The European Association of Urology (EAU) Guidelines Panel on Upper Urinary Tract Urothelial Carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice.To provide an overview of the EAU guidelines on UTUC as an aid to clinicians.The recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified following a systematic search of Medline. Data on urothelial malignancies and UTUC were searched using the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract carcinoma, renal pelvis, ureter, bladder cancer, chemotherapy, ureteroscopy, nephroureterectomy, neoplasm, adjuvant treatment, instillation, recurrence, risk factors, and survival. References were weighted by a panel of experts.Owing to the rarity of UTUC, there are insufficient data to provide strong recommendations. The 2017 tumour, node, metastasis (TNM) classification is recommended. Recommendations are given for diagnosis and risk stratification as well as for radical and conservative treatment, and prognostic factors are discussed. A single postoperative dose of intravesical mitomycin after nephroureterectomy reduces the risk of bladder tumour recurrence. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk tumour and two functional kidneys. After radical nephroureterectomy, cisplatin-based chemotherapy is indicated in locally advanced UTUC.These guidelines contain information on the management of individual patients according to a current standardised approach. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen, based on the proposed risk stratification of these tumours.Urothelial carcinoma of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, an appropriate diagnosis is most important. A number of known risk factors exist.Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Following the current guidelines, diagnosis and staging for upper urinary tract tumours (UTUC) can be performed with Computed Tomography, urography, ureterorenoscopy (URS) and selective cytology. The aim of the study was to evaluate the performance of the Xpert®-BC-Detection and the Bladder-Epicheck®-test in the detection of UTUC and compare it with cytology and the Urovysion®-FISH test using histology and URS as gold standard.A total of 97 analyses were collected through selective catheterization of the ureter before URS to test for cytology, Xpert®-BC-Detection, Bladder-Epicheck® and Urovysion®-FISH. Sensitivity, specificity, and predictive values were calculated using histology results/URS as reference.Overall sensitivity was 100% for Xpert®-BC-Detection, 41.9% for cytology, 64.5% for Bladder-Epicheck® and 87.1% for Urovysion®-FISH. The sensitivity of Xpert®-BC-Detection was 100% in both, LG and HG tumours, sensitivity of cytology increased from 30.8% in LG to 100% in HG, for Bladder-Epicheck® from 57.7% in LG to 100% in HG and of Urovysion®-FISH from 84.6% in LG to 100% in HG tumours. Specificity was 4.5% for Xpert®-BC-Detection, 93.9% for cytology, 78.8% for Bladder-Epicheck® and 81.8% for Urovysion®-FISH. PPV was 33% for Xpert®-BC-Detection, 76.5% for cytology, 58.8% for Bladder-Epicheck® and 69.2% for Urovysion®FISH. NPV was 100% for Xpert®-BC-Detection, 77.5% for cytology, 82.5% for Bladder-Epicheck® and 93.1% for Urovysion®FISH.Bladder-Epicheck® and Urovysion®FISH along with cytology could be a helpful ancillary method in the diagnosis and follow-up of UTUC while due to its low specificity Xpert®-BC Detection seems to be of limited usefulness.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

The cancer spectrum and genetic pathways underlying tumorigenesis vary among different ethnic populations due to genetic background and/or environment discrepancies. We have implied in our previous study that the genetic alterations found in bladder cancers of Chinese patients differ from those of Caucasians. We performed the present study to explore the genetic pathways of the urothelial carcinoma (UC) in Chinese patients. We carried out a partial allelotyping of Chinese UC on chromosome arms commonly deleted in Caucasian UC, and compared the allelo-typing between Chinese and Caucasian UC. Forty-five Chinese UC specimens were allelotyped using 30 microsatellite markers on 18 chromosome arms. The most frequent regions of loss of heterozygosity found included 9q (54.1%), 17p (51.2%), 9p (48.8%), 18q (42.2%), 3p (41.9%), 16q (33.5%) and 11p (30.0%). Compared with UC from the UK and US, the LOH frequencies on most chromosome arms in this study are higher, with statistically significant differences on 3p, 16q and 18q. Our results suggest that both consensus and different alterations exist between Chinese and Caucasian UC, indicating that genetic alterations of cancer can vary between different ethnic populations due to genetic and/or etiological discrepancies.

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.

We prospectively evaluated the utility of UroVysion in urothelial carcinomas of the upper urinary tract (UCUUTs).Ninety patients who received nephroureterectomy for UCUUT were enrolled. We performed urinary cytology and UroVysion before nephroureterectomy. We also performed the assays on 23 volunteers without a history of urothelial carcinoma.Seventy-five high-grade urothelial carcinomas (HGUCs), 10 low-grade urothelial carcinomas, and five other conditions were enrolled. Sensitivity, specificity, positive predictive value, and negative predictive value for HGUC detection by urinary cytology were 28.0%, 100.0%, 100.0%, and 31.6%, respectively; for detection by fluorescence in situ hybridization, these values were 60.0%, 84.0%, 93.8%, and 41.2%, respectively. UroVysion detected the only deletion of 9p21 in eight of 23 samples negative for HGUC by urinary cytology and in three of 23 volunteers.Combining urinary cytology and UroVysion can improve the diagnostic accuracy of UCUUT. Caution is advised in diagnosing UCUUT based only on deletion of 9p21.© American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The sensitivity of cytology for the detection of urothelial carcinoma (UC) is limited. Newer methods such as fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and protein markers have been developed to improve urine-based detection of UC. As only little is known regarding the combined application of these markers, we investigated whether combinations of 4 of the most broadly available tests (cytology, FISH, uCyt+, and nuclear matrix protein 22 [NMP22-ELISA]) may improve their diagnostic performance.The study was comprised of 808 patients who were suspected of having UC. All patients underwent urethrocystoscopy and upper urinary tract imaging and, in the case of positive findings, transurethral resection/biopsy. FISH, uCyt+, cytology, and NMP22-ELISA were performed in all patients.UC was diagnosed in 115 patients (14.2%). Cytology and FISH were found to be the single tests with the best overall performance (area under the curve [AUC], 0.78/0.79). Combinations of 2, 3, and 4 markers were found to increase the AUC to various extents compared with the use of single markers. Combining cytology and FISH improved the sensitivity and performance (AUC, 0.83) compared with the single tests and identified 12 tumors that were not detected by cytology alone. The percentage of WHO grade 3/carcinoma in situ tumors not detected by cytology was reduced by 62.5% when FISH was performed in cytology-negative patients. The addition of uCyt+ as a third test further improved performance (AUC, 0.86), whereas the addition of NMP22-ELISA was not found to have any additional influence on the performance of the test combination.The results of the current study support the combined use of urine markers and may form the basis of further studies investigating whether risk stratification based on urine marker combinations may individualize diagnostic algorithms and the surveillance of patients suspected of having UC.Copyright © 2012 American Cancer Society.

Urothelial carcinoma of the bladder comprises two long-recognized disease entities with distinct molecular features and clinical outcome. Low-grade non-muscle-invasive tumours recur frequently but rarely progress to muscle invasion, whereas muscle-invasive tumours are usually diagnosed de novo and frequently metastasize. Recent genome-wide expression and sequencing studies identify genes and pathways that are key drivers of urothelial cancer and reveal a more complex picture with multiple molecular subclasses that traverse conventional grade and stage groupings. This improved understanding of molecular features, disease pathogenesis and heterogeneity provides new opportunities for prognostic application, disease monitoring and personalized therapy.

The European Association of Urology guideline for upper tract urothelial carcinoma (UTUC) relies on two grading system: 1973 World Health Organization (WHO) and 2004/2016 WHO. No consensus has been made which classification should supersede the other and both are recommended in clinical practice. We hypothesized that one may be superior to the other.Newly diagnosed non-metastatic UTUC patients treated with radical nephroureterectomy were abstracted from the Surveillance, Epidemiology, and End Results database (2010-2016). Kaplan-Meier plots and multivariable Cox regression models (CRMs) tested cancer-specific mortality (CSM), according to 1973 WHO (G vs. G vs. G) or to 2004/2016 WHO (low-grade vs. high-grade) grading systems. Haegerty's C-index quantified accuracy.Of 4271 patients, according to 1973 WHO grading system, 134 (3.1%) were G, 436 (10.2%) were G and 3701 (86.7%) were G; while according to 2004/2016 WHO grading system, 508 (11.9%) were low grade vs 3763 (88.1%) high grade. In multivariable CRMs, high grade predicted higher CSM (Hazard ratio: 1.70, p < 0.001). Conversely, neither G (p = 0.8) nor G (p = 0.1) were independent predictors of worse survival. The multivariable models without consideration of either grading system were 74% accurate in predicting 5-year CSM. Accuracy increased to 76% after either addition of the 1973 WHO or 2004/2016 WHO grade.From a statistical standpoint, either 1973 WHO or 2004/2016 WHO grading system improves the accuracy of CSM prediction to the same extent. In consequence, other considerations such as intra- and interobserver variability may represent additional metrics to consider in deciding which grading system is better.

The multitarget fluorescence in situ hybridization probe set Vysis UroVysion, consisting of probes for chromosomes 3, 7, and 17 and for the 9p21 band, was studied to evaluate its value in the follow-up of patients with bladder cancer. The results were compared with conventional cytology and quantitative cytology (Quanticyt). The aim of this study was to evaluate whether UroVysion is a better adjunct to urethrocystoscopy than cytology and quantitative cytology.UroVysion, cytology, and quantitative cytology were performed on 113 voided urinary samples of 105 patients under surveillance for non-muscle-invasive bladder cancer. Before urethrocystoscopy or transurethral resection of the bladder, a voided urinary sample was obtained. Results of all tests were compared to evaluate the value of UroVysion.Sixty-four patients had biopsy-proven urothelial cell carcinoma. Sensitivity and specificity were, respectively, 39.1% and 89.7% for UroVysion, 40.6% and 89.7% for cytology, and 42.1% and 67.9% for quantitative cytology. When the UroVysion test and cytology were combined, sensitivity increased to 53.1%, but specificity decreased to 79.5%. Detection of Ta tumours was equal for cytology and UroVysion (26.7%), detection of T1 and T2-T4 samples by UroVysion was 60% and 50%, respectively. Detection of grade 1, 2, and 3 tumours by UroVysion was 21.4%, 36.8%, and 66.7%, respectively. In four cases the UroVysion test was positive, but no abnormalities were seen at cystoscopy.Our data suggest that the use of UroVysion provides no improvement over cytology or quantitative cytology in the diagnosis of recurrent non-muscle-invasive bladder tumours.

The number of patients with urothelial carcinoma (UC) is high, with a corresponding demand for detecting UC easily and non-invasively. Cystoscopy and urine cytology, with widely known diagnostic accuracies, are the gold standards for identifying UC originating from the bladder. However, cystoscopy or other tests, such as ureteroscopy or retrograde pyelography, are uncomfortable for patients. Tests for urinary biomarkers are expected to satisfy the demand for less invasive tests that will benefit patients with anxiety for invasive tests such as cystoscopy or ureteroscopy. Although several urinary biomarkers have been reported to support the diagnosis or follow-up of UC, their use in the clinic is uncommon. The UroVysion test examines urinary biomarkers using a multitarget, multicolor fluorescence in situ hybridization (FISH) assay. The test uses exfoliated cells found in urine and is a mixture of centromeric fluorescent denatured chromosome enumeration probes for chromosomes 3, 7, and 17 (labelled stratum red, spectrum green and spectrum aqua, respectively), and a locus-specific identifier probe for 9p21 (spectrum gold). It is used for the initial diagnosis of patients with hematuria or the monitoring of patients previously diagnosed with bladder cancer. Almost 20 years have passed since UroVysion was approved by the U.S. Food and Drug Administration, and so this is a well-established test. However, room exists for further research, with numerous reports on this test having been recently published. In order to update our knowledge, we herein present a brief overview of UroVysion and its features that follows the latest findings as they relate to UC.2021 Translational Andrology and Urology. All rights reserved.

We determine the sensitivity and specificity of various assays for the detection of urothelial carcinoma.A total of 280 voided urine specimens from 265 patients were obtained immediately before cystoscopy for BTA stat, (Bard Diagnostic, Redmond, Washington) hemoglobin dipstick, (Bayer, Elkhart, Indiana) telomerase and UroVysion (Vysis, a wholly owned subsidiary of Abbott Laboratories, Abbott Park, Illinois) analysis.Of the 265 patients 75 had biopsy proven urothelial carcinoma, and the sensitivity of the assays was determined from these patients. From most sensitive to least sensitive, the overall sensitivity of UroVysion (73 cases), BTA stat (72), hemoglobin dipstick (73) and telomerase (70) was 81%, 78%, 74%, and 46%, respectively. Each of the first 3 tests was statistically significantly more sensitive than the telomerase assay (p <0.05). However, the differences in overall sensitivity of UroVysion, BTA stat and hemoglobin dipstick were not statistically significant. The specificity of the tests was calculated for 80 of the 265 patients in this study who had no history of urothelial carcinoma and negative cystoscopy findings despite common urological complaints. From most specific to least specific, the specificity of UroVysion, telomerase, BTA stat and hemoglobin dipstick was 96%, 91%, 74% and 51%, respectively. UroVysion and telomerase were statistically significantly (p <0.01) more specific than the BTA stat and hemoglobin dipstick assays, and all of the assays were more specific than hemoglobin dipstick testing (p <0.001).Our study reveals that UroVysion is the most sensitive and specific assay among those tested for the detection of urothelial carcinoma. Telomerase testing had good specificity but poor sensitivity. The BTA stat and hemoglobin dipstick tests had good sensitivity but relatively poor specificity. UroVysion is a promising new assay for the detection of urothelial carcinoma in urine specimens. However, further studies are needed to explore the role of the various assays in the treatment of patients with superficial urothelial carcinoma.

The urine fluorescence in situ hybridization (FISH) assay (UroVysion™), with the current scoring criteria, has a higher sensitivity than routine cytopathology but a lower specificity. Among 215 urine FISH tests we performed, 45 had associated histopathology and clinical follow up. In this study, a cell with four signals for each probe was classified as a uniform tetraploid cell (UTC); a presumed reparative cell which is currently classified as an abnormal cell in the FDA approved assay. By using the existing criteria, the tests were scored as positive or negative before and after exclusion of the UTCs. Before the exclusion, 24 positive, 13 negative, seven false positive, and one false negative result were obtained with 96% sensitivity and 65% specificity. After the exclusion, the results changed to 22 positive, 19 negative, one false positive, and three false negatives resulting in a 88% sensitivity of 88% and a 95% specificity; a significant improvement in the specificity. We conclude that exclusion of the UTCs as abnormal cells would result in a more solid performance of the FISH assay.Copyright © 2011 Wiley Periodicals, Inc.

Fluorescence in situ hybridization (FISH) is routinely used to help clarify atypical urinary cytology. However, to the authors' knowledge, little is known regarding the frequency of chromosomal aberrations in non-neoplastic conditions that could potentially lead to false-positive FISH results. The objective of the current study was to evaluate the frequency of chromosomal aberrations in benign cells of the urinary tract using the UroVysion FISH test.The authors analyzed 77 Papanicolaou-stained benign urine cytology specimens with reactive epithelial atypia using a FISH assay detecting the chromosomes 3, 7, and 17 and the gene locus 9p21. A positive test result was defined as an increased copy number of at least 2 chromosomes in ≥ 4 of 25 cells, or > 10 cells with a tetraploid or octaploid pattern, or homozygous or heterozygous deletion of 9p21 (≥ 12cells).FISH was positive in 27 of 77 bladder washings (35.1%) including 25 of 65 bladder washings (40.5%) and 2 of 15 voided urines (13.5%) from patients with irritative bladder (15 of 36 patients), a history of radiotherapy (7 of 12 patients), nonspecific cystitis (3 of 11 patients), hematuria (3 of 8 patients), and lithiasis (1 of 4 patients). In 7 of 27 FISH-positive urothelial specimens, the positivity was solely due a polyploid pattern (tetraploid/octaploid pattern) in > 10 of the cells.Chromosomal aberrations can occur in reactive urothelial cells, with a tetraploid pattern being the most common. Even an aneuploid pattern of FISH signals does not always prove malignancy because it rarely occurs in reactive urothelial cells. Correlation of FISH results with cytomorphology and patient history is crucial to avoid false-positive diagnoses.Copyright © 2011 American Cancer Society.