The Impact of Histologic Subtypes on Clinical Outcomes After Radiation-Based Therapy for Muscle-Invasive Bladder Cancer.

PURPOSE: Outcomes of radiation-based therapy (RT) for muscle-invasive bladder cancer (MIBC) with histologic subtypes of urothelial cancer (HS-UC) are lacking. Our objective was to compare survival outcomes of pure urothelial carcinoma (PUC) to HS-UC after RT. MATERIALS AND METHODS: A multicenter retrospective study of 864 patients with MIBC who underwent curative-intent RT to the bladder for MIBC (clinical T2-T4aN0-2M0) between 2001 and 2018 was conducted. Regression models were used to test the association between HS-UC and complete response (CR) and survival outcomes after RT. RESULTS: In total, 122 patients (14%) had HS-UC. Seventy-five (61%) had HS-UC with squamous and/or glandular differentiation. A CR was confirmed in 69% of patients with PUC and 63% with HS-UC. There were 207 (28%) and 31 (25%) patients who died of metastatic bladder cancer in the PUC and HS-UC groups, respectively. There were 361 (49%) and 58 (48%) patients who died of any cause in the PUC and HS-UC groups, respectively. Survival outcomes were not statistically different between the groups. The HS-UC status was not associated with survival outcomes in multivariable Cox regression analyses. CONCLUSIONS: In our study, HS-UC responded to RT with no significant difference in CR and survival outcomes compared to PUC. The presence of HS-UC in MIBC does not seem to confer resistance to RT, and patients should not be withheld from bladder preservation therapy options. Due to low numbers, definitive conclusions cannot be drawn for particular histologic subtypes.

MRI-Based Machine Learning Radiomics for Preoperative Assessment of Human Epidermal Growth Factor Receptor 2 Status in Urothelial Bladder Carcinoma.

BACKGROUND: The human epidermal growth factor receptor 2 (HER2) has recently emerged as hotspot in targeted therapy for urothelial bladder cancer (UBC). The HER2 status is mainly identified by immunohistochemistry (IHC), preoperative and noninvasive methods for determining HER2 status in UBC remain in searching. PURPOSES: To investigate whether radiomics features extracted from MRI using machine learning algorithms can noninvasively evaluate the HER2 status in UBC. STUDY TYPE: Retrospective. POPULATION: One hundred ninety-five patients (age: 68.7 ± 10.5 years) with 14.3% females from January 2019 to May 2023 were divided into training (N = 156) and validation (N = 39) cohorts, and 43 patients (age: 67.1 ± 13.1 years) with 13.9% females from June 2023 to January 2024 constituted the test cohort (N = 43). FIELD STRENGTH/SEQUENCE: 3 T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin echo). ASSESSMENT: The HER2 status were assessed by IHC. Radiomics features were extracted from MRI images. Pearson correlation coefficient and the least absolute shrinkage and selection operator (LASSO) were applied for feature selection, and six machine learning models were established with optimal features to identify the HER2 status in UBC. STATISTICAL TESTS: Mann-Whitney U-test, chi-square test, LASSO algorithm, receiver operating characteristic analysis, and DeLong test. RESULTS: Three thousand forty-five radiomics features were extracted from each lesion, and 22 features were retained for analysis. The Support Vector Machine model demonstrated the best performance, with an AUC of 0.929 (95% CI: 0.888-0.970) and accuracy of 0.859 in the training cohort, AUC of 0.886 (95% CI: 0.780-0.993) and accuracy of 0.846 in the validation cohort, and AUC of 0.712 (95% CI: 0.535-0.889) and accuracy of 0.744 in the test cohort. DATA CONCLUSION: MRI-based radiomics features combining machine learning algorithm provide a promising approach to assess HER2 status in UBC noninvasively and preoperatively. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Music from Noise-Canceling Headphones Is Beneficial against Anxiety in Male Bladder Cancer Patients Undergoing Follow-Up Cystoscopy: A Prospective Randomized Trial.

INTRODUCTION: Bladder cancer, with a greater incidence in males than in females, requires frequent cystoscopies. We aimed to evaluate the effect of music played through noise-canceling headphones on male bladder cancer patients during follow-up cystoscopy. METHODS: A total of 160 male bladder cancer patients undergoing follow-up flexible cystoscopy were randomly divided into the noise-canceling headphones without music group and the noise-canceling headphones with music group (groups 1 and 2, respectively; n = 80 per group). The patients' clinical characteristics were examined, and objective and subjective measurements were compared before and after cystoscopy. The primary outcomes that were evaluated included the visual analog scale (VAS, 0-10) and the state-trait anxiety inventory (STAI, 20-80). Other outcomes, including vital signs and scores for assessing satisfaction and the willingness to repeat the procedure, were also examined. RESULTS: The characteristics of the patients in groups 1 and 2, and their pre-cystoscopy status, did not differ significantly. Although post-cystoscopy vital signs for the objective parameters and VAS pain scores were similar between the groups, subjective parameters were not. When compared with group 1, post-cystoscopy STAI-state scores were significantly lower in group 2, whereas patients' satisfaction scores and the willingness to repeat the procedure were significantly higher in group 2 (p = 0.002, 0.001, and 0.001, respectively). Additionally, in group 2, STAI-state scores changed significantly after the procedure when compared with before the procedure (p = 0.002). CONCLUSION: Providing music to male bladder cancer patients through noise-canceling headphones was found to reduce anxiety during cystoscopy and to improve patient satisfaction and willingness to undergo repeat cystoscopy.

Development and Validation of an MRI-Based Nomogram for Preoperative Detection of Muscle Invasion in VI-RADS 3.

BACKGROUND: The relationship between tumor and muscle layer in the vesical imaging-reporting and data system (VI-RADS) 3 is ambiguous, and there is a lack of preoperative and non-invasive procedures to detect muscle invasion in VI-RADS 3. PURPOSE: To develop a nomogram based on MRI features for detecting muscle invasion in VI-RADS 3. STUDY TYPE: Retrospective. POPULATION: 235 cases (Age: 67.5 ± 11.5 years) with 11.9% females were randomly divided into a training cohort (n = 164) and a validation cohort (n = 71). FIELD STRENGTH/SEQUENCE: 3T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin echo), and dynamic contrast-enhanced imaging (gradient echo). ASSESSMENT: 3 features were selected from the training cohort, including tumor contact length greater than maximum tumor diameter (TCL > Dmax), flat tumor morphology, and lower standard deviation of apparent diffusion coefficient (ADCSD ). Three readers assessed VI-RADS scores and the tumor morphology. STATISTICAL TESTS: Interobserver agreement was assessed by Kappa analysis. Features for final analysis were selected by logistic regression. The performance of the nomogram was evaluated by the receiver operating characteristic curve, decision curve analysis, and calibration curve. RESULTS: TCL > Dmax, flat morphology, and lower ADCSD were the independent risk factors for muscle invasive in VI-RADS 3. The AUCs, accuracy, sensitivity, and specificity of the nomogram 1 composed of three features for detecting muscle invasion were 0.852 (95% CI: 0.793-0.912), 0.756, 0.917, and 0.663 in the training cohort, and 0.885 (95% CI: 0.801-0.969), 0.817, 0.900, and 0.784 in the validation cohort. The nomogram 2 without ADCSD has nearly the same performance as the nomogram 1. DATA CONCLUSION: Nomogram can be an efficient tool for preoperative detection of muscle invasion in VI-RADS 3. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Influence of luminal and basal subtype in prognosis of high-grade non muscle invasive urothelial carcinoma.

BACKGROUND: Recent studies have shown that the classification of high-grade urothelial carcinoma non-muscle invasive (HGBCNMI) based on molecular subtypes might be a valuable strategy to identify patients with a worse clinical prognosis. OBJECTIVE: Determine the effect of the luminal and basal molecular subtype determined by immunistochemical on prognosis in patients with HGBC in Mexican population. METHODS: Phenotypes were evaluated by immunohistochemical staining of luminal (GATA3, FOXA1) and basal (CK5/6, CK14) markers in paraffin-embedded tissue samples from 45 patients with a diagnosis of HGBCNMI treated at Instituto Nacional de Cancerología-México (INCan) between 2009 and 2019. The association with prognosis was evaluated using Kaplan-Meier curves and multivariable-adjusted Cox models. RESULTS: HGBCNMI patients showed mean age of 58.77 years (SD: ±12.08 years). We identified expression of the luminal molecular subtype in 35 cases (77.78 %), and 10 cases (22.22 %) with "combined" expression of the molecular subtype (basal and luminal expression). The combined phenotype was statistically more frequent in metastatic cases (p-value = 0.028). In Kaplan-Meier curves, combined expression of luminal and basal molecular markers was associated with disease progression (p-value = 0.002, log-rank test). Cox regression models confirmed this association, which was not influenced by age (p-value = 0.007) or gender (p-value = 0.007). No association of phenotypes with overall survival (p-value = 0.860) or relapse (p-value = 0.5) was observed. CONCLUSION: The combined expression of immunohistochemical markers of the luminal and basal subtype might be considered as predictor for disease progression in patients with HGBCNMI in Mexican population.

Reporting and grading of complications for intracorporeal robot-assisted radical cystectomy: an in-depth short-term morbidity assessment using the novel Comprehensive Complication Index®.

OBJECTIVE: To assess suitability of Comprehensive Complication Index (CCI®) vs. Clavien-Dindo classification (CDC) to capture 30-day morbidity after robot-assisted radical cystectomy (RARC). MATERIALS AND METHODS: A total of 128 patients with bladder cancer (BCa) undergoing intracorporeal RARC with pelvic lymph node dissection between 2015 and 2021 were included in a retrospective bi-institutional study, which adhered to standardized reporting criteria. Thirty-day complications were captured according to a procedure-specific catalog. Each complication was graded by the CDC and the CCI®. Multivariable linear regression (MVA) was used to identify predictors of higher morbidity. RESULTS: 381 complications were identified in 118 patients (92%). 55 (43%), 43 (34%), and 20 (16%) suffered from CDC grade I-II, IIIa, and ≥ IIIb complications, respectively. 16 (13%), 27 (21%), and 2 patients (1.6%) were reoperated, readmitted, and died within 30 days, respectively. 31 patients (24%) were upgraded to most severe complication (CCI® ≥ 33.7) when calculating morbidity burden compared to corresponding CDC grade accounting only for the highest complication. In MVA, only age was a positive estimate (0.44; 95% CI = 0.03-0.86; p = 0.04) for increased cumulative morbidity. CONCLUSION: The CCI® estimates of 30-day morbidity after RARC were substantially higher compared to CDC alone. These measurements are a prerequisite to tailor patient counseling regarding surgical approach, urinary diversion, and comparability of results between institutions.

Assessment of Xpert Bladder Cancer Monitor test performance for the detection of recurrence during non-muscle invasive bladder cancer follow-up.

PURPOSE: To assess the performance of the Xpert Bladder Cancer (BC) Monitor during the follow-up of patients with non-muscle invasive bladder cancer (NMIBC). METHODS: Patients with previously diagnosed NMIBC and followed up in clinical practice settings in two French urology departments between September 2017 and July 2019 were consecutively enrolled in this prospective observational study. Patients with a positive cystoscopy or computed tomography urogram underwent subsequent transurethral resection of the bladder, and/or biopsy, and the specimens were pathologically assessed. Cytology and Xpert BC Monitor tests were performed on urine samples. Xpert BC Monitor performance was assessed versus cystoscopy for disease-negative patients or versus histology for disease-positive patients, and was compared to that of cytology. RESULTS: Overall, 500 patients with a median age of 70.0 years were included. NMIBC recurrence was diagnosed in 44 cases (8.8%). Overall sensitivity, specificity, and negative predictive values (NPVs) were 72.7% (32/44), 73.7% (330/448) and 96.5% (330/342) for the Xpert BC Monitor, and 7.7% (2/26), 97.8% (310/317) and 92.8% (310/334) for cytology, respectively. The Xpert BC Monitor detected 92.3% (12/13) of the high-grade tumours and ruled out their presence in 99.7% (330/331) of cases. Analysis of the areas under the receiver operating characteristic curves demonstrated the superior performance of the Xpert BC Monitor over that of cytology. CONCLUSION: Xpert BC Monitor performance was superior to that of cytology in the follow-up of NMIBC. The exclusion of aggressive tumours with a very high NPV (99.7%) supports the use of this urinary test in daily practice.

Effect of chlorpheniramine administration on postoperative catheter-related bladder discomfort in patients undergoing transurethral excision of bladder tumor: a prospective randomized study.

PURPOSE: Catheter-related bladder discomfort (CRBD) is postoperative distress caused by a urinary catheter. CRBD is related to muscarinic receptor activation. Chlorpheniramine has antimuscarinic properties. Hence, this investigation was undertaken to evaluate the efficacy of chlorpheniramine in preventing CRBD in patients undergoing transurethral resection of bladder tumor (TURBT). METHODS: Seventy-six patients scheduled for TURBT under general anesthesia were assigned into two groups. In the chlorpheniramine group (n = 38), 100 ml normal saline containing 0.1 mg/kg chlorpheniramine was infused after general anesthesia induction. In the control group (n = 38), 100 ml normal saline alone was infused. The incidence and severity of CRBD were assessed at 1, 6, and 24 h postoperatively. RESULTS: The 1-h postoperative incidence of CRBD was lower in the chlorpheniramine group based on the unadjusted analysis [16 (42%) vs. 28 (74%), risk difference 32%, 95% confidence interval 8-51, p = 0.005]. After adjusting the size of the urinary catheter, post hoc analysis showed that the 1-h postoperative incidence of CRBD was lower in the chlorpheniramine group (p = 0.004). The CRBD severity score was lower in the chlorpheniramine group at 1 and 6 h after operation based on the unadjusted analysis (p = 0.012 and p = 0.007, respectively). After adjusting the urinary catheter size, post hoc analysis showed that 1- and 6-h CRBD severity score was lower in the chlorpheniramine group (p = 0.012 and p = 0.008, respectively). The incidence of rescue medication was lower in the chlorpheniramine group [10 (26%) vs. 20 (53%), risk difference 26%, 95% confidence interval 3-47, p = 0.019]. The overall incidence of complications such as nausea, vomiting, dry mouth, flushing, dizziness, and blurred vision was comparable between the two groups. CONCLUSIONS: Chlorpheniramine administration significantly reduces the incidence and severity of CRBD in the patients undergoing TURBT. TRIAL REGISTRATION: KCT0004880 ( https://cris.nih.go.kr/ ).

A Case of Incidental Schwannoma Mimicking Necrotic Metastatic Lymph Node from Bladder Cancer.

Background and Objectives: Retroperitoneal schwannoma is a very rare case of schwannoma which commonly occurs in the other part of the body. However, it is difficult to distinguish schwannoma from other tumors before pathological examination because they do not show specific characteristics on imaging study such as ultrasound, computed tomography (CT), and magnetic resonance image (MRI). Case summary: A 60-year-old male showed a retroperitoneal cystic tumor which is found incidentally during evaluation of coexisted bladder tumor. Neurogenic tumor was suspicious for the retroperitoneal tumor through pre-operative imaging study. Finally, a schwannoma was diagnosed by immunohistochemical examination after complete surgical excision laparoscopically. Conclusion: As imaging technology is developed, there may be more chances to differentiate schwannoma from other neoplasm. However, still surgical resection and histopathological examination is feasible for diagnosis of schwannoma.

Health-related quality of life in the randomized phase 3 study of ramucirumab plus docetaxel versus placebo plus docetaxel in platinum-refractory advanced urothelial carcinoma (RANGE).

BACKGROUND: To evaluate patient-reported outcomes with ramucirumab plus docetaxel, a regimen which improved progression-free survival in platinum-refractory advanced urothelial carcinoma (aUC). METHODS: RANGE-a randomized, double-blinded, phase 3 trial in patients with platinum-refractory aUC. Ramucirumab (10 mg/kg) plus docetaxel (75 mg/m2) or placebo plus docetaxel were administered every 21 days until disease progression or unacceptable toxicity. Patients received maximum 10 cycles of docetaxel. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and EuroQoL five-dimensions (EQ-5D-5L) were administered at baseline, start of each cycle, and 30-day follow-up visit. A ≥ 10-point change in QLQ-C30 scores was considered meaningful. Rates of improved/stable scores were compared between treatment arms using Fisher's exact test. Time to deterioration (TtD) was estimated and compared using Kaplan-Meier estimation and log-rank test. RESULTS: Of the 530 patients, ~ 97% patients in each arm provided baseline QLQ-C30 data. On-treatment compliance was ≥ 88% for first 8 cycles. Mean baseline QLQ-C30 scores were similar between arms, with global quality of life (QoL), fatigue, pain, and insomnia having greatest impairment. Postbaseline rates of improved/stable QLQ-C30 scores were similar between treatment arms except for greater improvement in pain score with ramucirumab. TtD of QLQ-C30 scales favored ramucirumab arm. Baseline EQ-5D-5L index and visual analogue scale scores were similar between arms, followed by relatively stable on-treatment scores. EQ-5D-5L scores worsened at post-discontinuation follow-up visit. CONCLUSIONS: Ramucirumab plus docetaxel did not negatively impact QoL compared with docetaxel alone in platinum-refractory aUC. Improved TtD and tumor associated rates of pain favored ramucirumab treatment. CLINICAL TRAIL REGISTRATION: NCT02426125. https://clinicaltrials.gov/ct2/show/NCT02426125 . Date of registration: April 24th 2015.

Inhibition of stearoyl CoA desaturase-1 activity suppresses tumour progression and improves prognosis in human bladder cancer.

Urinary bladder neoplasm is one of the most common cancers worldwide. Cancer stem cells (CSCs) have been proven to be an important cause of cancer progression and poor prognosis. In the present study, we established bladder CSCs and identified the crucial differentially expressed genes (DEGs) between these cells and parental bladder cancer cells. Analyses of bioinformatics data and clinical samples from local hospitals showed that stearoyl CoA desaturase-1 (SCD) was the key factor among the DEGs. A significant correlation between SCD gene expression and poor prognosis among patients with bladder cancer was observed in our data. Loss-of-function experiments further revealed that the SCD inhibitor A939572 and SCD gene interference reduced cell proliferation and invasion. The above data suggest that SCD may serve as a novel marker for the prediction of tumour progression and poor prognosis in patients with bladder cancer.

Assessment of CEP55, PLK1 and FOXM1 expression in patients with bladder cancer in comparison with healthy individuals.

This case/control study is aimed at investigating the expression of CEP55, PLK1 and FOXM1 in bladder cancer tissues and comparing it with healthy tissue and their relationship with clinicopathological features of BC. Total RNA was extracted; then, gene expression was performed using real-time PCR relative to 18 s rRNA. 2-ΔΔCT method was used to calculate the relative expression of genes. A significant over expression of FOXM1, PLK1 and CEP55 was observed in tumor samples compared to adjacent and normal bladder tissues (all p = 0.001). Therefore, they may be supposed as potential candidate's biomarkers for early diagnosis and targets for cancer therapy.

Sarcopenia predicts 90-day mortality and postoperative complications after radical cystectomy for bladder cancer.

PURPOSE: A single-center study was conducted to investigate the impact of sarcopenia as a predictor for 90-day mortality (90 dM) and complications within 90 days after radical cystectomy for bladder cancer. METHODS: In total, 327 patients with preoperative available digital computed tomography (CT) scans of the abdomen and pelvis were identified. The lumbar skeletal muscle index was measured using preoperative abdominal CT to assess sarcopenia. Complications were recorded and graded according to Clavien-Dindo (CD). Predictors of 90 dM and complications within 90 days were analyzed by uni- and multivariable logistic regression. RESULTS: Of the 327 patients, 262 (80%) were male and 108 (33%) patients were classified as sarcopenic. Within 90 days, 28 (7.8%) patients died, of whom 15 patients were sarcopenic and 13 were not. In multivariable logistic regression analysis, sarcopenia (OR 2.59; 95% CI 1.13-5.95; p = 0.025), ASA 3-4 (OR 2.53; 95% CI 1.10-5.82; p = 0.029) and cM + (OR 7.43; 95% CI 2.34-23.64; p = 0.001) were independent predictors of 90-day mortality. Sarcopenic patients experienced significantly more complications, i.e., CD 4a-5 (p = 0.003), compared to non-sarcopenic patients. In multivariable logistic regression analysis, sarcopenia was independently associated with CD ≥ 3b complications corrected for age, BMI, ASA-Score and type of urinary diversion. CONCLUSIONS: We reported that sarcopenia proved an independent predictor for 90 dM and complications in patients undergoing RC for bladder cancer.

Prognostic Factors Related to Recurrence-Free Survival for Primary Carcinoma in situ of the Bladder after Bacillus Calmette-Guérin: A Retrospective Study.

INTRODUCTION: Primary carcinoma in situ (P-CIS) of the bladder is rare and its clinical behavior and predictive features have not been well described. The purpose of this study was to evaluate the effects of various factors including angiotensin-2 converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs) on recurrence-free survival (RFS)-related prognosis in patients with P-CIS. MATERIALS AND METHODS: In our medical center, 5,945 patients were diagnosed with bladder cancer from January 1999 to January 2014. Of these, 64 patients were diagnosed with CIS and were treated with at least 6 cycles of Bacillus Calmette-Guérin (BCG). We accessed variables including patient age, sex, initial presenting symptoms, smoking history, P-CIS descriptions, urine cytology, and medication history related to hypertension. RESULTS AND CONCLUSIONS: We evaluated the use of anti-hypertensive medications (ACEIs/ARBs, p = 0.028), the symptom of non-gross hematuria (p = 0.028), and older age (p = 0.015) as significant factors related to RFS. Older age was also a significant factor for influencing the RFS rate. We found that the use of anti-hypertensive medications (ACEIs/ARBs) improves RFS in patients with P-CIS after BCG therapy. The prognosis was poor when there was no gross hematuria and if patients were at older ages at the time of diagnosis of P-CIS.

Diagnostic and prognostic role of urinary collagens in primary human bladder cancer.

Collagen type 4 alpha 1 (COL4A1) and collagen type 13 alpha 1 (COL13A1) produced by urothelial cancer cells support the vital oncogenic property of tumor invasion. We investigated the diagnostic and prognostic capability of COL4A1 and COL13A1 in voided urine and compared the observed values with those of fragments of cytokeratin-19 (CYFRA21-1), nuclear matrix protein 22 (NMP-22), and voided urine cytology in bladder cancer (BCa). We collected voided urine samples from 154 patients newly diagnosed with BCa, before surgery and from 61 control subjects. Protein levels of COL4A1, COL13A1, CYFRA21-1, and NMP-22 in urine supernatants were measured using enzyme-linked immunosorbent assays. Diagnostic performance and optimal cut-off values were determined by receiver operating characteristic analysis. Urine levels of COL4A1, COL13A1, the combined values of COL4A1 and COL13A1 (COL4A1 + COL13A1), and CYFRA21-1 were significantly elevated in urine from patients with BCa compared to the controls. Among these biomarkers, the optimal cut-off value of COL4A1 + COL13A1 at 1.33 ng/mL resulted in 57.4%, 83.7%, 56.1%, 80.7%, and 91.7% sensitivity for low-grade tumors, high-grade tumors, Ta, T1, and muscle invasive disease, respectively. We evaluated the prognostic value of preoperative urine levels in 130 non-muscle invasive BCa samples after the initial transurethral surgery. A high urinary COL4A1 + COL13A1 was found to be an independent risk factor for intravesical recurrence. Although these data need to be externally validated, urinary COL4A1 and COL13A1 could be a potential diagnostic and prognostic biomarker for BCa. This easy-to-use urinary signature identifies a subgroup of patients with a high probability of recurrence and progression in non-muscle invasive and muscle invasive BCa.

Variation in the Diagnostic Evaluation among Persons with Hematuria: Influence of Gender, Race and Risk Factors for Bladder Cancer.

PURPOSE: We sought to determine whether race, gender and number of bladder cancer risk factors are significant predictors of hematuria evaluation. MATERIALS AND METHODS: We used self-reported data from SCCS (Southern Community Cohort Study) linked to Medicare claims data. Evaluation of subjects diagnosed with incident hematuria was considered complete if imaging and cystoscopy were performed within 180 days of diagnosis. Exposures of interest were race, gender and risk factors for bladder cancer. RESULTS: Of the 1,412 patients evaluation was complete in 261 (18%). On our adjusted analyses African American patients were less likely than Caucasian patients to undergo any aspect of evaluation, including urology referral (OR 0.72, 95% CI 0.56-0.93), cystoscopy (OR 0.67, 95% CI 0.50-0.89) and imaging (OR 0.75, 95% CI 0.59-0.95). Women were less likely than men to be referred to a urologist (OR 0.59, 95% CI 0.46-0.76). Also, although all patients with 2 or 3 risk factors had 31% higher odds of urology referral (OR 1.31, 95% CI 1.02-1.69), adjusted analyses indicated that this effect was only apparent among men. CONCLUSIONS: Only 18% of patients with an incident hematuria diagnosis underwent complete hematuria evaluation. Gender had a substantial effect on referral to urology when controlling for socioeconomic factors but otherwise it had an unclear role on the quality of evaluation. African American patients had markedly lower rates of thorough evaluation than Caucasian patients. Number of risk factors predicted referral to urology among men but it was otherwise a poor predictor of evaluation. There is opportunity for improvement by increasing the completion of hematuria evaluations, particularly in patients at high risk and those who are vulnerable.

A prospective comparison of UroVysion FISH and urine cytology in bladder cancer detection.

BACKGROUND: UroVysion fluorescence in situ hybridization (uFISH) was reported to have superior sensitivity to urine cytology. However uFISH studies are limited by varying definitions of what is considered a positive result, absence of histopathology and small sample size. The aim of our study was to better determine the performance characteristics of uFISH and urine cytology by overcoming some of the deficiencies of the current literature. METHODS: Intraoperative bladder wash cytology and uFISH were collected prospectively on all patients. Strict definitions for positivity of uFISH and cytology were determined before initiating the study. A re-review of false-negative uFISH specimens was performed to analyze potential sources of error. Sixteen bladder tumors embedded in paraffin were analyzed by uFISH and compared with the result in the urine. RESULTS: One hundred and twenty-nine specimens were analyzed. Sensitivity was 67% and 69% (p = 0.54); specificity was 72% and 76% (p = 1.0), for uFISH and cytology, respectively. Thirty-two false negative uFISH samples were re-reviewed. Low grade tumors often showed cells with abnormal morphology and patchy DAPI staining but diploid chromosomal counts and a few high grade tumors had tetraploid counts but less than needed to interpret uFISH as positive. uFISH study of the tumors revealed three categories; positive in both tumor and urine (9), negative in both tumor and urine (5) and positive in tumor but negative in urine (2). CONCLUSION: In a pathologically-confirmed analysis of bladder washed urine specimens, uFISH does not outperform urine cytology in cancer detection.

Factors affecting the timeliness and adequacy of haematuria assessment in bladder cancer: a systematic review.

OBJECTIVES: To review the literature to identify factors affecting haematuria assessment in bladder cancer. METHODS: We performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Publications indexed in EMBASE and Medline (PubMed) in March 2016 were searched, using the keywords 'hematuria', 'urinary bladder neoplasm(s)' and 'bladder tumor'. Studies evaluating the timeliness and adequacy of haematuria assessment in the context of bladder cancer were included. Exclusion criteria included age <18 years, animal studies and non-English articles. RESULTS: Following our search strategy, a total of 17 articles were included in our study. All 17 studies commented on gender, with female gender associated with delayed and inadequate haematuria evaluation. Women waited longer than men for urological review (three studies) and bladder cancer diagnosis (three studies). Women were also less likely to be referred to urology (two studies), receive imaging (three studies) or have cystoscopy (two studies). In all, 10 studies commented on age, with the impression that advancing age is associated with a more thorough assessment. Smokers and those with microscopic haematuria appear to undergo a less thorough evaluation. CONCLUSION: Female gender is associated with sub-optimal haematuria evaluation, while older patients are evaluated more thoroughly. Smokers paradoxically undergo less comprehensive assessment. Further research on the impact of other factors is required.

Predictors of delay to cystoscopy and adequacy of investigations in patients with haematuria.

OBJECTIVE: To identify factors that impact on the timeliness and adequacy of haematuria evaluation. PATIENTS AND METHODS: We undertook a retrospective cohort study identifying patients who underwent cystoscopy for investigation of haematuria at our institution between 1 January 2015 and 31 December 2015. Data on patient demographics, smoking status, anticoagulation, type of haematuria and referring clinician were collected. Exclusion criteria included patient age <18 years, known history of bladder/urinary tract/renal cancer, cystoscopy for indications other than haematuria and unknown date of urology consultation. Primary outcome measures were: i) time from general practitioner (GP) referral to urology consultation, ii) time from urology consultation to cystoscopy, and iii) receipt of investigations in the 180 days prior to cystoscopy. Comparisons between risk factors were carried out using negative binomial regression for count outcomes and chi-square test for categorical outcomes. RESULTS: Over the study period, 305 eligible cases (225 men, 80 women) were identified, of which 196 (64%) were referred by a GP. Patients waited a median of 38 days from GP referral to urology consultation and 28 days from urology consultation to cystoscopy. The median time to urology consultation was 65 days for women and 33.5 days for men (P = 0.020). However, the observed difference between men and women was no longer statistically significant on multivariable regression, with the only independent predictors of a shorter interval being visible haematuria and imaging suspicious for cancer. Anticoagulated patients were more likely to have imaging studies, in particular renal tract ultrasonography (P = 0.006), while only 61% of patients with visible haematuria received imaging. No significant differences in recent investigations between genders were observed. CONCLUSIONS: Gender is not a significant predictor of delayed haematuria assessment or receipt of recent investigations. Anticoagulated patients are more likely to receive imaging than patients without anticoagulation and patients with visible haematuria are not adequately imaged. Improved clinician and public education is required to ensure that all patients are evaluated appropriately.

Prediction model for recurrence probabilities after intravesical chemotherapy in patients with intermediate-risk non-muscle-invasive bladder cancer, including external validation.

PURPOSE: To develop a model to predict recurrence for patients with intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) treated with intravesical chemotherapy which can be challenging because of the heterogeneous characteristics of these patients. METHODS: Data from three Dutch trials were combined. Patients treated with intravesical chemotherapy with characteristics according to the IR definition of the EAU guideline 2013 were included. Uni- and multivariable Cox regression with selection methods were used to identify predictors of recurrence at 1, 2, and 5 years. An easy-readable table for recurrence probabilities was developed. An external validation was done using data from Spanish patients. RESULTS: A total of 724 patients were available for analyses, of which 305 were primary patients. Recurrences occurred in 413 patients (57%). History of recurrences, history of intravesical treatment, grade 2, multiple tumors, and adjuvant treatment with epirubicin were relevant predictors for recurrence-free survival with hazard ratios of 1.48, 1.38, 1.22, 1.56, and 1.27, respectively. A table for recurrence probabilities was developed using these five predictors. Based on the probability of recurrence, three risk groups were identified. Patients in each of the separate risk groups should be scheduled for less or more aggressive treatment. The model showed sufficient discrimination and good predictive accuracy. External validation showed good validity. CONCLUSION: In our model, we identified five relevant predictors for recurrence-free survival in IR-NMIBC patients treated with intravesical chemotherapy. These recurrence predictors allow the urologists to stratify patients in risk groups for recurrence that could help in deciding for an individualized treatment approach.