High-grade pT1 Research Articles

1963O JCOG1019: An open-label, non-inferiority, randomised phase III study comparing the effectiveness of watchful waiting (WW) and intravesical Bacillus Calmette-Guérin (BCG) in patients (Pts) with high-grade pT1 (HGT1) bladder cancer with pT0 on the second transurethral resection (TUR) specimen

1963O JCOG1019: An open-label, non-inferiority, randomised phase III study comparing the effectiveness of watchful waiting (WW) and intravesical Bacillus Calmette-Guérin (BCG) in patients (Pts) with high-grade pT1 (HGT1) bladder cancer with pT0 on the second transurethral resection (TUR) specimen

Profiling energy metabolism in normal bladder tissue and non-muscle-invasive bladder cancer cases of different histological grades

Bladder cancer (BC) stands as the second most common urinary tract malignancy. Recent years have witnessed a growing interest in investigating energy metabolism to help with better understanding the energy sources harnessed by tumor cells. The aims of the present study are to feature and compare cell energy metabolism profiles among different histological grades of non-muscle-invasive BC (NMIBC) by adjusting their bioenergetic cellular indexes based on the specific tumor types. Forty urinary bladder tissue samples from patients both with and without a diagnosis of urothelial lesions were collected. Subsequently, samples were categorized into four groups comprising ten samples each, namely: normal (no urothelial lesions) group, low-grade pTa group, high-grade pTa group, and high-grade pT1 group. These tissue samples were examined by means of immunohistochemistry and Western blotting to assess proteins involved in cell energy metabolism. Based on the current findings, the normal and low-grade pTa groups presented clear preference for the oxidative phosphorylation pathway; consequently, they recorded high bioenergetic cellular index. On the other hand, both the high-grade pTa and pT1 groups presented proclivity towards the glycolytic pathway. These observations, mainly those associated with the bioenergetic cellular index, hold promising clinical relevance in the management of BC. Given the often aggressive and potentially debilitating nature of treatments applied to this neoplasia type, the current study offers invaluable insights on this topic and emphasizes changes in the bioenergetic cellular index at different NMIBC grades, which could serve as potential markers for both the diagnosis and prognosis of NMIBC patients.

Monoamine oxidase as a potential target for the development of new therapeutic strategies for bladder cancer.

e16611 Background: Bladder cancer (BC) is the most common malignancy of the urinary tract and one of the most prevalent cancers worldwide. As the overall prognosis of BC has not changed over the past 30 years, there is a pressing medical need to develop new diagnostic and therapeutic approaches. At present, efforts to deeply understand the pathogenic mechanisms that support urothelial carcinogenesis could help in identifying new therapeutic targets. Monoamine oxidases (MAOs) A and B are oxidative isoenzymes that catalyze the conversion of biogenic amines into their corresponding aldehydes and ketones through oxidative deamination. Recently, MAOs expression have been associated with metastasis and decreased overall survival in various types of cancer. However, the role of MAOs in BC is still poorly explored. This study characterized and compared the molecular profiles of MAO-A and MAO-B isoenzymes in the different histological stages of non-muscle (NMIBC) and muscle (MIBC) invasive bladder cancer, aiming the adaptation of these biomarkers as a criterion of clinical response, risk stratification and outcome prognosis. Methods: Sixty formalin-fixed paraffin-embedded samples of bladder were obtained from 34 to 96-year-old patients (mean 65 years) with BC diagnosis in University of Campinas and Paulinia Municipal Hospital/ Brazil. Subsequently, the samples were divided into 6 groups: pTis group, low-grade pTa group, high-grade pTa group, pT1 group and pT2 group; and submitted to immunohistochemistry analysis for MAO-A and MAO-B. The retrospective anonymous study was approved by the local ethics committee (Clinical Trial: RBR-6swqd2). Results: All stages and grades of NMIBC and pT2 (MIBC) showed positive immunoreactivity for both MAO-A and MAO-B. MAO-A immunoreactivities were significantly higher (p < 0.01) in the high-grade pTa, pTis and pT2 groups in relation to low-grade pTa and pT1. Likewise, MAO-B immunoreactivities were remarkably higher (p < 0.01) in the high-grade pTa and pT2 groups. No statistical differences were found between pTis and low-grade pTa for MAO-B. Interestingly, pT1 group showed the lowest (p < 0.01) MAO-A and MAO-B immunoreactivities in relation to other stages and grades of BC, probably due to disruption of the extracellular matrix, with consequent reduction in O2 delivery (hypoxia). Conclusions: These findings collectively characterize the contribution of MAOs in BC pathogenesis and suggest that MAOs have potential as a therapeutic target in BC.

Clinical implications of T-Cells CX3CR1+, Toll-like Receptor 4 signaling pathway, and immune checkpoints in Non-Muscle Invasive Bladder Cancer

Background: This study characterized and compared the molecular profiles of CX3C chemokine receptor 1 (CX3CR1, a marker of T-cell differentiation), Toll-like receptor 4 (TLR4)-mediated interferon signaling pathway, and immune checkpoints in the different histological stages of non-muscle invasive bladder cancer (NMIBC), aiming the investigation of these biomarkers as a criterion of clinical response to immunotherapy. Methods: Seventy-five formalin-fixed paraffin-embedded samples of bladder were obtained from 34 to 96-year-old patients (mean 65 years) with NMIBC diagnosis in University of Campinas (UNICAMP) and Paulinia Municipal Hospital/ Brazil. Subsequently, the samples were divided into 3 groups (n= 25 samples per group): pTis group, high-grade pTa group, and pT1 group; and submitted to immunohistochemistry analysis: TLR4-mediated IFN-γ production signaling pathway (TRIF, TBK1, IRF-3, IFN-γ), CX3CR1+CD8+ T-cells, immune checkpoints (PD-1/PD-L1 and CTLA-4), and regulatory T (Treg) cells (FOXP3). The retrospective anonymous study was approved by the local ethics committee (Clinical Trial: RBR-6swqd2). Results: pTis group showed the lowest activation of TLR4-mediated IFN-γ signaling pathway when compared (p<0.01) to high-grade pTa and pT1 groups. Both the immunoreaction intensity and positive cells percentage were lower (p<0.01) for TLR4, TRIF, IRF-3, and IFN-γ in the pTis group with respect to other groups. No statistical difference was found between high-grade pTa and pT1 groups for these biomarkers. Likewise, CX3CR1 immunoreactivities were remarkably lower (p<0.01) in the pTis group in comparison with high-grade pTa and pT1 groups, which did not show statistical differences between them. Furthermore, immune checkpoints (PD-1/PD-L1 and CTLA4) and FOXP3+ Treg cells immunoreactivities were significantly higher (p<0.01) in the high-grade pTa and pT1 compared to the pTis group. Conclusions: Our data demonstrated that pTis stage was characterized by an immunosuppressive microenvironment in comparison with pTa and pT1 stages, showing decreased TLR4-mediated interferon signaling pathway and low activation of CX3CR1+CD8+ T-cells; which implies in low sensitivity to immunotherapy. The larger number of FOXP3+ Treg cells in pTa and pT1 was correlated with intensified immune checkpoints immunoreactivities, indicating higher sensitivity to immunotherapy. Finally, these biomarkers may be useful in the clinical management of patients with NMIBC.

MP08-08 EN BLOC RESECTION VERSUS CONVENTIONAL TURBT FOR T1HG BLADDER CANCER: A PROPENSITY SCORE-MATCHED ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023MP08-08 EN BLOC RESECTION VERSUS CONVENTIONAL TURBT FOR T1HG BLADDER CANCER: A PROPENSITY SCORE-MATCHED ANALYSIS Takafumi Yanagisawa, Akihiro Matsukawa, Kosuke Iwatani, Shun Sato, Yasushi Hayashida, Yohei Okada, Takashi Yorozu, Wataru Fukuokaya, Keigo Sakanaka, Fumihiko Urabe, Shoji Kimura, Shunsuke Tsuzuki, Jun Miki, Masayuki Shimoda, Hiroyuki Takahashi, Shahrokh F. Shariat, and Takahiro Kimura Takafumi YanagisawaTakafumi Yanagisawa More articles by this author , Akihiro MatsukawaAkihiro Matsukawa More articles by this author , Kosuke IwataniKosuke Iwatani More articles by this author , Shun SatoShun Sato More articles by this author , Yasushi HayashidaYasushi Hayashida More articles by this author , Yohei OkadaYohei Okada More articles by this author , Takashi YorozuTakashi Yorozu More articles by this author , Wataru FukuokayaWataru Fukuokaya More articles by this author , Keigo SakanakaKeigo Sakanaka More articles by this author , Fumihiko UrabeFumihiko Urabe More articles by this author , Shoji KimuraShoji Kimura More articles by this author , Shunsuke TsuzukiShunsuke Tsuzuki More articles by this author , Jun MikiJun Miki More articles by this author , Masayuki ShimodaMasayuki Shimoda More articles by this author , Hiroyuki TakahashiHiroyuki Takahashi More articles by this author , Shahrokh F. ShariatShahrokh F. Shariat More articles by this author , and Takahiro KimuraTakahiro Kimura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003223.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The potential benefits of en bloc resection of bladder tumor (ERBT) compared to cTURBT have not been well verified, specifically for pT1 bladder cancer. We aimed to assess the clinical, oncological, and pathological impact of en bloc resection of bladder tumors (ERBT) compared to conventional transurethral resection of bladder tumors (cTURBT) for pT1 high grade (HG) bladder cancer. METHODS: We retrospectively analyzed the record of 326 patients (cTURBT: n=216, ERBT: n=110) diagnosed with pT1 HG bladder cancer at multiple institutions. The cohorts were matched by one-to-one propensity scores based on patient and tumor demographics. Recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), perioperative and pathologic outcomes were compared. The prognosticators of RFS and PFS were analyzed using the Cox proportional hazard model. RESULTS: After matching, 202 patients (cTURBT: n=101, ERBT: n=101) were retained. There were no differences in perioperative outcomes between the two procedures. The 3-year RFS, PFS as well as CSS were not different between the two procedures (p=0.7, 1, 0.7, respectively). Among patients who underwent repeat transurethral resection (reTUR), the rate of any residue on reTUR were significantly lower in the ERBT group (cTURBT: 36% vs. ERBT: 15%, p=0.029). Adequate sampling of muscularis propria (83% vs. 93%, p=0.029), diagnostic rates of pT1a/b substaging (90% vs. 100%, p<0.001) were significantly better in ERBT specimen compared to cTURBT specimen. In multivariable analyses, pT1a/b substaging was a prognosticator of disease progression. CONCLUSIONS: In pT1HG bladder cancer patients, ERBT had similar perioperative and mid-term oncologic outcomes compared to cTURBT. However, ERBT improves the quality of resection and specimen, yielding less residue on reTUR and superior histopathologic information such as substaging. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e96 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takafumi Yanagisawa More articles by this author Akihiro Matsukawa More articles by this author Kosuke Iwatani More articles by this author Shun Sato More articles by this author Yasushi Hayashida More articles by this author Yohei Okada More articles by this author Takashi Yorozu More articles by this author Wataru Fukuokaya More articles by this author Keigo Sakanaka More articles by this author Fumihiko Urabe More articles by this author Shoji Kimura More articles by this author Shunsuke Tsuzuki More articles by this author Jun Miki More articles by this author Masayuki Shimoda More articles by this author Hiroyuki Takahashi More articles by this author Shahrokh F. Shariat More articles by this author Takahiro Kimura More articles by this author Expand All Advertisement PDF downloadLoading ...

V06-10 LEFT ROBOT-ASSISTED UPPER POLE HEMINEPHRECTOMY FOR UPPER URINARY TRACT UROTHELIAL CANCER IN LYNCH SYNDROME

You have accessJournal of UrologyCME1 Apr 2023V06-10 LEFT ROBOT-ASSISTED UPPER POLE HEMINEPHRECTOMY FOR UPPER URINARY TRACT UROTHELIAL CANCER IN LYNCH SYNDROME Abderrahmane Khaddad, Xavier Lacroix, Margue Gaëlle, Alezra Eric, Vincent Estrade, Grégoire Capon, Franck Bladou, Grégoire Robert, Jean-Jacques Patard, and Jean-Christophe Bernhard Abderrahmane KhaddadAbderrahmane Khaddad More articles by this author , Xavier LacroixXavier Lacroix More articles by this author , Margue GaëlleMargue Gaëlle More articles by this author , Alezra EricAlezra Eric More articles by this author , Vincent EstradeVincent Estrade More articles by this author , Grégoire CaponGrégoire Capon More articles by this author , Franck BladouFranck Bladou More articles by this author , Grégoire RobertGrégoire Robert More articles by this author , Jean-Jacques PatardJean-Jacques Patard More articles by this author , and Jean-Christophe BernhardJean-Christophe Bernhard More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003274.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Partial nephrectomy is not recommended in kidney urothelial carcinoma, but may be considered in exceptional cases, mainly in case of poor nephronic capital or a genetic disease with high risk of recurrence. We selected for this video one of these exceptional cases, performed by minimally invasive robotic approach. METHODS: The case is a 55-year-old patient in good general state followed for Lynch syndrome, with a history of subtotal colectomy. History of 2 localizations of low-grade urothelial carcinoma. The first one was in the upper calyx of the left kidney, treated conservatively with laser. The second one was in the bladder, treated by resection and mitomycin instillations. During follow-up, he presented with a recurrence in the superior calyx of the left kidney, which had become inaccessible endoscopically due to post-treatment stenosis. In this patient at high risk of recurrence, we performed a 3D image guided left robot-assisted upper pole heminephrectomy, with anatomical devascularisation and without opening of the excretory tract. The procedure was performed using the Da Vinci surgical robot (Intuitive Surgical) and the 3D model was created with Synapse 3D. RESULTS: The procedure begins with the complete release of the kidney and the precise dissection of the pedicle. The 3D model was used to perform the anatomical devascularization of the upper pole of the kidney. The tumor calicium stem was excluded before it section. The section of the parenchyma was performed without arterial clamping. Hemostasis of the renal slice was performed with V-lok wire, and Tachosyl sponge. The urinary tract was closed with absorbable monofilament, without drainage. Operative time was 5 h 45 and estimated blood loss was 250 ml. Patient discharge at post-operative day 1. Pathology report showed a high grade pT1 urothelial papillary carcinoma of complete resection. No upper tract recurence was observed at 7 months endoscopic control. CONCLUSIONS: Standard treatment of high-risk kidney urothelial carcinoma is radical nephroureterectomy. Partial nephrectomy and other conservative treatments may be considered in exceptional cases or poor nephronic capital, or high risk of recurrence (Lynch). In any case, the opening of the excretory tract must be avoided in order to avoid the risk of tumor dissemination. Moreover, all conservative treatment must require very regular and close endoscopic follow-up. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e511 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Abderrahmane Khaddad More articles by this author Xavier Lacroix More articles by this author Margue Gaëlle More articles by this author Alezra Eric More articles by this author Vincent Estrade More articles by this author Grégoire Capon More articles by this author Franck Bladou More articles by this author Grégoire Robert More articles by this author Jean-Jacques Patard More articles by this author Jean-Christophe Bernhard More articles by this author Expand All Advertisement PDF downloadLoading ...

En Bloc Resection Versus Conventional TURBT for T1HG Bladder Cancer: A Propensity Score-Matched Analysis

We aimed to assess the clinical, oncological, and pathological impact of en bloc resection of bladder tumors (ERBT) compared with conventional transurethral resection of bladder tumors (cTURBT) for pT1 high-grade (HG) bladder cancer. We retrospectively analyzed the record of 326 patients (cTURBT: n = 216, ERBT: n = 110) diagnosed with pT1 HG bladder cancer at multiple institutions. The cohorts were matched by one-to-one propensity scores based on patient and tumor demographics. Recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and perioperative and pathologic outcomes were compared. The prognosticators of RFS and PFS were analyzed using the Cox proportional hazard model. After matching, 202 patients (cTURBT: n = 101, ERBT: n = 101) were retained. There were no differences in perioperative outcomes between the two procedures. The 3-year RFS, PFS, and CSS were not different between the two procedures (p = 0.7, 1, and 0.7, respectively). Among patients who underwent repeat transurethral resection (reTUR), the rate of any residue on reTUR was significantly lower in the ERBT group (cTURBT: 36% versus ERBT: 15%, p = 0.029). Adequate sampling of muscularis propria (83% versus 93%, p = 0.029) and diagnostic rates of pT1a/b substaging (90% versus 100%, p < 0.001) were significantly better in ERBT specimen compared with cTURBT specimen. On multivariable analyses, pT1a/b substaging was a prognosticator of disease progression. In patients with pT1HG bladder cancer, ERBT had similar perioperative and mid-term oncologic outcomes compared with cTURBT. However, ERBT improves the quality of resection and specimen, yielding less residue on reTUR and yielding superior histopathologic information such as substaging.

Prospective Validation of the ROL System in Substaging pT1 High-Grade Urothelial Carcinoma: Results from a Mono-Institutional Confirmatory Analysis in BCG Treated Patients.

Patients with pT1 high-grade (HG) urothelial carcinoma (UC) and a very high risk of progression might benefit from immediate radical cystectomy (RC), but this option remains controversial. Validation of a standardized method to evaluate the extent of lamina propria (LP) invasion (with recognized prognostic value) in transurethral resection (TURBT) specimens is still needed. The Rete Oncologica Lombarda (ROL) system showed a high predictive value for progression after TURBT in recent retrospective studies. The ROL system was supposed to be validated on a large prospective series of primary urothelial carcinomas from a single institution. From 2016 to 2020, we adopted ROL for all patients with pT1 HG UC on TURBT. We employed a 1.0-mm threshold to stratify tumors in ROL1 and ROL2. A total of 222 pT1 HG UC were analyzed. The median age was 74 years, with a predominance of men (73.8%). ROL was feasible in all cases: 91 cases were ROL1 (41%), and 131 were ROL2 (59%). At a median follow-up of 26.9 months (IQR 13.8-40.6), we registered 81 recurrences and 40 progressions. ROL was a significant predictor of tumor progression in both univariable (HR 3.53; CI 95% 1.56-7.99; p < 0.01) and multivariable (HR 2.88; CI 95% 1.24-6.66; p = 0.01) Cox regression analyses. At Kaplan-Meier estimates, ROL showed a correlation with both PFS (p = 0.0012) and RFS (p = 0.0167). Our results confirmed the strong predictive value of ROL for progression in a large prospective series. We encourage the application of ROL for reporting the extent of LP invasion, substaging T1 HG UC, and improving risk tables for urological decision-making.

Meta-analysis of global variations in grade of pT1 urothelial bladder cancer and supplementary evaluation of a Sri Lankan cohort

Introduction: Bladder cancer grading is fraught with ambiguity. We aimed to conduct a meta-analysis of grading of pT1 urothelial cancers and assess histopathology and outcomes in a Sri Lankan pT1 bladder cancer cohort. Patients and Method: A meta-analysis of grading of pT1 urothelial cancers was conducted as per PRISMA guidelines. A second metaanalysis of the proportion of pTa/NMIBC at disease presentation was conducted to assess impact of delayed presentation on grading. Analysis was supplemented with data from a cohort of Sri Lankan patients. Results: In the meta-analysis, the overall pooled pT1 HG prevalence was 75.3% [95% CI:68.3%-81.7%]. The pT1 HG prevalence was significantly higher (p=4.916878e-11) among the European, Japanese and Taiwanese studies at 90.1% [95% CI: 85.3%-94.0%] compared to the rest of the countries at 56.1% [95% CI:46.5%-65.4%]. The overall pooled pTa/NMIBC prevalence was 44.2% [95% CI:36.4%-52.1%]. The pTa/NMIBC percentage among Europe, China and Taiwan was 66.9%[95% CI:62.4%-71.2%] and it was 37.6% [95% CI:29.0%-46.6%] in Turkey and other Asian countries indicating a significant difference(P=1.08e-08). In the Sri Lankan cohort of 66 enrolled patients, 31(47%) had pT1, of which 61% were low-grade (LG). The 5-year progressionfree survival (PFS) of pT1 was 60.9%. In LG it was 85.7% and 22.2% in high-grade (HG) (P = 0.0006). Conclusion: There is a global variation of percentages of pT1 LG versus HG disease in bladder cancer specimens at presentation which could be attributed to delay in treatment with stage migration, ethnic variations in tumour biology, and interobserver variability in assigning a grade of tumour, and needs further study.

P19 - Development of a specific miRNA signature to characterize the invasion potential of pT1 high grade tumors of the bladder

P19 - Development of a specific miRNA signature to characterize the invasion potential of pT1 high grade tumors of the bladder

Reduction of residual tumors by photodynamic diagnosis-assisted TURBT using 5-aminolevulinic acid for high-risk nonmuscle-invasive bladder cancer (BRIGHT study).

489 Background: High-risk non-muscle invasive bladder cancer (NMIBC) has high tumor residual rate of 40–60% after TURBT, and second TUR is strongly recommended. Photodynamic diagnosis-assisted TURBT (PDD-TURBT) using 5-aminolevulinic acid (5-ALA) has been reported to reduce residual tumors and intravesical recurrence. The purpose of this study is to investigate the residual tumor-reducing effect of PDD-TURBT for high-risk NMIBC and to explore the possibility that second TUR could be omitted by PDD-TURBT. Methods: We conducted an investigator-initiated multicenter prospective observational study (BRIGHT study; UMIN000035712) involving patients who underwent PDD-TURBT using 5-ALA and second TUR for high-risk NMIBC (high-grade UC or pT1 or concurrent CIS). The primary endpoint was tumor residual rate and the secondary endpoint was recurrence-free survival, which were compared with historical data (conventional TURBT) using propensity score-matching (PSM; caliper: 0.2). Assuming that the difference between the two groups was 20%, the planned number of cases was statistically set to 200 PDD-TURBT cases and 300 historical data cases, and the registration period was 2 years from January 2019 to December 2020, and the follow-up period was 2 years after second TUR. Results: In this study, 188 patients in the PDD-TURBT group and 313 patients in the historical group were enrolled, and 177 patients and 306 patients were included in the final analysis, respectively. After PSM adjustment, 167 patients in both groups were compared, and no significant differences were observed in age, gender, history of bladder cancer, tumor diameter, number of tumors, history of upper tract urothelial cancer, and period from initial TURBT to second TUR. The tumor residual rate was 25.8% in the PDD-TURBT group compared with 47.3% in the historical group, showing a significant decrease (odds ratio 0.39 [95% CI: 0.24–0.63]; p = 0.000064). Logistic regression analysis revealed that significant factors predicting residual tumors in PDD-TURBT were current or past smoking history, multiple tumors, and non-pTa (pT1 or pTis) tumors. Focusing on these three factors, patients with 0–1 of these three factors have a significant less tumor residual rate compared with patients with 2–3 factors (8.33% vs. 33.3%; odds ratio 5.46 [95% CI: 1.81–22.3]; p = 0.00052). Conclusions: PDD-TURBT for high-risk NMIBC significantly reduced the tumor residual rate at the second TUR compared to the conventional TURBT. PDD-TURBT using 5-ALA may enable to omit second TUR in some high-risk NMIBC cases. Clinical trial information: UMIN000035712.

Results of Repeat Transurethral Resection of Bladder Tumor After Macroscopically Complete Primary Resection

Introduction: Non-muscle invasive (NMI) bladder cancers (BC) account for 75% of BC cases, and most are initially diagnosed and treated with transurethral resection of bladder tumor (TURB). After primary TURB, a repeat resection (rTURB) should be carried out in cases of incomplete resection; however, rTURB is recommended by EAU guidelines in pT1 tumors even when the completeness of the original resection is believed by the surgeon, with reported rates of residual tumor in up to 33%-55% and upstaging in up to 25%. Since the quality of initial resection impacts in the result of a rTURB, these rates are largely dependent on the primary treatment and accurate prediction of completeness, with a probable high variability between surgeons and Centres. Our objectives to determine whether rTURB after initial perceived complete resection would frequently identify residual tumor and if this procedure would improve outcomes in NMIBC patients. Methods: Patients submitted to TURB from 2015 to 2017 were analysed, identifying which underwent rTURB after initial resection without follow-up cystoscopy in between. Primary perception of completeness, stage and grade were correlated with the eventual presence, stage and grade of residual tumor. Results: We analyzed 546 TURB procedures; of these, 275 (50.4%) were for primary bladder cancer. pT1 lesions were found in 85 (30.9%) of primary TURBs; 12 of these were selected for rTURB due to incomplete resection. Of the remaining 73 macros- copically completely resected primary pT1 tumors, 26 (30.6%) underwent elective rTURB. Repeat TURB after complete resection of primary pT1 tumors yielded residual tumor in 11.5% of patients (n= 3). All patients with residual tumor had primary pT1 high grade lesions; no upstaging or upgrading was observed. Patients had similar recurrence rates at 1-year regardless of rTURB. Discussion/Conclusion: Standard practice in primary TURB pro- cedures varies across surgeons and centers and will reflect on residual tumor rates. Indications for rTURB might not be suitable for all patients, and single Centre results should be taken in consideration when selecting patients for rTURB.

Use of a Small-Diameter Resectoscope on a Patient with Extensive Urethral Strictures for Transurethral Resection

This case refers to a 60-year-old male suffering from an extensive circular urethral stricture throughout the whole length of the urethra, with the coexistence of a papillomatous tumor of the urinary bladder. The insertion of the resectoscope through the urethra was impossible, despite previous dilations with Benique. Therefore, an internal urethrotomy was performed. From May 2020 to September 2022, the patient was submitted to three TUR-BTs with the use of a smaller diameter resectoscope (22ch). The histology report resulted in TCC (Transitional Cell Carcinoma) stage pT1 high grade. The patient was then administered intravesical bacillus Calmette-Guerin installations. The last TUR-BT took place in October 2022. It was impossible to insert the conventional 22ch resectoscope through the urethra, so the Delmont gynecological resectoscope was used instead. This resectoscope by the French company Delmont has the same length as the conventional urological resectoscopes, but the important fact is its smaller diameter (18, 5 ch), allowing the surgeon to pass through the urethra and approach the papillomatous lesion in the bladder. The lesion was resected transurethrally, and the histological examination resulted in TCC with focal infiltration of the muscle layer, stage pT2 high grade. In this way, it was possible to complete the surgical procedure in a case that the conventional resectoscope could not enter the urethra, and the outcome was exceptional. In November 2022, following the Oncology–Urology Council of the hospital, it was decided for the patient to receive neoadjuvant chemotherapy followed by radical cystoprostatectomy.

Simultaneous laparoscopic nephroureterectomy and robot-assisted anterior pelvic exenteration with intracorporeal ileal conduit urinary diversion: step-by-step video-illustrated technique

ABSTRACTIntroduction:One of the most remarkable characteristics of urothelial carcinomas is multifocality. However, occurrence of synchronous bladder cancer and upper urinary tract urothelial cancer (UTUC) is exceptional. Minimally invasive approach for these synchronous tumors was just occasionally reported (1-4). The aim of this video article is to describe step-by-step the technique for simultaneous laparoscopic nephroureterectomy and robot-assisted anterior pelvic exenteration with intracorporeal ileal conduit urinary diversion (ICUD). Patients and methods: A 66-year-old female presented with synchronous BCG refractory non-muscle invasive bladder cancer and a right-side UTUC. She was a former smoker and had previously been submitted to multiple transurethral resections of bladder tumor, BCG and right distal ureterectomy with ureteral reimplant. We performed a simultaneous laparoscopic right nephroureterectomy and robot-assisted anterior pelvic exenteration with totally intracorporeal ICUD. Combination of robot-assisted and pure laparoscopic approaches was proposed focusing on optimization of total operative time (TOT).Results:Surgery was uneventful. TOT was of 330 minutes. Operative time for nephroureterectomy, anterior pelvic exenteration and ICUD were 48, 135, 87 minutes, respectively. Estimated blood loss was 150mL. Postoperative course was unremarkable and patient was discharged after 7 days.Histopathological evaluation showed a pT1 high grade urothelial carcinoma plus carcinoma in situ both in proximal right ureter and bladder, with negative margins. Twelve lymph nodes were excised, all of them negative.Conclusion:In our preliminary experience, totally minimally invasive simultaneous nephroureterectomy and cystectomy with intracorporeal ICUD is feasible. Pure laparoscopic approach to upper urinary tract may be a useful tactic to reduce total operative time.

Prognostic analysis of patients with T1 stage high grade of bladder urothelial carcinoma and glandular differentiation

Objective: To evaluate the recurrence and progression of patients with pT1 high grade urothelial carcinoma of bladder (UCB) and glandular differentiation. Methods: We retrospectively analyzed the clinical and pathological information of 208 patients diagnosed as pT1 high grade urothelial carcinoma in the Fifth Central Hospital of Tianjin from January 2006 to February 2019.Among them, 78 cases were diagnosed as glandular differentiation (UCGD), the other 130 patients without histologic variants were served as control. The UCGD group included 62 male and 16 female, whose median age was 67 years old (range 38-81 years old). The control group contained 105 male and 25 female, whose median age was 66 years old (range 40-82 years old). Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate the predictors of oncologic outcomes. Results: The disease recurrence rate and progression rate in UCGD group were 65.4% (51/78) and 28.2% (22/78), higher than 38.5%(50/130) and 14.6%(19/130) of control group (P<0.05). The median recurrence time in UCGD group was 41 months while 55 months in the control group. The median progression time in UCGD group was 39 months while 54 months in the control group. According to the univariate analysis, largest tumor size (P=0.030), UCGD (P=0.003) and lymphovascular invasion (LVI) (P=0.032) were associated with disease recurrence. UCGD (P=0.036) and LVI (P=0.011) were associated with progression. Additionally, Cox multivariate analysis revealed that UCGD (P=0.001), LVI (P=0.038) were the independent factors of disease recurrence. UCGD (P=0.007) and LVI (P=0.037) were also found to be the independent factors of disease progression. Conclusions: Patients with T1 stage UCB and UCGD are at higher risk of disease recurrence and progression. Therefore, these patients should be followed up closely after being diagnosed and undergo individual treatment according to the situation.

Abstract B10: A simple immunohistochemical algorithm to evaluate molecular subtypes and clinical associations in non-muscle invasive bladder cancer

Abstract Introduction: Recent large-scale transcriptomic studies in muscle-invasive bladder cancer (MIBC) have identified promising predictive and prognostic properties of luminal, basal, and additional molecular subtypes. Transcriptomic profiling is laborious, expensive, and prone to errors due to infiltrating lymphocytes and variations in tumor cellularity. Immunohistochemistry (IHC) provides a faster, cheaper, and clinically feasible subtyping method that has been validated to subtype MIBC (1) and simplified into a three-antibody algorithm (2). Here we utilize this algorithm in non-muscle invasive bladder cancer (NMIBC), where, in contrast to MIBC, there are few data exploring IHC subtypes. Methods: We implemented the simplified three-antibody IHC-based algorithm to subtype a cohort of 523 non-muscle invasive (stages pTa low grade, pTa high grade, and pT1 high grade) transurethral resections of bladder tumor (TURBT) samples. Cases were sampled in duplicate on six tissue microarray blocks. Spatial localization, prevalence, and intensity of antibody staining was scored using digital image analysis. Results: Similar to previous transcriptome-based work (3), preliminary analysis identified the prevalence of Urothelial-Like (Uro-like), Genomically Unstable (GU), Basal-Squamous Cell Carcinoma-Like (BSq), and unclassified subtypes at 33% n=171, 48%, n=251, 9%, n=46, and 10%, n= 55, respectively. As expected, GU was enriched in pTa high grade and pT1 tumors, but surprisingly, BSq cancers were more similar to Uro-like in stage and grade distribution. Discussion: Molecular subtypes of bladder cancer can be identified easily using a three-antibody assay. Subtypes that signify high risk of metastasis in MIBC are surprisingly prevalent in NMIBC but may not yet have acquired the molecular lesions that drive metastatic progression. Further research into subtype and progression should be accelerated by the availability of rapid and inexpensive IHC-based assays.

Pure high-grade papillary urothelial bladder cancer: a luminal-like subgroup with potential for targeted therapy

PurposeNon-invasive high-grade (HG) bladder cancer is a heterogeneous disease that is characterized insufficiently. First-line Bacillus Calmette-Guérin instillation fails in a substantial amount of cases and alternative bladder-preserving treatments are limited, underlining the need to promote a further molecular understanding of non-invasive HG lesions. Here, we characterized pure HG papillary urothelial bladder cancer (pure pTa HG), a potential subgroup of non-invasive HG bladder carcinomas, with regard to molecular subtype affiliation and potential for targeted therapy.MethodsAn immunohistochemistry panel comprising luminal (KRT20, ERBB2, ESR2, GATA3) and basal (KRT5/6, KRT14) markers as well as p53 and FGFR3 was used to analyze molecular subtype affiliations of 78 pure pTa HG/papillary pT1(a) HG samples. In 66 of these, ERBB2 fluorescence in situ hybridization was performed. Additionally, targeted sequencing (31 genes) of 19 pTa HG cases was conducted, focusing on known therapeutic targets or those described to predict response to targeted therapies noted in registered clinical trials or that are already approved.ResultsWe found that pure pTa HG/papillary pT1(a) HG lesions were characterized by a luminal-like phenotype associated with frequent (58% of samples) moderate to high ERBB2 protein expression, rare FGFR3 alterations on genomic and protein levels, and a high frequency (89% of samples) of chromatin-modifying gene alterations. Of note, 95% of pTa HG/papillary pT1 HG cases harbored at least one potential druggable genomic alteration.ConclusionsOur data should help guiding the selection of targeted therapies for investigation in future clinical trials and, additionally, may provide a basis for prospective mechanistic studies of pTa HG pathogenesis.

Value of separate tumor base biopsy in transurethral resection of bladder tumors

IntroductionThe aim of our study was to evaluate whether a biopsy from the tumor base after transurethral resection of bladder tumor (TURBT) has an impact on subsequent management of patients with bladder tumors. While tumor base biopsy at the completion of TURBT is a common practice, there is no definition of its role within the major international professional guidelines.Material and methodsWe retrospectively reviewed the records of consecutive patients undergoing TURBT between 2015 and 2019 at our institution. We recorded demographic and tumor characteristics of initial TURBT, tumor base biopsy and restaging TURBT pathology outcomes. The pathologic outcomes were correlated to assess the additional value of a separate tumor base biopsy.ResultsA total of 532 patients underwent TURBT. A separate tumor base biopsy after completion of TURBT was performed in 154 patients. The mean patient's age was 72.8 ±11.7 years (range 48–94) and 119 (77.2%) were men. In 40 patients (25.9%) muscle was absent in the pathological specimen of the tumor resection. Muscle was present in all but 6 (3.9%) tumor base biopsies. Of the 33 patients who underwent repeated transurethral resection for pT1 tumors, 2 had residual low-grade pTa, 1 had residual high-grade pT1, and 3 patients were upstaged to pT2.ConclusionsAlthough tumor base biopsy at the completion of TURBT is a common practice, our analysis fails to demonstrate any tangible benefit in the staging of bladder tumors. In our experience tumor base biopsy did not change the management in patients with superficial or muscle invasive disease.

Intérêt de la résection complémentaire (ou « second look ») pour les carcinomes urothéliaux de vessie classés pTa haut grade

Second look TURB (Transurethral Resection of Bladder Tumor) is recommended for high-risk pT1 tumors. It is well acquired for tumors classified pT1 high grade but its interest is still discussed for high-grade pTa tumors in the absence of high level of evidence. We evaluated the impact of second-look resection for the high-grade pTa bladder tumor. We performed a retrospective study in 2 centers from 2007 to 2016. We included all urothelial tumors classified pTa high grade. We studied the anatomopathological findings of reTURB and its consequences on survival without recurrence and progression. Eighty-four patients were included. Thirty-five patients (41.7%) had reTURB and residual tumor was found in 42.9% of cases. The anatomopathology of reTURB was in 20% of cases high grade pTa, in 14.3% of cases pTis, and in 8.6% of cases pT1. Forty-three patients had recurrence, 13 reTURB patients (30.2%). In the patients who had a reTURB, 12 had recurrence (34.3%) against 31 without reTURB, (63.3%). After the first TURB, 45 patients (53.6%) had bladder instillation: 38 received BCG (45.2%) and 7 ametycin (8.3%). The main factor decreasing recurrence was BCG adjuvant therapy (HR=0.4 [0.2-0.9], P=0.02). The absence of reRTUV appeared to be a recurrence factor, but the result was not statistically significant (HR=1.4 [0.7-3], P=0.3). reTURB confirms that residual tumor is often found. His interest in survival without recurrence remains to be proved by a prospective study with a larger number of patients. 3.

Second Transurethral Resection (TUR) for Bladder Cancer Diagnosed with High Grade pT1 by Initial TUR Under Narrow Band Imaging

We evaluated 52 consecutive cases of patients undergoing second transurethral resections (TUR) for non-muscle invasive bladder cancer (NMIBC) in which the patients were diagnosed with high grade pT1 by the initial TUR under narrow band imaging (NBI). The initial TUR under NBI (NBI-TUR) was performed : Systematic intravesical observation under white light imaging (WLI) and NBI was followed by a multiple site biopsy (MSB), after which lesions detected in positive findings were resected completely under NBI. The tumor detection rates under WLI and NBI were calculated separately and compared with endoscopic findings and MSB samples. The second TUR was performed as a resection that included the surrounding mucosa and muscle layer of the initial NBI-TUR scar under WLI observation, 4-8 weeks after the initial NBI-TUR. The patients were divided into two groups : The residual cancer lesion-positive group (NBIR positive), and the residual cancer lesion-negative group (NBIR negative). The tumor detection rate under NBI was more sensitive compared with that under WLI in the initial NBI-TUR (89.4% vs 59.1% p< 0.0001), and the residual cancer detection rate in the 2nd TUR reached 34.6% (18/52). There was no significant difference in the background factors between the NBIR positive and NBIR negative. While the number of cancer lesions detected under NBI was significantly higher than that under WLI in the NMIBCdiagnosed high grade pT1, the rate of cancer lesions that were difficult to identify in the initial NBI-TUR was still high. These findings demonstrate the limitations of the mono-therapeutic effect of NBI-TUR.