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PURPOSE: Currently, markers are lacking that can identify patients with high risk nonmuscle invasive bladder cancer who will fail bacillus Calmette-Guérin treatment. Therefore, we evaluated the prognostic value of T1 substaging in patients with primary high risk nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Patients with primary high risk nonmuscle invasive bladder cancer who received ≥5 bacillus Calmette-Guérin induction instillations were included. All tumors were centrally reviewed, which included T1 substaging (microinvasion vs extensive invasion of the lamina propria). T1 patients were stratified into high risk or highest risk subgroups according to major urology guidelines. Primary end point was bacillus Calmette-Guérin failure, defined as development of a high grade recurrence. Secondary end points were high grade recurrence-free survival, defined as time from primary diagnosis to biopsy-proven high grade recurrence and progression-free survival. Time-to-event analyses were used to predict survival. RESULTS: A total of 264 patients with high risk nonmuscle invasive bladder cancer had tumor invasion of the lamina propria, of which 73% were classified as extensive invasion and 27% as microinvasion. Median followup was 68 months (IQR 43-98) and bacillus Calmette-Guérin failure was more common among patients with extensive vs microinvasive tumors (41% vs 21%, p=0.002). The 3-year high grade recurrence-free survival (defined as bacillus Calmette-Guerin failure) for patients with extensive vs microinvasive tumors was 64% vs 83% (p=0.004). In multivariate analysis, T1 substaging was an independent predictor of high grade recurrence-free survival (HR 3.2, p=0.005) and progression-free survival (HR 3.0, p=0.009). Patients with highest risk/microinvasive disease have an improved progression-free survival as compared to highest risk/T1e disease (p.adj=0.038). CONCLUSIONS: T1 substaging provides important prognostic information on patients with primary high risk nonmuscle invasive bladder cancer treated with bacillus Calmette-Guérin. The risk of bacillus Calmette-Guérin failure is higher in extensive vs microinvasive tumors. Substaging of T1 high risk nonmuscle invasive bladder cancer has the potential to guide treatment decisions on bacillus Calmette-Guérin vs alternative strategies at diagnosis.

This cross-sectional study examines atezolizumab as a second-line treatment for malignant urothelial carcinoma, which received accelerated US Food and Drug Administration approval, although the manufacturer’s confirmatory trial did not identify benefits.

Tumors of the upper urinary tract are discovered, either by clinical symptomatology or as part of the evaluation of a bladder tumor. Hypercalcemia is one of the most common paraneoplastic syndromes and an exceptional complication of urothelial carcinoma of the upper tract. Several physiopathological mechanisms have been proposed to explain this rare and serious complication. Hypercalcemia is often correlated with tumors with a poor prognosis.

The administration of antimicrobial prophylaxis for postoperative urinary tract infections following transurethral resection of bladder tumors is controversial. We aimed to systematically review evidence on the potential effect of antimicrobial prophylaxis on postoperative urinary tract infections and asymptomatic bacteriuria.We conducted a systematic search in Embase®, Medline® and the Cochrane Central Register of Controlled Trials. Randomized controlled trials and nonrandomized controlled trials assessing the effect of any form of antimicrobial prophylaxis in patients with transurethral resection of bladder tumors on postoperative urinary tract infections or asymptomatic bacteriuria were included. Risk of bias was assessed using RoB 2.0 or the Newcastle-Ottawa Scale. Fixed and random effects meta-analyses were conducted. As a potential basis for a scoping review, we exploratorily searched Medline for risk factors for urinary tract infections after transurethral resection of bladder tumors. The protocol was registered on PROSPERO (CRD42019131733).Of 986 screened publications, 7 studies with 1,725 participants were included; the reported effect sizes varied considerably. We found no significant effect of antimicrobial prophylaxis on urinary tract infections: the pooled odds ratio of the random effects model was 1.55 (95% CI 0.73-3.31). The random effects meta-analysis examining the effect of antimicrobial prophylaxis on asymptomatic bacteriuria showed an OR of 0.43 (0.18-1.04). Risk of bias was moderate. Our exploratory search identified 3 studies reporting age, preoperative pelvic radiation, preoperative hospital stay, duration of operation, tumor size, preoperative asymptomatic bacteriuria and pyuria as risk factors for urinary tract infections following transurethral resection of bladder tumors.We observed insufficient evidence supporting routine antimicrobial prophylaxis in patients undergoing transurethral resection of bladder tumors for the prevention of postoperative urinary tract infections; our findings may inform harmonization of international guidelines.

We reviewed the oncologic and surgical outcomes of endoscopic treatments for low grade upper tract urothelial carcinoma, and assessed the prognostic significance of tumor size, location and multifocality.We retrospectively reviewed all patients who underwent endoscopic treatment for low grade upper tract urothelial carcinoma at our institution between 2014 and 2019. Tumors were treated with a dual laser generator, which alternately produces holmium and neodymium lasers. A stringent ureteroscopic followup protocol was conducted. We looked for an association between outcome and tumor size, location or multifocality, and for predictive factors for time to local recurrence and progression.The cohort included 59 patients (62 renal units), 27% of tumors were multifocal and 40% were2 cm. The median followup time was 22 months (IQR 11-41), and the median number of ureteroscopies was 5.5 (4-9). Local recurrence was observed in 46 renal units (74.1%) at a median of 6.5 months after initial surgery. Four patients (6.4%) developed disease progression and were referred for radical surgery: 2 had pathological progression and 2 had a rapid and high volume local recurrence, and 1 later developed metastatic disease. The progression-free rate was 93.2%. Tumor location in kidney (p=0.03, HR 1.95) and multifocality (p=0.005, HR 3.25) significantly predicted time to local recurrence. No factor predicted time to progression.Ureteroscopic treatment of large, multifocal, low grade upper tract urothelial carcinoma is feasible, does not involve significant complications and has good short-term oncologic outcomes, with a 93.2% progression-free survival rate. Tumors located in the kidney and multifocality yielded shorter time to local recurrence but not progression.

Uruguay is the south American country which has the highest cancer incidence and mortality rates. The National Cancer Registry collects data on cancer cases nationwide since 1989 and has reached high quality standards in the last decades. This is the first report on incidence trends.Data from the National Cancer Registry of all new cases of invasive cancer from twelve sites diagnosed in 2002-2015 was analyzed. Age-standardized rates were calculated. Trends of incidence rates were analyzed using joinpoint regression models.For both, men and women, incidence rates trends for all cancer sites, colo-rectal and bladder cancer remained stable. Esophageal and gastric cancers descended while thyroid and kidney cancer incidence increased. In men lung cancer decreased; testicular cancer increased, and prostate cancer increased at the beginning of the period and decreased in the final years. In women, lung cancer increased, breast cancer remained stable and cervical cancer presented a significant decline from 2005 to 2010 and reached a plateau since then.Cancer incidence dynamics are complex and affected not only by Public Health policies such as tobacco control, vaccination and screening programs, but also by environmental and life style changes and the attitude of the medical community towards the application of diagnostic and therapeutic tools. The aim of this paper is to analyze cancer incidence time trends in the country and provide possible explanations to them.Uruguay es el país de Sudamerica que tiene las mayores tasas de incidencia y mortalidad por cáncer. El Registro Nacional de Cáncer recoge los datos de cáncer de todo el país desde 1989 y en las últimas décadas ha alcanzado los más altos estándares de calidad. Este es el primer reporte de tendencias de incidencia de cáncer de Uruguay.Se analizaron los datos de todos los casos de cáncer invasivo diagnosticados entre 2002 y 2015 incluidos en el Registro Nacional de Cáncer y los de once topografías en particular. Se calcularon las tasas de incidencia estandarizada y se analizaron las tendencias utilizando los modelos de regresión de Joinpoint.Las tasas de incidencia de cáncer colorrectal, vejiga y todos los sitios reunidos se mantuvieron estables tanto en hombres como en mujeres. La tasa de incidencia de cáncer de estómago y esófago disminuyeron mientras que las de tiroides y riñón aumentaron. En los hombres, el cáncer de pulmón disminuyó, el cáncer de testículo aumentó y el de próstata aumentó en un lapso inicial y decreció en los últimos años. En las mujeres el cáncer de pulmón aumentó y el de mama se mantuvo estable mientras que el cáncer de cérvix presentó un descenso significativo entre 2005 y 2010 alcanzando una meseta desde entonces.La dinámica de la incidencia de cáncer es compleja y está afectada no sólo por las políticas de Salud Pública como las campañas de control de tabaco, vacunación y programas de tamizaje sino por los cambios ambientales y de los estilos de vida y la actitud de los médicos respecto a la aplicación de técnicas diagnósticas y terapéuticas. En este trabajo se analizan las tendencias de incidencia en el país y se plantean posibles explicaciones para los cambios.

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The diagnosis of upper tract urothelial carcinoma (UTUC) can be a challenging diagnostic pursuit. To date, there is no large-scale study assessing the statistical utility (eg, sensitivity and specificity) of selective cytology. Herein, we systematically reviewed and meta-analyzed the published literature to evaluate the efficacy of selective cytology for the detection of UTUC in patients with a suspicious clinical profile Selective cytology confers a high specificity but marginal sensitivity for the detection of UTUC. The sensitivity is greater for high-grade UTUC lesions. The statistical assessment of its utility is limited by the heterogeneity and bias of previous studies.

Objectives: We assessed the performance of urine cytology using the Paris System for Reporting Urine Cytology (PSRUC) in comparison to our current system. Methods: In total, 124 specimens with histologic correlation were reviewed and assigned to the PSRUC categories: benign, atypical urothelial cells (AUCs), suspicious for high-grade urothelial carcinoma (SHGUC), and high-grade urothelial carcinoma (HGUC). Original cytological diagnoses were recorded. Results: Fewer cases were given an AUC diagnosis using the PSRUC in comparison to the original diagnoses (26% vs 39%), while the association of AUCs with subsequent HGUC increased from 33% to 53% with the PSRUC. Using the PSRUC resulted in a higher number of low-grade carcinomas assigned to the benign (40%) rather than the AUC (22%) category. The performance of SHGUC/HGUC diagnoses was similar in both systems (predictive value = 94%). Conclusions: The PSRUC seems to improve the performance of urine cytology by limiting the AUC category to cases that are more strongly associated with HGUC.

The most important criterion for optimal cancer treatment is a correct classification of the tumour. During the last three years, several very important progresses have been made with a better definition of urothelial carcinoma (UC), especially from a molecular point of view. We start having a global understanding of UC, although many details are still not completely understood.

Introduction: Because the reports in the literature of radiologic investigations for upper tract urothelial cancer (UTUC) are limited by the number of patients, and included patients with different pathologies, we aimed to study the overall accuracy of computed tomography (CT) in the diagnosis of UTUC and their accuracy on predicting tumor location. Methods: A retrospective review from 1990 to 2017 included patients who were treated for UTUC. Unenhanced CT scan was obtained first using Multi-Detector Computed Tomography (MDCT, Philips Medical Systems), then nonionic contrast medium, containing 350 mg iodine /ml was injected at 4 mL/s. Analysis was performed using SPSS®. Results: Of 275 patients, complete data on CT was available on 270 (98%) patients. CT reported only two false positive and six false negative results and the overall accuracy was 96-97%. In comparison to the final pathological reports, CT /CTU detected 85% of the tumor location of in the renal pelvic and 50% of the calyceal tumors. In ureteric tumors, they detected distal (66/71= 93%) more than proximal ureteric tumors (60%). Conclusion: In our cohort, CT/ CTU has a high overall accuracy (97%) in diagnosing UTUC, capability to well visualize tumors of distal ureter and renal pelvis, but could miss calyceal tumors. The matter to rely only on CT without ureteroscopic biopsy in the diagnosis of UTUC especially if radical surgery is planned needs further prospective studies.

Introduction/Objective The anaplastic lymphoma kinase (ALK) gene is a receptor tyrosine kinase gene located in the 2p23.2 region. Normally, dimerization of ALK receptor by binding to its ligand activates the ALK receptor by autophosphorylation of c-termius and activates downstream PI3K, MAPK and JAK3 pathways. The ALK gene is abnormally hyperactivated by fusion of the 3’ half containing the kinase domain with 5’ portion of other genes, resulting in the ligand independent dimerization and activation of the ALK receptor. The tumors harboring these translocations are termed as ALK-positive tumors and can be treated with ALK inhibitors. Methods We analyzed the status of clinically relevant ALK fusion driver mutations in 230 different cancer studies, containing tumors from 79222 different individuals, in The Cancer Genome Atlas database (TCGA) using the cbioportal web browser. Results We observed that, as expected ALK-positive mutations are predominantly present in NSCLC, with EML4- ALK being the most common. In addition, we were able to identify ALK positive mutations in colorectal carcinomas, papillary thyroid carcinomas, papillary renal cell carcinomas, sarcomas and invasive ductal carcinomas of the breast. Most important, our analysis identified extremely rare ALK positive cases in salivary duct carcinomas, urothelial carcinomas, cutaneous melanomas and prostatic adenocarcinomas. Conclusion Our analysis identified ALK positive cases were predominant in adenocarcinoma of lung with EML4-ALK being the most common ALK positive mutation, which is also consistent with the literature. However, the ALK positive mutations were at a lower prevalence rate than that described in the literature. We attribute the lower prevalence rate to underrepresentation of the Asian population in the TCGA database. In addition, we identified extremely rare ALK positive cases in salivary duct carcinomas, melanomas and prostate cancers, thus highlighting the need for testing for these mutations in these cancers.

Introduction/Objective The major limitation of urine cytology is the lack of consensus regarding the terminology and diagnostic criteria that should be used for urothelial atypia. The main goal of the newly proposed Paris System for Reporting Urine Cytology is to concentrate primarily on the detection of high grade urothelial carcinoma while minimizing the detection of low grade lesions. This study aimed to apply the criteria and categories of the Paris system in retrospectively collected urine cytology specimens and assess histologic correlation and reproducibility. Methods Two senior pathologists independently reviewed retrospectively collected urine cytology specimens strictly following the Paris system criteria for categorization. Cytologic diagnosis were compared with previous cytology result and histologic diagnosis. Results A total of 67 patients were included in the study. The mean age is 65.8 years (36-89 years), majority were males (73.1%) and African American (89.6%). Urine cytology using traditional method showed mostly atypical results (58.2%), followed by reactive (26.9%), high-grade urothelial carcinoma (11.9%) and suspicious (3.0%). On the other hand, the Paris system had more negative results (62.7%), followed by atypical (19.4%), high-grade urothelial carcinoma (11.9%) and lastly suspicious (6.0%). All of negative cases (18 out of 18) and majority of HGUC cases (7 out of 8) were concordant between the two cytology methods. Traditional urine cytology method only yielded 71.4% histologic concordance, while 100% Paris system results were concordant with bladder histology. Majority of the atypical cases using traditional method were converted to negative, and a few atypical cases were converted to suspicious and high-grade. All results using Paris system were concordant between two general pathologists. Conclusion Using the Paris system in analyzing urine cytology resulted to higher cytohistologic concordance than traditional method. Majority of atypical cases from traditional method were converted to more definitive categories. The cytopathologic analyses from two general pathologists applying the criteria of Paris system had superior reproducibility. Applying the Paris system, therefore, can significantly improve the performance of urine cytopathology.

This cohort study assesses for temporal selection bias in patients with lung, breast, colorectal, pancreatic, or urothelial cancer from a single institution who had tumor profiling using a next-generation sequencing protocol between 2013 and 2017.

Despite a similar histologic appearance, upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) tumors have distinct epidemiologic and clinicopathologic differences.To investigate whether the differences between UTUC and UCB result from intrinsic biological diversity.Tumor and germline DNA from patients with UTUC (n=83) and UCB (n=102) were analyzed using a custom next-generation sequencing assay to identify somatic mutations and copy number alterations in 300 cancer-associated genes.We described co-mutation patterns and copy number alterations in UTUC. We also compared mutation frequencies in high-grade UTUC (n=59) and high-grade UCB (n=102).Comparison of high-grade UTUC and UCB revealed significant differences in the prevalence of somatic alterations. Genes altered more commonly in high-grade UTUC included FGFR3 (35.6% vs 21.6%; p=0.065), HRAS (13.6% vs 1.0%; p=0.001), and CDKN2B (15.3% vs 3.9%; p=0.016). Genes less frequently mutated in high-grade UTUC included TP53 (25.4% vs 57.8%; p0.001), RB1 (0.0% vs 18.6%; p0.001), and ARID1A (13.6% vs 27.5%; p=0.050). Because our assay was restricted to genomic alterations in a targeted panel, rare mutations and epigenetic changes were not analyzed.High-grade UTUC tumors display a spectrum of genetic alterations similar to high-grade UCB. However, there were significant differences in the prevalence of several recurrently mutated genes including HRAS, TP53, and RB1. As relevant targeted inhibitors are being developed and tested, these results may have important implications for the site-specific management of patients with urothelial carcinoma.Comparison of next-generation sequencing of upper tract urothelial carcinoma (UTUC) with urothelial bladder cancer identified that similar mutations were present in both cancer types but at different frequencies, indicating a potential need for unique management strategies. UTUC tumors were found to have a high rate of mutations that could be targeted with novel therapies.

Resume Introduction La collision tumorale est la rencontre de deux tumeurs provenant de deux sites topographiques distincts. Les cas de collisions metastatiques ganglionnaires sont exceptionnels. Nous rapportons le cas d’une collision metastatique ganglionnaire d’un carcinome urothelial et d’un adenocarcinome prostatique. Observation Un homme de 61 ans etait hospitalise pour une nephro-ureterectomie droite avec curage peri-ureteral. Il etait suivi depuis 2004 pour un adenocarcinome prostatique et traite par prostatectomie radicale puis radiotherapie 4 ans plus tard du fait d’une reascension du PSA. Dans le cadre du suivi, un carcinome urothelial du bas uretere a ete decouvert en 2014. L’analyse anatomopathologique du curage ganglionnaire montrait, dans un ganglion, une double metastase d’origine urotheliale et prostatique de type acinaire et ductal. L’etude immuno-histochimique incluant les anticorps CK7, CK20, PSA, GATA3, P63 a confirme le phenotype distinct des 2 proliferations tumorales. Discussion La collision metastatique d’un carcinome urothelial et d’un adenocarcinome prostatique a ete rapportee dans 4 cas seulement. Notre revue de la litterature montre que l’adenocarcinome prostatique precede toujours le carcinome urothelial. L’etude immuno-histochimique, lorsqu’elle est realisee, repose sur les CK7, CK20 et PSA. Elle peut etre completee dans un second temps par le GATA3, le recepteur aux androgenes et la P63.

The aim of this multicenter study was to investigate the prognostic impact of residual T1 high-grade (HG)/G3 tumors at re-transurethral resection (TUR of bladder tumor) in a large multi-institutional cohort of patients with primary T1 HG/G3 bladder cancer (BC)., M.D.V is supported by the Scholarship Foundation of the Republic of Austria - OeAD and by the EUSP Scholarship - EAU., info:eu-repo/semantics/publishedVersion

Resume Objectif Proposer un etat-de-l’art des connaissances concernant les modalites cliniques, ureteroscopiques et photodynamiques pour le diagnostic des tumeurs de la voie excretrice superieure (TVES). Materiel et methode Une recherche bibliographique a ete conduite a partir de la base de donnees bibliographiques Medline (NLM outil Pubmed) a partir des mots cles suivants : carcinome urothelial ; voie excretrice urinaire ; uretere ; bassinet ; diagnostic ; fluorescence ; ureteroscopie ; technique photodynamique ; biopsie ; cytologie. Resultats L’hematurie macroscopique et les douleurs lombaires sont les deux principaux symptomes revelateurs d’une TVES en pratique clinique quotidienne. La cytologie urinaire et la cystoscopie sont necessaires pour eliminer une tumeur de la vessie concomittante synchrone. L’ureteroscopie souple a revolutionne le diagnostic des TVES en permettant une exploration exhaustive des voies excretrices, une visualisation endoscopique de la lesion et des biopsies pour determiner le grade. L’ureteroscopie souple doit etre faite dans le bilan diagnostique chaque fois qu’un traitement conservateur est envisage par la suite. Les nouvelles technologies d’investigation comme la fluorescence, le narrow band imaging et la tomographie optique de coherence (OCT) ± couplee a l’endo-echographie sont des voies d’exploration particulierement prometteuse pour l’avenir. Conclusion Le bilan diagnostique d’une TVES ne doit pas faire oublier qu’il s’agit d’un carcinome urothelial et que l’arbre urinaire doit etre explore dans son ensemble pour eliminer une autre tumeur. L’ureteroscopie souple a revolutionne la prise en charge diagnostique de ces lesions et fait desormais partie du bilan initial.

BACKGROUND Prior studies examining the value of lymph node (LN) dissection (LND) in patients with urothelial carcinoma of the upper urinary tract (UTUC) have produced conflicting results. The objective of the current study was to assess the relationship between LN yield and survival among patients undergoing radical nephroureterectomy (RNU). METHODS The National Cancer Data Base was used to identify patients with non-metastatic UTUC who were treated with RNU between 2004 and 2012. The association between LN yield and overall survival (OS) was assessed using Cox proportional hazards regression, with adjustment for patient, tumor, and facility characteristics. RESULTS Of the 14,472 patients, 2926 (20%) underwent LND. The median yield was 2 LNs (interquartile range 1-6 LNs). Among the entire cohort and the LN-negative (pN0) subgroup, a higher LN yield was associated with lower all-cause mortality (multivariable hazard ratio [HR] 0.94 per 5 LNs removed, 95% confidence interval [95% CI] 0.89-1.00 [P = .034] for the entire cohort and HR 0.86, 95% CI 0.79-0.94 [P = .001] for the pN0 subgroup). Among patients with positive LNs (pN+), there was no association noted between LN yield and OS; however, positive and negative LN counts were found to be independent predictors of OS (HR 1.27 per 5 positive LNs, 95% CI 1.16-1.39 [P

Purpose This review will summarize the literature relating urothelial carcinoma with squamous differentiation and its response to chemotherapy or radiation therapy. Methods The English literature in PubMED was extensively search for articles pertaining to urothelial carcinoma with squamous differentiation and its response to chemotherapy or radiation. Articles reference lists were then further scrutinized to ensure all relevant literature had been identified. Results Urothelial carcinoma with squamous differentiation is generally treated as if it were pure urothelial carcinoma. However, it remains unclear if such mixed histology portends a different prognosis for patients with bladder cancer, particularly regarding the response to chemotherapy and radiation. Initial studies suggested a worse response to such therapy in mixed histology but more recent data has challenged that observation. Unfortunately the literature is limited by the type and quality of the existent studies and mixed results among the data that is available. Conclusion The final word on whether urothelial carcinoma with squamous differentiation responds differently to chemotherapy or radiation therapy remains uncertain. This important question warrants careful study in the future.