Positive Urine Cytology Research Articles

Sequential Endoluminal Gemcitabine and Cabazitaxel with Intravenous Pembrolizumab as a Bladder-Preserving Strategy for Docetaxel-Unresponsive Non-Muscle Invasive Urothelial Carcinoma Following Transurethral Resection of Bladder Tumor.

Growing evidence suggests that many patients with high-risk non-muscle invasive urothelial carcinoma (NMIUC) can undergo bladder-sparing management with salvage intravesical therapies. However, inherent or developed disease resistance, particularly after multiple lines of prior salvage therapy, implores the continued pursuit of new treatment combinations. Herein, we describe the outcomes of 26 patients (31 treated units; 24 lower tract, 7 upper tract) with high-risk NMIUC treated with sequential intravesical gemcitabine and cabazitaxel with concomitant intravenous pembrolizumab (GCP) at the University of Iowa from August 2020 to February 2023. Median (IQR) follow-up was 30 (IQR: 17-35) months. Treated units had a history of high-risk NMIUC with a median of four prior endoluminal inductions. Overall, 87% of units presented with CIS or positive urine cytology. The 1- and 2-year recurrence-free survival was 77% (CI: 58-88%) and 52% (CI: 30-70%), respectively. The 2-year progression-free and cancer-specific survival was 70% (CI: 44-85%) and 96% (CI: 75-99%), respectively. In total, 22/26 (85%) patients reported any adverse event and 5/26 (19%) reported a grade ≥3 adverse event; however, all patients tolerated a full induction course. These results suggest that GCP is an effective and tolerable treatment option for patients with recurrent high-risk NMIUC.

Improving detection of carcinoma in situ in bladder cancer: urinary cytology vs the Xpert® BC Monitor.

To investigate and compare the performance of urinary cytology and the Xpert BC Monitor test in the detection of bladder cancer in various clinically significant patient cohorts, including patients with carcinoma in situ (CIS), in a prospective multicentre setting, aiming to identify potential applications in clinical practice. A total of 756 patients scheduled for transurethral resection of bladder tumour (TURBT) were prospectively screened between July 2018 and December 2020 at six German University Centres. Central urinary cytology and Xpert BC Monitor tests were performed prior to TURBT. The diagnostic performance of urinary cytology and the Xpert BC Monitor was evaluated according to sensitivity (SN), specificity (SC), negative predictive value (NPV) and positive predictive value (PPV). Statistical comparison of urinary cytology and the Xpert BC Monitor was conducted using the McNemar test. Of 756 screened patients, 733 (568 male [78%]; median [interquartile range] age 72 [62-79] years) were included. Bladder cancer was present in 482 patients (65.8%) with 258 (53.5%) high-grade tumours. Overall SN, SC, NPV and PPV were 39%, 93%, 44% and 92% for urinary cytology, and 75%, 69%, 59% and 82% for the Xpert BC Monitor. In patients with CIS (concomitant or solitary), SN, SC, NPV and PPV were 59%, 93%, 87% and 50% for urinary cytology, and 90%, 69%, 95% and 50% for the Xpert BC Monitor. The Xpert BC Monitor missed four tumours (NPV = 98%) in patients with solitary CIS, while potentially avoiding 63.3% of TURBTs in inconclusive or negative cystoscopy and a negative Xpert result. Positive urinary cytology may indicate bladder cancer and should be taken seriously. The Xpert BC Monitor may represent a useful diagnostic tool for correctly identifying patients with solitary CIS and unsuspicious or inconclusive cystoscopy.

Neoadjuvant nivolumab (N) + ipilimumab (I) in cisplatin-ineligible patients with upper tract urothelial cancer (UTUC): Updated results.

645 Background: Perioperative platinum-based chemotherapy for UTUC improves pathologic responses and disease-free survival (DFS). We report the updated results from our on-going phase II neoadjuvant trial of N+I for cisplatin-ineligible patients (pts) with UTUC (NCT03520491). Methods: Cisplatin-ineligible pts with histologically confirmed high-grade UTUC and/or radiographically invasive UTUC with positive selective urine cytology were eligible. Pts were treated with I 3mg/kg + N 1mg/kg (weeks 0, 6), and “N” 3mg/kg (week 3) prior to radical nephroureterectomy (NU). The primary endpoint (EP) was pathologic complete response (pCR, ypT0pN0) and secondary EPs included <ypT2pN0 rate, DFS, and toxicity. Next generation sequencing of pre-treatment tumors was correlated with pathologic response. Results: Seventeen pts (76% male) were enrolled between 2/2021-6/2023 with median age 73 (range 59-85). Primary sites included ureter in 10 pts, renal pelvis in 5 and both in 2. Median tumor diameter was 3.0 cm, (range: 1.5 - 4.2 cm), with 8 pts (47%) having hydronephrosis. To date, 11 pts (65%) have received all planned treatment, 6 pts had N+/-I stopped early due to treatment-related toxicities, 2 pts are pending NU, 13 pts have undergone NU, 1 declined surgery, and another progressed on N+I. A pCR was seen in 4/15 pts (27%) and <ypT2pN0 in 9/15 (60%). Median time from last treatment to NU was 1.6 months (range 0.5-4.9). Three pts developed metastatic recurrence at 3.9, 10.3 and 15.6 months after treatment initiation. CTCAE grade ≥3 treatment-related adverse events occurred in 5 pts (29%). Four pts died during follow up: two of metastatic disease, one of complications related to a bowel leak (7.2 months after N+I initiation and 4.7 months after NU), and one from complications of a fall unrelated to disease or treatment (9.2 months after N+I initiation and 4.7 months after NU). Median tumor mutational burden (TMB) in 9 pts with pre-treatment sequencing was 13.2 mutations/mb (range 4.1-106.3), with 4/5 pts with TMB>10 <ypT2pN0 at NU. Pathogenic germline variants in mismatch repair genes were confirmed in 4 pts (MSH2 in 3, MLH1 in 1) and MSI-high tumors without germline alterations in 2 pts, with 5 of 6 completing NU (1 pending surgery); all 5 achieved pCR (n=3) or ypTaN0 (n=2) and remain alive and disease-free at last follow-up (6, 13.4, 17, 17.9 and 31 months). Conclusions: Updated findings from an on-going phase II trial of cisplatin-ineligible pts with UTUC receiving neoadjuvant N+I shows clinical activity in line with our initial results. All pts with pathogenic germline variants in mismatch repair genes or MSI-high tumors without germline alteration who underwent NU achieved <ypT2pN0 and remain free of disease. Clinical trial information: NCT03520491 .

MRI for risk stratification of muscle invasion by upper tract urothelial carcinoma: a feasibility study

BackgroundMagnetic resonance imaging (MRI) is recommended in patients with upper tract urothelial carcinoma (UTUC) only when computed tomography (CT) is contraindicated. However, CT does not allow distinguishing ureter wall layers, making impossible to assess muscle invasion, a factor contributing to differentiate high- from low-risk UTUCs, which require different therapeutic approaches. We investigated the feasibility of MRI assessment of UTUC muscle invasion.MethodsFrom June 2022 to March 2023, we prospectively enrolled patients suspected of UTUC, i.e., with positive urinary tract ultrasound and/or ureteroscopy, or positive urinary cytology and/or hematuria but negative cystoscopy and bladder ultrasound at two Italian centers. They underwent CT followed by MRI (≤ 24 h apart), independently reported by two experienced radiologists, blinded from histopathology results. After imaging confirmation, they all underwent nephroureterectomy and histopathology analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the receiver operating characteristic curve (AUC) were calculated.ResultsThirty-nine lesions were detected in 30 patients on both CT and MRI. Muscle-invasive UTUC prevalence was 81% (21/26) among patients with MRI suspicion and 8% (1/13) among those without MRI suspicion (p < 0.001). Considering the assessment of muscle-layer invasion, the more experienced reader achieved 95% sensitivity (95% confidence interval 82−100), 71% specificity (47−88), 81% PPV (63−93), 92% NPV (70−100), 85% accuracy (67−96), and 0.84 AUC (0.70−0.98). Inter-reader agreement was substantial (κ = 0.73).ConclusionsMRI showed a promising diagnostic performance for the assessment of UTUC risk of muscle invasion.Relevance statementResulting feasible both in technical and clinical terms, MRI could be helpful for upper tract urothelial carcinomas pre-operative risk stratification, to allow a personalized patients’ management. These results play in favor of promoting preoperative MRI for UTUC, as already proven for bladder cancer.Key points• Muscle invasion is a crucial information for tailored treatments of upper tract urothelial carcinomas.• CT does not distinguish ureter wall layers, making muscle invasion risk assessment not feasible.• MRI was shown to reliably diagnose muscle-layer invasion by upper tract urothelial carcinomas (sensitivity 95%, specificity 71%).Graphical

Positioning the role of urine cytology within the diagnostic pathway for UTUC: supportive but inconclusive.

With the introduction of kidney-sparing surgery (KSS) for low-risk Upper Tract Urothelial Carcinoma (UTUC), correct risk-stratification has become crucial. High-grade cytology is one of the decisive variables to stratify a tumor as high-risk. To position the role of urine cytology in the diagnostic pathway of UTUC patients, we evaluated the accuracy of urine cytology by comparing the outcomes with histopathology. Patients with UTUC evaluated between 2010 and 2020, and diagnosed by imaging, cytology and histopathology were selected. Descriptive statistics were used to compare cytology with histopathological outcomes using crosstabs. Clinical performance characteristics of cytology were determined for the presence of a malignancy. This study included 176 patients with confirmed histopathological UTUC. Concordance between cytology and biopsy results was found in 14.8% of low-grade tumors and 16.8% of high-grade tumors. Comparing cytology with radical nephroureterectomy (RNU) specimens revealed concordance rates of 1.6% for low-grade tumors and 22.9% for high-grade tumors. Notably, 51.1% of urine cytology results were false negative. Sensitivity for detecting high-grade and low-grade tumors with a positive urine cytology was 56.6% and 52.6%, respectively, with specificities of 54.8% and 37.2%. In the current study, cytology appears to exhibit limited reliability when used as a sole diagnostic tool for assessing tumor grade and consequently risk stratification. It is imperative to recognize these limitations, optimize urine sampling techniques, and leverage a combination of diverse diagnostic methods for the most effective and individualized treatment decision-making.

The Role of Urine and Washing Cytology in Primary Transurethral Resection of Bladder Tumours

Introduction: Urine cytology (UC) is a recommended tool for the diagnosis of urothelial malignancies. Thus far, no specific recommendations regarding the role of washing cytology (WC) have been included in the guidelines. The goal of our study was to analyse the relationship between the histology of transurethrally (transurethral resection of the bladder [TURBT]) resected bladder tumours (BCa) and intraoperative UC or WC findings. Materials and Methods: Five hundred consecutive primary TURBT cases conducted between November 2010 and 2015 at our department of the University Hospital Luebeck were retrospectively analysed. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of UC and WC were evaluated to detect BCa. Multivariate logistic regression models were fit to further examine associations between patient- and tumour-related factors and a bladder UC or WC positive for BCa. Results: UC was performed in 297 patients, WC in 294 patients, and both in 261 patients. Sensitivity was 50.7% in UC, 58.1% in WC, and 62.1% for both tests combined. Specificity was 97.8% for UC, 98.0% for WC, and 96.4% for the combined tests. PPV was 98.0% for UC, 98.1% for WC, and 97.2% for combined tests. NPV was 47.8% for UC, 54.5% for WC, and 55.9% for the combined tests. The multivariate analyses revealed no association between positive UC or WC results and subsequent radical cystectomy (UC OR 1.35, 95% CI: 0.3–5.7; WC OR 2.0, 95% CI: 0.4–11.4). Neither UC nor WC was significantly correlated with local recurrence. Conclusions: Cytologic testing is an important diagnostic tool in BCa detection, showing acceptable sensitivity of around 60% and excellent specificity of over 90%. UC and WC present similar sensitivity. Our results advocate, however, against cytologic testing during primary TURBT, especially with regard to the lack of value in assessing the risk of recurrence. The clinical benefit of taking both types of samples at once is minimal. Furthermore, intraoperative WC collection does not reliably predict subsequent cystectomies.

MP63-17 PHOTODYNAMIC DIAGNOSIS (PDD) DIRECTED BIOPSIES VS WHITE LIGHT BLADDER MAPPING IN PATIENTS WITH POSITIVE CYTOLOGY AND NEGATIVE PREOPERATIVE WORKUP: AN INTERNATIONAL MULTICENTER RETROSPECTIVE STUDY

You have accessJournal of UrologyCME1 Apr 2023MP63-17 PHOTODYNAMIC DIAGNOSIS (PDD) DIRECTED BIOPSIES VS WHITE LIGHT BLADDER MAPPING IN PATIENTS WITH POSITIVE CYTOLOGY AND NEGATIVE PREOPERATIVE WORKUP: AN INTERNATIONAL MULTICENTER RETROSPECTIVE STUDY Luciano Ola, Francesco Soria, Beatrice Lillaz, Francesca Pisano, Rosazza Matteo, Dutto Daniele, Simone Livoti, Matteo Debellis, Simone Mazzoli, Gautier Marcq, Edouard Jarry, and Paolo Gontero Luciano OlaLuciano Ola More articles by this author , Francesco SoriaFrancesco Soria More articles by this author , Beatrice LillazBeatrice Lillaz More articles by this author , Francesca PisanoFrancesca Pisano More articles by this author , Rosazza MatteoRosazza Matteo More articles by this author , Dutto DanieleDutto Daniele More articles by this author , Simone LivotiSimone Livoti More articles by this author , Matteo DebellisMatteo Debellis More articles by this author , Simone MazzoliSimone Mazzoli More articles by this author , Gautier MarcqGautier Marcq More articles by this author , Edouard JarryEdouard Jarry More articles by this author , and Paolo GonteroPaolo Gontero More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003321.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder Carcinoma in situ (CIS) is a flat, non-vegetating, high-grade tumor and is associated with a high risk of progression to muscle invasive cancer (MIBC), especially if not timely diagnosed and treated. Since it may be often not visible with white light cystoscopy (WL), international guidelines therefore recommend the use of bladder mapping in case of suspected CIS (positive urine cytology and negative preoperative workup). Photodynamic diagnosis (PDD) has been shown to increase the sensitivity in diagnosing CIS compared to WL cystoscopy. However, a direct comparison between PDD-guided biopsies (PDD-GB) and WL bladder mapping (WL-M) is lacking. The aim of our study is therefore to compare the diagnostic capability of PDD-GB versus that of WL-M. METHODS: A retrospective analysis was conducted from March 2018 to May 2022 at two European referral Centers. Overall, 73 patients were enrolled according to the following inclusion criteria: positive urinary cytology or gross hematuria and negative flexible cystoscopy and / or negative CT scan. Patients underwent either PDD-GB or WL-M, as per international guidelines. The main endpoint of the study was the diagnostic accuracy in the diagnosis of bladder cancer (BCa) and, particularly, of CIS. Recurrence-free and progression-free survival were investigated as secondary endpoint. RESULTS: Overall, 50 patients (68%) underwent (PDD-GB) and 23 (32%) WL-M. No differences in baseline characteristics were observed among the two groups.BCa was found in 16 patients (32%) among the PDD-GB group and in 8 patients (34.78%) among the WL-M group (p=0.8); CIS was found in 11 (22%) patients undergoing PDD-GB and in 6 patients (26.09%) in the WL-M group (p=0.7). On univariable logistic regression the type of intervention (PDD-GB vs WL-M) was not associated with either BCa or CIS diagnosis (all p>0.05). Disease recurrence was found in 18 patients, but no statistically significant differences were observed among the two groups (p=0.3); disease progression was found in 7 patients and, again, no differences were observed (p=0.3). CONCLUSIONS: We did not observe statistically significant differences between the PDD-GB group and the WL-M group in the diagnosis of BCa and CIS. WL-M remains a valid alternative to PDD-GB in patients with suspected CIS. The main limitations of this study are inherent its retrospective nature and the small sample size. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e878 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luciano Ola More articles by this author Francesco Soria More articles by this author Beatrice Lillaz More articles by this author Francesca Pisano More articles by this author Rosazza Matteo More articles by this author Dutto Daniele More articles by this author Simone Livoti More articles by this author Matteo Debellis More articles by this author Simone Mazzoli More articles by this author Gautier Marcq More articles by this author Edouard Jarry More articles by this author Paolo Gontero More articles by this author Expand All Advertisement PDF downloadLoading ...

MP56-20 ETIOLOGY, EVALUATION, AND MANAGEMENT OF HEMATURIA FOLLOWING RADICAL CYSTECTOMY AND ORTHOTOPIC URINARY DIVERSION

You have accessJournal of UrologyCME1 Apr 2023MP56-20 ETIOLOGY, EVALUATION, AND MANAGEMENT OF HEMATURIA FOLLOWING RADICAL CYSTECTOMY AND ORTHOTOPIC URINARY DIVERSION Daniel I. Sanford, Muhannad Alsyouf, Sanam Ladi-Seyedian, Kevin Wayne, Alireza Ghoreifi, Anne Schuckman, Hooman Djaladat, and Siamak Daneshmand Daniel I. SanfordDaniel I. Sanford More articles by this author , Muhannad AlsyoufMuhannad Alsyouf More articles by this author , Sanam Ladi-SeyedianSanam Ladi-Seyedian More articles by this author , Kevin WayneKevin Wayne More articles by this author , Alireza GhoreifiAlireza Ghoreifi More articles by this author , Anne SchuckmanAnne Schuckman More articles by this author , Hooman DjaladatHooman Djaladat More articles by this author , and Siamak DaneshmandSiamak Daneshmand More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003309.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Up to 20% of patients presenting with gross hematuria have underlying urologic malignancy. In patients with orthotopic neobladder (ONB) following cystectomy, the occurrence of hematuria at follow-up has not been evaluated. Here, we assessed the etiology, evaluation, and subsequent management of patients who developed hematuria following ONB diversion. METHODS: All patients who underwent radical cystectomy and ONB between 2017-2022 and who subsequently underwent cystoscopy for hematuria were identified. Patient demographics, cystoscopy reports, cytology findings, and relevant imaging were reviewed to determine the etiology of hematuria and subsequent management. Causes of hematuria were categorized as recurrence, anticoagulation-related, inflammation/infection, or undetermined. A univariate analysis was performed to identify factors predictive of oncologic recurrence presenting with hematuria. RESULTS: Of 55 patients with ONB who underwent subsequent cystoscopy on follow-up, hematuria was the indication in 24 (44%) patients (Table 1a). Median patient age was 71 (IQR 66-74) years. Seven patients (29%) had hematuria secondary to cancer recurrence, including four with urethral recurrence, one with ureteral recurrence, and two with positive urine cytology. Other etiologies of hematuria included anticoagulation (13%), pouchitis (13%), mesh erosion into neobladder (4%), and bladder inflammation (4%). Nine patients (37%) had an undetermined cause of hematuria. In patients with recurrence, median time from cystectomy to development of hematuria was 20.1 (15.6–32.8) months. Positive surgical margins were associated with cancer recurrence in our cohort (p<0.05) (Table 1b). CONCLUSIONS: The majority of patients presenting with gross hematuria following radical cystectomy and ONB have benign etiology, yet up to one-third of patients will have underlying malignancy. A thorough evaluation is required for all patients, especially those with positive surgical margins. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e783 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel I. Sanford More articles by this author Muhannad Alsyouf More articles by this author Sanam Ladi-Seyedian More articles by this author Kevin Wayne More articles by this author Alireza Ghoreifi More articles by this author Anne Schuckman More articles by this author Hooman Djaladat More articles by this author Siamak Daneshmand More articles by this author Expand All Advertisement PDF downloadLoading ...

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.

Neoadjuvant nivolumab (N) + ipilimumab (I) in cisplatin-ineligible patients with upper tract urothelial cancer (UTUC).

511 Background: Perioperative platinum-based chemo for UTUC improves pathologic responses and disease-free survival (DFS) while anti-PD1 monotherapy has limited activity to date (PURE-02). Here, we report the results from stage 1 of a phase II neoadjuvant trial of N+I for cisplatin-ineligible patients (pts) with UTUC. Methods: Cisplatin-ineligible pts with histologically confirmed high-grade UTUC and/or radiographically invasive UTUC with positive selective urine cytology were eligible. Pts were treated with I 3mg/kg + N 1mg/kg (weeks [wk] 0, 6), and N 3mg/kg (wk 3) prior to radical nephroureterectomy (NU). The primary endpoint (EP) was pathologic complete response (pCR, ypT0pN0) and secondary EPs included &lt;ypT2pN0 rate, DFS, and toxicity. The study has a Simon optimal two-stage design: if ≥1/9 pts achieved pCR in stage 1, the trial would proceed to accrue 24 total pts. Next generation sequencing of pre-treatment tumors was correlated with pathologic response. Results: Nine pts were enrolled between 2/2021-7/2022 with median age 71 (range 62-86), 89% male. Primary sites included ureter, n=6; renal pelvis, n=2; and both, n=1. Four pts (44%) had hydronephrosis. Median tumor diameter was 3.0 cm, (range: not measurable to 4.2 cm). Six pts (67%) received all planned treatment; N+/-I was stopped early for CTCAE grade 2 hyperthryoidism, n = 1; grade 2 diarrhea, n = 1; and grade 3 pneumonitis, n = 1. Median time from last treatment to NU was 1.7 months (range 0.6-3.7). No progression was noted on systemic therapy and all pts underwent NU, with pCR in 3/9 pts (33%) and &lt;ypT2pN0 in 6/9 (67%). Two pts had metastatic recurrence at 10.3 and 15.6 months after treatment initiation, while 1 pt died of post-op complications related to bowel leak 7.2 months after N+I initiation (4.7 months after NU) and 1 died 9.2 months after N+I initiation (4.7 months after NU) from complications of a fall unrelated to disease, surgery or N+I. Median tumor mutational burden (TMB) in 7 pts with pre-treatment sequencing was 13.2 mutations/megabase (range 6.6-106.3); all 3 pts with TMB&lt;10 were &gt;ypT1 or node positive at NU and all 4 pts with TMB&gt;10 were &lt;ypT1pN0. Three pts (43%) had FGFR3 driver mutations. Three pts had confirmed pathogenic germline variants in mismatch repair genes (MSH2, n=2; MLH1, n=1), all of which achieved pCR (n=1) or ypTaN0 (n=2) and remained alive and disease-free at last follow-up. CTCAE grade ≥3 treatment-related adverse events occurred in 4 pts (1 myasthenia, 1 maculopapular rash, 1 pneumonitis, 1 hepatitis plus elevated lipase). Conclusions: In this cohort of cisplatin-ineligible pts with UTUC, neoadjuvant N+I showed clinical activity meeting the trial’s Simon optimal two-stage design’s criteria to proceed to the second stage. All pts with pathogenic germline variants in mismatch repair genes achieved &lt;ypT1pN0 and remain free of disease. Clinical trial information: NCT03520491 Clinical trial information: NCT03520491 .

Diagnosis of Upper Urinary Tract Urothelial Cell Carcinoma by Urine Cytology in a Patient with Valvular Heart Disease: A Case Report

A 58-year-old male was admitted to the hospital with severe gross hematuria and many comorbidities such as rheumatic heart disease and severe mitral valve stenosis. Because of atrial fibrillation, the patient took anticoagulant drug for stroke prevention. The patient was requested to stop anticoagulant agents and received blood replacement therapy for blood loss after hospitalization. Ureterorenoscopy was unable to visualize or biopsy the mass due to a massive blood clot. Urine cytology of left and right ureter showed high-grade urothelial carcinoma (HGUC) and few suspicious cells, respectively. Computed tomography angiography (CTA) of the whole abdomen revealed blood clot in the upper pole calyx and renal pelvis of the left kidney as well as the urinary bladder, but no abnormal enhancing lesion. The patient underwent the standard treatment for upper tract urothelial carcinoma (UTUC) with laparoscopic radical nephroureterectomy (RNU) with bladder cuff excision because the consulted cardiologist suggested to start anticoagulant agents as soon as possible. Surgical pathology analysis revealed high-risk tumors with multiple low grade papillary urothelial carcinoma. The patient required long term follow-up. Here, the authors reported a case of UTUC with valvular heart disease, earlier diagnosed by using only positive urinary cytology, rather than by radiological examinations and/or related symptoms before definite treatment. Keywords: Urine Cytology; Upper tract; Ureter; Ureteroscopy; Urothelial carcinoma; False positive; Nephroureterectomy

Does Bladder Cancer with Inchworm Sign Indicate Better Prognosis after TURBT?

Background: Inchworm sign is considered to be a characteristic finding in non-muscle invasive bladder cancer (NMIBC). Nevertheless, pathologically diagnosed muscle invasive bladder cancers (MIBCs) are occasionally diagnosed from tissue obtained by transurethral resection of bladder tumor (TURBT) in patients with inchworm sign. Methods: We retrospectively investigated the factors related to muscle invasive status in bladder cancer associated with inchworm sign and the role of inchworm sign in tumor outcomes following TURBT. Results: Of the 109 patients with inchworm sign, 94 (86.2%) and 15 (13.8%) were NMIBC and MIBC, respectively. Non-papillary tumors (hazard ratio (HR): 9.55, 95% confidence interval (CI): 2.07−44.10; p < 0.01) and tumors located in the bladder neck (HR: 7.73, 95% CI: 1.83−32.76; p < 0.01) were significant predictors of MIBC in bladder cancer with inchworm sign. Furthermore, recurrence-free survival (RFS) and progression-free survival were compared between patients with NMIBC with and without inchworm sign; however, no significant differences were found. In patients with NMIBC with inchworm sign, positive urine cytology was a prognostic factor for RFS (HR: 1.90, 95% CI: 1.04−3.48; p = 0.04). Conclusions: In bladder cancer with inchworm sign, 86.2% were NMIBC. Even in the case of inchworm sign, the presence of a non-papillary tumor or a bladder neck tumor before TURBT should be noted because of the possibility of MIBC. In this study, the inchworm sign was not a prognostic factor in patients with NMIBC.

Active surveillance for non-muscle-invasive bladder cancer: fallacy or opportunity?

This review aims to analyze the current place of active surveillance (AS) in non-muscle-invasive bladder cancer (NMIBC). A growing body of evidence suggests that AS protocols for pTa low-grade (TaLG) NMIBC are safe and feasible. However, current guidelines have not implemented AS due to a lack of high-quality data. Available studies included pTa tumors, with only one study excluding pT1-NMIBC. Inclusion/exclusion criteria were heterogeneously defined based on tumor volume, number of tumors, carcinoma in situ (CIS), or high-grade (HG) NMIBC. Tumor volume <10 mm and <5 lesions were used as cut-offs. Positive urinary cytology (UC) or cancer-related symptoms precluded inclusion. Surveillance within the first year consisted of quarterly cystoscopy. AS stopped upon the presence of cancer-related symptoms, change in tumor morphology, positive UC, or patient's request. With a median time on AS of 16 months, two-thirds of the patients failed AS. Progression to muscle-invasive bladder cancer (MIBC) was rare and occurred only in patients with pT1-NIMBC at inclusion. AS in NMIBC is an attractive concept in the era of personalized medicine, but strong evidence is still awaited. A more precise definition of patient inclusion, follow-up, and failure criteria is required to improve its implementation in daily clinical practice.

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.

Could We Safely Avoid a Second Resection in Selected Patients With T1 Non-Muscle-Invasive Bladder Cancer? Preliminary Results of Cost-Effectiveness Study From HUmanitas New Indications for ReTUR (HuNIRe) Multicenter Prospective Trial.

ObjectivesThe aim of this study is to assess whether restaging transurethral resection (ReTUR) could be safely replaced with urine cytology (UC) and in-office fiexible cystoscopy in selected T1 non-muscle-invasive bladder cancer (NMIBC).Materials and MethodsThis is an ongoing prospective multicenter trial enrolling patients diagnosed with T1 BC from 5 Italian centers. Patients with a macroscopically incomplete initial resection or absence of detrusor muscle were subjected to ReTUR according to European Association of Urology (EAU) guidelines. Conversely, those with a complete tumor resection at initial TUR underwent UC at 3–4 weeks and in-office fiexible white-light and narrow-band cystoscopy at 4–6 weeks. In case of positive UC, or evidence of recurrence at cystoscopy, ReTUR was performed within 2 weeks. Otherwise, patients started Bacillus Calmette–Guérin (BCG) induction course without ReTUR. The primary endpoint was to determine the feasibility and the clinical utility of not performing ReTUR in selected T1 NMIBC patients. The secondary endpoint was to perform a cost–benefit analysis of this alternative approach.ResultsSince May 2020, among 87 patients presenting with T1, 76 patients were enrolled. Nineteen (25%) patients underwent standard ReTUR after initial resection, 10 (13.2%) due to the absence of the detrusor muscle and 9 (11.8%) due to a macroscopically incomplete initial TUR. Overall, 57 (75%) patients initially avoided immediate ReTUR and underwent UC plus in-office flexible cystoscopy. Among them, 38 (66.7%) had no evidence of residual disease and immediately started the BCG induction course. Nineteen patients (33.3%) underwent “salvage” ReTUR due to either positive UC (7; 12.3%) or suspicious cystoscopy (12; 21%). Considering only the patients who initially avoided the ReTUR, disease recurrence was observed in 10/57. The saving of resource for each safely avoided ReTUR was estimated to be 1,759 €. Considering the entire sample, we estimated a saving of 855 € per patient if compared with the EAU guideline approach.ConclusionThe preliminary results of our trial suggested that ReTUR might be safely avoided in highly selected T1 BC patients with a complete resection at first TUR. Longer follow-up and larger sample size are needed to investigate the long-term oncological outcomes of this alternative approach.

MP54-09 URINE COMPREHENSIVE GENOMIC PROFILING PREDICTS RECURRENCE IN PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER TREATED WITH INTRAVESICAL THERAPY

You have accessJournal of UrologyCME1 May 2022MP54-09 URINE COMPREHENSIVE GENOMIC PROFILING PREDICTS RECURRENCE IN PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER TREATED WITH INTRAVESICAL THERAPY Goran Rac, Shalin Desai, Hiten D. Patel, Chirag Doshi, Ryan Dornbier, Vincent Caruso, Peter Lentz, Brian C. Mazzarella, Kevin G. Phillips, Trevor Levin, Alan J. Wolfe, and Gopal N. Gupta Goran RacGoran Rac More articles by this author , Shalin DesaiShalin Desai More articles by this author , Hiten D. PatelHiten D. Patel More articles by this author , Chirag DoshiChirag Doshi More articles by this author , Ryan DornbierRyan Dornbier More articles by this author , Vincent CarusoVincent Caruso More articles by this author , Peter LentzPeter Lentz More articles by this author , Brian C. MazzarellaBrian C. Mazzarella More articles by this author , Kevin G. PhillipsKevin G. Phillips More articles by this author , Trevor LevinTrevor Levin More articles by this author , Alan J. WolfeAlan J. Wolfe More articles by this author , and Gopal N. GuptaGopal N. Gupta More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002633.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intravesical therapy (IVT) is the standard of care for high grade NMIBC. Despite treatment, patients often recur. There is currently no reliable test to assist with risk stratification of patients after treatment. We evaluate an algorithm using urinary comprehensive genomic profiling (uCGP) for recurrence prediction in a prospective cohort with long term follow-up. METHODS: 26 NMIBC patients deemed to be IVT candidates without prior history of IVT were prospectively enrolled from 1/2019 - 3/2020. 88% of subjects received BCG while 12% received Gemcitabine induction. Urine was collected prior to IVT instillation and analyzed using CLIA-validated uCGP (UroAmplitude, Convergent Genomics) to comprehensively measure 60 genes. Blinded classification (high, intermediate, & low recurrence risk) was performed. Hazard ratio, sensitivity, specificity, and AUC for the ROC curve were calculated. Kaplan-Meier curves and log-rank tests were analyzed. RESULTS: High recurrence risk was predicted in 34.6% patients, intermediate in 19.2%, and low recurrence risk in 42.3%. At a mean follow up of 22 mo, 5 (19.2%) patients had a biopsy-confirmed recurrence with an additional 2 (7.7%%) having positive urine cytology without biopsy confirmation. Assessing both types of recurrence, high and intermediate risk prediction had a sensitivity of 100% and specificity of 63.2%. No low recurrence risk subjects experienced recurrence (NPV 100%). An AUC of 0.85 was achieved. High recurrence risk prediction was associated with a 6.5x elevated risk of future recurrence when compared to the other two risk categories, HR=6.5, 95%CI(1.2, 33.8), p=0.026. Kaplan-Meier curves confirmed distinct recurrence free survival between the prediction categories (log-rank p=0.013). Among recurrent patients, the high and intermediate risk groups predicted recurrence a median of 293 days ahead of clinical standard of care diagnosis. CONCLUSIONS: uCGP shows notable promise for prediction of NMBIC recurrence in patients undergoing IVT. Though further study is warranted, this tool may enable risk prognosis among patients with a clinically high risk of recurrence and disease progression. Source of Funding: Support for this research is provided by the NCI through a SBIR Grant, 5R44CA200174, provided to Convergent Genomics © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e929 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Goran Rac More articles by this author Shalin Desai More articles by this author Hiten D. Patel More articles by this author Chirag Doshi More articles by this author Ryan Dornbier More articles by this author Vincent Caruso More articles by this author Peter Lentz More articles by this author Brian C. Mazzarella More articles by this author Kevin G. Phillips More articles by this author Trevor Levin More articles by this author Alan J. Wolfe More articles by this author Gopal N. Gupta More articles by this author Expand All Advertisement PDF DownloadLoading ...

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

Secondary bladder cancer during long-term follow-up after iodine-125 permanent seed implantation for localized prostate cancer

IntroductionBrachytherapy for prostate cancer treatment may induce secondary bladder cancer during long-term follow-ups. This study reviews the risk and tumor characteristics of secondary bladder cancer after brachytherapy. MethodsThis single-institution retrospective study included 1162 patients treated with low-dose-rate permanent seed implantation brachytherapy with iodine-125, with or without external beam radiation therapy, for localized prostate cancer. We calculated and compared the rates of secondary bladder cancer among patients treated with brachytherapy and radical prostatectomy (n = 218) before and after a propensity score-matching analysis. Possible risk factors for secondary bladder cancer, such as patient age and external beam radiation therapy administration, were analyzed. ResultsOf 1162 patients with a median follow-up period of 11.4 (range: 0.7–15.5) years, 26 presented with urothelial carcinomas and 1 with adenocarcinoma at a median of 8.9 (range: 2.9–14.0) years after brachytherapy, although the incidence rates of secondary bladder cancer after brachytherapy were not significantly different from those after radical prostatectomy. No significant risk factors for secondary bladder cancer were identified. The initial symptoms of secondary bladder cancer were gross hematuria (74%) and microscopic hematuria with positive urine cytology (15%). Among 26 cases of secondary urothelial carcinoma, 54% were high-grade and 46% were invasive. After brachytherapy, invasive urothelial carcinoma occurred later than noninvasive urothelial carcinoma (p = 0.01). ConclusionsConsidering the aggressive malignancy of secondary bladder cancer, cystoscopy and urine cytology should be performed for further investigation of the causes of gross or microscopic hematuria and rule out secondary bladder cancer in cases followed longer than 3 years after brachytherapy.

No Added Benefit of Systematic Bladder Biopsies after BCG Induction in High-Risk Non-Muscle-Invasive Bladder Cancer Optimally Managed

Objectives: To evaluate the added detection benefit of routine transurethral biopsies after an induction course of intravesical Bacillus Calmette-Guérin (BCG) for high-grade NMIBC. Methods: We retrospectively included all patients who underwent white and blue light TURB, subsequent adjuvant induction scheme of BCG, followed by post-instillation biopsies. We excluded patients in whom a prior BCG induction course failed those with synchronous upper tract urothelial carcinoma, and those who did not receive the full 6-week course. A total of 62 patients met inclusion criteria and their records were analyzed. Cystoscopy findings, urine cytology and pathological results of transurethral biopsy were evaluated. Sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratios and diagnostic accuracy were calculated for cystoscopy and cytology separately and in combination. Results: After BCG, a total of 342 bladder biopsy were taken with a median of 5 (IQR 2) per case. The biopsy was positive in 13 patients (21%). The median number of positive biopsies was 2 (IQR 1) and the total number of positive biopsies was 27 (8%). The biopsy was positive at the initial tumor site in 8 patients (61.5%). No complications of Clavien III to V were reported. Out of 62 patients who underwent systematic transurethral biopsy, only 3 (5%) presented complications from grade I to II. We found a significant association of positive biopsy with positive urinary cytology (p &lt;0.001) and the presence of erythematous lesions (p &lt;0.02) or visible tumors (p &lt;0.001) at cystoscopy. The pre-BCG stage T (p = 0.32), the presence of CIS (p = 0.71), the multifocal tumor (p = 0.41) and the size (p = 0.52) were not associated with a positive biopsy occurrence. For normal bladder mucosa the predictive value of negative biopsy in cases with negative vs positive cytology was 98% vs 79% (p 0.001). Conclusion: Routine transurethral bladder biopsies after a BCG induction course are not mandatory in the modern era of NMIBC management.

Risk factor analysis of intravesical recurrence after retroperitoneoscopic nephroureterectomy for upper tract urothelial carcinoma

BackgroundOne of the major concerns of patients with upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy is intravesical recurrence (IVR). The purpose of the present study was to investigate the predictive risk factors for IVR after retroperitoneoscopic nephroureterectomy (RNU) for UTUC.MethodsClinicopathological and surgical information were collected from the medical records of 73 patients treated with RNU for non-metastatic UTUC, without a history of or concomitant bladder cancer. The association between IVR after RNU and clinicopathological and surgery-related factors, including preoperative urine cytology and pneumoretroperitoneum time, was analyzed using the Fisher exact test.ResultsDuring the median follow-up time of 39.1 months, 18 (24.7%) patients had subsequent IVR after RNU. The 1- and 3-year IVR-free survival rates were 85.9% and 76.5%, respectively. The Fisher exact test revealed that prolonged pneumoretroperitoneum time of ≥ 210 min was a risk factor for IVR in 1 year after RNU (p = 0.0358) and positive urine cytology was a risk factor for IVR in 3 years after RNU (p = 0.0352).ConclusionsIn UTUC, the occurrences of IVR in 1 and 3 years after RNU are highly probable when the pneumoretroperitoneum time is prolonged (≥ 210 min) and in patients with positive urine cytology, respectively. Strict follow-up after RNU is more probable recommended for these patients.