High Grade NMIBC Research Articles

The long noncoding RNA SUMO1P3 as urinary biomarker for monitoring bladder cancer progression

IntroductionUrothelial Bladder Cancer (BC) is the ninth most common cancer worldwide. It is classified into Non Muscle Invasive (NMIBC) and Muscle Invasive Bladder Cancer (MIBC), which are characterized by frequent recurrences and progression rate, respectively. The diagnosis and monitoring are obtained through invasive methods as cystoscopy and post-surgery biopsies. Thus, a panel of biomarkers able to discriminate BC based on grading or staging represents a significant step forward in the patients’ workup. In this perspective, long non-coding RNAs (lncRNAs) are emerged as reliable candidates as potential biomarker given their specific and regulated expression. In the present work we propose two lncRNAs, the Small Ubiquitin Modifier 1 pseudogene 3 (SUMO1P3), a poorly characterized pseudogene, and the Urothelial Carcinoma Associated 1 (UCA1) as candidates to monitor the BC progression.MethodsThis study was a retrospective trial enrolling NMIBC and MIBC patients undergoing surgical intervention: the expression of the lncRNA SUMO1P3 and UCA1 was evaluated in urine from 113 subjects (cases and controls). The receiver operating characteristic curve analysis was used to evaluate the performance of single or combined biomarkers in discriminating cases from controls.ResultsSUMO1P3 and UCA1 expression in urine was able to significantly discriminate low grade NMIBC, healthy control and benign prostatic hyperplasia subjects versus high grade NMIBC and MIBC patients. We also demonstrated that miR-320a, which binds SUMO1P3, was reduced in high grade NMIBC and MIBC patients and the SUMO1P3/miR-320a ratio was used to differentiate cases versus controls, showing a statistically significant power. Finally, we provided an automated method of RNA extraction coupled to ddPCR analysis in a perspective of clinical application.DiscussionWe have shown that the lncRNA SUMO1P3 is increased in urine from patients with high grade NMIBC and MIBC and that it is likely to be good candidate to predict bladder cancer progression if used alone or in combination with UCA1 or with miRNA320a.

Cost-utility of Initial Management of High-grade T1 Bladder Cancer With Intravesical BCG vs Immediate Radical Cystectomy

ObjectivesTo compare the cost-utility of initial management of high-grade T1 non-muscle invasive bladder cancer (HGT1 NMIBC) with intravesical BCG versus immediate radical cystectomy. High risk NMIBC patients may climb a costly ladder of treatments, culminating in radical cystectomy for oncologic or symptomatic benefit in up to one-third. This high healthcare resource utilization presents a challenging dilemma in balancing sufficiently aggressive management with cost, toxicity, and quality-of-life. MethodsCost-utility of initially managing HGT1 with intravesical BCG and early radical cystectomy with ileal conduit urinary diversion was compared using decision-analytic Markov models. Five-year oncologic outcomes, adverse event rates, and published utility values were extracted from literature. Costs were calculated from a US Medicare perspective in 2021 US dollars. Sensitivity analysis identified drivers of cost and break-even points for recurrence and progression. ResultsMean costs were $26,093 for intravesical BCG and $39,720 for immediate radical cystectomy, though cystectomy generated a gain of 2.2 QALYs compared to intravesical BCG. Immediate cystectomy was a more cost-effective management strategy for HGT1 NMIBC with an ICER of $7120/QALY.The costs associated with cystectomy, TURBT, and BCG toxicity had the greatest impact on ICER. One-way sensitivity analysis demonstrated that intravesical BCG became a cost-effective management strategy if the five-year recurrence rate of HG T1 was less than 56% or the five-year progression rate to MIBC was less than 4%. ConclusionsAt current prices, treatment of high-grade T1 NMIBC with early radical cystectomy is more cost-effective management strategy than initial treatment with intravesical BCG.

Preoperative Neutrophils to Lymphocytes Ratio in Predicting the Response to BCG in High Grade Non-Muscle Invasive Bladder Cancer

Background Urinary bladder cancer (BC) is a highly prevalent disease affecting more than 400, 000 new cases and 165, 000 deaths yearly, it is the ninth most common cancer in the world, the 13th cause of cancer deaths and the seventh most common cancer worldwide in men with marked male predominance. Aim of the Work To assess the role of preoperative Neutrophils to Lymphocytes Ratio as a predictor for the response to BCG in patients with Non-Muscle invasive Bladder Cancer in patients who underwent Trans-Uretheral Resection of Bladder Tumour (TURBT). Patients and Methods This retrospective cohort study was conducted at tertiary care hospital at Urology department, Ain Shams University hospitals from January 2020 to January 2022 and performed on a total of 46 patients with high grade non-Muscle invasive Bladder Cancer who underwent Trans-Urethral Resection of Bladder Tumor and took BCG course. Results Study results revealed that there was a highly statistically significant relation between preoperative NLR and pathological improvement during Follow up (p-value=0.00) in addition to Tstage and histological grade during Follow up, also there is a statistically significant relation between NLR and tumor size as well as the age of the patient. Conclusion Pre-TURBT NLR when it is high (above 3) is associated with an increased risk of disease recurrence and progression in patients with high grade NMIBC. Moreover, it is an independent predictor of disease recurrence and progression in patients treated with BCG for high grade NMIBC. Pre-TURBT NLR could be a useful blood-based biomarker to improve patients’ risk-stratification facilitating clinical decision-making regarding therapy and follow-up scheduling.

A study to assess the quality of life among patients with high grade non-muscle invasive carcinoma urinary bladder receiving immunotherapy

Background: Urinary bladder lesions are a great health concern as it lies among the top ten most common cancers in the world. These range from benign, harmless lesions that do not recur to life-threatening tumors. The present study was undertaken to assess the quality of life among patients with high-grade non-muscle invasive carcinoma of the urinary bladder receiving immunotherapy. Methods: A hospital-based experimental study was conducted in the Department of General Surgery of Sri Guru Ramdas Institute of Medical Sciences and Research, Amritsar from April 2021 to July 2022. To examine the Quality of Life of 60 patients before and after immunotherapy, the WHOQOL-BREF tool was employed. The participants were followed for a total of six months, with two follow-ups carried out at intervals of three months each. Results: The pre-test physical scores (20.70±8.66) were substantially lower than the other domains. At three and six months, the psychological scores were 21.93±8.51 and 49.37±12.27 respectively, while social scores were 23.93±12.16 and 49.15±24.09 correspondingly. Environment scores (p=0.45) showed no significant difference between groups after BCG treatment. Conclusions: It was vivid that the negative effects of NMIBC on QOL are most pronounced in the physical realm. Quality of life for those with high-grade NMIBC who had BCG treatment improved significantly across all dimensions except the environment. The quality of life of high-grade NMIBC patients was not affected by any of the socio-demographic characteristics except for education and occupational status.

Treatment decisions of bladder cancer in patients older than 85 years: a SEER-based analysis 2011-2015.

To compare the survival outcomes of patients over 85 years of age with bladder cancer. We used data collected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier (KM) curves were generated for overall survival with 95% confidence intervals (CIs). Cox proportional hazard models were used to estimate the hazard ratios among cases in different groups. Of the 9,321 patients who met the inclusion criteria, 6,703 (71.9%) were men and 2,618 (28.1%) were women, with a mean (standard deviation) age of 88.68 (3.216) years. The median follow-up time of this cohort was 18 months. In the low-grade non-muscle-invasive bladder cancer (LG NMIBC) group, our analysis showed that no further treatment led to a better prognosis after the first transurethral bladder tumor resection (TURBT). In the high-grade NMIBC (HG NMIBC) cohort, major therapy was correlated with better OS in univariable and multivariable analyses [hazard ratio (HR) 0.450; 95% CI: 0.351-0.577]. Trimodal therapy gave a better prognosis in the muscle-invasive bladder cancer (MIBC) cohort (HR 1.395; 95% CI: 1.147-1.697). In addition, none of the county factors were risk factors for prognosis in multivariable analysis. Minor and major therapies do not have a better prognosis after TURBT in LG NMIBC. Major therapy has better oncological outcomes in LG NMIBC and MIBC than minor therapy. Trimodal therapy leads to longer OS in MIBC. In addition, none of the county factors were risk factors for prognosis.

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 <0.001) and the presence of erythematous lesions (p <0.02) or visible tumors (p <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.

Expression of p53 Protein Associates with Anti-PD-L1 Treatment Response on Human-Derived Xenograft Model of GATA3/CR5/6-Negative Recurrent Nonmuscular Invasive Bladder Urothelial Carcinoma.

Background: The possible involvement of p53 signaling, FGFR3 expression, and FGFR3 mutation rates in the prediction of the NMIBC anti-PD-L1 treatment response needs to be clarified. The main aim of our study was to explore predictive value of p53 expression, FGFR3 expression, and its gene mutation status for the therapeutic success of anti-PD-L1 treatment in the patient-derived murine model of recurrent high-PD-L1(+) GATA3(−)/CR5/6(−) high-grade and low-grade NMIBC. Methods: twenty lines of patient-derived xenografts (PDXs) of relapsed high-PD-L1(+) double-negative NMIBC were developed, of which 10 lines represented high-grade tumors and the other ones—low-grade bladder cancer. Acceptors of each grade-related branch received specific anti-PD-L1 antibodies. Animals’ survival, tumor-doubling time, and remote metastasis were followed during the post-interventional period. PD-L1, GATA3, CR5/6, and p53 protein expressions in engrafted tumors were assessed by immunohistochemistry. The FGFR3 expression and FGFR3 mutations in codons 248 and 249 were detected by real-time polymerase chain reaction. Results: The expression of p53 protein is an independent factor affecting the animals’ survival time [HR = 0.036, p = 0.031] of anti-PD-L1-treated mice with low-grade high-PD-L1(+) double-negative NMIBC PDX. The FGFR3 expression and FGFR3 mutation rate have no impact on the anti-PD-L1 treatment response in the interventional groups. Conclusions: p53 expression may be considered as a prognostic factor for the anti-PD-L1 treatment efficacy of low-grade high-PD-L1-positive GATA3(−)/CR5/6(−)-relapsed noninvasive bladder cancer.

MP13-05 IMPACT OF MICTURITION HABITS ON FUNCTIONAL OUTCOMES OF PATIENTS WITH ORTHOTOPIC NEOBLADDER: RESULTS FROM A SINGLE CENTER PROSPECTIVE RANDOMISED CONTROLLED TRIAL

You have accessJournal of UrologyBladder Cancer: Invasive I (MP13)1 Sep 2021MP13-05 IMPACT OF MICTURITION HABITS ON FUNCTIONAL OUTCOMES OF PATIENTS WITH ORTHOTOPIC NEOBLADDER: RESULTS FROM A SINGLE CENTER PROSPECTIVE RANDOMISED CONTROLLED TRIAL Riccardo Mastroianni, Gabriele Tuderti, Umberto Anceschi, Alfredo Maria Bove, Aldo Brassetti, Mariaconsiglia Ferriero, Leonardo Misuraca, Salvatore Guaglianone, Ashanti Zampa, Michele Gallucci, and Giuseppe Simone Riccardo MastroianniRiccardo Mastroianni More articles by this author , Gabriele TudertiGabriele Tuderti More articles by this author , Umberto AnceschiUmberto Anceschi More articles by this author , Alfredo Maria BoveAlfredo Maria Bove More articles by this author , Aldo BrassettiAldo Brassetti More articles by this author , Mariaconsiglia FerrieroMariaconsiglia Ferriero More articles by this author , Leonardo MisuracaLeonardo Misuraca More articles by this author , Salvatore GuaglianoneSalvatore Guaglianone More articles by this author , Ashanti ZampaAshanti Zampa More articles by this author , Michele GallucciMichele Gallucci More articles by this author , and Giuseppe SimoneGiuseppe Simone More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001994.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Functional outcomes of radical cystectomy (RC) with orthotopic ileal neobladder and their predictive variables remain underinvestigated. We aimed to evaluate the impact of voiding time-intervals on both day (d)- and night (n)-time continence in a randomised controlled trial (RCT) cohort of patients comparing open RC (ORC) and robot-assisted RC (RARC) with totally intracorporeal (i) urinary diversion (UD) (NCT03434132). METHODS: Patients were eligible if they had a diagnostic TURBt with cT2-4, cN0, cM0, or recurrent high-grade NMIBC and no anesthesiologic contraindications to robotic surgery. Between Jan 2018 and Sept 2020, 116 patients were enrolled with a covariate adaptive randomization process based on the following variables: BMI, ASA score, preoperative hgb, UD [Padua ileal bladder (PIB) or ileal conduit], neoadjuvant chemotherapy and cT-stage. Logistic regression (LR) was performed to build a model to predict d- and n-time continence using a voiding cut-off time. RESULTS: Out of 116 patients enrolled, 88 received PIB and 71 were included in the study (12 patients died, 1 was lost to follow-up, 1 was hypercontinent, 1 had a stroke and 2 had permanent catheter). Baseline clinical data were reported in Table 1. RARC with iPIB was performed with no need of open conversion. At a median follow-up of 16 months (IQR: 11-28), 60 patients (85%) were d-time continent, and 45 (63%) were n-time continent. Patients who had d-time voiding intervals <3h had higher probability to be d-time continent (88%vs64%;p=0.04); similarly, n-time continence probabilities were higher when n-time voiding intervals were <3h (76%vs47%;p=0.01). At LR analysis, for each hour increase in voiding intervals, d-time and n-time continence probabilities decreased of 41% (HR: 0.587; 95%CI 0.424-0.813;p=0.001). In d-time continent patients, LR demonstrated that for each hour increase n-time continence probability decreased of 49% (HR: 0.514; 95%CI 0.353-0.749; p=0.001). CONCLUSIONS: This study supports the key role of micturition habits on functional outcomes of neobladder patients. Patients should be preoperatively counseled about the need to respect voiding cut-off time of 3h to achieve optimal functional results. Source of Funding: none © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e244-e244 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Riccardo Mastroianni More articles by this author Gabriele Tuderti More articles by this author Umberto Anceschi More articles by this author Alfredo Maria Bove More articles by this author Aldo Brassetti More articles by this author Mariaconsiglia Ferriero More articles by this author Leonardo Misuraca More articles by this author Salvatore Guaglianone More articles by this author Ashanti Zampa More articles by this author Michele Gallucci More articles by this author Giuseppe Simone More articles by this author Expand All Advertisement Loading ...

Vesical Imaging Reporting and Data System (VI-RADS): Are the individual MRI sequences equivalent in diagnostic performance of high grade NMIBC and MIBC?

PurposeTo investigate the diagnostic performance of the overall Vesical Imaging Reporting and Data System (VI-RADS) score and its individual magnetic resonance imaging (MRI) parameters in assessing grade and muscle invasiveness of bladder cancer (BC). MethodsThis IRB-approved retrospective, single-center, cross-sectional study included patients with BC wo underwent 3 Tesla preoperative multiparametric (mp)-MRI including T2-weighted (T2w), diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) sequences. An independent evaluation according to VI-RADS was performed by two radiologists in separate sessions, blinded to histological findings. ResultsThe mean age of 59 included patients was 68.2 (±13.6 standard deviation) years. Among bladder cancer patients, 26 (51%) were identified as high grade and 14 (27.5%) as muscle invasive urothelial carcinomas in histological sections. The area under the curve (AUC) for the overall VI-RADS score to predict muscle invasion was 0.986 (R1) and 0.992 (R2). The AUC to diagnose high grade bladder cancer was 0.908 (R1) and 0.905 (R2). There was no significance difference between the AUC of single parameters (T2w, DWI and DCE) compared to the total VI-RADS score (P > 0.05, respectively). Upon multivariate logistic regression, only the T2w VI-RADS score contributed independently to the diagnosis of high grade and muscle invasive bladder cancer (P = 0.001 (R1) and P = 0.0022 (R2) for high grade cancer; P = 0.0007 (R1) and P = 0.0019 (R2) for muscle invasiveness). ConclusionVI-RADS provides high diagnostic accuracy to diagnose high grade and muscle invasive BC. Our results suggest, that mp-MRI parameters provide overlapping information and for sake of clinical simplicity, a biparametric, contrast free image acquisition may be approached without sacrificing diagnostic accuracy.

Oncological outcomes of high-grade T1 non-muscle-invasive bladder cancer treatment in octogenarians

PurposeTo evaluate the outcomes of high-grade T1 non-muscle-invasive bladder cancer treatment (NMIBC) in elderly patients over 80 years of age.MethodsThis is a retrospective single tertiary-centre study. Medical records of patients with T1 high-grade NMIBC treated with transurethral resection of the bladder tumour (TURBT) were reviewed. Among 269 patients with high-grade T1 NMIBC, 74 individuals were over 80 years of age at the time of surgery. Finally, 67 patients met the inclusion criteria.ResultsOnly 47.8% of patients (N = 32) received at least five of the six instillations of the BCG immunotherapy induction course. Oncological outcomes were compared between patients who received at least the induction course of BCG and non-BCG-treated patients matched to each other based on age and Charlson comorbidity index. Thirty case–control pairs were included in the final analysis. Rates of disease recurrence (80% vs. 53%) and cancer-specific mortality (40% vs. 10%) were significantly higher in the group of patients who did not receive BCG. BCG therapy, Charlson comorbidity index, haemoglobin concentration and the number of tumours > 3 in TURBT constituted independent prognostic factors for cancer-specific survival (CSS).ConclusionBCG should be strongly recommended to patients with T1HG NMIBC despite advanced age and comorbidities. Already BCG induction improves CSS and reduces the recurrence rate in octogenarians with T1HG bladder cancer.

The Outcome of Induction Only Versus Induction and Maintenance With A Low Dose Intravesical BCG Therapy For High-Grade NMIBC

The Outcome of Induction Only Versus Induction and Maintenance With A Low Dose Intravesical BCG Therapy For High-Grade NMIBC

Impact of tumor size on the oncological outcome of high-grade nonmuscle invasive bladder cancer – examining the utility of classifying Ta bladder cancer based on size

PurposeTo examine survival rates and to calculate the risk of disease recurrence, progression, overall, and cancer-specific mortality in patients diagnosed with high-risk NMIBC using a multi-institutional dataset to evaluate differences between the guidelines of the European Association of Urology and the guidelines of the National Comprehensive Cancer Network (NCCN) with regard to tumor size in risk stratification. Methods and MaterialIn total 1,116 individuals diagnosed with high-risk NMIBC between 2001 and 2013 were included in the analysis. Patients were stratified to NCCN guideline recommendations (high-grade T1, high-grade Ta ≤ 3 cm, and high-grade Ta > 3 cm). Recurrence and progression rates were calculated. Kaplan-Meier curves were fitted to examine differences in recurrence-free (RFS) and progression-free survival (PFS). Multivariable Cox proportional hazards regression models were employed to calculate differences in the RFS, PFS, overall, and cancer-specific survival (CSS). ResultsThe majority of patients were diagnosed with high-grade T1 disease (N = 576, 51.6%), while 34.2% and 14.2% of patients were diagnosed with high-grade Ta ≤ 3 cm and Ta > 3 cm NMIBC, respectively. The 1- and 5-year RFS (1-year: 80.5% vs. 64.9%; 5-year: 58.6% vs. 48.3%, P = 0.048) and PFS (1-year: 99.1% vs. 98.6%; 5-year: 97.7% vs. 92.4%, P = 0.054) rates were higher in patients with Ta ≤ 3 cm. Patients diagnosed with high-grade Ta > 3 cm experienced unfavorable progression-free, and cancer-specific survival compared to high-grade Ta ≤ 3 cm, respectively (PFS: 2.41, 95% confidence interval [CI] 1.05–5.56, P = 0.038; CSS: hazard ratios [HR] 2.22, 95% CI 1.02–4.89, P = 0.048). ConclusionPatients diagnosed with high-grade Ta NMIBC ≤3 cm demonstrated a favorable progression-free, and cancer-specific survival compared to patients diagnosed with high-grade Ta > 3 cm and high-grade T1 NMIBC.

Safety and efficacy of neoadjuvant intravesical oncolytic MV-NIS in patients undergoing radical cystectomy (RC) for urothelial carcinoma but ineligible for neoadjuvant cisplatin-based chemotherapy.

TPS3172 Background: Bladder cancer is a leading cause of cancer death in the United States. Over 90% of bladder cancer cases are urothelial carcinomas (UC) that may present as a non-muscle-invasive (NMIBC) or muscle-invasive disease (MIBC). Standard of care for NMIBC includes transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and immunotherapy with Bacillus Calmette-Guerin (BCG). Patients (pts) with high-grade BCG-refractory NMIBC or MIBC undergo RC, which involves complete bladder removal and pelvic lymphadenectomy. RC severely impacts quality of life with significant morbidity. Oncolytic viruses are showing promise in UC, and MV-NIS has proven efficacy in other tumor types. MV-NIS is an investigational oncolytic measles virus with an excellent safety profile, irrespective of route of administration (n &gt; 100). MV-NIS-related adverse events are limited to infusion reactions and transient CBC changes, and little local toxicity is anticipated with intravesical therapy. Clinical efficacy of this oncolytic may be related to absence of measles immunity. Based on this, the clinical strategy for MV-NIS is focused on targeting immune-privileged sites via intra-tumoral or intravesical routes, alone or in combination with checkpoint inhibitors. We hypothesize that intravesical therapy with oncolytic MV-NIS can improve clinical outcomes for (a) BCG refractory NMIBC pts to avoid or delay the need for RC; and (b) MIBC pts undergoing RC. Methods: This study is enrolling pts undergoing RC who are ineligible to receive neoadjuvant chemotherapy. The trial has 2 stages to (a) determine the safety and tolerability of intravesical MV-NIS, and (b) assess preliminary efficacy. Part (a) includes 4-24 pts in a timing cohort with doses administered at increasing durations (1-4 weeks) prior to RC to establish safety of a single MV-NIS dose. Part (b) includes an expansion cohort (n = 12) to evaluate the safety and efficacy of 2 intravesical doses of MV-NIS at 2-week intervals prior to RC. Safety is assessed using NCI-CTCAE V5 and Clavien-Dindo grading of operative complications. The efficacy endpoint is pathologic stage at time of RC (pT0 rate), which can be compared to pre-study TURBT stage. Additional exploratory studies include PK and PD analyses in urine, blood and tumor. Enrollment is ongoing at 2 Mayo Clinic sites (Rochester, MN and Jacksonville, FL) and the study has now progressed from the timing cohort into the expansion cohort. Clinical trial information: NCT03171493 .

MP73-10 QUANTIFYING THE OVERALL SURVIVAL BENEFIT WITH EARLY RADICAL CYSTECTOMY FOR PATIENTS WITH HISTOLOGICALLY CONFIRMED T1 NON-MUSCLE-INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Non-invasive IV (MP73)1 Apr 2020MP73-10 QUANTIFYING THE OVERALL SURVIVAL BENEFIT WITH EARLY RADICAL CYSTECTOMY FOR PATIENTS WITH HISTOLOGICALLY CONFIRMED T1 NON-MUSCLE-INVASIVE BLADDER CANCER Karl H. Tully*, Florian Roghmann, Joachim Noldus, Xi Chen, Lorine Haeuser, Adam S. Kibel, Guru P. Sonpavde, Matthew Mossanen, and Quoc-Dien Trinh Karl H. Tully*Karl H. Tully* More articles by this author , Florian RoghmannFlorian Roghmann More articles by this author , Joachim NoldusJoachim Noldus More articles by this author , Xi ChenXi Chen More articles by this author , Lorine HaeuserLorine Haeuser More articles by this author , Adam S. KibelAdam S. Kibel More articles by this author , Guru P. SonpavdeGuru P. Sonpavde More articles by this author , Matthew MossanenMatthew Mossanen More articles by this author , and Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000959.010AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To examine the overall survival in patients diagnosed with high-grade T1 non-muscle invasive bladder cancer treated with early radical cystectomy versus local treatment of the primary tumor defined as endoscopic management with or without intravesical chemotherapy or immunotherapy. METHODS: We identified 4,900 patients with histologically confirmed, clinically non-metastatic high-grade T1 bladder cancer undergoing surgical intervention using the National Cancer Database for the period 2010-2015. Multivariable logistic regression was used to examine predictors for the receipt of early radical cystectomy (defined as radical cystectomy within 90 days of diagnosis). We then employed multivariable Cox proportional hazards regression models and Kaplan-Meier curves to evaluate the overall survival (OS) according to surgical treatment (early radical cystectomy versus local treatment). RESULTS: A minority of patients underwent early radical cystectomy (23.7%). Independent predictors of undergoing early radical cystectomy included: Lower age, White race, and lower comorbidity status. The median OS was 74.0 months for patients diagnosed with high-grade T1 bladder cancer. The 1- and 5- survival rates of patients undergoing early radical cystectomy were 94.8% and 71.0%, whereas it was 85.2% and 52.4% for patients undergoing initial local treatment, respectively (p<0.001). Compared to patients undergoing local treatment, patients undergoing early radical cystectomy had a lower risk of all-cause mortality (Hazard-ratio 0.78, 95% Confidence Interval 0.67–0.91, p=0.002). CONCLUSIONS: In this cohort of patients presenting with high-grade T1 NMIBC, we found that early radical cystectomy was associated with an overall survival benefit compared to initial local treatment. Source of Funding: None. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1124-e1125 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Karl H. Tully* More articles by this author Florian Roghmann More articles by this author Joachim Noldus More articles by this author Xi Chen More articles by this author Lorine Haeuser More articles by this author Adam S. Kibel More articles by this author Guru P. Sonpavde More articles by this author Matthew Mossanen More articles by this author Quoc-Dien Trinh More articles by this author Expand All Advertisement PDF downloadLoading ...

Characterization of the urinary microbiota in bladder cancer patients.

535 Background: Mounting evidence indicates that the microbiota plays an important role in carcinogenesis and response to treatments. The dogma that urine is sterile has been overturned and dysbiosis of the urinary microbiota has been linked to urological disorders. We tested the hypothesis that alteration in urinary microbial community composition may be associated to bladder cancer development and progression. Therefore, we performed a study to characterize the urinary microbiota associated with non-muscle invasive and muscle invasive bladder cancer (NMIBC, MIBC). Methods: Urines were collected with a catheter from BC patients before transurethral resection or cystectomy, and age-matched non-neoplastic subjects. Subjects with prior history of sexually transmitted infection, chronic intestinal inflammation, urinary tract infection and recent usage of antibiotic or immunomodulatory agents were excluded. Bacterial DNA was extracted and amplified for 16S rDNA sequencing. Results: We isolated bacterial DNA from urine samples of 12 non-neoplastic control subjects and 27 BC patients. The most abundant phyla in both groups were Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria, with Bacteroidetes being slightly more abundant in bladder cancer at the expense of Proteobacteria. Interestingly, we found that NMIBC displayed a reduction in the abundance of Sphingobacteriaceae, Bifidobacteriaceae and Enterobacteriaceae. High grade NMIBC and MIBC showed decreased Bifidobacterium and Ruminococcus, which are known to protect from inflammation, and increased Corynebacterium, a potential opportunistic bacteria. No correlation with environmental risk factors (i.e. smoking) was investigated. Conclusions: The urinary microbiota of BC patients displayed a significantly different pattern relative to control group, suggesting that the tumor microenvironment can influence dysbiosis. In particular, we found specific bacteria to associate with aggressive tumors. A better understanding of the urinary microbiota could pave the way for exploring new therapeutic options based on the manipulation of the microbial community. Analysis of additional samples is ongoing.

Mutational Analysis of 472 Urothelial Carcinoma Across Grades and Anatomic Sites.

The purpose of this study is to characterize the mutational landscape across the spectrum of urothelial carcinoma (UC) to identify mutational features and potential therapeutic targets. Using targeted exome sequencing (n = 237 genes), we analyzed the mutation spectra of 82 low-grade nonmuscle-invasive bladder cancers (LG-NMIBC), 126 high-grade (HG) NMIBC, 199 muscle-invasive bladder cancers (MIBC), 10 LG-upper tract urothelial cancers (LG-UTUC), and 55 HG-UTUC. FGFR3 and KDM6A mutations were significantly more common in LG-NMIBC (72% and 44%, respectively) versus other bladder subtypes. FGFR3 alterations were also enriched in LG-UTUC versus HG-UTUC tumors (80% vs. 16%). In contrast, TP53 and RB1 mutations were significantly more frequent in all 3 HG urothelial carcinoma subtypes than in LG-NIMBC (45%-58% vs. 4%; 9%-22% vs. 0; respectively). Among LG-NMIBC tumors, KDM6A mutations were more common in women than in men (71% vs. 38%). HG-NMIBC and MIBC had higher tumor mutational burden (TMB) than LG-NMIBC (P = 0.001 and P < 0.01, respectively). DNA-damage repair (DDR) alterations were associated with a higher TMB in HG-NMIBC and MIBC tumors, and these two tumor types were also enriched for an APOBEC mutational signature compared with LG-NMIBC and HG-UTUC. Alterations in FGFR3, PIK3CA, and EP300 correlated with worse overall survival in HG-UTUC and occurred concurrently. Our analysis suggests that a fraction of MIBCs likely arise from precursor lesions other than LG-NMIBC. KDM6A mutations are twice as common in women with LG-NIMBC than those in men. DDR gene mutations and APOBEC mutagenesis drive mutations in HG-NMIBC and MIBC. UTUC has a distinct mutation profile from bladder cancer.

Digital holography can differentiate between bladder cancer grades.

413 Background: Treatment of high grade non-muscle invasive bladder cancer (HG NMIBC) is controversial with BCG instillation and early cystectomy as viable options. However, accurate predictive markers for HG NMIBC are lacking. Refractive index (RI) is an optical feature of tissues and has been shown to be correlated with various oncologic outcomes in prostate and breast cancers. The role of RI in NMIBC has not been explored yet. The aim of this study is to measure and compare RI values of benign and malignant low and high grade NMIBC. Methods: After IRB approval, tissue samples were obtained from high and low grade NMIBC patients. Measurements were performed on non-stained slides using digital holography. Areas of benign and malignant tissues were marked by a fellowship trained GU pathologist. The average RI (RIavg) and RI variance (RIvar) over malignant and benign cell nuclei were measured. Comparison between benign and malignant tissue and between low and high grade tumors was performed with the Student's t-test. Results: Multiple nuclei of LG and HG patients were measured . Mean difference of RIavg between malignant and benign cells was 0.03 in HG patients (p &lt; 0.001). Mean difference of RIvar between malignant and benign tissues was 0.016 in HG patients (p &lt; 0.001). In LG tissues, there was no significant difference in RIavg or RIvar between benign and malignant cells. Finally, there was a significant difference in RIavg between HG and LG cells (p &lt; 0.001). Conclusions: For the first time, RI was measured in bladder cancer tissue by digital holography. The RI values and variance were different between malignant and benign cells in HG tissues. Furtheremore, we found a significant difference in RI values between HG and LG cells. This technology may assist in the future in tissue diagnosis and classification of bladder tumor.

Metabolomics of Non-muscle Invasive Bladder Cancer: Biomarkers for Early Detection of Bladder Cancer.

Background: Clinical outcomes of bladder cancer (BC) are tightly associated with the stage and grade of the initial diagnosis of BC because early detection is clearly important for patients with BC. However, the diagnostic capability of current detection methods, such as urinary cytology, cystoscopy, imageology method, and several urine-based tests, is inadequate for early detection of BC. The objective of our study is to discover novel biomarkers for detecting BC at an early stage, called non-muscle invasive (NMI) BC, using liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based metabolomics.Methods: First, morning midstream urine samples were collected from healthy adult and NMIBC patients. The LC-HRMS-based metabolomics were applied to distinguish the NMIBC group without hematuria from the controls (gender- and age-matched volunteers with normal clinically healthy index), low-grade NMIBC from the controls, and high-grade from low-grade NMIBC.Results: A total of 284 subjects were enrolled in our study including 117 healthy adults, 80 NMIBC patients without hematuria, and 87 NMIBC patients with hematuria. The metabolite panel including dopamine 4-sulfate, MG00/1846Z,9Z,12Z,15Z/00, aspartyl-histidine, and tyrosyl-methionine was found in a discovery set, which showed the predictive ability to distinguish the NMIBC group from the control group with an area under the curve (AUC) of 0.838 in an external validation set. The AUC of the panel for low-grade NMIBC samples, which consisted of 3-hydroxy-cis-5-tetradecenoylcarnitine, 6-ketoestriol, beta-cortolone, tetrahydrocorticosterone, and heptylmalonic acid, was 0.899. The sensitivity and specificity were 0.881 and 0.786, respectively. The AUC of the panel for distinction of low-grade NMIBC with and without hematuria against high-grade NMIBC with and without hematuria were 0.827 and 0.755, respectively. In addition, metabolites involved in tryptophan metabolism were upregulated in the urine of high-grade NMIBC patients when compared with low-grade NMIBC patients with the presence or absence of hematuria.Conclusion: The NMIBC urine metabolic profiling was able to assist in the early detection of BC. Panels of metabolites were discovered to have a potential value for high-grade NMIBC and low-grade NMIBC diagnosis as well as for NMIBC grading distinction.

Systemic Inflammatory Markers and Oncologic Outcomes in Patients with High-risk Non–muscle-invasive Urothelial Bladder Cancer

BackgroundSerum levels of neutrophils, platelets, and lymphocytes have been recognized as factors related to poor prognosis for many solid tumors, including bladder cancer (BC). ObjectiveTo evaluate the prognostic role of the combination of the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) in patients with high-risk non–muscle-invasive urothelial BC (NIMBC). Design, setting, and participantsA total of 1151 NMIBC patients who underwent first transurethral resection of the bladder tumor (TURBT) at 13 academic institutions between January 1, 2002 and December 31, 2012 were included in this analysis. The median follow-up was 48 mo. InterventionTURBT with intravesical chemotherapy or immunotherapy. Outcome measurements and statistical analysisMultivariable Cox regression analysis was performed to identify factors predictive of recurrence, progression, cancer-specific mortality, and overall mortality. A systemic inflammatory marker (SIM) score was calculated based on cutoffs for NLR, PLR, and LMR. Results and limitationsThe 48-mo recurrence-free survival was 80.8%, 47.35%, 20.67%, and 17.06% for patients with an SIM score of 0, 1, 2, and 3, respectively (p<0.01, log-rank test) while the corresponding 48-mo progression free-survival was 92.0%, 75.67%, 72.85%, and 63.1% (p<0.01, log-rank test). SIM scores of 1, 2, and 3 were associated with recurrence (hazard ratio [HR] 3.73, 7.06, and 7.88) and progression (HR 3.15, 4.41, and 5.83). Limitations include the lack of external validation and comparison to other clinical risk models. ConclusionsPatients with high-grade T1 stage NMIBC with high SIM scores have worse oncologic outcomes in terms of recurrence and progression. Further studies should be conducted to stratify patients according to SIM scores to identify individuals who might benefit from early cystectomy. Patient summaryIn this study, we defined a risk score (the SIM score) based on the measurement of routine systemic inflammatory markers. This score can identify patients with high-grade bladder cancer not invading the muscular layer who are more likely to suffer from tumor recurrence and progression. Therefore, the score could be used to select patients who might benefit from early bladder removal.

MP83-05 ONCOLOGICAL OUTCOME IN A RETROSPECTIVE COHORT OF T1G3 PRIMARY PATIENTS. DOES THE LOCATION OF CIS REALLY MATTER?

You have accessJournal of UrologyBladder Cancer: Non-invasive II1 Apr 2018MP83-05 ONCOLOGICAL OUTCOME IN A RETROSPECTIVE COHORT OF T1G3 PRIMARY PATIENTS. DOES THE LOCATION OF CIS REALLY MATTER? Francesca Pisano, Oscar Rodriguez Faba, Ferran Algaba, Lucia Mosquera Seoane, Josè Maria Gaya, Ruben Parada, Helena Vila Reies, and Joan Palou Francesca PisanoFrancesca Pisano More articles by this author , Oscar Rodriguez FabaOscar Rodriguez Faba More articles by this author , Ferran AlgabaFerran Algaba More articles by this author , Lucia Mosquera SeoaneLucia Mosquera Seoane More articles by this author , Josè Maria GayaJosè Maria Gaya More articles by this author , Ruben ParadaRuben Parada More articles by this author , Helena Vila ReiesHelena Vila Reies More articles by this author , and Joan PalouJoan Palou More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2753AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES CIS has been already identified as one of the most important prognostic risk factors in NMIBC in BCG treated patients. Interestingly, this information mostly derived from studies that did not analysed the prognostic relevance of the localization of CIS or that not all the patients underwent multiple bladder diopsies. The aim of this study is to evaluate the role of CIS in prostatic urethra to predict recurrence, progression and cancer specific mortality. METHODS A total of 300 consecutive patients with primary T1G3 that all underwent multiple bladder biopsies including prostatic urethra, were retrospectively analysed. The variables analysed for recurrence, progression, and death due to bladder cancer (BCa) were gender, age, tumour multiplicity, diameter, aspect, concomitant carcinoma in situ (CIS), and CIS in the prostatic urethra. A back stepwise multivariate cox model was performed including clinical variables at baseline with a p value <0.2 in the bivariate analysis as independent variables. RESULTS The median follow-up was 8.5 yr; 261 (87%) were males, with a mean age at diagnosis of 67 years (SD 10). Globally concomitant CIS was present in 151 patients (50.3%) and 30 (10%) presented CIS in prostatic urethra. Tumors were multiple 160 cases (53.3%), 118 (39.3%) were >3cm. One-hundred and sixty-five patients (55%) had recurrence, 70 patients (23%) had progression, and 46 patients (16.1%) died because of BCa. Among patients with CIS in prostatic urethra 46% progressed. Patients presenting CIS in prostatic urethra have 3 times more risk to progress (HR=3.059, p=0.014), and 2 times more risk of death due to BCa (HR=3.794,p=0.004). Moreover female gender and multifocal tumours were confirmed as significant prognostic risk factors for progression (HR 2.73, p=0.014; HR 1.83, p=0.043 respectively) and CSS (HR 2.73, p=0.029; HR 2.65, p=0.012). CONCLUSIONS Since the presence of CIS in prostatic urethra strongly affects the risk of progression and death due to BCa, a routine evaluation of prostatic urethra is mandatory in primary high grade NMIBC. It is confirmed as well that female gender and multifocal disease are strongly related with worse outcomes. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1117 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Francesca Pisano More articles by this author Oscar Rodriguez Faba More articles by this author Ferran Algaba More articles by this author Lucia Mosquera Seoane More articles by this author Josè Maria Gaya More articles by this author Ruben Parada More articles by this author Helena Vila Reies More articles by this author Joan Palou More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...