Diagnosis Of Urothelial Carcinoma Research Articles

Immunohistochemical evaluation of SOX-10 in patients with urinary bladder cancer.

Aim: To evaluate the expression levels of SOX-10 in tissues of bladder tumor and to prove the correlation between SOX-10 expression and clinicopathological characteristics of bladder tumors, including patient age, sex, tumor grade, and muscle invasion. Materials and Methods: Forty formalin fixed paraffin embedded FFPE tissue blocks gathered by transurethral resection of bladder tumor are collected from teaching hospitals at Al-Najaf governorate. Those blocks were stained by hematoxylin and eosin. The histopathological characteristics were examined and immunostained by SOX10. Results: An assessment of the expression of SOX-10 in urothelial carcinoma showed that the SOX-10 test was positive in five samples of urothelial carcinoma, while the SOX-10 test was negative in thirty-five samples. The correlation of SOX-10 with other variables (age, sex, and grade) was statistically non-significant. Conclusions: SOX-10 is an immunohistochemical sensitive marker for the diagnosis of urothelial carcinoma. SOX-10 expression appeared to be non-significant relation with age, gender and histopathological parameters and its expression has been showed to be lost or decreased in substantial proportion in relation to urothelial carcinoma. This variation or down regulation of SOX-10 is correlated with higher tumor grade and stage.

Clinical, Pathological Characteristics and Progression of Urothelial Bladder Cancer in Young Adult Patients. Our Experience and Literature Review.

Bladder cancer is highly prevalent even though its incidence is considerably lower in patients younger than 40 years, thus raising the issue of the influence of age at diagnosis on the natural history of this disease. This study aimed to evaluate the characteristics and progression of young patients with urothelial bladder carcinoma with at least 10 years of follow-up and to compare the results with those of previously reported studies. A retrospective study between 1990 and 2007 was conducted. The medical records and tissue samples of patients with urothelial bladder tumours were reviewed, and patients with a first diagnosis of urothelial carcinoma of the bladder at age 40 years or younger were selected. Their clinical and pathological data and disease-free survival were analysed. This study included 43 patients, with a median follow-up of 152 months (interquartile range (IQR): 96-222) and a mean age at diagnosis of 34 years (SD: 4.6). Thirty-five patients (81.4%) had non-muscle invasive tumours at diagnosis, and 53.5%, 27.9% and 18.6% had tumour grades of G1, G2 and G3, respectively. Fifteen patients (34.9%) experienced recurrence, and eight (18.6%) progressed. At 24 and 60 months, the recurrence-free survival rates were 84.8% (95% confidence interval (CI): 69.2%-92.9%) and 68.9% (95% CI: 51.7%-81%), respectively, and the progression-free survival rates were 94.9% (95% CI: 81%-98.7%) and 92.2% (95% CI: 77.8%-97.4%), respectively. Bladder cancer is an uncommon disease in young patients. In most cases, it consists of non-muscle-invasive tumours, with a low rate of recurrence and progression. The prognosis is based on the tumour's characteristics and not on the patient's age.

Changes in Urinary Exosomal Nuclear Matrix Protein-22 in Dogs With Urothelial Carcinoma: A Pilot Study.

Nuclear matrix protein-22 (NMP-22) is widely used in human medicine as a prognostic and diagnostic tool for urothelial carcinoma (UC). In addition, the use of urinary exosomes as a liquid biopsy tool is emerging for the diagnosis of certain types of cancer in human medicine. This study aimed to investigate the change in urinary exosomal NMP-22 for the diagnosis of UC in dogs. Among canine patients who visited the veterinary hospital, urine was collected from those whose owners provided consent. A total of 23 dogs (UC group, n=6; control group, n=17) were included in the analysis. After exosomes were isolated from the urine, NMP-22 was measured using enzyme-linked immunosorbent assay. In the UC group, the expression of NMP-22 in urinary exosomes was significantly higher than that in non-UC groups (p<0.0001). NMP-22 is significantly increased in exosomes in the urine of dogs diagnosed with UC, suggesting that urinary exosome NMP-22 can be considered as one of the liquid biopsy tools for diagnosing UC in dogs.

Incidental detection of FGFR3 fusion via liquid biopsy leading to earlier diagnosis of urothelial carcinoma

The rising utilization of circulating tumor DNA (ctDNA) assays in Precision Oncology may incidentally detect genetic material from secondary sources. It is important that such findings are recognized and properly leveraged for both diagnosis and monitoring of response to treatment. Here, we report a patient in whom serial cell-free DNA (cfDNA) monitoring for his known prostate adenocarcinoma uncovered the emergence of an unexpected FGFR3-TACC3 gene fusion, a BRCA1 frameshift mutation, and other molecular abnormalities. Due to the rarity of FGFR3 fusions in prostate cancer, a workup for a second primary cancer was performed, leading to the diagnosis of an otherwise-asymptomatic urothelial carcinoma (UC). Once UC-directed treatment was initiated, the presence of these genetic abnormalities in cfDNA allowed for disease monitoring and early detection of resistance, well before radiographic progression. These findings also uncovered opportunities for targeted therapies against FGFR and BRCA1. Overall, this report highlights the multifaceted utility of longitudinal ctDNA monitoring in early cancer diagnosis, disease prognostication, therapeutic target identification, monitoring of treatment response, and early detection of emergence of resistance.

Urinary tract cytology showing variant morphology and divergent differentiation.

Urothelial carcinoma represents a diverse group of tumours with distinct histologic subtypes, each exhibiting unique cytomorphologic features, architectural growth patterns, and/or well-developed aberrant differentiation. In fact, there are more than 13 subtypes of urothelial carcinoma recognized in the 2022 WHO classification of tumours in the urinary tract. The identification of these subtypes is crucial for an accurate diagnosis of urothelial carcinoma, and many have important clinical implications. Variant/divergent features may coexist with conventional high-grade urothelial carcinoma (HGUC) or present with 100% variant morphology. In urinary tract cytology (UTC), urothelial carcinoma can display divergent differentiation, such as squamous, glandular, or small cell carcinoma differentiation. The use of cell block preparations and immunohistochemistry with available residual urine can enhance diagnostic accuracy. On the other hand, identifying urothelial carcinoma variants, including nested, micropapillary, and plasmacytoid subtypes, poses significant challenges in UTC. Many cases of these variants are only detected retrospectively after variant histology has been established from resection specimens. Moreover, some variants exhibit features inconsistent with the diagnostic criteria for HGUC according to the Paris System for Reporting Urinary Tract Cytology. Nevertheless, the rarity of pure variant morphology and the occurrence of some false negatives for these variant cases are essential to maintain the specificity of UTC overall. This review covers the histology, cytomorphology, and important clinical aspects observed in urothelial carcinoma exhibiting divergent differentiation and various urothelial carcinoma variants detected in UTC.

Bladder Epicheck Test: A Novel Tool to Support Urothelial Carcinoma Diagnosis in Urine Samples.

Bladder cancer and upper urothelial tract carcinoma are common diseases with a high risk of recurrence, thus necessitating follow-up after initial treatment. The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection involves surveillance, intravesical therapy, and cytology with cystoscopy. Urinary cytology, cystoscopy, and radiological evaluation of the upper urinary tract are recommended during follow-up in the international urological guidelines. Cystoscopy is the standard examination for the first assessment and follow-up of NMIBC, and urine cytology is a widely used urinary test with high sensitivity for high-grade urothelial carcinoma (HGUC) and carcinoma in situ (CIS). In recent years, various urinary assays, including DNA methylation markers, have been used to detect bladder tumors. Among these, the Bladder EpiCheck test is one of the most widely used and is based on analysis of the methylation profile of urothelial cells to detect bladder neoplasms. This review assesses the importance of methylation analysis and the Bladder EpiCheck test as urinary biomarkers for diagnosing urothelial carcinomas in patients in follow-up for NMIBC, helping cytology and cystoscopy in doubtful cases. A combined approach of cytology and methylation analysis is suggested not only to diagnose HGUC, but also to predict clinical and histological recurrences.

Is a Single Nephrographic Phase Computed Tomography Sufficient for Detecting Urothelial Carcinoma in Patients with Visible Haematuria? A Prospective Paired Noninferiority Comparison

BackgroundThere is uncertainty about the utility of multiphase computed tomography (CT) compared with single-phase CT in the routine examination of patients with visible haematuria (VH). ObjectiveTo compare the accuracies of single nephrographic phase (NP) CT and four-phase CT in detecting urothelial carcinoma (UC). Design, setting, and participantsThis was a single-centre, prospective, paired, noninferiority study of patients with painless VH referred for CT before cystoscopy between September 2019 and June 2021. Patients were followed up for 1 yr to ascertain UC diagnosis. InterventionAll patients underwent four-phase CT (control), from which single NP CT (experimental) was extracted. Both were independently assessed for UC. Outcome measurements and statistical analysisThe primary outcome was the difference in accuracy between the control and experimental CT using a 7.5% noninferiority limit. Histologically verified UC defined a positive reference standard. Secondary outcomes included differences in sensitivity, specificity, negative (NPV) and positive (PPV) predictive values, and area under the curve (AUC). All results are reported per patient. Results and limitationsOf the 308 patients included, UC was diagnosed in 45 (14.6%). The difference in accuracy between the control and experimental CT was 1.9% (95% confidence interval −2.8 to 6.7), demonstrating noninferiority. Sensitivity was 93.3% versus 91.1%, specificity was 83.7% versus 81.8%, NPV was 98.7% versus 98.2%, PPV was 49.4% versus 46.1%, and AUC was 0.96 versus 0.94 for the control versus experimental CT. Limitations included a low number of UC cases and no definite criteria for selecting a noninferiority limit. ConclusionsThe accuracy of NP CT is not inferior to that of four-phase CT for detecting UC. Patient summaryThis study shows that a computed tomography (CT) examination with only one contrast phase is no worse than a more complex CT examination for detecting cancer in the urinary tract among patients presenting with visible blood in the urine.

Development and Multicenter Case-Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction.

Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk. This is a multicenter case-control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology. uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%. uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients.

Tumor cell-based glycolytic metabolism and single-cell sequencing of urinary exfoliated cells for the diagnosis and molecular profiling of urothelial carcinoma

Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.

MP14-04 ESTABLISHMENT OF BLOOD-BASED DIAGNOSTIC MARKERS OF UROTHELIAL CARCINOMA USING CHIRAL AMINO ACIDS

You have accessJournal of UrologyCME1 Apr 2023MP14-04 ESTABLISHMENT OF BLOOD-BASED DIAGNOSTIC MARKERS OF UROTHELIAL CARCINOMA USING CHIRAL AMINO ACIDS Atsunari Kawashima, Akinaru Yamamoto, Sassi Nesrine, Toshihiro Uemura, Tomonori Kimura, Masashi Mita, Toshiki Oka, Yohei Okuda, Gaku Yamamichi, Eisuke Tomiyama, Yu Ishizuya, Yoshiyuki Yamamoto, Taigo Kato, Koji Hatano, Ryoichi Imamura, and Norio Nonomura Atsunari KawashimaAtsunari Kawashima More articles by this author , Akinaru YamamotoAkinaru Yamamoto More articles by this author , Sassi NesrineSassi Nesrine More articles by this author , Toshihiro UemuraToshihiro Uemura More articles by this author , Tomonori KimuraTomonori Kimura More articles by this author , Masashi MitaMasashi Mita More articles by this author , Toshiki OkaToshiki Oka More articles by this author , Yohei OkudaYohei Okuda More articles by this author , Gaku YamamichiGaku Yamamichi More articles by this author , Eisuke TomiyamaEisuke Tomiyama More articles by this author , Yu IshizuyaYu Ishizuya More articles by this author , Yoshiyuki YamamotoYoshiyuki Yamamoto More articles by this author , Taigo KatoTaigo Kato More articles by this author , Koji HatanoKoji Hatano More articles by this author , Ryoichi ImamuraRyoichi Imamura More articles by this author , and Norio NonomuraNorio Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003234.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There are no clinically established blood-based diagnostic biomarkers for urothelial carcinoma patients. Amino acids (AA) have two isoforms of L- and D-AA and D-AA have been believed to be physiologically nonexistent. However, it becomes clear that some D-AA has clinical significance in the human body. Here, we evaluated circulating D-AA levels in the blood and their clinical possibilities as diagnostic biomarkers in urothelial cancer patients. METHODS: We enrolled 345 patients just before surgery for urothelial carcinoma (UC) (n=123), renal cell carcinoma (RCC) (n=143), and healthy donor of kidney transplantation (n=79). We collected 345 serum samples just before surgery and 16 samples one week after surgery. D-AA levels in serum were measured using two-dimensional high-performance liquid chromatography. We evaluated its usefulness as a diagnostic biomarker of UC in the derivation cohort (n=22) and two independent validation cohorts in 254 (Cohort-1) and 69 (Cohort-2) participants, respectively. RESULTS: In the derivation cohort, only four D-AA (D-Asparagine (D-Asn), D-Serine (D-Ser), D-Alanine (D-Ala), and D-Proline (D-Pro)) could be measured in serum samples among 22 kinds of D-AA. D-Asn and D-Ala levels were significantly higher in UC patients compared to RCC patients and healthy donors (p<0.05 and p<0.01, respectively). The area under the curve (AUC) of each D-Asn to diagnose UC was 0.800. Sensitivity and specificity were 100% and 60% using a cut-off level of 0.233 IU/ml. In validation Cohort-1, D-Asn levels had a high accuracy of diagnosis for UC (AUC: 0.851). Sensitivity and specificity were 77.8% and 79.3% using the same cut-off level as the derivation cohort. In validation cohort-2, D-Asn levels had the high accuracy of diagnosis for UC (AUC: 0.836) and its sensitivity and specificity were 61.9% and 81.2% using the same cut-off level as the derivation cohort. Also, serum D-Asn levels of 16 UC patients just after surgery significantly decreased compared to those just before surgery (p=0.005). CONCLUSIONS: D-Asn levels in the blood could become the promising diagnostic markers of UC patients. Source of Funding: This work was supported by a KAKENHI grant (22H03213) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e183 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Atsunari Kawashima More articles by this author Akinaru Yamamoto More articles by this author Sassi Nesrine More articles by this author Toshihiro Uemura More articles by this author Tomonori Kimura More articles by this author Masashi Mita More articles by this author Toshiki Oka More articles by this author Yohei Okuda More articles by this author Gaku Yamamichi More articles by this author Eisuke Tomiyama More articles by this author Yu Ishizuya More articles by this author Yoshiyuki Yamamoto More articles by this author Taigo Kato More articles by this author Koji Hatano More articles by this author Ryoichi Imamura More articles by this author Norio Nonomura More articles by this author Expand All Advertisement PDF downloadLoading ...

MP22-19 URINARY COMPREHENSIVE GENOMIC PROFILING PREDICTS UROTHELIAL CANCER UP TO 12 YEARS AHEAD OF CLINICAL DIAGNOSIS. AN EXPANDED ANALYSIS OF THE GOLESTAN COHORT STUDY

MP22-19 URINARY COMPREHENSIVE GENOMIC PROFILING PREDICTS UROTHELIAL CANCER UP TO 12 YEARS AHEAD OF CLINICAL DIAGNOSIS. AN EXPANDED ANALYSIS OF THE GOLESTAN COHORT STUDY

Circulating and urinary tumour DNA in urothelial carcinoma- upper tract, lower tract and metastatic disease.

Precision medicine has transformed the way urothelial carcinoma is managed. However, current practices are limited by the availability of tissue samples for genomic profiling and the spatial and temporal molecular heterogeneity observed in many studies. Among rapidly advancing genomic sequencing technologies, non-invasive liquid biopsy has emerged as a promising diagnostic tool to reproduce tumour genomics, and has shown potential to be integrated in several aspects of clinical care. In urothelial carcinoma, liquid biopsies such as plasma circulating tumour DNA (ctDNA) and urinary tumour DNA (utDNA) have been investigated as a surrogates for tumour biopsies and might bridge many shortfalls currently faced by clinicians. Both ctDNA and utDNA seem really promising in urothelial carcinoma diagnosis, staging and prognosis, response to therapy monitoring, detection of minimal residual disease and surveillance. The use of liquid biopsies in patients with urothelial carcinoma could further advance precision medicine in this population, facilitating personalized patient monitoring through non-invasive assays.

The efficacy of ultrasonography for the detection of upper tract urothelial carcinoma

Ultrasonography and computed tomography urography are two commonly used modalities to image the upper tracts for the evaluation of hematuria. This study evaluated the efficacy of ultrasonography for the detection of upper tract urothelial carcinoma compared to computed tomography urography as a standard reference. This retrospective study included patients with urothelial carcinoma of the renal pelvis and/or ureter who were diagnosed using computed tomography urography and underwent surgical treatment. We calculated the sensitivity of ultrasonography in upper tract urothelial carcinoma diagnosis, further classified the degree of hydronephrosis on ultrasonography, and analyzed the relationship between the sensitivity and the degree of hydronephrosis and tumor location. Additionally, the usefulness of the combination of the screening ultrasonography findings, the presence of gross hematuria, and/or urine cytology was analyzed. This study included 136 patients with upper urothelial carcinoma. Ultrasonography in the diagnosis had 45.6% sensitivity, and ultrasonography findings, including the detection of hydronephrosis, were present in 72.8%. The presence of hydronephrosis and tumor location were associated with detection by ultrasonography. The tumor was identified in a total of 134 (98.5%) patients by combining tumor detection and hydronephrosis using ultrasonography with gross hematuria and positive urine cytology as screening. Ultrasonography showed acceptable sensitivity for upper tract urothelial carcinoma diagnosis. Considering the hydronephrosis findings, ultrasonography is a useful screening tool for upper tract urothelial carcinoma. Additionally, excessive computed tomography examinations can be reduced by adding gross hematuria and positive urine cytology.

Clinical application of the anti-human telomerase reverse transcriptase (hTERT) antibody (SCD-A7) immunocytochemistry in liquid-based urine cytology: Aprospective, single institute study.

Urine cytology is the most widely used noninvasive screening tool for urothelial carcinoma diagnosis and surveillance. Although highly specific, urine cytology exhibits suboptimal sensitivity. This study aimed to determine whether hTERT immunocytochemistry (ICC) could be applicable as an ancillary test in routine cytology practice. A total of 561 urinary tract samples were initially screened in this study. All of them were prepared using SurePath liquid-based cytology (LBC), while additional LBC slides were made and subsequently used for hTERT (SCD-A7) ICC. From the 561 samples screened, 337 were finally analyzed, all having an adequate cellularity and available follow-up histology. The hTERT ICC-positive rate was 95.9% (n=208/217), 96% (n=24/25), and 100% (n=4/4) in cytology samples with high-grade urothelial carcinoma, carcinoma in situ, and low-grade urothelial carcinoma subsequent histology. Among the 64 atypical cytology cases histologically confirmed as urothelial carcinomas, 92.2% (n=59/64) were immunoreactive to hTERT, whereas the two histologically benign cases were ICC-negative. 87/90 (96.7%) of the cytology cases confirmed to be benign in follow-up were hTERT-negative. The overall sensitivity and specificity of hTERT ICC were 96.3% and 98.8%, respectively (AUROC=0.963; 95% CI=0.960-0.967). The hTERT ICC test exhibited consistent and intense staining in malignant urothelial cells, suggesting its value as an ancillary test in liquid-based urine cytology.

A Retrospective Analysis of the Challenges of Urothelial Cancer Management during the COVID-19 Pandemic at a Single Academic Center in Romania.

The COVID-19 pandemic caused major changes in the healthcare sector due to adaptations required to hospitalize and treat an impressive number of patients. This retrospective study intended to collect reliable information on urothelial cancer patients in Romania. The primary objective was to compare the pre-pandemic and pandemic periods to observe the differences that occurred in the management of patients with urothelial carcinoma. The secondary objective was to determine the risk factors for urothelial cancer progression in the study cohort correlated with the COVID-19 pandemic. All patients that were diagnosed and treated at our clinic with a diagnosis of urothelial carcinoma (transitional cell carcinoma) during 2019-2021 were included in the current study. A total of 1122 eligible unique cases were identified during the study period. The number of patients who underwent intervention in the pre-pandemic year was 421, followed by a 22.6% decrease in 2020 to 326 cases and a 13.1% increase in 2021 to 375 cases. The proportion of muscle-invasive bladder cancer (MIBC) cases was significantly higher during the pandemic years, from 30.5% MIBC cases in 2019 to 37.4% in 2020 and 39.4% in 2021, suggesting a delay in presentations during the pandemic. Stage III and IV (TNM) cases were significantly more frequent, even though approximately 40% of all patients were operated on in stage I. The number of cystectomies increased significantly, from 5.2% in 2019 and 4.3% in 2020 to 10.1% in 2021, while the number of elective surgeries decreased, although no significant difference was observed regarding the in-hospital mortality and disease progression at six months. Patients with stage III and IV at presentation had the highest likelihood of disease progression at six months (HR = 5.61). Distant invasion was the second highest risk factor (HR = 5.13), followed by MIBC type (HR = 2.49). Nevertheless, the duration of hospitalization and year of diagnosis during the COVID-19 pandemic were not significant risk factors for cancer progression at six months. It can be concluded that there was a significant delay in patient presentations in 2020, and we advocate for increased public health awareness for urothelial cancer and increased attention toward the screening and management of these patients in the following years.

CDCP1 (CUB domain containing protein 1) is a potential urine-based biomarker in the diagnosis of low-grade urothelial carcinoma.

Urine-based cytology is non-invasive and widely used for clinical diagnosis of urothelial carcinoma (UC), but its sensitivity is less than 40% for low-grade UC detection. As such, there is a need for new diagnostic and prognostic biomarkers of UC. CUB domain containing protein 1 (CDCP1) is a type I transmembrane glycoprotein highly expressed in various cancers. Using tissue array analysis, we demonstrated that CDCP1 expression in UC patients (n = 133), especially in those with low-grade UC, was significantly higher than in 16 normal persons. In addition, CDCP1 expression in urinary UC cells could also be detected by using immunocytochemistry method (n = 11). Furthermore, in 5637-CD cells, overexpression of CDCP1 affected the expression of epithelial mesenchymal transition-related markers and increased matrix metalloproteinase 2 expression and migration ability. Conversely, the knockdown of CDCP1 in T24 cells had the opposite effects. Using specific inhibitors, we demonstrated the involvement of c-Src/PKCδ signaling in the CDCP1-regulated migration of UC. In conclusion, our data suggest that CDCP1 contributes to the malignant progression of UC and may have the potential as a urine-based biomarker for detecting low-grade UC. However, a cohort study needs to be conducted.

UCseek: ultrasensitive early detection and recurrence monitoring of urothelial carcinoma by shallow-depth genome-wide bisulfite sequencing of urinary sediment DNA.

Current methods for the detection and surveillance of urothelial carcinomas (UCs) are often invasive, costly, and not effective for low-grade, early-stage, and minimal residual disease (MRD) tumors. We aimed to develop and validate a model from urine sediments to predict different grade and stage UCs with low cost and high accuracy. We collected 167 samples, including 90 tumors and 77 individuals without tumors, as a discovery cohort. We assessed copy number variations and methylation values for them and constructed a diagnostic classifier to detect UC, UCseek, by using an individual read-based method and support vector machine. The performance of UCseek was validated in an independent cohort derived from three hospitals (n=206) and a relapse cohort (n=42) for monitoring recurrence. We constructed UCseek, which could predict UCs with high sensitivity (92.7%), high specificity (90.7%), and high accuracy (91.7%) in the independent validation set. The accuracy of UCseek in low-grade and early-stage patients reached 91.8% and 94.3%, respectively. Notably, UCseek retained great performance at ultralow sequencing depths (0.3X-0.5X). It also demonstrated a powerful ability to monitor recurrence in a surveillance cohort compared with cystoscopy (90.91% vs. 59.09%). We optimized an improved approach named UCseek for the noninvasive diagnosis and monitoring of UCs in both low- and high-grade tumors and in early- and advanced-stage tumors, even at ultralow sequencing depths, which may reduce the burden of cystoscopy and blind second surgery. A full list of funding bodies that contributed to this study can be found in the Acknowledgments section.

Real-world treatment and quality of life (QOL) in locally advanced or metastatic urothelial carcinoma (la/mUC) in Saudi Arabia, Singapore, South Korea, Taiwan, and Turkey.

462 Background: Little is known about treatment and QOL of la/mUC in Saudi Arabia, South Korea, Turkey, and Taiwan. Therefore, this study assessed patient (pt), tumor, and disease characteristics; treatment sequencing; and QOL in pts with la/mUC treated in these countries. Methods: Data were drawn from the Adelphi mUC Disease-Specific Programme, a real-world, multinational, point-in-time study using validated methodology (Anderson et al. Curr Med Res Opin. 2008;24:3063-72) and included physician surveys, chart reviews, and pt questionnaires (Saudi Arabia, Turkey, and Taiwan only). Data were collected (12/2021–3/2022) from oncologists and urologists and adult pts with confirmed la/mUC. EQ-5D visual analogue scale (VAS; scores: 0 [worst health] to 100 [best health]) and the global health status (QL2) from the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (scores: 0 [low functioning] to 100 [high functioning]) questionnaires were used to assess QOL. Results: Data were provided by 175 physicians for 988 pts (Turkey, n=300; Saudi Arabia, n=240; South Korea, n=298; Taiwan, n=150) with la/mUC. Mean pt age was 66.3 y; 77% were men. Most (77%) pts had no family history of urothelial carcinoma (UC); 30% recorded no risk factors (eg, genetic risk, smoking, occupational exposure). At initial UC diagnosis, the bladder was the initial tumor location in 82% of pts, of whom 67% had la/mUC, and 83% of pts had an Eastern Cooperative Oncology Group performance status 0–2. At data collection, the most common metastatic sites were the lymph nodes (53%), lungs (29%), liver (27%), and bone (21%). Biomarker/tumor testing was not done in 45% of pts. In pts initially diagnosed with nonmetastatic UC (n=346), 28% received neoadjuvant and 31% received adjuvant therapy. Of pts receiving ≥1 line of therapy (LOT) for la/mUC (n=988), 74% received gemcitabine, 60% received cisplatin, 18% received carboplatin, 17% received a programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor, and 4% received best supportive care (BSC) in the first-line (1L) setting; mean duration of therapy (DOT) in 1L was 5.7 mo. Of pts receiving ≥2 LOTs for la/mUC (n=290), 63% received a PD-1/L1 inhibitor and 35% received chemotherapy in the second-line (2L) setting; mean DOT in 2L was 4.9 mo. Of pts receiving ≥3 LOTs for la/mUC (n=87), 59% received chemotherapy (most often cisplatin [46%] or gemcitabine [38%]), 34% received a PD-1/L1 inhibitor, and 10% received BSC only in the third-line (3L) setting; mean DOT in 3L was 4.3 mo. Questionnaires were available for 319 pts. Mean (SD) EQ-5D VAS score was 51.8 (15.6); EORTC QL2 score was 44.6 (19.9). Conclusions: Pts with la/mUC in this multinational study generally received 1L platinum-based and 2L PD-1/L1 inhibitor therapies. These results highlight the need for therapies that improve clinical and QOL outcomes.

Omics sciences and precision medicine in Urothelial Carcinoma.

This comprehensive review explores the potential of omics sciences - such as genomics, transcriptomics, proteomics, and metabolomics - in advancing the diagnosis and therapy of urothelial carcinoma (UC), a prevalent and heterogeneous cancer affecting the urinary tract. The article emphasizes the significant advancements in understanding the molecular mechanisms underlying UC development and progression, obtained through the application of omics approa-ches. Genomic studies have identified recurrent genetic alterations in UC, while transcriptomic analyses have revealed distinct gene expression profiles associated with different UC subtypes. Proteomic investigations have recognized protein biomarkers with diagnostic and prognostic potential, and metabolomic profiling has found metabolic alterations that are specific to UC. The integration of multi-omics data holds promises in refining UC subtyping, identifying therapeutic targets, and predicting treatment response. However, challenges like the standardization of omics technologies, validation of biomarkers, and ethical considerations need to be addressed to successfully translate these findings into clinical practice. Omics sciences offer tremendous potential in revolutionizing the diagnosis and therapy of UC, enabling more precise diagnostic methods, prognostic evaluations, and personalized treatment selection for UC patients. Future research efforts should focus on overcoming these challenges and translating omics discoveries into meaningful clinical applications to improve outcomes for UC patients.

Artificial intelligence to improve cytology performance in bladder urothelial carcinoma diagnosis: Results of the French, multicenter, prospective VISIOCYT1 trial

Artificial intelligence to improve cytology performance in bladder urothelial carcinoma diagnosis: Results of the French, multicenter, prospective VISIOCYT1 trial