Predictors of persistent opioid use in bladder cancer patients undergoing radical cystectomy: A SEER-Medicare analysis.

PURPOSE: To evaluate patient and provider characteristics that predict persistent opioid use following radical cystectomy for bladder cancer including non-opioid naïve patients. METHODS: Patients undergoing cystectomy between July 2007 and December 2015 were identified using the SEER-Medicare database. Opioid exposure was identified before and after cystectomy using Medicare Part D data. Multivariable analyses were used to identify predictors of the primary outcomes: persistent opioid use (prescription 3-6 months after surgery) and postoperative opioid prescriptions (within 30 days of surgery). Secondary outcomes included physician prescribing practices and rates of persistent opioid use in their patient cohorts. RESULTS: A total of 1,774 patients were included; 29% had prior opioid exposure. Compared to opioid-naïve patients, non-opioid naïve patients were more frequently younger, Black, and living in less educated communities. The percentage of persistent postoperative use was 10% overall and 24% in non-opioid naïve patients. Adjusting for patient factors, opioid naïve individuals were less likely to develop persistent use (OR 0.23) while a 50-unit increase in oral morphine equivalent per day prescribed following surgery nearly doubled the likelihood of persistent use (OR 1.98). Practice factors such as hospital size, teaching affiliation, and hospital ownership failed to predict persistent use. 29% of patients filled an opioid prescription postoperatively. Opioid naïve patients (OR 0.13) and those cared for at government hospitals (OR 0.59) were less likely to fill an opioid script along with those residing in the Northeast. Variability between physicians was seen in prescribing practices and rates of persistent use. CONCLUSIONS: Non-opioid naïve patients have higher rates of post-operative opioid prescription than opioid-naïve patients. Physician prescribing practices play a role in persistent use, as initial prescription amount predicts persistent use even in non-opioid naïve patients. Significant physician variation in both prescribing practices and rates of persistent use suggest a role for standardizing practices.

MRI evaluation of vesical imaging reporting and data system for bladder cancer after neoadjuvant chemotherapy.

BACKGROUND: The Vesical Imaging-Reporting and Data System (VI-RADS) has demonstrated effectiveness in predicting muscle invasion in bladder cancer before treatment. The urgent need currently is to evaluate the muscle invasion status after neoadjuvant chemotherapy (NAC) for bladder cancer. This study aims to ascertain the accuracy of VI-RADS in detecting muscle invasion post-NAC treatment and assess its diagnostic performance across readers with varying experience levels. METHODS: In this retrospective study, patients with muscle-invasive bladder cancer who underwent magnetic resonance imaging (MRI) after NAC from September 2015 to September 2018 were included. VI-RADS scores were independently assessed by five radiologists, consisting of three experienced in bladder MRI and two inexperienced radiologists. Comparison of VI-RADS scores was made with postoperative histopathological diagnosis. Receiver operating characteristic curve analysis (ROC) was used for evaluating diagnostic performance, calculating sensitivity, specificity, and area under ROC (AUC)). Interobserver agreement was assessed using the weighted kappa statistic. RESULTS: The final analysis included 46 patients (mean age: 61 years ± 9 [standard deviation]; age range: 39-70 years; 42 men). The pooled AUC for predicting muscle invasion was 0.945 (95% confidence interval (CI): 0.893-0.977) for experienced readers, and 0.910 (95% CI: 0.831-0.959) for inexperienced readers, and 0.932 (95% CI: 0.892-0.961) for all readers. At an optimal cut-off value ≥ 4, pooled sensitivity and specificity were 74.1% (range: 66.0-80.9%) and 94.1% (range: 88.6-97.7%) for experienced readers, and 63.9% (range: 59.6-68.1%) and 86.4% (range: 84.1-88.6%) for inexperienced readers. Interobserver agreement ranged from substantial to excellent between all readers (k = 0.79-0.92). CONCLUSIONS: VI-RADS accurately assesses muscle invasion in bladder cancer patients after NAC and exhibits good diagnostic performance across readers with different experience levels.

Trimodal therapy vs radical cystectomy in patients with muscle-invasive bladder cancer: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: To perform a systematic review and meta-analysis of trials comparing trimodal therapy (TMT) and radical cystectomy (RC), evaluating differences in terms of oncological outcomes, quality of life, and costs. MATERIALS AND METHODS: In July 2023, a literature search of multiple databases was conducted to identify studies analysing patients with cT2-4 N any M0 muscle-invasive bladder cancer (MIBC; Patients) receiving TMT (Intervention) compared to RC (Comparison), to evaluate survival outcomes, recurrence rates, costs, and quality of life (Outcomes). The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and metastasis-free survival (MFS). Hazard ratios (HRs) were used to analyse survival outcomes according to different treatment modalities and odds ratios were used to evaluate the likelihood of receiving each type of treatment according to T stage. RESULTS: No significant difference in terms of OS was observed between RC and TMT (HR 1.07, 95% confidence interval [CI] 0.81-1.4; P = 0.6), even when analysing radiation therapy regimens ≥60 Gy (HR 1.02, 95% CI 0.69-1.52; P = 0.9). No significant difference was observed in CSS (HR 1.12, 95% CI 0.79-1.57, P = 0.5) or MFS (HR 0.88, 95% CI 0.66-1.16; P = 0.3). The mean cost of TMT was significantly higher than that of RC ($289 142 vs $148 757; P < 0.001), with greater effectiveness in terms of cost per quality-adjusted life-year. TMT ensured significantly higher general quality-of-life scores. CONCLUSION: Trimodal therapy appeared to yield comparable oncological outcomes to RC concerning OS, CSS and MFS, while providing superior patient quality of life and cost effectiveness.

Association of preoperative sarcopenia with the long-term prognosis of patients with bladder cancer undergoing radical cystectomy.

PURPOSE: This retrospective study aimed to assess the correlation between preoperative sarcopenia and long-term oncologic outcomes in patients undergoing radical cystectomy for bladder cancer. METHODS: We included 528 patients who underwent radical cystectomy for bladder cancer between 2000 and 2010 at Asan Medical Center, Seoul, Korea. Preoperative skeletal muscle mass was quantified by analyzing computed tomography images at the third lumbar vertebra. Sarcopenia was defined based on the skeletal muscle index. We evaluated various clinical and pathological factors to analyze the association between sarcopenia and long-term oncologic outcomes. RESULTS: The median follow-up time was 104 months. Sarcopenia was identified in 37.9% of the patients. Although no significant differences were observed in traditional pathological factors between the sarcopenic and non-sarcopenic groups, sarcopenia was significantly associated with worse oncologic outcomes. Compared to the non-sarcopenic groups, the sarcopenic group had lower overall survival rates (52.0% vs. 67.1% at 5 years, 35.5% vs. 52.7% at 10 years) and higher cancer-specific mortality (63.3% vs. 74.3% at 5 years, 50.7% vs. 67.4% at 10 years). Multivariable Cox regression analysis demonstrated that sarcopenia was an independent predictor of cancer-specific survival (hazard ratio: 1.49, 95% confidence interval: 1.11-2.01, p = 0.008), alongside body mass index, tumor stage, lymph node metastasis, and lymphovascular invasion. CONCLUSION: Sarcopenia was significantly associated with poor cancer-specific survival in patients undergoing radical cystectomy for bladder cancer. Detecting sarcopenia may assist in preoperative risk stratification and long-term management after radical cystectomy.

Robotic-assisted radical cystectomy with cutaneous ureterostomies: a contemporary multicenter analysis.

BACKGROUND: Robotic-assisted radical cystectomy (RARC) offers decreased blood loss during surgery, shorter hospital length of stay, and lower risk for thromboembolic events without hindering oncological outcomes. Cutaneous ureterostomies (UCS) are a seldom utilized diversion that can be a suitable alternative for a selected group of patients with competing co-morbidities and limited life expectancy. OBJECTIVE: To describe operative and perioperative characteristics as well as oncological outcomes for patients that underwent RARC + UCS. METHODS: Patients that underwent RARC + UCS during 2013-2023 in 3 centers (EU = 2, US = 1) were identified in a prospectively maintained database. Baseline characteristics, pathological, and oncological outcomes were analyzed. Descriptive statistics and survival analysis were performed using R language version 4.3.1. RESULTS: Sixty-nine patients were included. The median age was 77 years (IQR 70-80) and the median follow-up time was 11 months (IQR 4-20). Ten patients were ASA 4 (14.5%). Nine patients underwent palliative cystectomy (13%). The median operation time was 241 min (IQR 202-290), and the median hospital stay was 8 days (IQR 6-11). The 30-day complication rate was 55.1% (grade ≥ 3a was 14.4%), and the 30-day readmission rate was 17.4%. Eleven patients developed metastatic recurrence (15.9%), and 14 patients (20.2%) died during the follow-up period. Overall survival at 6, 12, and 24 months was 84%, 81%, and 73%, respectively. CONCLUSIONS: RARC + UCS may offer lower complication and readmission rates without the need to perform enteric anastomosis, it can be considered in a selected group of patients with competing co-morbidities, or limited life expectancy. Larger prospective studies are necessary to validate these results.

Multimodal imaging findings of sarcomatoid carcinoma of the urinary bladder.

Sarcomatoid carcinoma, a rare and aggressive subtype of bladder cancer, accounting for 0.3% of cases, is more aggressive than urothelial carcinomas. Accurate diagnosis, crucial for treatment, can be challenging. We present a characterized case of sarcomatoid carcinoma of the urinary bladder using multimodal imaging and pathology.

Type III interferon inhibits bladder cancer progression by reprogramming macrophage-mediated phagocytosis and orchestrating effective immune responses.

BACKGROUND: Interferons (IFNs) are essential for activating an effective immune response and play a central role in immunotherapy-mediated immune cell reactivation for tumor regression. Type III IFN (λ), related to type I IFN (α), plays a crucial role in infections, autoimmunity, and cancer. However, the direct effects of IFN-λ on the tumor immune microenvironment have not been thoroughly investigated. METHODS: We used mouse MB49 bladder tumor models, constructed a retroviral vector expressing mouse IFN-λ3, and transduced tumor cells to evaluate the antitumor action of IFN-λ3 in immune-proficient tumors and T cell-deficient tumors. Furthermore, human bladder cancer samples (cohort 1, n=15) were used for immunohistochemistry and multiplex immunoflurescence analysis to assess the expression pattern of IFN-λ3 in human bladder cancer and correlate it with immune cells' infiltration. Immunohistochemistry analysis was performed in neoadjuvant immunotherapy cohort (cohort 2, n=20) to assess the correlation between IFN-λ3 expression and the pathological complete response rate. RESULTS: In immune-proficient tumors, ectopic Ifnl3 expression in tumor cells significantly increased the infiltration of cytotoxic CD8+ T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Transcriptomic analyses revealed significant upregulation of many genes associated with effective immune response, including lymphocyte recruitment, activation, and phagocytosis, consistent with increased antitumor immune infiltrates and tumor inhibition. Furthermore, IFN-λ3 activity sensitized immune-proficient tumors to anti-PD-1/PD-L1 blockade. In T cell-deficient tumors, increased Ly6G-Ly6C+I-A/I-E+ macrophages still enhanced tumor cell phagocytosis in Ifnl3 overexpressing tumors. IFN-λ3 is expressed by tumor and stromal cells in human bladder cancer, and high IFN-λ3 expression was positively associated with effector immune infiltrates and the efficacy of immune checkpoint blockade therapy. CONCLUSIONS: Our study indicated that IFN-λ3 enables macrophage-mediated phagocytosis and antitumor immune responses and suggests a rationale for using Type III IFN as a predictive biomarker and potential immunotherapeutic candidate for bladder cancer.

Sequential endoluminal gemcitabine and docetaxel vs. Bacillus Calmette-Guérin for the treatment of upper tract carcinoma in situ.

INTRODUCTION: Nephroureterectomy is commonly performed for high-grade (HG) upper tract (UT) urothelial carcinoma (UC). However, some patients may benefit from a de-escalation of surgical management, particularly for noninvasive disease and carcinoma in situ (CIS). Bacillus Calmette-Guerin (BCG) is currently the only guideline-recommended endoluminal treatment option. Gemcitabine/Docetaxel (Gem/Doce) has shown promising efficacy as a treatment for noninvasive HG UTUC, though a comparison to BCG is lacking. We report the outcomes of patients treated with endoluminal Gem/Doce vs. BCG for UT-CIS. METHODS: A single-institutional retrospective review of patients treated with Gem/Doce vs. BCG for UT-CIS was performed. Treatment was instilled via nephrostomy or retrograde ureteral catheter. In both treatment groups, induction consisted of 6 weekly instillations. Maintenance was initiated if disease-free and consisted of 6 monthly instillations in the Gem/Doce group and a reduced dose (one-tenth) 3-week course at 3 months in the BCG group. Recurrence was defined as biopsy-proven disease or HG cytology. RESULTS: The final cohort included 53 patients with 65 upper tract units; 31 received BCG and 34 received Gem/Doce. Median follow-up was 88 and 29 months in the BCG and Gem/Doce groups, respectively. Presenting pathology included biopsy-proven CIS and HG cytology in 9.7% and 90% of the BCG group, and 8.8% and 91% of the Gem/Doce group, respectively. The 2-year estimates for recurrence-free and nephroureterectomy-free survival were 61% and 89% for the BCG group and 54% and 100% for the Gem/Doce group, respectively. Upon multivariable analysis, instillation via percutaneous nephrostomy tube was associated with an increased risk of recurrence (HR 3.89, 95% CI 1.59-9.53). The development of any symptom was not statistically different between treatment groups (P = 0.12). There were 2 treatment-related deaths that occurred, 1 within each treatment group. CONCLUSION: Endoluminal Gem/Doce and BCG have similar oncological outcomes and major adverse event rates in the treatment of UT-CIS. Further prospective evaluation is warranted.

Rare case of enteric type of urachal adenocarcinoma: A case report.

Urachal adenocarcinomas, constituting 10 % of bladder adenocarcinomas, pose a significant challenge with limited literature. A 43-year-old male presented with haematuria and abdominal pain, leading to surgical intervention for a 13 cm pelvic tumor. Histopathology identified an intestinal-type primary urachal adenocarcinoma, staged as IIIA, no recurrence on follow-up. Early detection is crucial for improved outcomes in these rare malignancies. While surgery remains the primary treatment, outcomes vary, emphasizing the need for research on standardized protocols. Enhanced awareness and interdisciplinary collaboration are vital for effective management. Comprehensive guidelines are essential for optimizing patient prognoses in urachal adenocarcinomas.

Bladder MRI with deep learning-based reconstruction: a prospective evaluation of muscle invasiveness using VI-RADS.

PURPOSE: To investigate the influence of deep learning reconstruction (DLR) on bladder MRI, specifically examination time, image quality, and diagnostic performance of vesical imaging reporting and data system (VI-RADS) within a prospective clinical cohort. METHODS: Seventy participants with bladder cancer who underwent MRI between August 2022 and February 2023 with a protocol containing standard T2-weighted imaging (T2WIS), standard diffusion-weighted imaging (DWIS), fast T2WI with DLR (T2WIDL), and fast DWI with DLR (DWIDL) were enrolled in this prospective study. Imaging quality was evaluated by measuring signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and qualitative image quality scoring. Additionally, the apparent diffusion coefficient (ADC) of bladder lesions derived from DWIS and DWIDL was measured and VI-RADS scoring was performed. Paired t-test or paired Wilcoxon signed-rank test were performed to compare image quality score, SNR, CNR, and ADC between standard sequences and fast sequences with DLR. The diagnostic performance for VI-RADS was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Compared to T2WIS and DWIS, T2WIDL and DWIDL reduced the acquisition time from 5:57 min to 3:13 min and showed significantly higher SNR, CNR, qualitative image quality score of overall image quality, image sharpness, and lesion conspicuity. There were no significant differences in ADC and AUC of VI-RADS between standard sequences and fast sequences with DLR. CONCLUSIONS: The application of DLR to T2WI and DWI reduced examination time and significantly improved image quality, maintaining ADC and the diagnostic performance of VI-RADS for evaluating muscle invasion in bladder cancer.

Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/SUO GUIDELINE (2017; Amended 2020, 2024).

PURPOSE: Although representing approximately 25% of patients diagnosed with bladder cancer, muscle-invasive bladder cancer (MIBC) carries a significant risk of death that has not significantly changed in decades. Increasingly, clinicians and patients recognize the importance of multidisciplinary collaborative efforts that take into account survival and quality of life concerns. This guideline provides a risk-stratified, clinical framework for the management of muscle-invasive urothelial bladder cancer. METHODOLOGY/METHODS: In 2024, the MIBC 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 May 2020 to November 2023. This review identified 3739 abstracts, of which 46 met inclusion criteria.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for 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 regarding neoadjuvant/adjuvant chemotherapy, radical cystectomy, pelvic lymphadenectomy, multi-modal bladder preserving therapy, 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 MIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

Non-coding RNA transcripts, incredible modulators of cisplatin chemo-resistance in bladder cancer through operating a broad spectrum of cellular processes and signaling mechanism.

Bladder cancer (BC) is a highly frequent neoplasm in correlation with significant rate of morbidity, mortality, and cost. The onset of BC is predominantly triggered by environmental and/or occupational exposures to carcinogens, such as tobacco. There are two distinct pathways by which BC can be developed, including non-muscle-invasive papillary tumors (NMIBC) and non-papillary (or solid) muscle-invasive tumors (MIBC). The Cancer Genome Atlas project has further recognized key genetic drivers of MIBC along with its subtypes with particular properties and therapeutic responses; nonetheless, NMIBC is the predominant BC presentation among the suffering individuals. Radical cystoprostatectomy, radiotherapy, and chemotherapy have been verified to be the common therapeutic interventions in metastatic tumors, among which chemotherapeutics are more conventionally utilized. Although multiple chemo drugs have been broadly administered for BC treatment, cisplatin is reportedly the most effective chemo drug against the corresponding malignancy. Notwithstanding, tumor recurrence is usually occurred following the consumption of cisplatin regimens, particularly due to the progression of chemo-resistant trait. In this framework, non-coding RNAs (ncRNAs), as abundant RNA transcripts arise from the human genome, are introduced to serve as crucial contributors to tumor expansion and cisplatin chemo-resistance in bladder neoplasm. In the current review, we first investigated the best-known ncRNAs, i.e. microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), correlated with cisplatin chemo-resistance in BC cells and tissues. We noticed that these ncRNAs could mediate the BC-related cisplatin-resistant phenotype through diverse cellular processes and signaling mechanisms, reviewed here. Eventually, diagnostic and prognostic potential of ncRNAs, as well as their therapeutic capabilities were highlighted in regard to BC management.

A Proposal for Standardization of Early Outcomes Following Robot-Assisted Radical Cystectomy (RARC): RARC Tetrafecta.

BACKGROUND: Currently, there is no dedicated tool to record the early outcomes of robot-assisted radical cystectomy (RARC), and existing criteria for longer-term outcomes require a minimum of 3 months for assessment. However, early evaluation is essential to prevent future morbidity and mortality, especially in surgeries with a high risk of complications in the short term. We propose a comprehensive approach to report early RARC outcomes and investigate the influence of surgeon experience on these results. PATIENTS AND METHODS: We retrospectively analyzed the outcomes of patients who underwent RARC for bladder cancer between April 2009 and April 2020. The cohort was divided chronologically into three groups: patients 1-60 in group 1, 61-120 in group 2, and 121-192 in group 3. Patients with yields of ≥ 16 lymph nodes (LN), negative soft tissue surgical margins, absence of transfusion, and absence of major complications at 30 days were regarded as attaining the RARC tetrafecta. RESULTS: Of the 192 included patients, 93 (48.4%) achieved RARC tetrafecta, with the proportion increasing with surgical experience from 41.7% in group 1 to 55.6% in group 3. Age [odds ratio (OR) 0.947; 95% confidence interval (CI) 0.924-0.970; P = 0.021], LN yield (OR 1.432; 95% CI 1.139-1.867; P = 0.001), and greater surgical experience with RARC (> 120 patients; OR 2.740; 95% CI 1.231-6.100; P = 0.014) were significantly associated with the achievement of RARC tetrafecta. CONCLUSIONS: RARC tetrafecta could be a comprehensive method for reporting early outcomes in patients undergoing RARC, with improvements aligned with the surgeon's experience.

Comparisons of in-hospital fee and surgical outcomes between robot-assisted, laparoscopic, and open radical cystectomy: a Japanese nationwide study.

OBJECTIVE: To evaluate in-hospital fees and surgical outcomes of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC) using a Japanese nationwide database. METHODS: All data were obtained from the Diagnosis Procedure Combination database between April 2020 and March 2022. Basic characteristics and perioperative indicators, including in-hospital fees, were compared among the RARC, LRC and ORC groups. Propensity score-matched comparisons were performed to assess the differences between RARC and ORC. RESULTS: During the study period, 2931, 1311 and 2435 cases of RARC, LRC and ORC were identified, respectively. The RARC group had the lowest in-hospital fee (median: 2.38 million yen), the shortest hospital stay (26 days) and the lowest blood transfusion rate (29.5%), as well as the lowest complication rate (20.9%), despite having the longest anesthesia time (569 min) among the three groups (all P < 0.01). The outcomes of LRC were comparable with those of RARC, and the differences in these indicators between the RARC and ORC groups were greater than those between the RARC and LRC groups. In propensity score-matched comparisons between the RARC and ORC groups, the differences in the indicators remained significant (all P < 0.01), with an ~50 000 yen difference in in-hospital fees. CONCLUSIONS: RARC and LRC were considered to be more cost-effective surgeries than ORC due to their superior surgical outcomes and comparable surgical fees in Japan. The widespread adoption of RARC and LRC is expected to bring economic benefits to Japanese society.

Differentiation of Muscular Invasion in Bladder Cancer: Additional Value of Synthetic Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES: To evaluate the potential of Synthetic Magnetic Resonance Imaging (SynMRI) in identifying muscular invasion in bladder cancer (BCa), and explore whether there is additional value in combination with the Vesical Imaging-Reporting and Data System (VI-RADS). METHODS: In this prospective single-center study, pathologically-confirmed BCa were enrolled between May 2023 and November 2023. All participants underwent preoperative multiparametric MRI, including T1/T2 weighted, SynMRI and diffusion-weighted imaging. T1/T2/PD values and apparent diffusion coefficient (ADC) values were compared between muscle invasive (MIBC) and non-invasive (NMIBC) groups. Receiver operating characteristic (ROC) analysis with the variables and their combination was performed to explore the performance of distinguishing the MIBC from NMIBC, and the ROC curves were compared using DeLong's test. RESULTS: A total of 54 BCa patients were enrolled (38 males; NMIBC/MIBC=37/19) and all assessed with VI-RADS without dynamic enhanced imaging (DCE). Compared to NMIBC group, MIBC group had significantly larger diameter, higher VI-RADS score, lower T2 and ADC values (P < 0.05). VI-RADS score and T2 showed independent predictive value in differentiating NMIBC and MIBC. The combined model (T2 + VI-RADS+Diameter) resulted in significantly improved specificity (0.842), sensitivity (0.914), and AUC (0.943), in comparison to VI-RADS or ADC alone (P < 0.05). CONCLUSION: T2 relaxation time can be easily obtained from SynMRI in routine clinical protocol and assist VI-RADS score system without DCE to improve differentiation performance in identifying NMIBC and MIBC.

Longitudinal Tumor-informed Circulating Tumor DNA Status Predicts Disease Upstaging and Poor Prognosis for Patients Undergoing Radical Cystectomy.

BACKGROUND AND OBJECTIVE: Decision-making on the use of neoadjuvant and adjuvant treatment for patients with bladder cancer undergoing radical cystectomy (RC) currently depends on assessment of clinical and pathological features, which lack sensitivity. Circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. Our aim was to assess whether ctDNA status before RC is predictive of pathological and oncological outcomes. We also evaluated the dynamic changes in ctDNA status after RC in relation to recurrence-free survival (RFS). METHODS: We analyzed data for patients who underwent RC during 2021-2023 for whom prospective tumor-informed ctDNA analyses were conducted before and after RC. RFS was evaluated using the Kaplan-Meier method. Predictors for disease recurrence were assessed using Cox proportional-hazards models. Pathological outcomes associated with detectable ctDNA before RC were assessed in univariable and multivariable regression analyses. KEY FINDINGS AND LIMITATIONS: We included 112 patients in the analysis. Median follow-up was 8 mo (interquartile range 4-13). ctDNA was detected before RC in 59 patients (53%) and was associated with poor RFS (log-rank p < 0.0001). Detectable ctDNA before RC was associated with poor outcomes regardless of clinical stage (

Caracterización del cáncer vesical en adultos según variables clínicas y epidemiológicas / Characterization of bladder cancer in adults according to clinical and epidemiological variables

Introducción: El cáncer de la vejiga es uno de los más frecuentes del tracto urinario y se manifiesta de dos formas: como tumor superficial de bajo grado o como neoplasia invasora de alto grado. Objetivo: Caracterizar el cáncer vesical en adultos, según variables clínicas, epidemiológicas y de servicio. Métodos: Se realizó un estudio observacional descriptivo y retrospectivo, para caracterizar el cáncer vesical en adultos, según variables clínicas, epidemiológicas y de servicio de los pacientes atendidos en el servicio de Urología del Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro» en el periodo comprendido de octubre 2019 y 2022. Población del estudio: 242 pacientes diagnosticados con cáncer vesical. Resultados: La mayoría de los pacientes diagnosticados con cáncer vesical corresponden al año 2019 (45,86 %): masculinos (75,20 %); blancos (89,25 %); mayores de 70 o más años (64,46 %) y fumadores (95,45 %). La hematuria fue el síntoma principal (91,73 %), como expresión del carcinoma urotelial papilar de bajo grado (36,77 %). Tratamiento: la resección transuretral (88,01 %), sin metástasis a distancia (88,42 %). Conclusiones: La mayoría de los pacientes diagnosticados con cáncer vesical corresponden al año 2019, masculinos, blancos, mayores de 70 o más años, fumadores y con hematuria. Más frecuente: el carcinoma urotelial papilar de bajo grado. El tiempo trascurrido antes del diagnóstico de la enfermedad fue de 36-40 días, y un mes, el tiempo trascurrido antes del tratamiento de la enfermedad.

Introduction: bladder cancer is one of the most frequent cancers of the urinary tract and manifests itself in two ways: as a superficial low-grade tumor or as a high-grade invasive neoplasm. Objective: to characterize bladder cancer in adults according to clinical, epidemiological and service variables. Methods: a descriptive and retrospective observational study was carried out to characterize bladder cancer in adults according to clinical, epidemiological and service variables of patients treated in the Urology service at "Arnaldo Milián Castro" Clinical and Surgical University Hospital from October 2019 and 2022. The study population was 242 patients diagnosed with bladder cancer. Results: most of the patients diagnosed with bladder cancer correspond to the year 2019 (45.86%): male (75.20%); whites (89.25%); older than 70 or more years (64.46%) and smokers (95.45%). Hematuria was the main symptom (91.73%), as an expression of low-grade papillary urothelial carcinoma (36.77%). The treatment was transurethral resection (88.01%), without distant metastasis (88.42%). Conclusions: most of the patients diagnosed with bladder cancer correspond to the year 2019, male, whites, older than 70 years or older, smokers and with hematuria. Low-grade papillary urothelial carcinoma was the most frequent cancer. The time elapsed before the diagnosis of the disease was 36-40 days, and the time elapsed before the treatment of the disease was 1 month.

A phase 2 pilot study of water irrigation after transurethral resection of bladder tumor (WATIP) demonstrating safety, feasibility and activity.

PURPOSE: Non-muscle-invasive bladder cancer (NMIBC) can recur, partly due to seeding of free tumour cells after transurethral resection of bladder tumour (TURBT). Intravesical chemotherapy post-TURBT can reduce the risk but is used infrequently and inconsistently due to cost, complexity and side effects. The objective of this study was to prospectively assess continuous bladder irrigation using water, which may be a safer and easier alternative with comparable effectiveness. METHODS: WATIP was a prospective, single-arm phase 2 study of water irrigation during and for at least 3 h after TURBT for bladder tumours noted on imaging or flexible cystoscopy. Participants were assessed clinically for adverse effects and with blood tests within 24 h for sodium, haemoglobin and lactate dehydrogenase. The primary endpoints were safety (defined as < 10% adverse events of CTCAE grade ≥ 3), and feasibility (defined as the intervention being delivered as planned in > 90% of cases) and secondary endpoint was recurrence-free rates (RFR). RESULTS: Water irrigation was delivered as planned in 29 (97%) of 30 participants (median age 67 years, 25 (83%) males). The only adverse event (grade 2) was clot retention in one (3.3%) participant. Water irrigation significantly reduced urothelial cell counts in catheter effluent over time, unlike saline irrigation which did not. RFR was 56.2% (9/16 participants with low-risk NMIBC) at first cystoscopy (median interval 108 days) and 62.5% (5/8 evaluable low-risk NMIBC) at 12 months. CONCLUSION: Water irrigation during and after TURBT is feasible and safe. Prospective assessment of its effect on NMIBC recurrence compared to post-TURBT intravesical chemotherapy is needed before recommending its use in routine clinical practice. Trial registration ANZCTR registration ID ACTRN12619000517178 on 1 April 2019.

The optimal number of induction chemotherapy cycles in clinically lymph node-positive bladder cancer.

OBJECTIVE: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. PATIENTS AND METHODS: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni- and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer-specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. RESULTS: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2-year OS estimates were 63% (95% confidence interval [CI] 0.53-0.74) and 63% (95% CI 0.58-0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni- or multivariable Cox regression analyses. CONCLUSION: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

Health-related Quality of Life in Patients with Previously Treated Advanced Urothelial Carcinoma from EV-301: A Phase 3 Trial of Enfortumab Vedotin Versus Chemotherapy.

BACKGROUND AND OBJECTIVE: In comparison to chemotherapy, enfortumab vedotin (EV) prolonged overall survival in patients with previously treated advanced urothelial carcinoma in EV-301. The objective of the present study was to assess patient experiences of EV versus chemotherapy using patient-reported outcome (PRO) analysis of health-related quality of life (HRQoL). METHODS: For patients in the phase 3 EV-301 trial randomized to EV or chemotherapy we assessed responses to the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, weekly for the first 12 wk, and then every 12 wk until discontinuation. We analyzed the QLQ-C30 change from baseline to week 12, the confirmed improvement rate, and the time to improvement or deterioration. KEY FINDINGS AND LIMITATIONS: Baseline PRO compliance rates were 91% for the EV arm (n = 301) and 89% for the chemotherapy arm (n = 307); the corresponding average rates from baseline to week 12 were 70% and 67%. Patients receiving EV versus chemotherapy had reduced pain (difference in change from baseline to week 12: -5.7, 95% confidence interval [CI] -10.8 to -0.7; p = 0.027) and worsening appetite loss (7.3, 95% CI 0.90-13.69; p = 0.026). Larger proportions of patients in the EV arm reported HRQoL improvement from baseline than in the chemotherapy arm; the odds of a confirmed improvement across ten QLQ-C30 function/symptom scales were 1.67 to 2.76 times higher for EV than for chemotherapy. Patients in the EV arm had a shorter time to first confirmed improvement in global health status (GHS)/QoL, fatigue, pain, and physical, role, emotional, and social functioning (all p < 0.05). EV delayed the time to first confirmed deterioration in GHS/QoL (p = 0.027), but worsening appetite loss occurred earlier (p = 0.009) in comparison to chemotherapy. CONCLUSIONS AND CLINICAL IMPLICATIONS: HRQoL with EV was maintained, and deterioration in HRQoL was delayed with EV in comparison to chemotherapy. Better results with EV were reported for some scales, with the greatest difference observed for pain. These findings reinforce the EV safety and efficacy outcomes and benefits observed in EV-301. PATIENT SUMMARY: Patients with previously treated advanced cancer of the urinary tract receiving the drug enfortumab vedotin maintained their HRQoL in comparison to patients treated with chemotherapy. The EV-301 trial is registered on ClinicalTrials.gov as NCT03474107 and on EudraCT as 2017-003344-21.