Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline: 2024 Amendment.

PURPOSE: The purpose of this American Urological Association (AUA)/Society of Urologic Oncology (SUO) guideline amendment is to provide a useful reference on the effective evidence-based treatment strategies for non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: In 2023, the NMIBC guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines in an effort to maintain currency. The amendment allowed for the incorporation of additional literature released since the previous 2020 amendment. The updated search gathered literature from July 2019 to May 2023. This review identified 1918 abstracts, of which 75 met inclusion criteria.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) in support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: Updates were made to statements on variant histologies, urine markers after diagnosis of bladder cancer, intravesical therapy, BCG maintenance, enhanced cystoscopy, and future directions. Further revisions were made to the methodology and reference sections as appropriate. CONCLUSIONS: This guideline seeks to improve clinicians' ability to evaluate and treat patients with NMIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

Utility of Blue Light Cystoscopy for Post-bacillus Calmette-Guérin Bladder Cancer Recurrence Detection: Implications for Clinical Trial Recruitment and Study Comparisons.

PURPOSE: The utility of blue light cystoscopy (BLC) in patients receiving bacillus Calmette-Guérin (BCG) during post-treatment cystoscopy is not well understood. Our objective was to determine if BLC improves recurrence detection in patients with non-muscle invasive bladder cancer (NMIBC) undergoing BCG. MATERIALS AND METHODS: Using the prospective multi-institutional Cysview® Registry (2014-2019), patients with NMIBC who received BCG within 1 year prior to BLC were identified. Primary outcomes were recurrences and whether lesions were detected on white light cystoscopy (WLC), BLC or both. We calculated the percentage of cystoscopies with recurrences that were missed with WLC alone. The cystoscopy-level BLC false-positive rate was the proportion of cystoscopies with biopsies only due to BLC suspicious lesions without recurrence. RESULTS: Of 1,703 BLCs, 282 cystoscopies were in the analytic cohort. The overall recurrence rate was 45.0% (127). With only WLC, 13% (16/127) of recurrences would have been missed as 5.7% (16/282) of cystoscopies performed had recurrence only identified with BLC. Among 16 patients with recurrence missed with WLC, 88% (14) had carcinoma in situ. The cystoscopy-level BLC false-positive rate was 5% (15). CONCLUSIONS: BLC helped detect recurrences after recent BCG that would have been missed with WLC alone. Providers should consider BLC for high-risk patients undergoing BCG and should discuss the risk of false-positives with these patients. As clinical trials of novel therapies for BCG-unresponsive disease increase and there are no clear guidelines on BLC use for post-treatment cystoscopies, it is important to consider how variable BLC use could affect enrollment in and comparisons of these studies.

Role of blue-light cystoscopy in detecting invasive bladder tumours: data from a multi-institutional registry.

OBJECTIVES: To evaluate the role of blue-light cystoscopy (BLC) in detecting invasive tumours that were not visible on white-light cystoscopy (WLC). PATIENTS AND METHODS: Using the multi-institutional Cysview registry database, patients who had at least one white-light negative (WL-)/blue-light positive (BL+) lesion with invasive pathology (≥T1) as highest stage tumour were identified. All WL-/BL+ lesions and all invasive tumours in the database were used as denominators. Relevant baseline and outcome data were collected. RESULTS: Of the 3514 lesions (1257 unique patients), 818 (23.2%) lesions were WL-/BL+, of those, 55 (7%) lesions were invasive (48 T1, seven T2; 47 unique patients) including 28/55 (51%) de novo invasive lesions (26 unique patients). In all, 21/47 (45%) patients had WL-/BL+ concommitant carcinoma in situ and/or another T1 lesions. Of 22 patients with a WL-/BL+ lesion who underwent radical cystectomy (RC), high-risk pathological features leading to RC was only visible on BLC in 18 (82%) patients. At time of RC, 11/22 (50%) patients had pathological upstaging including four (18%) with node-positive disease. CONCLUSIONS: A considerable proportion of invasive lesions are only detectable by BLC and the rate of pathological upstaging is significant. Our present findings suggest an additional benefit of BLC in the detection of invasive bladder tumours that has implications for treatment approach.

Effect of prior radiation on stage, differentiation, and survival in bladder cancer.

PURPOSE: Clinically significant differences in radiation-related bladder tumors are not well-characterized, and survival analyses are needed. In this study, we aimed to utilize a national cancer database to evaluate the effect of prior radiation on tumor characteristics and survival in bladder cancer patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) 9 database was queried to identify patients diagnosed with bladder cancer as a second malignancy. Patients having undergone radiation prior to developing bladder cancer were selected for comparative analysis. Logistic regression was used to generate odds ratios to evaluate differences in differentiation, stage, grade, and tumor size. Kaplan-Meier analysis and Cox non-proportional hazards regression models were used to assess the association between previous radiation and bladder cancer survival. RESULTS: A total of 25,408 patients were identified, of which 14,570 patients had sufficient data for analysis. Of these, 5968 (41.0%) received radiation for their primary malignancy. Prior radiation conferred a lower risk of developing moderately- or poorly-differentiated bladder tumors and muscle invasive or node-positive disease. An increased risk of squamous cell carcinoma was noted (OR 1.43, CI 1.06-1.93). Prior radiation led to an increased risk of bladder cancer-specific (HR 1.13, CI 1.03-1.24) mortality at 5 years. The greatest effect of prior radiation was an increased risk of bladder cancer-specific mortality for carcinoma in situ at 5 years (OR 2.37, CI 1.45-3.86). CONCLUSION: Prior radiation is associated with lower grade and stage of bladder tumors in addition to worse cancer-specific survival.

Comparative effectiveness of neoadjuvant chemotherapy in bladder and upper urinary tract urothelial carcinoma.

OBJECTIVE: To assess the differential response to neoadjuvant chemotherapy (NAC) in patients with urothelial carcinoma of the bladder (UCB) compared to upper tract urothelial carcioma (UTUC) treated with radical surgery. PATIENTS AND METHODS: Data from 1299 patients with UCB and 276 with UTUC were obtained from multicentric collaborations. The association of disease location (UCB vs UTUC) with pathological complete response (pCR, defined as a post-treatment pathological stage ypT0N0) and pathological objective response (pOR, defined as ypT0-Ta-Tis-T1N0) after NAC was evaluated using logistic regression analyses. The association with overall (OS) and cancer-specific survival (CSS) was evaluated using Cox regression analyses. RESULTS: A pCR was found in 250 (19.2%) patients with UCB and in 23 (8.3%) with UTUC (P < 0.01). A pOR was found in 523 (40.3%) patients with UCB and in 133 (48.2%) with UTUC (P = 0.02). On multivariable logistic regression analysis, patients with UTUC were less likely to have a pCR (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.27-0.70; P < 0.01) and more likely to have a pOR (OR 1.57, 95% CI 1.89-2.08; P < 0.01). On univariable Cox regression analyses, UTUC was associated with better OS (hazard ratio [HR] 0.80, 95% CI 0.64-0.99, P = 0.04) and CSS (HR 0.63, 95% CI 0.49-0.83; P < 0.01). On multivariable Cox regression analyses, UTUC remained associated with CSS (HR 0.61, 95% CI 0.45-0.82; P < 0.01), but not with OS. CONCLUSIONS: Our present findings suggest that the benefit of NAC in UTUC is similar to that found in UCB. These data can be used as a benchmark to contextualise survival outcomes and plan future trial design with NAC in urothelial cancer.

Glycemic impact of a diet and lifestyle intervention on diabetics and prediabetics during treatment for non-muscle invasive bladder cancer.

Introduction: Patients with Type II Diabetes Mellitus (DM2) have increased risk of recurrence and progression of non-muscle invasive bladder cancer (NMIBC). Glucose control through lifestyle intervention is an uninvestigated, attractive strategy to decrease risk of cancer recurrence. We test the feasibility of a diet and exercise program and its glycemic impact in patients with DM2 and NMIBC.Materials/methods: Five participants with NMIBC and pre-diabetes or DM2 were recruited for a pilot, prospective clinical trial. Each participant received dietary counseling for 16 sessions during clinical visits. The intervention included a carbohydrate-restricted (CR) diet (<130 grams per day), 30 min, walking 5×/wk, and 5000 steps daily. Diet compliance was measured with 24-hour diet recall. Exercise was monitored with accelerometer and self-report.Results: Five participants enrolled and two participants completed the 12-month intervention. Adherence was 60% to CR diet and 84% to exercise goals. Participants reduced carbohydrate consumption by 44%. Participants showed reductions in fasting blood glucose, HbA1c, glucosuria, fasting blood insulin, and body weight, and increased euglycemia on continuous glucose monitoring.Conclusions: Adherence to a CR diet and exercise goals is feasible in patients with NMIBC and DM2 and also leads improved glucose control. A phase-II trial on bladder cancer-specific outcomes is warranted.

Alternol eliminates excessive ATP production by disturbing Krebs cycle in prostate cancer.

BACKGROUND: Alternol is a natural compound isolated from fermentation products of a mutant fungus. Our previous studies demonstrated that Alternol specifically kills cancer cells but spares benign cells. METHODS: To investigate the mechanism underlying alternol-induced cancer cell-specific killing effect, we took a comprehensive strategy to identify Alternol's protein targets in prostate cancer cells, including PC-3, C4-2, and 22RV1, plus benign BPH1 cell lines. Major experimental techniques included biotin-streptavidin pulldown assay coupled with mass-spectrometry, in vitro enzyme activity assay for Krebs cycle enzymes and gas chromatography-mass spectrometry (GC-MS) for metabolomic analysis. RESULTS: Among 14 verified protein targets, four were Krebs cycle enzymes, fumarate hydratase (FH), malate dehydrogenase-2 (MDH2), dihydrolipoamide acetyltransferase (DLAT) in pyruvate dehydrogenase complex (PDHC) and dihydrolipoamide S-succinyltransferase (DLST) in a-ketoglutarate dehydrogenase complex (KGDHC). Functional assays revealed that PDHC and KGDHC activities at the basal level were significantly higher in prostate cancer cells compared to benign prostate BPH1 cells, while alternol treatment reduced their activities in cancer cells close to the levels in BPH1 cells. Although FH and MDH2 activities were comparable among prostate cancer and benign cell lines at the basal level, Alternol treatment largely increased their activities in cancer cells. Metabolomic analysis revealed that Alternol treatment remarkably reduced the levels of malic acid, fumaric acid, and isocitric acid and mitochondrial respiration in prostate cancer cells. Alternol also drastically reduced mitochondrial respiration and ATP production in PC-3 cells in vitro or in xenograft tissues but not in BPH1 cells or host liver tissues. CONCLUSIONS: Alternol interacts with multiple Krebs cycle enzymes, resulting in reduced mitochondrial respiration and ATP production in prostate cancer cells and xenograft tissues, providing a novel therapeutic strategy for prostate cancer treatment.

The Feasibility of a Health Care Application in the Treatment of Patients Undergoing Radical Cystectomy.

PURPOSE: Patients who undergo radical cystectomy of bladder cancer are at high risk for complications and hospital readmissions. Studies indicate insufficient preoperative education and perioperative monitoring. The aim of this study was to demonstrate the feasibility of implementing a health care application to provide more patient education and more thorough monitoring perioperatively. MATERIALS AND METHODS: Participants with home Wi-Fi access who were undergoing radical cystectomy were recruited for this pilot trial. Each subject was provided a tablet preloaded with the m.Care (LifeScience Technologies, Leawood, Kansas) health care application, an accelerometer and vital sign equipment. Participants were asked to watch educational videos, use the provided accelerometer and perform vital sign monitoring. RESULTS: In 1 year 20 participants enrolled in the study and 15 completed it. The most frequently viewed videos were "Ileal Conduit versus Neobladder" and "Comprehensive Care Pathway." All participants used the accelerometer and 60% kept up with syncing the data regularly. The average step count preoperatively was 5,679 reflecting a sedentary population. Step counts decreased during the inpatient stay (1,351 steps) and trended toward baseline during the postoperative period (3,156 steps). Vital signs were recorded on 85% of assigned days and generated 33 triggers for intervention. While most triggers led to repeat assessment, education and encouragement, 4 participants underwent outpatient treatment, including cultures, intravenous fluids, antibiotics or dronabinol prescription, without the need for hospital readmission. CONCLUSIONS: Providing more education and monitoring perioperatively is feasible using a health care application. Testing is warranted to determine the extent to which implementation will improve patient triaging and reduce readmissions.

Perioperative Immunonutrition Modulates Inflammatory Response after Radical Cystectomy: Results of a Pilot Randomized Controlled Clinical Trial.

PURPOSE: Poor preoperative nutritional status is associated with a higher complication rate after radical cystectomy in patients with bladder cancer. Given the short interval between diagnosis and radical cystectomy, we compared the effect of short-term specialized immunonutrition to that of a standard oral nutritional supplement on the acute inflammatory response and arginine status in patients treated with radical cystectomy. MATERIALS AND METHODS: In this prospective, randomized study in 29 men 14 received specialized immunonutrition and 15 received oral nutritional supplement. Each group drank 3 cartons per day for 5 days before and 5 days after radical cystectomy. The Th1-Th2 balance, plasma interleukin-6 and plasma amino acids were measured at baseline, intraoperatively and on postoperative days 2, 14 and 30. Body composition was measured by dual energy x-ray absorptiometry at baseline and on postoperative days 14 and 30. Differences in outcomes were assessed using the generalized linear mixed model. RESULTS: In the specialized immunonutrition group there was a 54.3% average increase in the Th1-Th2 balance according to the tumor necrosis factor-α-to-interleukin-13 ratio from baseline to intraoperative day, representing a shift toward a Th1 response. In the oral nutritional supplement group the Th1-Th2 balance decreased 4.8%. The change in the Th1-Th2 balance between the specialized immunonutrition and oral nutritional supplement groups significantly differed (p <0.027). Plasma interleukin-6 was 42.8% lower in the specialized immunonutrition group compared to the oral nutritional supplement group on postoperative day 2 (p = 0.020). In the specialized immunonutrition group plasma arginine was maintained from baseline to postoperative day 2 and yet the oral nutritional supplement group showed a 26.3% reduction from baseline to postoperative day 2 (p = 0.0003). The change in appendicular muscle loss between the groups was not statistically significant. CONCLUSIONS: Th1-to-Th2 ratios, peak interleukin-6 levels and plasma arginine suggest that consuming specialized immunonutrition counteracts the disrupted T-helper balance, lowers the inflammatory response and prevents arginine depletion due to radical cystectomy.

Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non-Muscle-Invasive Bladder Cancer on Tumor Recurrence: SWOG S0337 Randomized Clinical Trial.

Importance: Low-grade non-muscle-invasive urothelial cancer frequently recurs after excision by transurethral resection of bladder tumor (TURBT). Objective: To determine whether immediate post-TURBT intravesical instillation of gemcitabine reduces recurrence of suspected low-grade non-muscle-invasive urothelial cancer compared with saline. Design, Setting, and Participants: Randomized double-blind clinical trial conducted at 23 US centers. Patients with suspected low-grade non-muscle-invasive urothelial cancer based on cystoscopic appearance without any high-grade or without more than 2 low-grade urothelial cancer episodes within 18 months before index TURBT were enrolled between January 23, 2008, and August 14, 2012, and followed up every 3 months with cystoscopy and cytology for 2 years and then semiannually for 2 years. Patients were monitored for tumor recurrence, progression to muscle invasion, survival, and toxic effects. The final date of follow-up was August 14, 2016. Interventions: Participants were randomly assigned to receive intravesical instillation of gemcitabine (2 g in 100 mL of saline) (n = 201) or saline (100 mL) (n = 205) for 1 hour immediately following TURBT. Main Outcomes and Measures: The primary outcome was time to recurrence of cancer. Secondary end points were time to muscle invasion and death due to any cause. Results: Among 406 randomized eligible patients (median age, 66 years; 84.7% men), 383 completed the trial. In the intention-to-treat analysis, 67 of 201 patients (4-year estimate, 35%) in the gemcitabine group and 91 of 205 patients (4-year estimate, 47%) in the saline group had cancer recurrence within 4.0 years (hazard ratio, 0.66; 95% CI, 0.48-0.90; P<.001 by 1-sided log-rank test for time to recurrence). Among the 215 patients with low-grade non-muscle-invasive urothelial cancer who underwent TURBT and drug instillation, 34 of 102 patients (4-year estimate, 34%) in the gemcitabine group and 59 of 113 patients (4-year estimate, 54%) in the saline group had cancer recurrence (hazard ratio, 0.53; 95% CI, 0.35-0.81; P = .001 by 1-sided log-rank test for time to recurrence). Fifteen patients had tumors that progressed to muscle invasion (5 in the gemcitabine group and 10 in the saline group; P = .22 by 1-sided log-rank test) and 42 died of any cause (17 in the gemcitabine group and 25 in the saline group; P = .12 by 1-sided log-rank test). There were no grade 4 or 5 adverse events and no significant differences in adverse events of grade 3 or lower. Conclusions and Relevance: Among patients with suspected low-grade non-muscle-invasive urothelial cancer, immediate postresection intravesical instillation of gemcitabine, compared with instillation of saline, significantly reduced the risk of recurrence over a median of 4.0 years. These findings support using this therapy, but further research is needed to compare gemcitabine with other intravesical agents. Trial Registration: clinicaltrials.gov Identifier: NCT00445601.

Characterization of a novel p110ß-specific inhibitor BL140 that overcomes MDV3100-resistance in castration-resistant prostate cancer cells.

BACKGROUND: Our previous studies demonstrated that the class IA PI3K/p110ß is critical in castration-resistant progression of prostate cancer (CRPC) and that targeting prostate cancer with nanomicelle-loaded p110ß-specific inhibitor TGX221 blocked xenograft tumor growth in nude mice, confirming the feasibility of p110ß-targeted therapy for CRPCs. To improve TGX221's aqueous solubility, in this study, we characterized four recently synthesized TGX221 analogs. METHODS: TGX221 analog efficacy were examined in multiple prostate cancer cell lines with the SRB cell growth assay, Western blot assay for AKT phosphorylation and cell cycle protein levels. Target engagement with PI3K isoforms was evaluated with cellular thermal shift assay. PI3K activity was determined with the Kinase-Glo Plus luminescent kinase assay. Cell cycle distribution was evaluated with flow cytometry after propidium iodide staining. RESULTS: As expected, replacing either one of two major functional groups in TGX221 by more hydrophilic groups dramatically improved the aqueous solubility (about 40-fold) compared to TGX221. In the CETSA assay, all the analogs dramatically shifted the melting curve of p110ß protein while none of them largely affected the melting curves of p110α, p110γ, or Akt proteins, indicating target-specific engagement of these analogs with p110ß protein. However, functional evaluation showed that only one of the analogs BL140 ubiquitously inhibited AKT phosphorylation in all CRPC cell lines tested with diverse genetic abnormalities including AR, PTEN, and p53 status. BL140 was superior than GSK2636771 (IC50 5.74 vs 20.49 nM), the only p110ß-selective inhibitor currently in clinical trials, as revealed in an in vitro Kinase-Glo assay. Furthermore, BL140 exhibited a stronger inhibitory effect than GSK2636771 on multiple CRPC cell lines including a MDV3100-resistant C4-2B cell subline, indicating BL140 elimination of MDV3100 resistance. Mechanistic studies revealed that BL140 blocked G1 phase cell cycle entry by reducing cyclin D1 but increasing p27kip1 protein levels. CONCLUSION: These studies suggested that BL140 is a promising p110ß-specific inhibitor with multiple superb properties than GSK2636771 worthy for further clinical development.

Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline.

PURPOSE: This multidisciplinary, evidence-based guideline for clinically non-metastatic muscle-invasive bladder cancer focuses on the evaluation, treatment and surveillance of muscle-invasive bladder cancer guided toward curative intent. MATERIALS AND METHODS: A systematic review utilizing research from the Agency for Healthcare Research and Quality as well as additional supplementation by the authors and consultant methodologists was used to develop the guideline. Evidence-based statements were based on body of evidence strengths Grade A, B or C and were designated as Strong, Moderate and Conditional Recommendations with additional statements presented in the form of Clinical Principles or Expert Opinions. RESULTS: For the first time for any type of malignancy, the American Urological Association, American Society of Clinical Oncology, American Society for Radiation Oncology and Society of Urologic Oncology have formulated an evidence-based guideline based on a risk-stratified clinical framework for the management of muscle-invasive urothelial bladder cancer. This document is designed to be used in conjunction with the associated treatment algorithm. CONCLUSIONS: The intensity and scope of care for muscle-invasive bladder cancer should focus on the patient, disease and treatment response characteristics. This guideline attempts to improve a clinician's ability to evaluate and treat each patient, but higher quality evidence in future trials will be essential to improve level of care for these patients.

The importance of clinical stage among patients with a complete pathologic response at radical cystectomy after neoadjuvant chemotherapy.

PURPOSE: Patients without evidence of disease at radical cystectomy (RC) following neoadjuvant chemotherapy (NAC) have the greatest potential for survival in muscle-invasive bladder cancer. Historically, 15 % of such patients will experience disease recurrence and cancer-specific mortality. We sought to evaluate the effect of pre-treatment clinical factors on the risk of recurrence in patients who were ypT0N0 at RC. METHODS: We performed a multi-institutional review of patients treated with NAC + RC for muscle-invasive bladder cancer (≥cT2) without pathologic evidence of disease at surgery (ypT0N0). The association of pre-treatment clinicopathologic features with recurrence was evaluated using Cox proportional hazards. RESULTS: A total of 78 patients were identified with ypT0 disease at RC after NAC. Median postoperative follow-up was 32.4 months (IQR 16.8, 60.0), during which time 17 patients recurred at a median of 6.4 months after RC. Estimated 3-year recurrence-free survival (RFS) of this cohort was 74.8 %. In univariate analysis, cT4 disease (HR 3.12; p = 0.04) and time to RC (HR 1.17 for each month increase; p < 0.01) were associated with inferior RFS. CONCLUSION: Patients without evidence of disease at the time of RC are still at risk of recurrence and death from bladder cancer. Higher clinical stage and increased time to RC were associated with an increased risk of recurrence and subsequent death. These data highlight the importance of timely RC and the continued risk of recurrence in higher clinically staged patients-underscoring the need for close monitoring and patient counseling.

KU675, a Concomitant Heat-Shock Protein Inhibitor of Hsp90 and Hsc70 that Manifests Isoform Selectivity for Hsp90α in Prostate Cancer Cells.

The 90-kDa heat-shock protein (Hsp90) assists in the proper folding of numerous mutated or overexpressed signal transduction proteins that are involved in cancer. Inhibiting Hsp90 consequently is an attractive strategy for cancer therapy as the concomitant degradation of multiple oncoproteins may lead to effective antineoplastic agents. Here we report a novel C-terminal Hsp90 inhibitor, designated KU675, that exhibits potent antiproliferative and cytotoxic activity along with client protein degradation without induction of the heat-shock response in both androgen-dependent and -independent prostate cancer cell lines. In addition, KU675 demonstrates direct inhibition of Hsp90 complexes as measured by the inhibition of luciferase refolding in prostate cancer cells. In direct binding studies, the internal fluorescence signal of KU675 was used to determine the binding affinity of KU675 to recombinant Hsp90α, Hsp90ß, and Hsc70 proteins. The binding affinity (Kd) for Hsp90α was determined to be 191 µM, whereas the Kd for Hsp90ß was 726 µM, demonstrating a preference for Hsp90α. Western blot experiments with four different prostate cancer cell lines treated with KU675 supported this selectivity by inducing the degradation of Hsp90α -: dependent client proteins. KU675 also displayed binding to Hsc70 with a Kd value at 76.3 µM, which was supported in cellular by lower levels of Hsc70-specific client proteins on Western blot analyses. Overall, these findings suggest that KU675 is an Hsp90 C-terminal inhibitor, as well as a dual inhibitor of Hsc70, and may have potential use for the treatment of cancer.

The effect of concomitant carcinoma in situ on neoadjuvant chemotherapy for urothelial cell carcinoma of the bladder: inferior pathological outcomes but no effect on survival.

PURPOSE: It is generally believed that carcinoma in situ is refractory to chemotherapy but specific data are lacking to validate this. We evaluated the effect of concomitant clinical carcinoma in situ on cancer specific outcomes after neoadjuvant chemotherapy for muscle invasive bladder cancer. MATERIALS AND METHODS: We performed an institutional review board approved, multi-institutional, retrospective review of the records of patients treated with neoadjuvant chemotherapy followed by radical cystectomy for muscle invasive bladder cancer from 2008 to 2012. Pretreatment clinical variables were collected and patients were stratified by the presence of clinical carcinoma in situ on precystectomy transurethral bladder tumor resection specimens. Pathological outcomes, including the complete response rate (pT0N0Mx) after neoadjuvant chemotherapy, were compared between the 2 groups. Recurrence-free, cancer specific and overall survival was analyzed. RESULTS: Of 189 patients who met study criteria 56 (29.6%) had concomitant carcinoma in situ. The condition was associated with a significant decrease in the pathological complete response rate (10.7% vs 26.3%, p = 0.02). This difference was significant on univariate and multivariable analysis (OR 0.34, 95% CI 0.13-0.85, p = 0.02 and OR 0.31, 95% CI 0.12-0.81, p = 0.02, respectively). Despite the decreased complete response rate clinical carcinoma in situ was not associated with a difference in recurrence-free, cancer specific or overall survival. Additionally, when down-staging to pathological carcinoma in situ only disease was considered a complete response, there was no significant change in recurrence-free, cancer specific or overall survival. CONCLUSIONS: Concomitant carcinoma in situ is associated with a decrease in the complete response rate but this does not appear to impact the survival outcome.

Can we predict the need for clean intermittent catheterization after orthotopic neobladder construction?

INTRODUCTION: We aimed to identify peri-operative and pathologic characteristics that may predict the need for clean intermittent catheterization (CIC) following radical cystectomy (RC) with orthotopic neobladder (ONB) in order to improve patient counseling on choice of urinary diversion. MATERIALS AND METHODS: Between July 2004 and February 2013, all patients who underwent RC with ONB were identified. Peri-operative clinical and pathological features were evaluated and correlated with patients reported need for CIC. The independent T-test was performed for continuous variables and Chi-square test was performed for categorical variables. Multivariate forward stepwise logistic regression analysis was used to identify variables that correlated with need for CIC after ONB. RESULTS: During the study period, 114 patients underwent RC with ONB creation. On univariate analysis, patients with higher body mass index, younger age, and non-vaginal or non-nerve-sparing procedures were more likely to require catheterization for complete emptying. Multivariate analysis demonstrates that conservative surgery (nerve sparing in males or vaginal sparing in females) was associated with a significantly lower rate of requiring CIC (Odds Ratio [OR] 0.20, P < 0.01). Surprisingly, older age was also associated with a slightly lower, but statistically significant, rate of requiring CIC (OR 0.92,P < 0.01). CONCLUSIONS: When counseling patients regarding the different types of diversions after RC, the potential need for long-term CIC after ONB must be discussed. The clinical factors that appear to increase the need for CIC include non-conservative RC (non-nerve sparing in males and non-vaginal sparing in females) and, to a certain degree, younger age.

Racial Differences in the Detection Rate of Bladder Cancer Using Blue Light Cystoscopy: Insights from a Multicenter Registry.

The use of blue light cystoscopy (BLC) has been shown to improve bladder tumor detection. However, data demonstrating the efficacy of BLC across different races are limited. Herein, we aim to evaluate heterogeneity in the characteristics of BLC for the detection of malignant lesions among various races. Clinicopathologic information was collected from patients enrolled in the multi-institutional Cysview® registry (2014-2021) who underwent transurethral resection or biopsy of bladder tumors. Outcome variables included sensitivity and negative and positive predictive values of BLC and white light cystoscopy (WLC) for the detection of malignant lesions among various races. Overall, 2379 separate lesions/tumors were identified from 1292 patients, of whom 1095 (85%) were Caucasian, 96 (7%) were African American, 51 (4%) were Asian, and 50 (4%) were Hispanic. The sensitivity of BLC was higher than that of WLC in the total cohort, as well as in the Caucasian and Asian subgroups. The addition of BLC to WLC increased the detection rate by 10% for any malignant lesion in the total cohort, with the greatest increase in Asian patients (18%). Additionally, the positive predictive value of BLC was highest in Asian patients (94%), while Hispanic patients had the highest negative predictive value (86%). Our study showed that regardless of race, BLC increases the detection of bladder cancer when combined with WLC.

Is a restaging TURBT necessary in high-risk NMIBC if the initial TURBT was performed with blue light?

OBJECTIVES: To evaluate whether a restaging transurethral resection of bladder tumor (TURBT) is necessary in high-risk nonmuscle invasive bladder cancer (NMIBC) if the initial TURBT was performed using blue light (BL) technology. METHODS AND MATERIALS: Using the multi-institutional Cysview registry between 2014 and 2021, all consecutive adult patients with known NMIBC (Ta and T1 disease) who underwent TURBT followed by a restaging TURBT within 8 weeks were reviewed. Patients were stratified according to their initial TURBT, BL vs. white light (WL), and compared to determine rates of residual disease and upstaging. Univariate analysis was performed using Mann-Whitney U and chi-square tests, with P < 0.05 considered significant. RESULTS: Overall, 115 patients had TURBT for NMIBC followed by a restaging TURBT within 8 weeks and were included in the analysis. Patients who underwent BL compared to WL for their initial TURBT had higher rates of benign pathology on restaging TURBT, although this was not statistically significant (47% vs. 30%; P = 0.08). Of patients with residual tumors on restaging TURBT, there were no differences in rates of Ta (22% vs. 26.5%; P = 0.62), T1 (22% vs. 26.5%; P = 0.62), or CIS (5.5% vs. 13%; P = 0.49) when the initial TURBT was done using BL compared to WL. Rates of upstaging to muscle invasive disease were also not different when initial TURBT was performed using BL compared to WL (3% vs. 4%; P = 0.78). CONCLUSIONS: TURBT using BL does not reduce rates of residual disease or risk of upstaging on restaging TURBT in Ta or T1 disease. Thus, a restaging TURBT is still necessary even if initial TURBT was performed using BL.