MULTICENTRIC EUROPEAN STUDY

You have accessJournal of UrologyBladder Cancer: Non-invasive I (PD03)1 Apr 2020PD03-05 DIAGNOSTIC PERFORMANCE OF MCM5 IN THE DIAGNOSIS OF RECURRENT BLADDER CANCER: RESULTS FROM A LARGE PROSPECTIVE, BLINDED, MULTICENTRIC EUROPEAN STUDY Joan Palou*, Paolo Gontero, Tim Dudderidge, Stuart McCracken, Fabrizio Longo, Emanuele Montanari, J.A. Witjes, Caroline Sieverink, Oscar Rodriguez, Felicien Vanie, Marco Allasia, Richard Sylvester, Marc Colombel, and Morgan Roupret Joan Palou*Joan Palou* More articles by this author , Paolo GonteroPaolo Gontero More articles by this author , Tim DudderidgeTim Dudderidge More articles by this author , Stuart McCrackenStuart McCracken More articles by this author , Fabrizio LongoFabrizio Longo More articles by this author , Emanuele MontanariEmanuele Montanari More articles by this author , J.A. WitjesJ.A. Witjes More articles by this author , Caroline SieverinkCaroline Sieverink More articles by this author , Oscar Rodriguez Oscar Rodriguez More articles by this author , Felicien VanieFelicien Vanie More articles by this author , Marco AllasiaMarco Allasia More articles by this author , Richard SylvesterRichard Sylvester More articles by this author , Marc ColombelMarc Colombel More articles by this author , and Morgan RoupretMorgan Roupret More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000823.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The gold standard for surveillance in follow up of NMIBC is cystoscopy, combined with cytology. However, the established sensitivity of cytology is very low. ADXBLADDER is a test based upon the detection of the MCM5 protein in the urine sediment, with MCM5 detection being indicative of the presence of a tumour. The objective of this study was to determine the diagnostic performance of ADXBLADDER in the detection of NMIBC recurrence. METHODS: Between Aug 2017 and Jul 2019 a multicentric prospective, blinded study was carried out at 21 centres. Ethical approval was obtained from all sites (Research Ethics committee reference 17/NE/0174). Patients over 18 years of age, with a previous diagnosis of NMIBC undergoing cystoscopic surveillance, able to provide 10 mL of urine and informed consent were recruited. Full void urine samples were collected and the ADXBLADDER test performed. ADXBLADDER results were compared to diagnosis obtained by cystoscopy and pathology. RESULTS: Of 1431 eligible patients enrolled, 127 bladder cancer recurrences were diagnosed (8.9% prevalence). Overall sensitivity (Se) for ADXBLADDER was 44.9% (95% CI 36.1%-54%) with specificity 71.1% (95% CI 68.5-73.5%) and NPV of 93% (95% CI 91.2-94.5%). ADXBLADDER Se in detecting non-pTaLG tumours was 75.6% (95% CI 59.7-87.6%), with a NPV of 99.0% (95% CI 98.2-99.5%) (Figure 1). A subset of the study population (n=503) had matching cytology. In this sub-group ADXBLADDER demonstrated a significantly higher Se of 51.9% (95% CI: 37.8-65.7%), vs the Se of cytology 16.7%; (95% CI: 7.9-29.3%) (p=0.0002). There were no significant differences in performance of ADXBLADDER due to age, sex or treatment received, as measured by area under the ROC curve. CONCLUSIONS: This study demonstrates that in the follow up of NMIBC patients ADXBLADDER is able to exclude the presence of the most aggressive tumours with a NPV of 99%, with significantly higher sensitivity than cytology in all tumour types. These results support the incorporation of ADXBLADDER into the follow up strategy of NMIBC in all patients. Source of Funding: Arquer Diagnostics Ltd © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e73-e74 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joan Palou* More articles by this author Paolo Gontero More articles by this author Tim Dudderidge More articles by this author Stuart McCracken More articles by this author Fabrizio Longo More articles by this author Emanuele Montanari More articles by this author J.A. Witjes More articles by this author Caroline Sieverink More articles by this author Oscar Rodriguez More articles by this author Felicien Vanie More articles by this author Marco Allasia More articles by this author Richard Sylvester More articles by this author Marc Colombel More articles by this author Morgan Roupret More articles by this author Expand All Advertisement PDF downloadLoading ...

EDITORIAL COMMENT

In the study “Nonmuscle Invasive Bladder Cancer Influences Physical Health Related Quality of Life and Urinary Incontinence, Wayne G. Brisbane and colleagues examine patient-reported quality of life (QOL) and urinary incontinence outcomes associated with the diagnosis and management of nonmuscle invasive bladder cancer. The study is based on SEER cancer registry data linked to patient-reported outcomes (PROs) data collected as part of the Medical Health Outcomes Survey (SEER-MHOS), which allowed the authors to not only evaluate patient-reported outcomes in a representative sample of bladder cancer patients managed with endoscopic and intravesical treatments, but also benchmark those outcomes to surveys taken from noncancer controls who participated in MHOS as part of their Medicare Advantage plan. Though changes in patient-reported QOL and urinary function were apparent in both groups, declines in PRO scores were more pronounced among NMIBC patients than in noncancer controls. For example, SF-36 physical component summary (PCS) scores decreased by 3.0 points among bladder cancer patients from before diagnosis to after treatment (assessments were performed at 2 year intervals according to MHOS assessment frames) but only 1.5 in the control group (P = .01). Similarly, problems with urinary incontinence were more commonly reported by patients than controls; 15.2% of NMIBC patient respondents endorsed new urinary incontinence compared to 11.2% of controls (P = .09), and 20.0% of patients reported increased severity of incontinence compared to 11.4% of controls (P <.01). Notably, significant deficits in physical health and QOL were driven primarily by low scores in high-risk NMIBC cases (high-grade Ta disease, CIS, and T1 disease), implicating a close association between frequent interventions, such as repeated cystoscopy, biopsy, resection and intravesical therapies, and poorer patient-reported outcomes. Although these results may not be surprising and likely confirm the observations of practicing urologists who often manage bladder cancer, they provide empirical evidence that quantifies the burdens associated with the diagnosis and treatment of NMIBC. Moreover, these data have several palpable implications in my opinion. First, they represent a step forward and knowledge gained; they pencil in previously undescribed details about patient-reported symptoms and QOL outcomes within the outlines of a relatively understudied area. Second, they underscore the importance of PROs and QOL assessments among bladder cancer patients managed with endoscopic and intravesical therapies, which is particularly relevant given the exploding number of clinical trials evaluating emerging NMIBC therapies that are currently underway. 1 Nykopp TK Batista da Costa J Mannas M Black PC Current clinical trials in non-muscle invasive bladder cancer. Curr Urol Rep. 2018; 19: 101 Crossref PubMed Scopus (20) Google Scholar Patient-report outcome and QOL measures should be compulsory components in these trials. Finally, they foreshadow a not-distant future in which PROs will enter routine clinical care. The salutary effects of using PRO measures to inform and guide clinical care have come into focus in recent years, and increasingly health systems are steering toward them. 2 Rotenstein LS Huckman RS Wagle NW Making patients and doctors happier – the potential of patient-reported outcomes. N Engl J Med. 2017; 377: 1309-1312 Crossref PubMed Scopus (151) Google Scholar

Bacillus Calmette-Guérin may have clinical benefit for glandular or squamous differentiation in non-muscle invasive bladder cancer patients: retrospective multicenter study

To clarify the efficacy of intravesical Bacillus Calmette-Guérin (BCG) instillation for non-muscle invasive bladder (NMIBC) cancer with variant histology, especially glandular differentiation or squamous differentiation. From May 1991 through June 2016, 53 patients were diagnosed retrospectively as having NMIBC with variant histology. Among these patients, 47 NMIBC patients with squamous differentiation or glandular differentiation were analyzed for this study. The median follow-up interval from diagnosis of NMIBC with variant histology was 28.9 months (1.5-168.8). Of these patients, 38 (80.9%) and 9 (19.1%) were diagnosed as having glandular differentiation and squamous differentiation, respectively. Radical cystectomy was conducted for six (12.8%) immediately after the diagnosis of NMIBC with variant histology. Of the 41 patients with bladder preservation, 20 (48.8%), 3 (7.3%), 3 (7.3%) and 15 (36.6%) underwent BCG, THP, MMC and no additional treatment, respectively. There were significant differences between BCG and other treatments or no additional treatment for recurrence (P = 0.034), progression (P = 0.004) and cancer-specific survival (P = 0.014). Overall, our results show that intravesical BCG instillation for variant histology in NMIBC leads to a better prognosis with regard to progression and cause-specific survival than other intravesical treatments or no additional treatment. BCG treatment may also have a clinical benefit for variant histology in non-muscle invasive bladder cancer patients.

Optical improvements in the diagnosis of bladder cancer: implications for clinical practice

For over 100 years white-light cystoscopy has remained the gold-standard technique for the detection of bladder cancer (BCa). Some limitations in the detection of flat lesions (CIS), the differentiation between inflammation and malignancy, the inaccurate determination of the tumor margin status as well as the tumor depth, have led to a variety of technological improvements. The aim of this review is to evaluate the impact of these improvements in the diagnosis of BCa and their effectiveness in clinical practice. A systematic literature search was conducted according to the PRISMA statement to identify studies reporting on imaging modalities in the diagnosis of NMIBC between 2000 and 2017. A two-stage selection process was utilized to determine eligible studies. A total of 74 studies were considered for final analysis. Optical imaging technologies have emerged as an adjunct to white-light cystoscopy and can be classified according to their scope as macroscopic, microscopic and molecular. Macroscopic techniques including photodynamic diagnosis (PDD), narrow-band imaging (NBI) and the Storz Professional Image Enhancement System (IMAGE1 S, formerly known as SPIES) are similar to white-light cystoscopy, but are superior in the detection of bladder tumors by means of contrast enhancement. Especially the detection rate of very mute lesions in the bladder mucosa (CIS) could be significantly increased by the use of these methods. Microscopic imaging techniques like confocal laser endomicroscopy and optical coherence tomography permit a real-time high-resolution assessment of the bladder mucosa at a cellular and sub-cellular level with spatial resolutions similar to histology, enabling the surgeon to perform an 'optical biopsy'. Molecular techniques are based on the combination of optical imaging technologies with fluorescence labeling of cancer-specific molecular agents like antibodies. This labeling is intended to favor an optical distinction between benign and malignant tissue. Optical improvements of the standard white-light cystoscopy have proven their benefit in the detection of BCa and have found their way into clinical practice. Especially the combination of macroscopic and microscopic techniques may improve diagnostic accuracy. Nevertheless, HAL-PDD guided cystoscopy is the only approach approved for routine use in the diagnosis of BCa by most urological associations in the EU and USA to date.

Effect of statins as a secondary chemopreventive agent among individuals with non–muscle-invasive bladder cancer: A population-based analysis

BackgroundNon–muscle-invasive bladder cancer (NMIBC) is especially prevalent among the elderly. Many patients with NMIBC also have significant concomitant comorbidities, including cardiovascular diseases and hypercholesterolemia. Statins are the most commonly used cholesterol-depleting agents, and they may possess anticancer properties. The objective of this population-based study was to evaluate the effect of statins on the survival of individuals diagnosed with NMIBC. MethodsThis is a retrospective population-based cohort study that used administrative databases to identify individuals 66 years of age and older who were diagnosed with NMIBC between 1992 and 2012. Subjects with documented use of statins before they were 66 years of age were excluded from the analysis. Cumulative daily use of statins was calculated before and after the diagnosis of NMIBC. Their effect on cancer-specific survival and overall survival was estimated using a multivariable competing risk and Cox proportional hazards model, respectively. ResultsThe final cohort was composed of 13,811 individuals≥66 years diagnosed with NMIBC. Of these, 4,748 individuals (34%) were exposed to statins during follow-up. The median statin exposure after NMIBC diagnosis was 21.4 months (interquartile range: 7.8–45.4). After a median follow-up of 7.1 years (interquartile range: 4.0–11.3) from NMIBC diagnosis, 8,900 (64%) individuals had died. The cumulative use of statins after NMIBC diagnosis did not significantly affect cancer-specific survival (P = 0.10). However, its cumulative use after NMIBC diagnosis was associated with a better overall survival ([0.93; 95% CI: 0.91–0.96], per year of use). ConclusionsThis large population-based study has provided evidence that cumulative statin use was not associated with an improved cancer-specific survival among individuals with NMIBC. However, our findings did demonstrate that statin users had a better overall survival than nonusers.

MP13-04 CONCENTRATION OF MITOMYCIN-C IN URINE ACCORDING TO URINE PH AFTER INTRAVESICAL INSTILLATION OF MITOMYCIN-C IN NON-MUSCLE INVASIVE BLADDER CANCER PATIENTS

Aim of this study was to evaluate HRQoL of patients affected by NMIBC underwent intravesical instillations of Bacillus Calmette-Gu erin (BCG) or Mytomicin C (MMC) with a short-term follow-up. METHODS: From December 2011 to December 2014 we recruited 108 consecutive patients in a single academic center with a first-time diagnosis of NMIBC at intermediate or high risk. The median age was 73 years (38-94) and 55.3% (N 57) patients underwent BCG and 44.7% (N 46) patients underwent MMC after TURBT respectively. The assessment of HRQoL was performed using two questionnaires from EORTC: QLQ-C30 and QLQ-BLS24 specific for NMIBC. Patients self-completed the questionnaires in three different times: T0 (before intravesical instillation), T1 (after intravesical instillation), T2 (at three months after last instillation). The above analysis was stratified by gender, age (?70 years and >70 years), tumour degree risk (intermediate and high risk) and type of intravesical therapy (MMC and BCG). Wilcoxon two sample test was used to verify differences. Statistical significance was achieved if pvalue was 1⁄40.05 (two-sides). RESULTS: Treatment was well tolerated in both groups of patients underwent intravesical instillations of BCG and MMC respectively. Grade I and II side effects, as CTCAE classification, were reported by 46.6% of patients at T1 and 47.5% at T2. 5 patients dropped out of the study (3 lost in follow-up and 2 developed side effects of BCG). At T1 we founded a drop in QoL, with reference to Physical, Role, Emotional and Social functioning domains and a worsening of urinary bladder symptoms with a generally decrease of Global Quality of Life Score. The sexual sphere was affected by adjuvant therapy with persistence or worsening of sexual disorders. At T2 patients showed a progressive return to baseline QoL, in particular in the Social and clinical symptoms domains. Male gender, age>70 years, high-risk tumours and BCG seem to be the factors that worsening HRQoL of these patients. CONCLUSIONS: Intravesical instillations seem to modify the HRQoL of these patients with a return at 3 months to baseline conditions.

Bladder Carcinoma Data with Clinical Risk Factors and Molecular Markers: A Cluster Analysis

Bladder cancer occurs in the epithelial lining of the urinary bladder and is amongst the most common types of cancer in humans, killing thousands of people a year. This paper is based on the hypothesis that the use of clinical and histopathological data together with information about the concentration of various molecular markers in patients is useful for the prediction of outcomes and the design of treatments of nonmuscle invasive bladder carcinoma (NMIBC). A population of 45 patients with a new diagnosis of NMIBC was selected. Patients with benign prostatic hyperplasia (BPH), muscle invasive bladder carcinoma (MIBC), carcinoma in situ (CIS), and NMIBC recurrent tumors were not included due to their different clinical behavior. Clinical history was obtained by means of anamnesis and physical examination, and preoperative imaging and urine cytology were carried out for all patients. Then, patients underwent conventional transurethral resection (TURBT) and some proteomic analyses quantified the biomarkers (p53, neu, and EGFR). A postoperative follow-up was performed to detect relapse and progression. Clusterings were performed to find groups with clinical, molecular markers, histopathological prognostic factors, and statistics about recurrence, progression, and overall survival of patients with NMIBC. Four groups were found according to tumor sizes, risk of relapse or progression, and biological behavior. Outlier patients were also detected and categorized according to their clinical characters and biological behavior.

Transurethral Resection of Bladder Cancer: A Simple and Diffusely-Performed Technique but with Controversial Outcomes

Nowadays TUR is considered the golden standard for the diagnosis and treatment of NMIBC. However, TUR should be adequate: all bladder lesions should be resected and muscle must be present in the specimen in order to correctly stage the tumor. No bladder perforation should be performed and CIS diagnosed. Bimanual palpation pre- and post-TUR should be encouraged, especially in teaching institutions. Urethroscopy should always precede the visualization of the bladder. All the visible tumors should be resected preferably with bipolar resectoscope, to avoid tissue charring and to facilitate the pathological diagnosis. The exophytic part of the tumor should be first resected and the fragment collected in a separate bottle. Tumor base must be biopsied with cold cup. Muscle must be present in the specimen. Fulguration of the tumor base and 1-2 cm around is of paramount importance. One of the most important parameters for evaluating the quality of TUR is tumor recurrence after 3 months. The EORTC GU Group showed that the 3-month recurrence varied from 0 to 46% between the European institutions participating in randomized prospective EORTC studies. This variability was not explained by the tumor characteristics nor by the adjuvant therapy administered, but by the poor quality of the TUR. The surgeon’s performance and poor TUR quality were therefore suggested as being responsible for the results. A second EORTC study confirmed in fact that using a bladder diagram at the moment of diagnosis (signing the areas where the lesions are) and the presence of an experienced surgeon performing TUR were the two significant factors that could reduce the recurrence after 3 months. A complete, adequate first TUR is of paramount importance for the outcome of patients with NMIBC. It could be more important than any further adjuvant therapy administered.

Fluorescence Cystoscopy with Hexaminolevulinate: Our Preliminary Experience of 184 Procedures

Fluorescence cystoscopy (FC) with hexaminolevulinate (HAL) is a recently introduced technique of photodynamic diagnosis (PDD), which aims to improve the accuracy of white light cystoscopy (WLC) in the diagnosis of superficial bladder tumors (NMIBC), and especially of flat urothelial lesions (dysplasia and Ca in situ). We report our experience of a number of cases of WLC and FC in a single moment with HAL in the diagnosis and follow-up of NMIBC. The method was applied to 184 selected patients with a diagnosis or clinical suspicion - instrumental or early recurrence of bladder neoplasia. The lesions found in white light (WL) and/or blue light (FC) were sampled separately for histological examination. We evaluated the results in terms of diagnostic gain compared to treatment with one WL, false positivity and recurrence-free survival compared to historical reference group treated with WL only. 26.1% of the lesions were found only by the PDD method. The false positivity due to the method adopted was 21.2%. The gain in terms of recurrence-free survival (compared with historical reference group treated only with WL) was 22.3% at 12 months and 24.4% at 20 months. It did not show any systemic side effects. The PDD is a technique that can significantly increase the diagnostic accuracy of NMIBC.