Negative Urine Cytology Research Articles

Acu‐URO17 is a highly sensitive and specific bladder cancer biomarker

AbstractObjectiveThis study evaluates the efficacy of Acu‐URO17, a highly sensitive and specific immunocytochemistry (ICC) test targeting Keratin 17, in comparison to urine cytology and UroVysion™ fluorescence in situ hybridization (FISH) for detecting bladder cancer cells in voided urine specimens.MethodsAcupath conducted a large‐scale comparison study using 2378 voided urine specimens. Acu‐URO17, urine cytology and UroVysion™ FISH were performed on these specimens according to standardized protocols. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for Acu‐URO17 in comparison to urine cytology and UroVysion™ FISH.ResultsIn cases diagnosed with high‐grade urothelial cancer via urine cytology, Acu‐URO17 demonstrated a sensitivity of 96% and a specificity of 82%. When compared to UroVysion™ FISH results, Acu‐URO17 exhibited a sensitivity of 97.1% and a specificity of 77.8%, surpassing the sensitivity of UroVysion™ FISH (57.1%). Notably, Acu‐URO17 showed a high NPV of 99.9%, indicating its reliability in confirming negative urine cytology results and risk‐stratifying atypical and suspicious cytology results.ConclusionThe results of this large‐scale prospective study support Acu‐URO17 as a clinically relevant, non‐invasive and cost‐effective tool for detecting bladder cancer cells in voided urine specimens. Its high sensitivity, specificity and NPV make it a valuable adjunct to urine cytology and UroVysion™ FISH in the diagnosis and management of urothelial carcinoma (UC).

Effect of Clinical Complete Remission Following Neoadjuvant Pembrolizumab or Chemotherapy in Bladder-Preservation Strategy in Patients with Muscle-Invasive Bladder Cancer Declining Definitive Local Therapy.

This study aimed to evaluate the outcomes and identify the predictive factors of a bladder-preservation approach incorporating maximal transurethral resection of bladder tumor (TURBT) coupled with either pembrolizumab or chemotherapy for patients diagnosed with muscle-invasive bladder cancer (MIBC) who opted against definitive local therapy. We conducted a retrospective analysis on 53 MIBC (cT2-T3N0M0) patients who initially planned for neoadjuvant pembrolizumab or chemotherapy after maximal TURBT but later declined radical cystectomy and radiotherapy. Post-therapy clinical restaging and conservative bladder-preservation measures were employed. Clinical complete remission was defined as negative findings on cystoscopy with biopsy confirming the absence of malignancy if performed, negative urine cytology, and unremarkable cross-sectional imaging (either CT scan or MRI) following neoadjuvant therapy. Twenty-three patients received pembrolizumab, while thirty received chemotherapy. Our findings revealed that twenty-three (43.4%) patients achieved clinical complete response after neoadjuvant therapy. The complete remission rate was marginally higher in pembrolizumab group in comparison to chemotherapy group (52.1% vs. 36.7%, p = 0.26). After a median follow-up of 37.6 months, patients in the pembrolizumab group demonstrated a longer PFS (median, not reached vs. 20.2 months, p = 0.078) and OS (median, not reached vs. 26.8 months, p = 0.027) relative to those in chemotherapy group. Those achieving clinical complete remission post-neoadjuvant therapy also exhibited prolonged PFS (median, not reached vs. 10.2 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.004). In the multivariate analysis, clinical complete remission subsequent to neoadjuvant therapy was independently associated with superior PFS and OS. In conclusion, bladder preservation emerges as a viable therapeutic strategy for a carefully selected cohort of MIBC patients without definitive local therapy, especially those achieving clinical complete remission following neoadjuvant treatment. For patients unfit for chemotherapy, pembrolizumab offers a promising alternative treatment option.

Feasibility and tissue concordance of genomic sequencing of urinary cytology in upper tract urothelial carcinoma

BackgroundThere is limited ability to accurately diagnose and clinically stage patients with upper tract urothelial carcinoma (UTUC). The most easily available and widely used urinary biomarker is urine cytology, which evaluates cellular material yet lacks sensitivity. We sought to assess the feasibility of performing next-generation sequencing (NGS) on urine cytology specimens from patients with UTUC and evaluate the genomic concordance with tissue from primary tumor. MethodsIn this retrospective study, we identified 48 patients with a diagnosis of UTUC treated at Memorial Sloan Kettering Cancer Center (MSK) between 2019 and 2022 who had banked or fresh urine samples. A convenience cohort of matching, previously sequenced tumor tissue was used when available. Urine specimens were processed and the residual material, including precipitated cell-free DNA, was sequenced using our tumor-naïve, targeted exome sequencing platform that evaluates 505 cancer-related genes (MSK-IMPACT). The primary outcome was at least 1 detectable mutation in urinary cytology specimens. The secondary outcome was concordance to matched tissue (using ANOVA or Chi-Square, as indicated). ResultsGenomic sequencing was successful for 45 (94%) of the 48 urinary cytology patient samples. The most common mutations identified were TERT (62.2%), KMT2D (46.7%), and FGFR3 (35.6%). All patients with negative urine cytology and low-grade tissue had successful cytology sequencing. Thirty-six of the 45 patients had matching tumor tissue available; concordance to matched tissue was 55% overall (131 of the total 238 oncogenic or likely oncogenic somatic mutations identified). However, in 94.4% (n = 34/36) of patients, the cytology had at least 1 shared mutation with tissue. Eleven (30.6%) patients had 100% concordance between cytology and tissue. ConclusionsSequencing urinary specimens from selective UTUC cytology is feasible in nearly all patients with UTUC. Prospective studies are underway to investigate a clinical role for this promising technology.

International Bladder Cancer Group Intermediate-risk Non-muscle Invasive Bladder Cancer (IBCG IR-NMIBC) Scoring System Predicts Outcomes of Patients on Active Surveillance.

To determine if the International Bladder Cancer Group (IBCG) intermediate risk (IR)-NMIBC scoring system can predict the requirement of delayed transurethral resection of bladder tumor (TURBT) in low grade (LG) non-muscle invasive bladder cancer (NMIBC) managed by active surveillance (AS). A prospective study of recurrent LG Ta/T1 NMIBC patients managed with AS with the following characteristics were used: LG papillary NMIBC, ≤5 apparent LG NMIBC, tumor diameter ≤1 cm, absence of gross hematuria and negative urinary cytology. Subsequent TURBT was offered to patients who no longer met the inclusion criteria or patient choice. The ability of the IBCG IR-NMIBC scoring system to predict receipt of subsequent TURBT was determined. Multivariable Cox proportional-hazards analysis was used to determine factors associated with subsequent TURBT. A total of 163 patients with LG Ta/T1 NMIBC were included for analysis. After a median follow-up of 33 months (21-46), TURBT was performed on 109 patients. At landmark timepoint of 24 months, patients with 0 RF factors were over two-fold more likely to continue AS compared to patients with ≥3 RF (59% versus 24%). Multivariable Cox regression suggest that the IBCG IR-NMIBC scoring system was associated with subsequent TURBT (1-2 RF [HR: 1.66, 95% CI: 0.96-2.90, P = .072], ≥3 RF [HR: 3.21, 95% CI: 1.70-6.09, P < .001]) after adjusting for age, T-stage and sex. The IBCG IR-NMIBC scoring system can predict the risk of a subsequent TURBT in patients with LG NMIBC on AS.

Phase 2 trial of intravesical cabazitaxel, gemcitabine, and cisplatin (CGC) for the treatment of non-muscle invasive BCG unresponsive urothelial carcinoma of the bladder.

TPS4616 Background: For patients with non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacille Calmette-Guerin (BCG), multi-agent intravesical trials have been limited. The goal of this Phase 2 study is to investigate the efficacy of intravesical chemotherapy consisting of sequential cabazitaxel, gemcitabine, and cisplatin (CGC) in the salvage setting. Phase 1 results reporting on 18 subjects demonstrated adverse events limited to local Grade 1 and 2 toxicities. Partial funding support for the trial was provided by a pharmaceutical company. Methods: This is a Phase 2 trial (NCT02202772) presently enrolling patients with BCG unresponsive NMIBC as defined by the FDA who refuse or are ineligible for radical cystectomy. All patients undergo pre-treatment transurethral resection of bladder tumor (TURBT) and a 6-week regimen of intravesical cisplatin (100mg), gemcitabine (2gm), and cabazitaxel (5mg). Each drug is instilled weekly except for cisplatin, which is given every other week. Complete response is defined as having no evidence of cancer on post-induction biopsy and negative urine cytology at 3 months. Complete responders proceed with monthly and bimonthly maintenance therapy without cisplatin in the first and second years, respectively, for a total of 24 months. Results: To date thirty-one patients have been enrolled (with target accrual of 33), of whom seven are female. One patient withdrew consent before first evaluation cystoscopy. Mean age thus far is 72 years. All patients have previously received at least two prior induction cycles of BCG, and meet FDA criteria for BCG unresponsive disease. All patients have biopsy proven high grade disease at enrollment; 8 (27%) have high grade T1 disease; and 20 (67%) patients have CIS. Conclusions: Salvage options for BCG unresponsive NMIBC are limited. The CGC protocol has been demonstrated to be safe in a previous Phase 1 study, and accrual for this Phase 2 is near completion. Clinical trial information: NCT02202772 .

A phase 3 multicenter study to evaluate the safety and efficacy of padeliporfin vascular targeted photodynamic therapy (VTP) in treatment of low-grade (LG) upper tract urothelial cancer (UTUC).

TPS4613 Background: Padeliporfin VTP is a combination product: drug, padeliporfin is administered IV and a device, a laser light delivery system, includes a source of light (the laser) that emits near-infrared (NIR) light at 753 nm, and optic fiber that delivers the light to the target lesion(s) in the upper tract urothelium. In Phase 1 NCT03617003 study 19 patients(pts) received up to 2 endoscopic VTP treatments with 6 mos follow-up(FU). Pts with residual or recurrent UTUC (high grade(HG)or LG) who failed prior endoscopic treatment/unable/unwilling to undergo surgery were included. Primary endpoint, Maximum tolerated dose (MTD) of laser light fluence, was identified using dose escalation model with a modified continual reassessment method with increasing light fluence (100-200 mW/cm). Secondary endpoint was efficacy, defined by absence of visible tumor and negative urine cytology 30 days post-treatment. 14(74%) pts received the MTD of 200mW/cm, 2 (11%) of whom experienced DLTs (flank pain grade 2 and 3). Response rate at 30 days was 94% (50% CR, 44% partial). 8 pts received 2nd VTP, with a final observed 68% complete response (CR) rate. Most frequent adverse events: transient flank pain (79%) and hematuria (84%). No treatment-associated ureteral strictures were reported. All patients had preserved kidney at the 6-mos FU(Wesley Yip,2022). Methods: Padeliporfin VTP is being evaluated in a phase 3 study in patients with UTUC LG,100 patients are planned to be enrolled. Enrollment started in Mar 2021 and is ongoing in USA, EU&amp;Israel,3 pts are enrolled. Pts are being treated with padeliporfin VTP in two phases: Induction and Maintenance treatment Phases (ITP and MTP). ITP consists of 1-3 VTPs every 28 days. If CR is not achieved after 1st VTP, up to 2 additional VTPs are allowed. If CR is achieved in the ITP, pts are allowed into the MTP (12 mos). In the MTP VTPs can be provided every 3 mos for pts with recurrent tumor that is deemed treatable, defined as LG with the largest tumor (index) 5 -15 mm, in up to 2 locations in the kidney or one ureter location ≤20 mm. Long Term FU Phase: Pts completing the MTP, will be followed for safety for 48 mos with no VTPs. Primary objective is to demonstrate efficacy and durability of effect of padeliporfin VTP treatment. Secondary objective-evaluation of padeliporfin VTP‐related safety and tolerability. Key inclusion criteria: Up to 2 biopsy-proven LG UTUC tumors with the largest tumor (index) 5-15 mm, located in the calyces, renal pelvis or in the ureter, with no HG cells. Ureter involvement in one location ≤ 20 mm. Key exclusion criteria: Current HG or muscle invasive urothelial bladder cancer . CIS current or previous in the upper urinary tract. History of ≥ T2 urothelial cancer in the past 2 years. DSMB last reviewed the trial in Sep 2022 and suggested the trial continue as planned. Clinical trial information: NCT04620239 .

The natural course of bacillus Calmette-Guérin induced bladder lesions: A long-term follow-up study and systematic review

ObjectiveBacillus Calmette-Guérin (BCG) instillation is the standard adjuvant treatment for intermediate- and high-risk non-muscle-invasive bladder cancer after transurethral resection. Nevertheless, its toxicity often causes bladder complications. On follow-up cystoscopy, post-BCG bladder lesions can be pathologically benign, urothelial carcinoma recurrence, or other types of bladder malignancy. Only a small number of case reports have been published on post-BCG bladder lesions. Their clinical features, natural course, and management remain unknown. MethodsWe retrospectively studied cystoscopic videos and medical records of BCG-treated bladder cancer patients at our center. During a long-term follow-up, we took biopsies on tumor-like lesions and described their changes. In addition, we summarized previous studies on post-BCG bladder lesions by systematic literature searching and review. ResultsWe described a series of three cases with post-BCG bladder lesions mimicking tumor recurrence from a total of 38 cases with follow-up data for more than 5 years. Those lesions could last, grow, or disappear spontaneously, and remain pathological benign for years. In systematic review, we identified and analyzed a total of 15 cases with post-BCG bladder lesions with detailed clinical information. Eleven of the 15 were benign and have a good prognosis with nephrogenic adenoma being the most common pathological type. ConclusionBased on previous studies and our experience, benign lesions after BCG instillation cannot distinguish with cancer recurrence by cystoscopy alone, even under narrow band imaging mode. Nonetheless, given most of them have a good prognosis, random biopsy or transurethral resection might be spared in the patients with long-term negative biopsy and urine cytology.

PD09-02 THE IMPACT OF VARIANT HISTOLOGY ON CLINICAL OUTCOMES AFTER RADIATION-BASED THERAPY FOR MUSCLE-INVASIVE BLADDER CANCER

You have accessJournal of UrologyCME1 Apr 2023PD09-02 THE IMPACT OF VARIANT HISTOLOGY ON CLINICAL OUTCOMES AFTER RADIATION-BASED THERAPY FOR MUSCLE-INVASIVE BLADDER CANCER Daniel Halstuch, Ronald Kool, Gautier Marcq, Rodney H Breau, Peter C Black, Bobby Shayegan, Michael Kim, Ionut Busca, Hamidreza Abdi, Mark T. Dawidek, Michael Uy, Gagan Fervaha, Fabio L. Cury, Nimira S. Alimohamed, Claudio Jeldres, Ricardo Rendon, D. Robert Siemens, Girish S. Kulkarni, Wassim Kassouf, and Jonathan I. Izawa Daniel HalstuchDaniel Halstuch More articles by this author , Ronald KoolRonald Kool More articles by this author , Gautier MarcqGautier Marcq More articles by this author , Rodney H BreauRodney H Breau More articles by this author , Peter C BlackPeter C Black More articles by this author , Bobby ShayeganBobby Shayegan More articles by this author , Michael KimMichael Kim More articles by this author , Ionut BuscaIonut Busca More articles by this author , Hamidreza AbdiHamidreza Abdi More articles by this author , Mark T. DawidekMark T. Dawidek More articles by this author , Michael UyMichael Uy More articles by this author , Gagan FervahaGagan Fervaha More articles by this author , Fabio L. CuryFabio L. Cury More articles by this author , Nimira S. AlimohamedNimira S. Alimohamed More articles by this author , Claudio JeldresClaudio Jeldres More articles by this author , Ricardo RendonRicardo Rendon More articles by this author , D. Robert SiemensD. Robert Siemens More articles by this author , Girish S. KulkarniGirish S. Kulkarni More articles by this author , Wassim KassoufWassim Kassouf More articles by this author , and Jonathan I. IzawaJonathan I. Izawa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003240.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radiation-based therapy (RT) is an acceptable bladder-preserving treatment for selected patients with muscle-invasive bladder cancer (MIBC). Real-world outcomes of RT-based therapy for histologic variants are lacking. Our objective was to compare oncological outcomes between pure urothelial carcinoma (PUC) and variant urothelial carcinoma (UC-HV) patients with MIBC treated with RT-based therapy. METHODS: A collaborative Canadian multicenter retrospective study of 864 patients with MIBC who underwent curative-intent bladder-sparing RT for T2-4a N0-3 M0 MIBC between 2001-2018. Tumours were classified based on the presence of non-urothelial components as either PUC or UC-HV. A complete response (CR) was defined by a negative tumour bed biopsy and/or the combination of a negative urine cytology, negative cystoscopy and normal imaging post-RT. Loco-regional disease-free survival (LR-DFS), disease-free survival (DFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were calculated using Kaplan-Meier method. Cox regression models were used to estimate the effect of UC-VH on oncologic outcomes for patients with MIBC treated with RT-based therapy. RESULTS: Of 864 patients treated with RT-based therapy, 123 (14.2%) had UC-HV. Seventy-five (61%) had UC-HV with squamous and/or glandular differentiation and 48 (39%) had other variants. A CR after RT-based therapy was confirmed in 69.1% of patients with PUC and 63.4% with UC-HV (p=0.266). The 5-yr CSS was 62.0% in PUC vs. 66.8% in UC-HV. The 5-yr OS was 47.7% in PUC and 53.3% in UC-HV. Rates of LR-DFS, DFS and MFS at 5 years were not statistically different between the groups. Salvage cystectomy (sRC) rates were similar (p=0.781). In the univariate Cox regression analyses, UC-HV status was not associated with inferior LR-DFS, DFS, MFS, CSS, and OS. CONCLUSIONS: Variant histology of urothelial carcinoma responded to RT-based therapy with no significant difference in CR, LR-DFS, DFS, MFS, CSS, OS, or rates of salvage cystectomy compared to PUC. The presence of variant histology in MIBC does not confer resistance to RT-based therapy and these patients should not be excluded from bladder preservation treatment. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e239 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Halstuch More articles by this author Ronald Kool More articles by this author Gautier Marcq More articles by this author Rodney H Breau More articles by this author Peter C Black More articles by this author Bobby Shayegan More articles by this author Michael Kim More articles by this author Ionut Busca More articles by this author Hamidreza Abdi More articles by this author Mark T. Dawidek More articles by this author Michael Uy More articles by this author Gagan Fervaha More articles by this author Fabio L. Cury More articles by this author Nimira S. Alimohamed More articles by this author Claudio Jeldres More articles by this author Ricardo Rendon More articles by this author D. Robert Siemens More articles by this author Girish S. Kulkarni More articles by this author Wassim Kassouf More articles by this author Jonathan I. Izawa More articles by this author Expand All Advertisement PDF downloadLoading ...

Atypical Category of the Johns Hopkins Template Has Higher Risk of Malignancy than the Paris System but the Paris System Is More Applicable for Suspicious Category

Introduction: The aim of this study was to compare performance of individual categories between the Johns Hopkins template and the Paris system for reporting urinary cytology. Methods: Medical records of patients with bladder biopsy and relevant cytology slides were obtained from archived material. Slides were reclassified according to Johns Hopkins template and the Paris system. Results were compared to histological diagnoses. Results: BD SurePath preparations from 205 cases with biopsy follow-up (118 benign, 5 dysplasia, 23 low, and 59 malignant urothelial carcinoma [UC]) were reviewed. There were 2 inadequate specimens in each system. According to the Johns Hopkins template, there were 96 (46.8%) no urothelial atypia or malignancy, 37 (18%) atypical urothelial cells of uncertain significance (AUC-US), 21 (10.2%) atypical urothelial cells, cannot exclude high-grade urothelial carcinoma (HGUC), 38 (18.5%) HGUC, and 11 (5.4%) low-grade urothelial carcinoma (LGUC). The Paris system categorized 111 (54.1%) negative for high-grade urothelial carcinoma, 29 (14.1%) atypical urothelial cells (AUCs), 25 (12.2%) suspicious for HGUC (SHGUC), 36 (17.6%) HGUC, and 2 (1%) LGUC. The Johns Hopkins template had a sensitivity of 95.6%, specificity of 73.6%, positive predictive value of 61.5%, negative predictive value of 96.3, with an overall diagnostic accuracy of 79.8%. The Paris System had a sensitivity of 93.6%, specificity of 77.9%, positive predictive value of 65.6%, negative predictive value of 96.5, with an overall diagnostic accuracy of 82.8%. The risk of malignancy (ROM) for atypical category (AUC-US/AUC) in the Johns Hopkins template was 43.2%, while it has been 24.1% for the Paris System. The ROM for suspicious category was 47.6% and 68.0%, respectively. There were statistically significant differences between negative and atypical, suspicious, and HGUC categories in each system (p < 0.0001). Conclusions: Discrete negative or benign urine cytology had the same sensitivity and specificity between two systems. Although atypical category was associated with a higher ROM with the Hopkins template, the ROM for the suspicious category yielded better result with the Paris system.

Abstract 5104: Extracellular vesicles expressing CEACAM proteins in the urine of bladder cancer patients

Abstract Purpose: Early detection and long-term monitoring are important for urothelial carcinoma of the bladder (UCB). Urine cytology and existing markers have insufficient diagnostic performance. Here, we used medium-sized extracellular vesicles (EVs) in urine to find specific markers for UCB and evaluate their usefulness as diagnostic material. Experimental Design: To search for specific markers in urinary EVs derived from UCB, we performed a comparative analysis using shotgun proteomics with urine from four UCB patients and four healthy subjects. Next, we used male 24 healthy specimens, 18 non-cancer specimens, and 29 UCB specimens for analysis of urinary EVs using a flow cytometer to evaluate the diagnostic performance of UCB-specific EVs. Results. NTA analysis showed that the size of EVs extracted from urine by centrifugation was mostly less than 400 nm. By shotgun analysis of EVs, we detected several proteins characteristic of UCB and found that CEACAM proteins was increased in patients. Flow cytometric analysis revealed that the degree of expression of CEACAM1, 5, and 6 antigens on the surface of EVs varied among patients. EVs expressing CEACAM antigens also expressed MUC1, suggesting that they were derived from tumorigenic uroepithelial cells. The number of EVs expressing CEACAM1, 5, and 6 proteins (CEACAMs+EVs) was significantly increased in UCB (Mean9.5%±SD14%), non-bladder cancer (0.69±0.46), and healthy (0.37±0.31) by flow cytometry. The results of ROC analysis showed a good score of AUC=0.929. A provisional CEACAMs+EVs cutoff % was established with a sensitivity of 83% and specificity of 98%. Here, seven out of nine cases of negative urine cytology (class 2) were determined to be positive. Conclusions: The presence of CEA antigen in the urine of patients with bladder cancer is known, but it has not yet been practically used for diagnosis. We have discovered EVs that specifically express these antigens and have obtained useful diagnostic performance. EVs expressing CEACAM proteins in urine are expecting target as a new liquid biopsy for UCB patients. Citation Format: Ko Igami, Takeshi Uchiumi, Masaki Shiota, Saori Ueda, Masatoshi Eto, Dongchon Kang. Extracellular vesicles expressing CEACAM proteins in the urine of bladder cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5104.

Head-to-Head Comparison between High-Resolution Microultrasound Imaging and Multiparametric MRI in Detecting and Local Staging of Bladder Cancer: The BUS-MISS Protocol.

MRI has been proposed as a new staging tool for bladder cancer (BC), but use is limited by its high costs and low availability. 29-MHz high-resolution micro-ultrasound (mUS) technology has been suggested as an alternative to detect BC and distinguish between muscle-invasive and non-muscle invasive BC. The aim was to compare the diagnostic accuracy of mUS vs. magnetic resonance imaging (MRI) in differentiating NMIBC and MIBC at definitive pathological examination. This is a prospective study of patients with a primary diagnosis of BC with either positive urine cytology (UC) or negative UC and a tumor size > 25 mm from a tertiary care high volume center. mUS, with the ExactVu system with an EV29L 29 MHz side-fire transducer, and a 3-Tesla MRI were performed before transurethral resection of bladder tumor (TURBT) in every patient before undergoing TURBT. We compared the imaging results with pathological reports. The analyzed population consisted of 58 individuals. The reported mUS and MRI sensitivity, specificity, positive, and negative predictive values were 85.0%, 76.3%, 65.4%, and 90.6%, versus 85.0%, 50.0%, 47.2%, and 86.4%, respectively. In accuracy analysis, the AUC for mUS and MRI were respectively 0.807 and 0.675. In our population mUS seems to have a better performance in distinguishing NMIBC from MIBC. The main limitation of mUS is the probe shape that makes its use problematic in cases with a large prostate and inadequate rectal preparation. Further studies with a larger population are ongoing to compare and validate these techniques in this setting.

Cyto-histo correlation and false-negative urine: Before and after the Paris system for reporting urinary cytology.

The impact of implementing the Paris system (TPS) on the rate of discrepant cases in the negative for high-grade urothelial carcinoma (NHGUC) category that had a subsequent diagnosis of high-grade urothelial carcinoma (HGUC) on histology is not well studied. We adopted TPS in May 2019. We searched discrepant cases with negative urine cytology 2017-2019 in our cyto-histo correlation database. The urine cytology and follow-up biopsy/resection were reviewed by a cytopathologist who also did Genitourinary (GU) Pathology subspecialty sign-out. Voided urine and instrumented urine were included in this study. There were total of 70 discrepant cases with negative cytology interpretation but HGUC on the subsequent biopsy or resected specimen. Following the TPS criteria, the rate of discrepant negative cytology cases increased from 6 cases between January 2017 and May 2019 to 64 cases after May 2019 when we adopted TPS. There were 2 discrepant negative cases in 2017, 3 cases in 2018, and 65 cases in 2019. Out of 65 cases in 2019, 64 cases were identified after May 2019. Additional 55 urine cytology slides were reviewed according to the TPS criteria, of which, the diagnoses remained unchanged in 45 (82%) cases and 10 (19%) cases were reassigned to either atypical or suspicious categories. The discrepancy was noted more on the instrumented urine and the upper tract urine. However, the false-negative rate rose faster in voided urine and lower tract urine. The risk of HGUC with the category of NHGUC was 0.03% in 2017, 0.05% in 2018, and 1.06% in 2019 at our institution. The increase in false-negative rate could not be attributed to a single cytopathologist. After adopting TPS for reporting urine cytology, there was an increase in HGUC from negative urine cytology which was subsequently confirmed on histology as cases of HGUC. The quality control of negative urines could be important monitoring the process when implementing TPS.

VISIOCYT1 clinical trial: Artificial intelligence for the diagnosis of bladder urothelial lesions.

e16558 Background: Voided urinary cytology is a non-invasive test, but it suffers from a lack of sensitivity (Se), particularly in low-grade urothelial lesions, and it remains pathologist-dependent. In order to improve the performance of urinary cytopathology, the VitaDX company (France) developed a medical device which uses whole-slide digitalization and artificial intelligence algorithms to identify tumor cells. The device allows complete analysis of morphological characters of voided urothelial cells, such as the shape, size and color of the nuclei. Methods: VISIOCYT1 is a prospective, multicenter clinical trial involving 319 patients divided into two groups: 1) patients with non-muscle invasive bladder tumors (NMIBC) confirmed by histology, and 2) control patients with negative urinary cytology and cystoscopy. The primary objective of the study was to evaluate the Se of the VisioCyt test. Specificity (Sp) and comparison of Se and Sp of conventional urinary cytology vs. the VisioCyt test were also calculated. Results: A total of 319 patients were included (170 in the NIMBC group vs. 149 controls). Overall Se was 80.9% and 45.9% for VisioCyt test and conventional urinary cytology, respectively (p = .002). Negative cytology being an inclusion criterion, a 100% Sp was attributed to the control group. It was calculated at 61.8% for the VisioCyt test. Concerning grade, the VisioCyt test allowed higher Se to be obtained in the low grade tumor category (66.7% vs. 26.1% for conventional urinary cytology, Mc Nemar test, p &lt; .0001). A higher Se was also observed in high grade tumors: 93.7% vs. 62.8% (p &lt; .0001). Conclusions: The VisioCyt test greatly improves the performance of urinary cytopathology in the diagnosis of urothelial bladder tumors, particularly in low grade, pTa lesions. Its implementation could dramatically reduce the need for cystoscopy in patients followed after conservative treatment of bladder cancer. Clinical trial information: NCT02966691. [Table: see text]

MP54-13 THE UPDATE FROM BLADDER CANCER ITALIAN ACTIVE SURVEILLANCE (BIAS) PROJECT FOR LOW-GRADE BLADDER TUMORS: LONG-TERM ONCOLOGICAL OUTCOMES OF PATIENTS UNDER ACTIVE SURVEILLANCE

MP54-13 THE UPDATE FROM BLADDER CANCER ITALIAN ACTIVE SURVEILLANCE (BIAS) PROJECT FOR LOW-GRADE BLADDER TUMORS: LONG-TERM ONCOLOGICAL OUTCOMES OF PATIENTS UNDER ACTIVE SURVEILLANCE

Xpert Bladder Cancer Monitor May Avoid Cystoscopies in Patients Under "Active Surveillance" for Recurrent Bladder Cancer (BIAS Project): Longitudinal Cohort Study.

ObjectivesTo test the hypothesis that patients under active surveillance (AS) for Non-muscle Invasive Bladder Cancer (NMIBC) who were negative on longitudinal re-testing by the Xpert® Bladder Cancer Monitor (Xpert BC Monitor) assay may avoid unnecessary cystoscopies and urine cytology (UC).Subjects/Patients (or Materials) and MethodsThis is a prospective cohort study of patients enrolled in the AS protocol for recurrent NMIBC (Bladder Cancer Italian Active Surveillance, BIAS project), whose urine samples were analyzed by Xpert BC Monitor upon entry in the study (T0). Patients who had a negative Xpert test and did not fail AS, underwent additional Xpert tests after 4 (T1), 8 (T2), and 12 (T3) months. The clinical utility of Xpert was assessed by determining the number of cystoscopies and UC that could be avoided within 1 year.ResultsOverall, 139 patients were tested with Xpert at T0. Median follow-up was 23 (IQR 17–27) months. Sixty-eight (48.9%) patients failed AS, 65 (46.7%) are currently on AS, and 6 (4.3%) were lost at follow-up. At T0 57 (41.0%) patients had a negative test and 36 (63.2%) are still in AS. In patients with 2 consecutives negative Xpert tests, we could have avoided 73.9% of unnecessary cystoscopies, missing 26.4% failure, up to avoid all cystoscopies with 4 negative tests missing only 12% of failure. All the patients with negative Xpert had negative UC. Failure-free-survival at median follow-up (23 month) stratified for having 0, 1, or ≥2 negative tests was 67.0, 55.1. and 84.1, respectively.ConclusionOur findings suggest that Xpert BC Monitor assay, when it is longitudinally repeated, could significantly reduce the number of unnecessary cystoscopies and UC during their follow-up.

Indeterminate atypia in urinary tract cytology: Does it really matter?

The study of atypia in urinary cytology has been ongoing for decades but most studies have focused primarily on test performance in patients with concurrent biopsies and/or limited follow-up periods. While these data are useful, many studies fail to consider patient factors that may alter the pretest probability, which can subsequently affect test performance. An isolated diagnosis of malignancy in urinary cytology usually has a high positive predictive value and allows a urologist to conduct a rigorous workup of the patient to establish a tissue diagnosis. However, it is less certain how an atypical diagnosis impacts patient care, given that many patients have a history of bladder cancer and are already under surveillance with cystoscopy at regular screening intervals. Furthermore, a discrete negative urine cytology is unlikely to allow a patient to forego a cystoscopy procedure due to limitations in the sensitivity of urine cytology. Over the last several years, the introduction of The Paris System for Reporting Urinary Cytology (TPS) has improved the predictive value of atypical diagnoses, but additional studies are needed to evaluate the performance of these diagnoses in specific clinical situations. Such data could better inform urologists on how to manage patients with atypical diagnoses. This review discussed the diagnosis of atypia in urinary cytology and the impact of such a diagnosis in various clinical contexts.

PD43-01 UPDATED TREATMENT RESULTS FROM A PHASE I STUDY OF WST11 PHOTOTHERAPY (VTP) FOR UPPER TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma I (PD43)1 Sep 2021PD43-01 UPDATED TREATMENT RESULTS FROM A PHASE I STUDY OF WST11 PHOTOTHERAPY (VTP) FOR UPPER TRACT UROTHELIAL CARCINOMA Lucas Nogueira, Andrew Tracey, Ricardo Alvim, Peter Reisz, Daniel Sjoberg, Quinlan Demac, Nicole Benfante, Karan Nagar, Jasmine Thomas, Jie Chen, Kwanghee Kim, David Solit, Avigdor Scherz, and Jonathan Coleman Lucas NogueiraLucas Nogueira More articles by this author , Andrew TraceyAndrew Tracey More articles by this author , Ricardo AlvimRicardo Alvim More articles by this author , Peter ReiszPeter Reisz More articles by this author , Daniel SjobergDaniel Sjoberg More articles by this author , Quinlan DemacQuinlan Demac More articles by this author , Nicole BenfanteNicole Benfante More articles by this author , Karan NagarKaran Nagar More articles by this author , Jasmine ThomasJasmine Thomas More articles by this author , Jie ChenJie Chen More articles by this author , Kwanghee KimKwanghee Kim More articles by this author , David SolitDavid Solit More articles by this author , Avigdor ScherzAvigdor Scherz More articles by this author , and Jonathan ColemanJonathan Coleman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002057.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The treatment of upper tract urothelial carcinoma (UTUC) presents technical challenges with endoscopic access and treatment delivery, representing a significant barrier to organ-preserving treatments in UTUC, limiting endoscopic management to small, low-grade tumors. Vascular-targeted photodynamic therapy (VTP) using intravascular photosensitizing agent padeliporfin (WST11) has demonstrated preclinical efficacy in preclinical animal models and provides an alternative to extirpative surgery in patients unable or unwilling to undergo extirpative surgery. Herein we present updated results from a phase 1 dose-finding study of WST11-VTP of the upper tract. METHODS: 18 patients with recurrent UTUC were treated with up to 2 sessions of endoscopic WST11-VTP. Eligibility included residual or recurrent urothelial carcinoma of the ureter or renal pelvis failing prior endoscopic treatment, who are unable or unwilling to undergo surgical management by resection of the involved ureter or kidney. A light dose escalation model was employed with increasing light fluence from 100mW/cm up to a maximally tolerated dose of 200mW/cm. The primary endpoint was the determination of maximally tolerated laser light fluence rate, with the secondary objective to evaluate treatment efficacy defined by absence of visible tumor and negative urine cytology following treatment. RESULTS: Complete response (CR) and tumor recurrence rates at 30 days after treatment were 67% and 28%, respectively. A second VTP treatment was performed in 8 (44%) patients, with 67% CR rate. The efficacy rates were comparable among patients who received the intermediate and highest light fluence and between the first and second treatment. Graded adverse events related to treatment are showed in table 1. No ureteral strictures were identified with the procedure. No evidence of increased toxicity was identified among patients who received a second VTP treatment. CONCLUSIONS: WST11-VTP shows promising evidence of therapeutic treatment effect in low- and high-grade upper tract urothelial tumors with limited treatment related toxicity. These early results provide support for further investigation to evaluate the curative potential for this therapy in a planned multicenter trial. Source of Funding: Steba Biotech © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e730-e730 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lucas Nogueira More articles by this author Andrew Tracey More articles by this author Ricardo Alvim More articles by this author Peter Reisz More articles by this author Daniel Sjoberg More articles by this author Quinlan Demac More articles by this author Nicole Benfante More articles by this author Karan Nagar More articles by this author Jasmine Thomas More articles by this author Jie Chen More articles by this author Kwanghee Kim More articles by this author David Solit More articles by this author Avigdor Scherz More articles by this author Jonathan Coleman More articles by this author Expand All Advertisement Loading ...

PD63-09 HEAD-TO-HEAD COMPARISON BETWEEN HIGH-RESOLUTION MICROULTRASOUND IMAGING AND MULTIPARAMETRIC MRI IN DETECTING AND LOCAL STAGING OF BLADDER CANCER: THE BUS-MISS PROTOCOL

You have accessJournal of UrologyBladder Cancer: Non-invasive III (PD63)1 Sep 2021PD63-09 HEAD-TO-HEAD COMPARISON BETWEEN HIGH-RESOLUTION MICROULTRASOUND IMAGING AND MULTIPARAMETRIC MRI IN DETECTING AND LOCAL STAGING OF BLADDER CANCER: THE BUS-MISS PROTOCOL Pietro Diana, Alessandro Uleri, Giovanni Lughezzani, Nicola Frego, Roberto Contieri, Pier Paolo Avolio, Davide Maffei, Piergiuseppe Colombo, Luca Balzarini, Federico D'Orazio, Nicolomaria Buffi, Alberto Saita, Paolo Casale, Massimo Lazzeri, and Rodolfo Hurle Pietro DianaPietro Diana More articles by this author , Alessandro UleriAlessandro Uleri More articles by this author , Giovanni LughezzaniGiovanni Lughezzani More articles by this author , Nicola FregoNicola Frego More articles by this author , Roberto ContieriRoberto Contieri More articles by this author , Pier Paolo AvolioPier Paolo Avolio More articles by this author , Davide MaffeiDavide Maffei More articles by this author , Piergiuseppe ColomboPiergiuseppe Colombo More articles by this author , Luca BalzariniLuca Balzarini More articles by this author , Federico D'OrazioFederico D'Orazio More articles by this author , Nicolomaria BuffiNicolomaria Buffi More articles by this author , Alberto SaitaAlberto Saita More articles by this author , Paolo CasalePaolo Casale More articles by this author , Massimo LazzeriMassimo Lazzeri More articles by this author , and Rodolfo HurleRodolfo Hurle More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002107.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: MRI has been proposed as a new staging tool for bladder cancer (BC), but its use is limited by its high costs and availability. 29-MHz high-resolution micro-ultrasound (mUS) technology has been suggested as a potential alternative to MRI for the detection of prostate cancer. The feasibility of mUS to detect BC and to distinguish between non-muscle invasive BC (NMIBC) and MIBC has been showed. However, no comparative analysis between mUS and MRI was performed. The aim of this study is to compare the diagnostic accuracy of mUS vs. MRI in differentiating histologic NMIBC and MIBC. METHODS: This is a prospective on going study of patients with a primary diagnosis of BC with either positive urine cytology (UC) or negative UC and a tumor size >25mm from a tertiary care high volume center. mUS, with the ExactVu system with an EV29L 29 MHz side-fire transducer, and a 3-Tesla MRI were performed before transurethral resection of bladder tumor (TURBT) in every patient before undergoing TURBT. We finally compared the results with the pathological report. RESULTS: Between April 2018 and November 2020, we prospectively enrolled 72 consecutive patients. After exclusion of 14 individuals, the analyzed population consisted of 58 individuals. The reported sensitivity, specificity, and positive, and negative predictive values for mUS were 85.0%, 76.3%, 65.4%, and 90.6%, respectively for mUS. The reported sensitivity, specificity, and positive, and negative predictive values for MRI were 85.0%, 50.0%, 47.2%, and 86.4%, respectively. In accuracy analysis, the AUC for mUS and MRI were respectively 0.807 and 0.675. Main limitation provided by mUS is the longitudinal sections of the bladder, thus, its accuracy to determine the location of a lesion may be suboptimal with a dislocation of lesions. CONCLUSIONS: These results demonstrate that the measures of diagnostic accuracy indexes demonstrate an overall superiority of the mUS compared to MRI, which instead shows an important tendency in lesion upstaging compared to mUS. Further studies with a larger population are ongoing and warranted to better compare and to validate these techniques in the BC diagnostic work-up. Source of Funding: none © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1141-e1141 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pietro Diana More articles by this author Alessandro Uleri More articles by this author Giovanni Lughezzani More articles by this author Nicola Frego More articles by this author Roberto Contieri More articles by this author Pier Paolo Avolio More articles by this author Davide Maffei More articles by this author Piergiuseppe Colombo More articles by this author Luca Balzarini More articles by this author Federico D'Orazio More articles by this author Nicolomaria Buffi More articles by this author Alberto Saita More articles by this author Paolo Casale More articles by this author Massimo Lazzeri More articles by this author Rodolfo Hurle More articles by this author Expand All Advertisement Loading ...

PD63-05 ONCOLOGICAL LONG-TERM OUTCOMES OF PATIENTS UNDER ACTIVE SURVEILLANCE FOR LOW-GRADE BLADDER TUMORS: AN UPDATE FROM BLADDER CANCER ITALIAN ACTIVE SURVEILLANCE (BIAS) PROJECT

You have accessJournal of UrologyBladder Cancer: Non-invasive III (PD63)1 Sep 2021PD63-05 ONCOLOGICAL LONG-TERM OUTCOMES OF PATIENTS UNDER ACTIVE SURVEILLANCE FOR LOW-GRADE BLADDER TUMORS: AN UPDATE FROM BLADDER CANCER ITALIAN ACTIVE SURVEILLANCE (BIAS) PROJECT Roberto Contieri, Nicola Frego, Marco Paciotti, Pietro Diana, Pier Paolo Avolio, Alessandro Uleri, Davide Maffei, Vittorio Fasulo, Massimo Lazzeri, Alberto Saita, Nicolò Maria Buffi, Giovanni Lughezzani, Paolo Casale, Giorgio Guazzoni, and Rodolfo Hurle Roberto ContieriRoberto Contieri More articles by this author , Nicola FregoNicola Frego More articles by this author , Marco PaciottiMarco Paciotti More articles by this author , Pietro DianaPietro Diana More articles by this author , Pier Paolo AvolioPier Paolo Avolio More articles by this author , Alessandro UleriAlessandro Uleri More articles by this author , Davide MaffeiDavide Maffei More articles by this author , Vittorio FasuloVittorio Fasulo More articles by this author , Massimo LazzeriMassimo Lazzeri More articles by this author , Alberto SaitaAlberto Saita More articles by this author , Nicolò Maria BuffiNicolò Maria Buffi More articles by this author , Giovanni LughezzaniGiovanni Lughezzani More articles by this author , Paolo CasalePaolo Casale More articles by this author , Giorgio GuazzoniGiorgio Guazzoni More articles by this author , and Rodolfo HurleRodolfo Hurle More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002107.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Natural history of Low-risk Non-Muscle-Invasive Bladder Cancers (NMIBCs) is characterized by a high recurrence rate and a very low progression rate. Active Surveillance (AS) has emerged as a validated therapeutic approach in Low-risk NMIBCs patients in order to avoid or, at least, postpone invasive surgical treatment. The aim of this study was to confirm the oncological long-term safety of AS and to present the last updated results from Bladder Cancer Italian Active Surveillance (BIAS) project. METHODS: This prospective observational cohort study started in January 2013 and it included 214 patients with pathologically confirmed NMIBC experiencing recurrence during the follow-ups and accepted AS monitoring. AS monitoring was based on the Urine Cytology (UC) and flexible in-office cystoscopy every 3 months for the first year, and every 6 months afterwards. The inclusion criteria was: history of Low Grade NMIBC (G1–2) pTa/ pT1a; number of tumors: between one to five; size of the single tumor: <1 cm; absence of gross hematuria and negative urine cytology for high-grade carcinoma. Failure was defined as reaching the exclusion criteria after being enrolled. RESULTS: The BIAS protocol included 214 patients (251 AS events), with a median age of 72 years (IQR 66-78). Most patients were male (175/214, 81.7%) and 109 (50.9%) patients were active or former smokers. After the first TUR 55 patients had received intravesical therapy with mitomycin C and 20 with BCG. The median follow-up was 38.8 months (IQR 28.6-55.5) while the median time on AS was 13 months (IQR 7-24). Pathological characteristics before entry into AS were: 196 TaG1-G2 and 17 T1aG1G2. The median interval between the primary diagnosis and AS enrolment was 36 months (IQR 16-62.5). Of 251 AS events, 130 (51.8%) were estimated to require surgical treatment, because of: increases in the size of tumors (n=51); increases in the number of tumors (n=34); increase in both the number and size (n=29); positive UC (n=11) and gross hematuria (n=3); in two cases surgery was performed due to patients request. An upstage from LG tumor to HG/CIS was found in 14 cases (11.6%), while pT2 tumor was found in 1 case (0.07%). In 25 cases (19,2%) pathological specimens from AS failures didn't show tumor. 114 patients are still under observation. CONCLUSIONS: Our study findings confirmed the oncological safety of AS which might be a reasonable strategy to avoid unnecessary TURBT in patients with small LG pTa/pT1a recurrent BC. Additional studies are required to avoid unnecessary TURB. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1139-e1140 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Roberto Contieri More articles by this author Nicola Frego More articles by this author Marco Paciotti More articles by this author Pietro Diana More articles by this author Pier Paolo Avolio More articles by this author Alessandro Uleri More articles by this author Davide Maffei More articles by this author Vittorio Fasulo More articles by this author Massimo Lazzeri More articles by this author Alberto Saita More articles by this author Nicolò Maria Buffi More articles by this author Giovanni Lughezzani More articles by this author Paolo Casale More articles by this author Giorgio Guazzoni More articles by this author Rodolfo Hurle More articles by this author Expand All Advertisement Loading ...

TRANSURETHRAL BLADDER BIOPSY AFTER POST INTRAVESICAL BCG THERAPY FOR SUPERFICIAL BLADDER CANCER PATIENTS

This study evaluated the role of routine biopsy from the site of previously resected superficialbladder tumor three months following resection and intravesical BCG therapy in the presenceof negative urine cytology and cystoscopy. Thirty-two patients (21males and 11 females)with high-risk superficial transitional cell carcinoma (TCC) of the bladder were followed prospectively.All patients received a single six weeks course of intravesical Bacillus Chalmette-Guerin (BCG). Three months following resection, urine cytology was done. Cystoscopy wasthen performed and a routine biopsy from the previous resection site was taken. All patientsincluded in the study had negative urine cytology and cystoscopy at the time of biopsy. Four(12.5%) patients were having TCC although they had negative urine cytology and cystoscopyat the time of biopsy. The histological recurrence was corresponded to T1G1 in two patientsand T1G2 in the other two patients and the pathology after BCG treatment for the four patientswas the same as before instillation. There were no statistically significant differences betweenpatients with positive and negative biopsies with regard to the stage and grade of the tumor beforeresection, or the number of resected lesions.