The role of neoadjuvant chemotherapy for patients with variant histology muscle invasive bladder cancer undergoing robotic cystectomy: Data from the International Robotic Cystectomy Consortium.

OBJECTIVE: To assess the role of neoadjuvant chemotherapy (NAC) before robot-assisted radical cystectomy (RARC) for patients with variant histology (VH) muscle-invasive bladder cancer (MIBC). METHODS: Retrospective review of 988 patients who underwent RARC (2004-2023) for MIBC. Primary outcomes included the utilization of NAC among this cohort of patients, frequency of downstaging, and discordance between preoperative and final pathology in terms of the presence of VH. Secondary outcomes included disease-specific (DSS), recurrence-free (RFS), and overall survival (OS). RESULTS: A total of 349 (35%) had VH on transurethral resection or at RARC. The 4 most common VH subgroups were squamous (n = 94), adenocarcinoma (n = 64), micropapillary (n = 34), and sarcomatoid (n = 21). There was no difference in OS (log-rank: P = 0.43 for adenocarcinoma, P = 0.12 for micropapillary, P = 0.55 for sarcomatoid, P = 0.29 for squamous), RFS (log-rank: P = 0.25 for adenocarcinoma, P = 0.35 for micropapillary, P = 0.83 for sarcomatoid, P = 0.79 for squamous), or DSS (log-rank P = 0.91 for adenocarcinoma, P = 0.15 for micropapillary, 0.28 for sarcomatoid, P = 0.92 for squamous) among any of the VH based on receipt of NAC. Patients with squamous histology who received NAC were more likely to be downstaged on final pathology compared to those who did not (P < 0.01). CONCLUSION: Our data showed no significant difference in OS, RFS, or DSS for patients with VH MIBC cancer who received NAC before RARC. Patients with the squamous variant who received NAC had more pathologic downstaging compared to those who did not. The role of NAC among patients with VH is yet to be defined. Results were limited by small number in each individual group and lack of exact proportion of VH.

Phase II Trial of Concurrent Nivolumab and Radiation Therapy for Muscle-Invasive Bladder Cancer of Older or Chemotherapy-Ineligible Patients.

PURPOSE: Bladder cancer is predominantly a disease of older individuals. Concurrent chemotherapy and radiation is a bladder-sparing strategy for management of muscle-invasive bladder cancer; however, many patients are not candidates for chemotherapy due to comorbidities or impaired performance status. We conducted a study in a chemotherapy-ineligible patient population with the objectives of evaluating the safety, efficacy, and quality-of-life effect of the combination of nivolumab and radiation therapy in patients with localized/locally advanced urothelial cancer. METHODS AND MATERIALS: Eligible patients had muscle-invasive bladder cancer and were not candidates for standard chemoradiation strategy due to at least one of the following: performance status of 2, creatinine clearance ≤60 mL/min, cardiac disease, neuropathy, and intolerance to previous treatment. Creatinine clearance ≥40 mL/min, normal marrow, and liver function were required. The primary endpoint was progression-free survival at 12 months. Nivolumab was started within 3 days of radiation therapy and administered at a dose of 240 mg intravenously every 2 weeks for a maximum of 6 months. Radiation therapy was per standard of care for bladder cancer. Imaging and cystoscopy and biopsy evaluation were required at months 3, 6, and 12 and then annually until progression. RESULTS: Twenty patients were enrolled, with a median age of 78.5 years (range, 58-95 years); 80% of patients were >70 years of age, and 8 (40%) were >80 years of age. Median creatinine clearance was 52 mL/min. Nine patients (48%) were progression free at 12 months. Median progression-free survival was 11.4 months (90% CI, 7.5-23.7 months), and median overall survival was 15.6 months (90% CI, 9.1-26.1 months). CONCLUSIONS: Concurrent nivolumab and radiation therapy is tolerable but demonstrated limited efficacy in an older population with multiple comorbidities. Immune correlates demonstrated that patients with baseline programmed cell death ligand 1 combined prognostic score ≥5% had numerically longer progression-free survival.

The impact of NCCN-compliant multidisciplinary conference on the uptake of active surveillance among eligible patients with localized prostate cancer.

INTRODUCTION: We sought to investigate the impact of National Comprehensive Cancer Network (NCCN)-compliant multidisciplinary conference on the uptake of active surveillance (AS) among eligible patients with prostate cancer. METHODS: Retrospective review of our AS database was performed. Patients who are eligible for AS who sought a second opinion at a comprehensive cancer center (2010-2021) were presented to the multidisciplinary Localized Prostate Cancer Conference (LPCC) that includes urologists, radiation oncologists, pathologists, and patient advocates. Cochrane Armitage test was used to examine trends over time. Multivariable regression models were fit to evaluate variables associated with the receipt of AS. RESULTS: Seven hundred twelve patients were identified (19% NCCN very low risk, 32% low risk, and 49% intermediate favorable risk). 43% were recommended AS as the preferred option by the community compared to 68% by LPCC, and 65% elected AS. Recommending AS significantly increased between 2010 and 2021 by the community (from 26% to 57%) and by LPCC (from 52% to 82%), while the proportion of men who received AS increased from 47% to 80% during the same period (P < 0.0001 for all). More recent LPCC era 2017 to 2021 (OR 12.31, 95% CI, 5.60-27.03, P < 0.0001), African American race (OR 0.42, 95% CI, 0.18-0.96, P = 0.04), positive cores at biopsy (OR 0.96, 95% CI, 0.94-0.97, P < 0.0001), age (OR 1.14, 95% CI, 1.10-1.18, P < 0.0001), NCCN low risk (OR 0.25, 95% CI, 0.08-0.81, P = 0.02) and NCCN intermediate favorable risk (OR 0.03, 95% CI, 0.01-0.09, P < 0.0001) were associated with receipt of AS. CONCLUSION: AS recommendation increased significantly over time by community urologists and to a higher extent by NCCN-compliant multidisciplinary conference. The Uptake of AS significantly increased within the same period. More recent LPCC era 2017 to 2021, African American race, the proportion of positive cores at biopsy, age, and NCCN risk were the main determinants of receipt of AS.

Does the urinary microbiome profile change after treatment of bladder cancer?

INTRODUCTION: We sought to investigate the change in the urinary microbiome profile after transurethral resection of bladder tumor (TURBT). METHODS: Urine specimens were collected from consecutive patients with bladder cancer. Patients were divided into those with bladder tumors ("Tumor group": de novo tumors or recurrent/progressed after TURBT ± intravesical therapy) versus those without evidence of recurrence after treatment "No Recurrent Tumor group". Samples were analyzed using 16S rRNA sequencing. Alteration in the urinary microbiome was described in terms of alpha (diversity within a sample measured by Observed, Chao, Shannon, and Simpson indices), beta diversities (diversity among different samples measured by Brady Curtis Diversity index), and differential abundance of bacteria at the genus level. Analyses were adjusted for gender, method of preservation (frozen vs preservative), and method of collection (mid-stream vs. catheter). RESULTS: Sixty-eight samples were analyzed (42 in "Tumor" vs 26 in "No Recurrent Tumor" groups). The median age was 70 years (IQR 64-74) and 85% were males. All patients in the "No Recurrent Tumor" group had non-muscle invasive bladder cancer and 85% received BCG compared to 69% and 43% for the "Tumor" group, respectively. There was no significant difference in alpha diversity (p > 0.05). Beta diversity was significantly different (p = 0.04). Veillonella and Bifidobacterium were more abundant in the "Tumor" group (> 2FC, p = 0.0002), while Escherichia-Shigella (> 2FC, p = 0.0002) and Helococcus (> 2FC, p = 0.0008) were more abundant in the "No Recurrent Tumor" group. CONCLUSION: Bladder cancer patients with no recurrence and/or progression exhibited a different urinary microbiome profile compared to those with tumors.

Does testosterone replacement therapy increase the risk of conversion to treatment in patients with prostate cancer on active surveillance?

PURPOSE: We aimed to evaluate the impact of testosterone replacement therapy (TRT) in patients with localized prostate cancer (CaP) who elected active surveillance (AS). METHODS: A retrospective review of our CaP database was performed. Patients who received TRT while on AS were identified and were matched to a cohort of patient on AS while not on TRT (1:3) using propensity score matching. Treatment-free survival (TFS) was computed using Kaplan Meier method. Multivariable Cox regression model was used to evaluate variables associated with treatment. RESULTS: Twenty-four patients in the TRT group were matched to 72 patients without TRT. Median follow-up was 5.82 years (IQR 3.27-9.30). There was no significant difference in conversion to treatment (24% vs. 21%, P = 1.00) There was no significant difference in TFS (log rank P = 0.87). Prostate specific antigen (PSA) density was the only variable associated TFS (HR 1.08, 95%CI 1.03-1.13, P = 0.001). CONCLUSION: TRT was not associated with conversion to treatment in this matched analysis among patients with localized prostate cancer on AS.

Excitation of a Single Compound by Light and Ultrasound Enhanced the Long-Term Cure of Mice Bearing Prostate Tumors.

Current treatment for prostate cancer is dependent on the stages of the cancer, recurrence, and genetic factors. Treatment varies from active surveillance or watchful waiting to prostatectomy, chemotherapy, and radiation therapy in combination or alone. Although radical prostate cancer therapy reduces the advancement of the disease and its mortality, the increased disease treatment associated morbidity, erectile dysfunction, and incontinence affect the quality of life of cancer survivors. To overcome these problems, photodynamic therapy (PDT) has previously been investigated using PhotofrinTM as a photosensitizer (PS). However, Photofrin-PDT has shown limitations in treating prostate cancer due to its limited tumor-specificity and the depth of light penetration at 630 nm (the longest wavelength absorption of PhotofrinTM). The results presented herein show that this limitation can be solved by using a near infrared (NIR) compound as a photosensitizer (PS) for PDT and the same agent also acts as a sonosensitizer for SDT (using ultrasound to activate the compound). Compared to light, ultrasound has a stronger penetration ability in biological tissues. Exposing the PS (or sonosensitizer) to ultrasound (US) initiates an electron-transfer process with a biological substrate to form radicals and radical ions (type I reaction). In contrast, exposure of the PS to light (PDT) generates singlet oxygen (type II reaction). Therefore, the reactive oxygen species (ROS) produced by SDT and PDT follow two distinct pathways, i.e., type I (oxygen independent) and type II (oxygen dependent), respectively, and results in significantly enhanced destruction of tumor cells. The preliminary in vitro and in vivo results in a PC3 cell line and tumor model indicate that the tumor specificality of the therapeutic agent(s) can be increased by targeting galectin-1 and galectin-3, known for their overexpression in prostate cancer.

Development and validation of nomogram to improve the specificity of multiparametric MRI for clinically significant prostate cancer.

OBJECTIVE: To develop and validate a nomogram to improve the specificity of prostate imaging reporting and data system (PI-RADS) on multiparametric magnetic resonance imaging (MRI) for clinically significant prostate cancer on targeted fusion biopsy. METHODS: A retrospective review of patients who underwent fusion biopsy for PI-RADS 3-5 lesions using UroNav and Artemis systems between 2016 and 2022 was performed. Patients were divided into those with CS disease on fusion biopsy (Gleason grade group ≥2) versus those without. Multivariable analysis was used to identify variables associated with CS disease. A 100-point nomogram was constructed, and ROC curve was generated. RESULTS: 1485 lesions (1032 patients) were identified, 510 (34%) were PI-RADS 3, 586 (40%) were PI-RADS 4, and 389 (26%) were PI-RADS 5. Of these, 11% of PI-RADS 3, 39% of PI-RADS 4, and 61% of PI-RADS 5 showed CS disease. CS disease was associated with older age (OR 1.04, 95% CI 1.02-1.06, p < 0.01), previous negative biopsy (OR 0.52, 95% CI 0.36-0.74, p < 0.01), presence of multiple PI-RADS 3-5 lesions (OR 0.61, 95% CI 0.45-0.83, p < 0.01), peripheral zone location (OR 1.88, 95% CI 1.30-2.70, p < 0.01), PSA density (OR 1.48 per 0.1 unit, 95% CI 1.33-1.64, p < 0.01), PI-RADS score 4 (OR 3.28, 95% CI 2.21-4.87, p < 0.01), and PI-RADS score 5 (OR 7.65, 95% CI 4.93-11.85, p < 0.01). Area under ROC curve was 82% for nomogram compared to 75% for PI-RADS score alone. CONCLUSION: We report a nomogram that combines PI-RADS score with other clinical parameters. The nomogram outperforms PI-RADS score for the detection of CS prostate cancer.

Robot-assisted Radical Cystectomy Versus Open Radical Cystectomy: A Systematic Review and Meta-analysis of Perioperative, Oncological, and Quality of Life Outcomes Using Randomized Controlled Trials.

CONTEXT: Differences in recovery, oncological, and quality of life (QoL) outcomes between open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC) for patients with bladder cancer are unclear. OBJECTIVE: This review aims to compare these outcomes within randomized trials of ORC and RARC in this context. The primary outcome was the rate of 90-d perioperative events. The secondary outcomes included operative, pathological, survival, and health-related QoL (HRQoL) measures. EVIDENCE ACQUISITION: Systematic literature searches of MEDLINE, Embase, Web of Science, and clinicaltrials.gov were performed up to May 31, 2022. EVIDENCE SYNTHESIS: Eight trials, reporting 1024 participants, were included. RARC was associated with a shorter hospital length of stay (LOS; mean difference [MD] 0.21, 95% confidence interval [CI] 0.03-0.39, p = 0.02) than and similar complication rates to ORC. ORC was associated with higher thromboembolic events (odds ratio [OR] 1.84, 95% CI 1.02-3.31, p = 0.04). ORC was associated with more blood loss (MD 322 ml, 95% CI 193-450, p < 0.001) and transfusions (OR 2.35, 95% CI 1.65-3.36, p < 0.001), but shorter operative time (MD 76 min, 95% CI 39-112, p < 0.001) than RARC. No differences in lymph node yield (MD 1.07, 95% CI -1.73 to 3.86, p = 0.5) or positive surgical margin rates (OR 0.95, 95% CI 0.54-1.67, p = 0.9) were present. RARC was associated with better physical functioning or well-being (standardized MD 0.47, 95% CI 0.29-0.65, p < 0.001) and role functioning (MD 8.8, 95% CI 2.4-15.1, p = 0.007), but no improvement in overall HRQoL. No differences in progression-free survival or overall survival were seen. Limitations may include a lack of generalization given trial patients. CONCLUSIONS: RARC offers various perioperative benefits over ORC. It may be more suitable in patients wishing to avoid blood transfusion, those wanting a shorter LOS, or those at a high risk of thromboembolic events. PATIENT SUMMARY: This study compares robot-assisted keyhole surgery with open surgery for bladder cancer. The robot-assisted approach offered less blood loss, shorter hospital stays, and fewer blood clots. No other differences were seen.

Impact of an NCCN-Compliant Multidisciplinary Conference on Treatment Decisions for Localized Prostate Cancer.

BACKGROUND: We sought to investigate the impact of an NCCN-compliant multidisciplinary conference on treatment decisions of patients with localized prostate cancer. METHODS: A retrospective review of our quality assurance localized prostate cancer database was performed. All patients with localized prostate cancer who sought a second opinion at Roswell Park Comprehensive Cancer Center between 2009 and 2019 were presented to the multidisciplinary Localized Prostate Cancer Conference (LPCC) that includes urologists, radiation oncologists, pathologists, and patient advocates. Multivariable regression models were fit to evaluate variables associated with concordance between community recommendations, LPCC recommendations, and treatment received by patients. RESULTS: A total of 1,164 patients were identified, of whom 26% had NCCN very low-/low-risk, 27% had favorable intermediate-risk, 25% had unfavorable intermediate-risk, and 22% had high-/very high-risk prostate cancer. Pathology changed in 11% of patients after genitourinary pathologist review, which caused disease reclassification in 9%. Concordance between community and LPCC recommendations occurred in 78%, with lowest concordance for androgen deprivation therapy (21%) and radiotherapy (53%). Concordance between community recommendations and treatment received occurred in 65%, with lowest concordance for androgen deprivation therapy and radiotherapy; among those who were recommended radiotherapy as the only option by their community urologist, only 26% received it. Concordance between LPCC recommendations and treatment received occurred in 92%. CONCLUSIONS: Community recommendations differed from the multidisciplinary NCCN-compliant recommendations in 22% of patients, primarily for radiotherapy. Multidisciplinary recommendations matched the treatment received in 92% of patients compared with 65% for community recommendations.

Development of a predictive model for recurrence-free survival in pTa low-grade bladder cancer.

BACKGROUND: Data on Ta low-grade (LG) non-muscle invasive bladder cancer (NMIBC) have shown that follow-up cystoscopies are normal in 82% and 67% of patients with single and multiple tumors, respectively. OBJECTIVE: To develop a predictive model associated with recurrence-free survival (RFS) at 6, 12, 18 and 24 months in TaLG cases that consider the patients' risk aversion. MATERIALS AND METHODS: Data from a prospectively maintained database of 202 newly diagnosed TaLG NMIBC patients treated at Scandinavian institutions were used for the analysis. To identify risk groups associated with recurrence, we performed a classification tree analysis. Association between risk groups and RFS was evaluated by Kaplan Meier analysis. A Cox proportional hazard model selected significant risk factors associated with RFS using the variables defining the risk groups. The reported C index for the Cox model was 0.7. The model was internally validated and calibrated using 1000 bootstrapped samples. A nomogram to estimate RFS at 6, 12, 18, and 24 months was generated. The performance of our model was compared to EUA/AUA stratification using a decision curve analysis (DCA). RESULTS: The tree classification found that tumor number, tumor size and age were the most relevant variables associated with recurrence. The patients with the worst RFS were those with multifocal or single, ≥ 4cm tumors. All the relevant variables identified by the classification tree were significantly associated with RFS in the Cox proportional hazard model. DCA analysis showed that our model outperformed EUA/AUA stratification and the treat all/none approaches. CONCLUSION: We developed a predictive model to identify TaLG patients that benefit from less frequent follow-up cystoscopy schedule based on the estimated RFS and personal recurrence risk aversion.

The Association Between the Urinary Microbiome and Bladder Cancer.

Many studies are currently investigating the association between the urinary microbiome and bladder cancer, focusing on differences between stages and with risk of recurrence and progression. However, many of these studies are limited by the small number of patients, presence of confounders and issues with sampling, DNA extraction, and analyses. Recently there has been a shift toward examining the microbiome of bladder tissues rather than urine samples; however, these studies remain a minority. Identification of the differences in microbiome composition between different stages of bladder cancer can provide biomarkers to identify the patients who are more likely to respond to intravesical treatment. Further, these differences in microbiome composition could provide novel therapeutic targets, whereby the modulation of specific bacterial taxa could selectively promote or inhibit response to intravesical therapy.

Analysis of Complications After Robot-Assisted Radical Cystectomy Between 2002-2021.

OBJECTIVE: To identify trends in complications following robot-assisted radical cystectomy (RARC) using a multi-institutional database, the International Robotic Cystectomy Consortium (IRCC). METHODS: A retrospective review of the IRCC database was performed (2976 patients, 26 institutions from 11 countries). Postoperative complications were categorized as overall or high grade (≥ Clavien Dindo III) and were further categorized based on type/organ site. Descriptive statistics was used to summarize the data. Multivariate analysis (MVA) was used to identify variables associated with overall and high-grade complications.  Cochran-Armitage trend test was used to describe the trend of complications over time. RESULTS: 1777 (60%) patients developed postoperative complications following RARC, 51% of complications occurred within 30 days of RARC, 19% between 30-90 days, and 30% after 90 days. 835 patients (28%) experienced high-grade complications. Infectious complications (25%) were the most prevalent, while bleeding (1%) was the least. The incidence of complications was stable between 2002-2021. Gastrointestinal and neurologic postoperative complications increased significantly (P < .01, for both) between 2005 and 2020 while thromboembolic (P = .03) and wound complications (P < .01) decreased. On MVA, BMI (OR 1.03, 95%CI 1.01-1.05, P < .01), prior abdominal surgery (OR 1.26, 95%CI 1.03-1.56, P = .03), receipt of neobladder (OR 1.52, 95%CI 1.17-1.99, P < .01), positive nodal disease (OR 1.33, 95%CI 1.05-1.70, P = .02), length of inpatient stay (OR 1.04, 95%CI 1.02-1.05, P < .01) and ICU admission (OR 1.67, 95%CI 1.36-2.06, P < .01) were associated with high-grade complications. CONCLUSION: Overall and high-grade complications after RARC remained stable between 2002-2021. GI and neurologic complications increased, while thromboembolic and wound complications decreased.

Uretero-enteric Strictures After Robot Assisted Radical Cystectomy: Prevalence and Management Over Two Decades.

INTRODUCTION: To evaluate the prevalence, predictors, management, and trends for ureteroenteric strictures (UES) after robot-assisted radical cystectomy (RARC). METHODS: Retrospective review of our RARC database was performed (2005-2022). UES was described in terms of timing, laterality, and management. Kaplan-Meier curves were used to depict time to UES. Local regression was used to assess trend of UES over time and multivariable regression to identify variables associated with UES. RESULTS: UES occurred in 109 patients (15%). UES occurred in 13%, 17%, and 19% at 1, 3, and 5 years after RARC, respectively. Incidence of UES decreased in 2017, coinciding with stentless uretero-enteric anastomosis. UES occurred on the right in 33%, on the left in 46%, and bilaterally in 21%. All patients were initially managed by nephrostomy/stent. Surgical revision was required in 45% of patients, of which 13% developed recurrent UES after revision. On MVA, UES formation was associated with ureteral stents (OR 2.27, 95%CI 1.01-5.10, P = .05) and receipt of neoadjuvant chemotherapy (OR 2.01, 95%CI 1.24-3.25, P = .005). CONCLUSION: UES occurred in 15% of patients after RARC, with 45% of patients requiring surgical reimplantation. Ureteral stents and the receipt of neoadjuvant chemotherapy were associated with UES formation.

Transition from da Vinci to Versius robotic surgical system: initial experience and outcomes of over 100 consecutive procedures.

We sought to describe the development of the robotic urology program at Sindh Institute of Urology and Transplantation (SIUT) and the feasibility of transitioning from the da Vinci to Versius robotic systems. The SIUT robotics program began in 2017 utilizing the da Vinci Si robotic system, transitioning to the Versius system in 2021. Retrospective review of our quality assurance database was performed. All procedures performed utilizing the two systems were identified, analyzed, and compared. Data were described with descriptive statistics. Matched procedures (by type of procedure) performed by the same surgeons utilizing the da Vinci and Versius were compared. All tests were double-sided with statistical significance set at p < 0.05.106 cases were performed by the Versius robotic surgical system in 2021. Median age was 42 years (IQR 26-56), and 69 (65%) were males. Procedures included both benign (83%) and malignant disorders (17%), several upper tract (75%), and pelvic/lower tract (25%). No major intraoperative complications were observed. Conversion to open occurred in six procedures. Malfunction of the robotic arms occurred in two procedures: the erroneous bedside units (BSU) were replaced. Eight patients developed postoperative high-grade complications. Matched analysis of various procedures (pyeloplasty, stone surgery, radical, partial, and simple nephrectomy) showed no significant difference in perioperative outcomes. To our knowledge, this is the first and largest series of urologic procedures performed by the Versius robotic surgical system.

IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.

IL-15 Superagonist NAI in BCG-Unresponsive NMIBCIn this trial, patients with BCG-unresponsive bladder CIS with or without Ta/T1 papillary disease or BCG-unresponsive high-grade Ta/T1 papillary NMIBC were treated with intravesical NAI, an IL-15 superagonist, plus BCG. Primary end points were CR at 3 or 6 months for patients with CIS disease and DFS rate at 12 months for those with high-grade Ta/T1 disease. CR rate was 71% (58 of 82 patients), and the DFS rate was 55.4%.

NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022.

The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non-muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non-muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody-drug conjugates for metastatic bladder cancer.

Relapses Rates and Patterns for Pathological T0 After Robot-Assisted Radical Cystectomy: Results From the International Robotic Cystectomy Consortium.

OBJECTIVES: To investigate the oncologic outcomes of pT0 after robot-assisted radical cystectomy (RARC). METHODS: A retrospective review of the International Robotic Cystectomy Consortium database was performed. Patients with pT0 after RARC were identified and analyzed. Data were reviewed for demographics and pathologic outcomes. Kaplan-Meier curves were used to depict recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). Multivariate stepwise Cox regression models were used to identify variables associated with RFS and OS. RESULTS: Four hundred seventy-one patients (18%) with pT0 were identified. Median age was 68 years (interquartile range (IQR) 60-73), with a median follow up of 20 months (IQR 6-47). Thirty-seven percent received neoadjuvant chemotherapy and 5% had pN+ disease. Seven percent of patients experienced disease relapse; 3% had local and 5% had distant recurrence. Most common sites of local and distant recurrences were pelvis (1%) and lungs (2%). Five-year RFS, DSS, and OS were 88%, 93%, and 79%, respectively. Age (hazards ratio [HR] 1.05, 95% confidence interval [CI] 1.01-1.09, P = 0.02), pN+ve (HR 11.48, 95% CI 4.47-29.49, P < .01), and reoperations within 30 days (HR 5.53, 95% CI 2.08-14.64, P < .01) were associated with RFS. Chronic kidney disease (HR 3.24, 95% CI 1.45-7.23, P < .01), neoadjuvant chemotherapy (HR 0.41, 95% CI 0.18-0.92, P = .03), pN+ve (HR 4.37, 95% CI 1.46-13.06, P < .01), and reoperations within 30 days (HR 2.64, 95% CI, 1.08-6.43, P = .03) were associated with OS. CONCLUSIONS: Despite pT0 status at RARC, 5% had pN+ disease and 7% of patients relapsed. Node status was the variable strongest associated with RFS and OS in pT0.

A Preclinical Study to Repurpose Spironolactone for Enhancing Chemotherapy Response in Bladder Cancer.

Neoadjuvant chemotherapy (NAC) followed by radical cystectomy is the standard-of-care for patients with muscle-invasive bladder cancer (MIBC). Defects in nucleotide excision repair (NER) are associated with improved responses to NAC. Excision Repair Cross-Complementation group 3 (ERCC3) is a key component of NER process. No NER inhibitors are available for treating patients with bladder cancer. We have developed an ex vivo cell-based assay of 6-4 pyrimidine-pyrimidinone (6-4PP) removal as a surrogate measure of NER capacity in human bladder cancer cell lines. The protein expression of ERCC3 was examined in human MIBC specimens and cell lines. Small molecule inhibitors were screened for NER inhibition in bladder cancer cell lines. Spironolactone was identified as a potent NER inhibitor. Combined effects of spironolactone with chemo-drugs were evaluated in vitro and in vivo. The efficacy between platinum and spironolactone on cytotoxicity was determined by combination index. A correlation between NER capacity and cisplatin sensitivity was demonstrated in a series of bladder cancer cell lines. Further, siRNA-mediated knockdown of ERCC3 abrogated NER capacity and enhanced cisplatin cytotoxicity. Spironolactone inhibited ERCC3 protein expression, abrogated NER capacity, and increased platinum-induced cytotoxicity in bladder cancer cells in vivo and in patient-derived organoids. Moreover, spironolactone exhibited the potential synergism effects with other clinical chemotherapy regimens in bladder cancer cell lines. Our data support the notion of repurposing spironolactone for improving the chemotherapy response of NAC in patients with MIBC. Further clinical trials are warranted to determine the safety and efficacy of spironolactone in combination with chemotherapy.

Perioperative and Functional Outcomes of Robot-assisted Ureteroenteric Reimplantation: A Multicenter Study of Seven Referral Institutions.

BACKGROUND: Open revision of ureteroenteric strictures (UESs) is associated with considerable morbidity. There is a lack of data evaluating the feasibility of robotic revisions. OBJECTIVE: To analyze the perioperative and functional outcomes of robot-assisted ureteroenteric reimplantation (RUER) for the management of UESs after radical cystectomy (RC). DESIGN SETTING AND PARTICIPANTS: A retrospective multicenter study of 61 patients, who underwent 63 RUERs at seven high-volume institutions between 2009 and 2020 for benign UESs after RC, was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data were reviewed for demographics, stricture characteristics, and perioperative outcomes. Variables associated with being stricture free after an RUER were evaluated using a multivariate Cox regression analysis. RESULTS AND LIMITATIONS: Among 63 RUERs, 22 were right sided (35%), 34 left sided (54%), and seven bilateral (11%). Twenty-seven (44%) had prior abdominal/pelvic surgery and five (8%) radiotherapy (RT). Thirty-two patients had American Society of Anesthesiologists (ASA) scores I-II (52%) and 29 ASA III (48%). Forty-two (68%) RUERs were in ileal conduits, 18 (29%) in neobladders, and two (3%) in Indiana pouch. The median time to diagnosis of a UES from cystectomy was 5 (3-11) mo. Of the UESs, 28 (44%) failed an endourological attempt (balloon dilatation/endoureterotomy). The median RUER operative time was 195 (175-269) min. No intraoperative complications or conversions to open approach were reported. Twenty-three (37%) patients had postoperative complications (20 [32%] were minor and three [5%] major). The median length of hospital stay was 3 (1-6) d and readmissions were 5%. After a median follow-up of 19 (8-43) mo, 84% of cases were stricture free. Lack of prior RT was the only variable associated with better stricture-free survival after RUER (hazard ratio 6.8, 95% confidence interval 1.10-42.00, p = 0.037). The study limitations include its retrospective nature and the small number of patients. CONCLUSIONS: RUER is a feasible procedure for the management of UESs. Prospective and larger studies are warranted to prove the safety and efficacy of this technique. PATIENT SUMMARY: In this study, we investigate the feasibility of a novel minimally invasive technique for the management of ureteroenteric strictures. We conclude that robotic reimplantation is a feasible and effective procedure.