The Role of Tumor and Host Microbiome on Immunotherapy Response in Urologic Cancers.

Introduction & Objective: The role of the microbiome in the development and treatment of genitourinary malignancies is just starting to be appreciated. Accumulating evidence suggests that the microbiome can modulate immunotherapy through signaling in the highly dynamic tumor microenvironment. Nevertheless, much is still unknown about the immuno-oncology-microbiome axis, especially in urologic oncology. The objective of this review is to synthesize our current understanding of the microbiome's role in modulating and predicting immunotherapy response to genitourinary malignancies. Methods: A literature search for peer-reviewed publications about the microbiome and immunotherapy response in bladder, kidney, and prostate cancer was conducted. All research available in PubMed, Google Scholar, clinicaltrials.gov, and bioRxiv up to September 2023 was analyzed. Results: Significant differences in urinary microbiota composition have been found in patients with genitourinary cancers compared to healthy controls. Lactic acid-producing bacteria, such as Bifidobacterium and Lactobacillus genera, may have value in augmenting BCG responsiveness to bladder cancer. BCG may also be a dynamic regulator of PD-L1. Thus, the combination of BCG and immune checkpoint inhibitors may be an effective strategy for bladder cancer management. In advanced renal cell carcinoma, studies show that recent antibiotic administration negatively impacts survival outcomes in patients undergoing immunotherapy, while administration of CBM588, a live bacterial product, is associated with improved progression-free survival. Specific bacterial taxa, such as Streptococcus salivarius, have been linked with response to pembrolizumab in metastatic castrate-resistant prostate cancer. Fecal microbiota transplant has been shown to overcome resistance and reduce toxicity to immunotherapy; it is currently being investigated for both kidney and prostate cancers. Conclusions: Although the exact mechanism is unclear, several studies identify a symbiotic relationship between microbiota-centered interventions and immunotherapy efficacy. It is possible to improve immunotherapy responsiveness in genitourinary malignancies using the microbiome, but further research with more standardized methodology is warranted.

From Diagnosis to Precision Surgery: The Transformative Role of Artificial Intelligence in Urologic Imaging.

The multidisciplinary nature of artificial intelligence (AI) has allowed for rapid growth of its application in medical imaging. Artificial intelligence algorithms can augment various imaging modalities, such as X-rays, CT, and MRI, to improve image quality and generate high-resolution three-dimensional images. AI reconstruction of three-dimensional models of patient anatomy from CT or MRI scans can better enable urologists to visualize structures and accurately plan surgical approaches. AI can also be optimized to create virtual reality simulations of surgical procedures based on patient-specific data, giving urologists more hands-on experience and preparation. Recent development of artificial intelligence modalities, such as TeraRecon and Ceevra, offer rapid and efficient medical imaging analyses aimed at enhancing the provision of urologic care, notably for intraoperative guidance during robot-assisted radical prostatectomy (RARP) and partial nephrectomy.

The Association Between Duration of Antibiotics and Infectious Complications Following Radical Cystectomy: Analysis of the 2019-2021 NSQIP Database.

OBJECTIVES: To identify the impact of the duration of peri-operative antibiotics on infectious complications following radical cystectomy. METHODS: The National Surgical Quality Improvement Project (NSQIP) targeted database was queried for patients undergoing radical cystectomy from 2019 to 2021. Baseline patient characteristics were collected. Antibiotic duration was classified as <24 hours (short), 24-72 hours (intermediate) or >72 hours (long). Infectious complication data were collected including surgical site infection (SSI), urinary tract infection (UTI), organ space infection, pneumonia, sepsis, and clostridium difficile infection up to 30 days after surgery. Univariate and multivariable analyses were performed to compare duration of antibiotic therapy to infectious outcomes. RESULTS: Of the 4363 patients who underwent radical cystectomy, 3250 (74%), 827 (19%) and 286 (6.6%) received short, intermediate, and long duration of peri-operative antibiotics, respectively. Infectious complication occurred in 954 (22%) patients, including 227 (5.2%) SSI, 280 (6.4%) UTI, 268(6.1%) organ space infection, 87 (2%) pneumonia, and 378 (8.7%) sepsis. Clostridium difficile infection occurred in 89 (2%) patients. On multivariable analysis, there was no significant difference in overall infectious complication rates with long-duration antibiotics. However, intermediate duration of antibiotics in open surgery was associated with a decreased risk of SSI (OR 0.58; 95%CI 0.37-0.91) compared to those treated with short-term antibiotics. CONCLUSION: Despite guideline recommendations, 26% of patients in this database received >24 hours of peri-operative antibiotics without decreased risk of overall infectious complication. An intermediate course of antibiotics decreased risk of SSI in open surgery compared to the guideline recommend <24-hour course. Greater education regarding antibiotic stewardship and further studies investigating infectious complications are warranted.

Pelvic lymphadenectomy: Evaluating nodal stage migration and will rogers effect in bladder cancer.

INTRODUCTION: Pelvic lymphadenectomy (PLND) alongside radical cystectomy (RC), provides crucial diagnostic and therapeutic value in patients with bladder cancer. With the advent of neoadjuvant chemotherapy and prospective data supporting standard PLND, controversy remains regarding the optimal PLND extent and patient selection. Nearly 40% of patients may not receive adequate PLND, even though 25% of patients have positive lymph nodes (LN) at time of RC. We hypothesized that PLND still remains an important facet of bladder cancer treatment. To clarify the prognostic importance of nodal yield, we performed a retrospective investigation of a heterogenous population (pTanyNx/0M0) of patients undergoing RC. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) program, we identified pTanyNx/0M0 bladder cancer patients undergoing RC from 2004 to 2015. Kaplan Meier curves and Cox proportional hazards models assessed cancer-specific survival. Patients were analyzed with PLND performed as the primary covariate. Survival analysis then stratified patients undergoing PLND by LN yield, both as a continuous and categorial variable (≤10, 11-20, 21-30, and >30), and T stage. RESULTS: The final cohort included pTanyNx/0M0 patients with urothelial bladder cancer (n = 12,096); median follow up was 39 (IQR: 17-77) months. PLND was performed in 81.45% of patients with a median LN yield of 14 (IQR: 7-23). Most commonly, patients had T2 disease (44.68%). After controlling for age and T stage, patients receiving PLND had improved CSS (HR = 0.56, [95% CI: 0.51-0.62]) compared to those that did not receive PLND. When grouping patients by LN yield, survival improved in a "dose dependent" manner (>30 LN: HR = 0.76, [95% CI: 0.66-0.87]). We noted similar results when stratifying patients into non-muscle-invasive (NMIBC) and muscle-invasive bladder cancer (MIBC). CONCLUSIONS: In a large contemporary series of pTanyNx/0M0 bladder cancer patients, we found a significant oncologic benefit to PLND. Higher LN yield correlated to improved CSS in non-muscle-invasive and muscle-invasive disease. Our data support the possibility of occult micrometastasis even in non-muscle-invasive disease. Additionally, in light of recent advances in adjuvant immunotherapy, our results emphasize the importance of adequate nodal yield for accurate staging and optimal treatment.

Comparison of a Valveless Trocar System and Conventional Insufflation in Pediatric Urologic Surgery.

Background: Conventional operative insufflation uses a one-way trocar to handle instruments while maintaining pneumoperitoneum. In 2007, the AirSeal® valveless trocar insufflation system was introduced, which maintains stable pneumoperitoneum while continuously evacuating smoke. Although this device has been validated in adult patients, it has not been extensively validated in the pediatric population. Materials and Methods: A retrospective cohort study of pediatric urology patients aged 0 to 21 who underwent laparoscopic pyeloplasty between March 2016 and October 2021 was performed. Intraoperative physiologic parameters, procedure characteristics, postoperative outcomes, and demographics of each patient in whom either AirSeal insufflation system (AIS) or conventional insufflation system (CIS) was utilized were obtained from hospital records. Data were compared across the AIS and CIS cohorts. The primary outcomes were intraoperative anesthetic and physiologic parameters, including end tidal carbon dioxide, oxygen saturation, body temperature, positive inspiratory pressure, systolic blood pressure, and heart rate. Results: There were no significant differences in the anesthetic and physiologic parameters in the AIS and CIS groups. In addition, no differences in demographics, procedural characteristics, or complication rates were found between the cohorts. Conclusion: The AirSeal valveless trocar insufflation system demonstrates comparable intraoperative anesthetic and physiologic outcomes compared to conventional one-way valve insufflation in pediatric laparoscopic pyeloplasty. Certain surgeon-related qualitative metrics are underappreciated in this study, however, including improved visualization with vigorous suctioning and pressure maintenance with frequent instrument exchanges. Surgeon experience may mask the benefits of these characteristics as it pertains to quantitative surgical outcomes such as estimated blood loss, operative time, and perioperative complications.

Infections After Adoption of Antibiogram-directed Prophylaxis and Intracorporeal Urinary Diversion for Robot-assisted Radical Cystectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) has significantly decreased the morbidity associated with radical cystectomy. However, infectious complications including sepsis, urinary tract (UTIs), wound (WIs), and intra-abdominal (AIs) infections remain common. OBJECTIVE: To assess whether intracorporeal urinary diversion (ICUD) and antibiogram-directed antimicrobial prophylaxis would decrease infections after robotic-assisted radical cystectomy (RARC). DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was performed of a prospectively maintained database of patients undergoing RARC between 2014 and 2022 at a tertiary care institution, identifying two groups based on adherence to a prospectively implemented modified ERAS protocol for RARC: modified-ERAS-ICUD and antibiogram-directed ampicillin-sulbactam, gentamicin, and fluconazole prophylaxis were utilized (from January 2019 to present time), and unmodified-ERAS-extracorporeal urinary diversion (UD) and guideline-recommended cephalosporin-based prophylaxis regimen were utilized (from November 2014 to June 2018). Patients receiving other prophylaxis regimens were excluded. INTERVENTION: ICUD and antibiogram-directed infectious prophylaxis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was UTIs within 30 and 90 d postoperatively. The secondary outcomes were WIs, AIs, and sepsis within 30 and 90 d postoperatively, and Clostridioides difficile infection (CDI) within 90 d postoperatively. RESULTS AND LIMITATIONS: A total of 396 patients were studied (modified-ERAS: 258 [65.2%], unmodified-ERAS: 138 [34.8%]). UD via a neobladder was more common in the modified-ERAS cohort; all other intercohort demographic differences were not statistically different. Comparing cohorts, modified-ERAS had significantly reduced rates of 30-d (7.8% vs 15.9%, p = 0.027) and 90-d UTIs (11.2% vs 25.4%, p = 0.001), and 30-d WIs (1.2% vs. 8.7%, p < 0.001); neither group had a WI after 30 d. Rates of AIs, sepsis, and CDI did not differ between groups. On multivariate regression, the modified-ERAS protocol correlated with a reduced risk of UTIs and WIs (all p < 0.01). The primary limitation is the retrospective study design. CONCLUSIONS: Utilization of ICUD and antibiogram-based prophylaxis correlates with significantly decreased UTIs and WIs after RARC. PATIENT SUMMARY: In this study of infections after robotic radical cystectomy for bladder cancer, we found that intracorporeal (performed entirely inside the body) urinary diversion and an institution-specific antibiogram-directed antibiotic prophylaxis regimen led to fewer urinary tract infections and wound infections at our institution.

Metastasis-Directed Therapy for Oligometastatic Castration-Sensitive Prostate Cancer: An Alternative to ADT?

PURPOSE OF REVIEW: The standard treatment of patients with metastatic prostate cancer is systemic treatment with androgen-deprivation therapy (ADT). The spectrum-based model of metastatic disease includes the presence of an oligometastatic state, an intermediary between localized and widespread metastatic disease, in which radical local treatment might improve systemic control. Our purpose is to review the literature on metastasis-directed therapy in the treatment of oligometastatic prostate cancer. RECENT FINDINGS: Several prospective clinical trials have reported improvements in ADT-free survival and progression-free survival with metastasis-directed therapy of oligometastatic prostate cancer. Retrospective studies have found improvements in oncologic outcomes for patients with oligometastatic prostate cancer undergoing metastasis-directed therapy, and several recent prospective clinical trials have confirmed these results. Advancements in imaging as well as an understanding of the genomics of oligometastatic prostate cancer may allow for better patient selection for metastasis-directed therapy and the potential for cure in selected patients.

Comparing Oncological and Perioperative Outcomes of Open versus Laparoscopic versus Robotic Radical Nephroureterectomy for the Treatment of Upper Tract Urothelial Carcinoma: A Multicenter, Multinational, Propensity Score-Matched Analysis.

OBJECTIVES: To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). METHODS: We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990-2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien-Dindo > 3) were assessed between groups. RESULTS: Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan-Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22-2.28, p = 0.001 and HR 1.73, 95%CI 1.22-2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta -1.1, 95% CI -2.2-0.02, p = 0.047 and beta -6.1, 95% CI -7.2-5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31-0.79, p = 0.003 and OR 0.27, 95% CI 0.16-0.46, p < 0.001, respectively). CONCLUSIONS: In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs.

Adjuvant Therapy for Renal Cell Carcinoma: End Points, Outcomes, and Risk Assessments.

PURPOSE: Targeted tyrosine kinase inhibitors (TKIs) and immune-checkpoint inhibitors (ICIs) revolutionized the treatment of metastatic renal cell carcinoma (RCC). Efforts to translate these therapies into the adjuvant setting for local and locoregional RCC have been pursued over the past decade. We sought to provide an updated review of the literature regarding adjuvant therapy in RCC, as well as an analysis of patient characteristics that may portend the most favorable responses. MATERIALS AND METHODS: Using PubMed, Google Scholar, and Wiley Online Library, we reviewed articles between 2000 and 2022. Search terms included "tyrosine kinase inhibitors," "adjuvant," "immunotherapy," and "renal cell carcinoma." The articles included were original and published in English. Information on clinical trials was collected from ClinicalTrials.gov, accessed in June 2022. RESULTS: Landmark trials investigating adjuvant vascular endothelial growth factor (VEGF) inhibitors produced conflicting results, with only a single trial of sunitinib (S-TRAC) resulting in US Food and Drug Administration-approval on the basis of a slightly prolonged progression-free survival (PFS). Subsequent meta-analyses failed to show a benefit for adjuvant VEGF inhibitors. Several trials evaluating ICIs are currently ongoing, with pembrolizumab (KEYNOTE-564) earning US Food and Drug Administration-approval for a prolonged PFS, although overall survival data are not yet mature. Preliminary results from other adjuvant ICI trials have been conflicting. CONCLUSION: There remains a lack of clear benefit for the use of adjuvant VEGF inhibitors in local and locoregional RCC. Adjuvant ICI investigations are ongoing, with promising results from KEYNOTE-564. It remains to be seen if PFS is an adequate surrogate end point for overall survival. Selection of patients at greatest risk for recurrence, and identification of those at greatest risk of rare but serious adverse events, may improve outcomes.

Higher preoperative eGFR is a predictor of worse renal function decline after robotic assisted radical cystectomy: Implications for postoperative management.

INTRODUCTION: In patients with muscle invasive bladder cancer or high risk noninvasive bladder cancer, renal function decline is a concern after radical cystectomy with urinary diversion. The pathophysiology of this decline is multifactorial, with subclinical acidosis and metabolic derangements from the diversion thought to contribute. It is unknown whether patients with baseline chronic kidney disease (CKD) are at increased risk of further decline in renal function. METHODS: We performed a retrospective review of two high volume robotic assisted radical cystectomy (RARC) centers between 2016 and 2020. Preoperative demographics and comorbidities were collected. Postoperative estimated glomerular filtration rate (eGFR) was calculated at 12 and 24 months to determine short-term rate in decline of eGFR. Absolute and percent changes in eGFR were calculated. RESULTS: There were a total of 555 patients who underwent RARC. Men comprised 76.2% of the cohort. Neoadjuvant chemotherapy was given in 31% of patients and adjuvant chemotherapy was given in 4.81% of patients. Higher preoperative eGFR (B -0.549, 95% CI -0.708 to -0.391, P < 0.001) and presence of diabetes mellitus (B -15.414, 95% CI -24.820 to -6.008, P = 0.001) were significant predictors of eGFR decline at 12 months. At 24 months, presence of diabetes mellitus (B -11.799, 95% CI -21.816 to -1.782, P = 0.021) and higher preoperative eGFR (B -0.621, 95% CI -0.796 to -0.446, P < 0.001) were correlated with a steeper decline in eGFR. Higher preoperative eGFR was also predictive of upstaging to CKD3 or higher post operatively (OR 1.019, 95% CI 1.004-1.034, P = 0.015). Intracorporeal diversion was protective, whereas presence of hypertension, diabetes mellitus, and higher preoperative eGFR predicted greater decline in eGFR. CONCLUSION: Patients with higher preoperative eGFR and diabetes are at increased risk of renal function decline post RARC at 12 and 24 months. This suggests that patients with risk factors for renal function decline, but otherwise normal renal function at baseline, are a particularly vulnerable population for progression to CKD after RARC and should be counseled and closely followed postoperatively for renal function deterioration.

Pentafecta for Radical Nephroureterectomy in Patients with High-Risk Upper Tract Urothelial Carcinoma: A Proposal for Standardization of Quality Care Metrics.

Background: Measuring quality of care indicators is important for clinicians and decision making in health care to improve patient outcomes. Objective: The primary objective was to identify quality of care indicators for patients with upper tract urothelial carcinoma (UTUC) and to validate these in an international cohort treated with radical nephroureterectomy (RNU). The secondary objective was to assess the factors associated with failure to validate the pentafecta. Design: We performed a retrospective multicenter study of patients treated with RNU for EAU high-risk (HR) UTUC. Outcome measurements and statistical analysis: Five quality indicators were consensually approved, including a negative surgical margin, a complete bladder-cuff resection, the absence of hematological complications, the absence of major complications, and the absence of a 12-month postoperative recurrence. After multiple imputations and propensity-score matching, log-rank tests and a Cox regression were used to assess the survival outcomes. Logistic regression analyses assessed predictors for pentafecta failure. Results: Among the 1718 included patients, 844 (49%) achieved the pentafecta. The median follow-up was 31 months. Patients who achieved the pentafecta had superior 5-year overall- (OS) and cancer-specific survival (CSS) compared to those who did not (68.7 vs. 50.1% and 79.8 vs. 62.7%, respectively, all p < 0.001). On multivariable analyses, achieving the pentafecta was associated with improved recurrence-free survival (RFS), CSS, and OS. No preoperative clinical factors predicted a failure to validate the pentafecta. Conclusions: Establishing quality indicators for UTUC may help define prognosis and improve patient care. We propose a pentafecta quality criteria in RNU patients. Approximately half of the patients evaluated herein reached this endpoint, which in turn was independently associated with survival outcomes. Extended validation is needed.

Neobladder creation in patients with chronic kidney disease: A viable diversion strategy.

INTRODUCTION: Renal function impairment is often cited as a contraindication to continent diversion strategies. There is little evidence exploring renal function changes between continent and incontinent surgery in patients with preoperative chronic kidney disease (CKD), in particular CKD3B. METHODS: This was a retrospective review of two high-volume centers performing robotic assisted radical cystectomy (RARC) with orthotopic neobladder (ONB) or ileal conduit (IC) between 2014 to 2020. Patients were stratified based on CKD estimated glomerular filtration (eGFR) stage, which was estimated via the CKD-EPI equation. Postoperative renal function was compared for up to 60 months postoperative. Surgical, post-surgical, complications, and readmission data were gathered and compared between all patients RESULTS: 522 cystectomy patients, 430 with IC and 125 with ONB, were included. eGFR decline was statistically significant in a matched cohort of IC and ONB patients only at 3 months. There were no statistically significant differences between readmission rates, time to readmission, or complications. 34.6% of stage 3B patients had hydronephrosis on imaging prior to surgery, compared to 11.4%, 22.1% and 21.8% of CKD stage 1, 2, and 3A patients. CKD stage 3B had statistically and clinically improved eGFR through 24 months. CONCLUSION: ONB surgery may be a viable diversion strategy in patients previously thought to be contraindicated due to low renal function.

The impact of discharge location on outcomes following radical cystectomy.

PURPOSE: Hospital readmission is associated with adverse outcomes and increased cost, and as such, has been identified as a metric for surgical quality and a target for shifts in health policy. However, the disposition of patients who undergo radical cystectomy for bladder cancer and the association between discharge locations and readmission rates is poorly understood. Understanding the patterns and characteristics of readmission after radical cystectomy will help inform discharge planning and expectations and may have long-term impacts on quality and cost of care delivery. We hypothesize that patients will have varying readmission rates based on their discharge location. MATERIALS AND METHODS: An observational analysis of the Nationwide Readmissions Database was performed for all patients who underwent elective radical cystectomy in 2016 to 2017. The patients were grouped by the following criteria: whether they were discharged home, home with care, or to a facility. Univariate analysis was performed using the Chi-square test for categorical variables and the Kruskal-Wallis test for continuous variables. A multivariable logistic regression was conducted to evaluate if discharge locations impact patient readmissions at 30- and 90-days. RESULTS: The final dataset included 4,947 patients discharged home with care, 2,127 patients discharged to home or self-care, and 1,232 patients discharged to a facility. Discharge to a facility was strongly associated with higher 30-day (OR 1.49, CI 1.26-1.76) and 90-day readmission rates (OR 1.46, CI 1.23-1.74). Additionally, home health care was strongly associated with increased 30-day readmission rates (OR 1.22, CI 1.08-1.37) relative to routine discharge home. CONCLUSIONS: Our analysis suggests that discharge location independently predicts readmission following RC. Further study with more granular patient- and system-level data may aid in identifying structural characteristics and processes that can reduce readmissions and their associated economic impact, while maintaining quality of care delivered.

Tips and tricks in achieving zero peri-operative opioid used in onco-urologic surgery.

PURPOSE: To review non-opioid based protocols in urologic oncologic surgery and describe our institutional methods of eliminating peri-operative opioids. METHODS: A thorough literature review was performed using PUBMED to identify articles pertaining to reducing or eliminating narcotic use in genitourinary cancer surgery. Studies were analyzed pertaining to protocols utilized in genitourinary cancer surgery, major abdominal and/or pelvic non-urologic surgery. RESULTS: Reducing or eliminating peri-operative narcotics should begin with an institutionalized protocol made in conjunction with the anesthesia department. Pre-operative regimens should consist of appropriate counseling, gabapentin, and acetaminophen with or without a non-steroidal anti-inflammatory medications. Prior to incision, a regional block or local anesthetic should be delivered. Anesthesiologists may develop opioid-free protocols for achieving and maintaining general anesthesia. Post-operatively, patients should be on a scheduled regimen of ketorolac, gabapentin, and acetaminophen. CONCLUSION: Eliminating peri-operative narcotic use is feasible for major genitourinary oncologic surgery. Patients not only have improved peri-operative outcomes but also are at significantly reduced risk of developing long-term opioid use. Through the implementation of a non-opioid protocol, urologists are able to best serve their patients while positively contributing to reducing the opioid epidemic.

Bladder Cancer (NMIBC) in a population-based cohort from Stockholm County with long-term follow-up; A comparative analysis of prediction models for recurrence and progression, including external validation of the updated 2021 E.A.U. model.

INTRODUCTION: Non muscle invasive bladder cancer (NMIBC) has recurrence and progression rates of approximately 55-75% and 5-45% respectively. After diagnosis, risk stratification guides management decisions regarding surveillance, intravesical therapy or surgery. This prospective cohort of patients from Stockholm County is ideal for external validation of the current risk stratification models used in clinical practice. PATIENTS & METHODS: The cohort consisted of 395 patients diagnosed with bladder cancer across all the hospitals in Stockholm County between the years 1995-96, with up to 25 years follow up. All patients with pathologic Ta or T1 disease were included. Patients with muscle invasive disease (MIBC) referred for radical treatment at diagnosis were excluded. External validation of EORTC, CUETO and updated EAU Sylvester et al. (2021) models was done and multivariate Cox regression analysis was performed to generate hazard ratios for covariables of interest using both WHO '73 and WHO '04/16 pathological grade classifications. RESULTS: Overall Harrel's C-indices (CIs) for EORTC and CUETO models for recurrence were 0.66 and 0.63 respectively. The CIs for the EORTC, CUETO and EAU Sylvester et al. (2021) WHO '73 and '04/16 models for progression were higher at 0.82, 0.84, 0.83 and 0.83 respectively. All models tended to underestimate both recurrence and progression rates at 1 and 5 yrs. A simplified model devised to include only multifocality, tumor stage, size and grade performed with similar accuracy to all models for both recurrence and progression. CONCLUSION: Current risk stratification models are clinically useful but only moderately accurate across different patient populations, and the results of this study suggest a model using fewer variables is of similar accuracy to all models tested. In the future, research into the use of genomic classifiers will hopefully contribute to more accurate, modern risk stratification models.

Real World Outcomes of Patients with Bladder Cancer: Effectiveness Versus Efficacy of Modern Treatment Paradigms.

Bladder cancer remains a common and insidious disease in the United States. There have been several advances in the understanding of the biology of bladder cancer, novel diagnostic tools, improvements in multidisciplinary care pathways, and new therapeutics for advanced disease over the past few decades. Clinical trials have demonstrated efficacy for new treatments in each disease state, but additional work is needed to advance the effectiveness of bladder cancer care. Real world data provide critical information regarding patterns of care, adverse events, and outcomes helping to bridge the efficacy versus effectiveness gap.

Implementation of a nonopioid protocol following robot-assisted radical cystectomy with intracorporeal urinary diversion.

PURPOSE: The implementation of robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) for management of patients with muscle-invasive or high-risk noninvasive bladder cancer has increased in utilization over the last decade. Here, we seek to describe institutional opioid prescription and utilization patterns following implementation of a nonopioid (NOP) perioperative pain management protocol in patients who received RARC with ICUD. MATERIALS AND METHODS: The records of all patients who underwent RARC that utilized a NOP perioperative pain management protocol at a single academic institution from 2016 to 2020 were retrospectively reviewed. Descriptive statistical analyses were performed. For comparison, we included 74 consecutive patients who received the same NOP protocol with extracorporeal urinary diversion (ECUD). RESULTS: A total of 116 patients who received ICUD were included in our analysis. The median operation time for the ICUD group was 305 minutes (interquartile range [IQR]: 262-352). 12.1% (n = 14) of patients who underwent ICUD required narcotics during inpatient hospitalization. For these patients, the median morphine milligram equivalent requirement was 52.0 (IQR: 7.62-157). Additionally, only 12.1% (n = 14) of patients were prescribed opioids postoperatively at discharge. We identified that within 6 months of surgery only 5 (4.3%) patients required a second narcotic prescription. Furthermore, of patients who did not use mu-opioid blockers, a minority experienced postoperative ileus (15.7%, n = 16). 30- and 90-day all Clavien complication rates for patients were 44.8% (n = 52) and 49.1% (n = 57), respectively. Nineteen (16.4%) patients were readmitted within 30 days of discharge, of which none were pain related. When compared to ECUD, patients who received ICUD experienced similar complication and readmission rates. CONCLUSIONS: The implementation of a NOP protocol for patients undergoing RARC with ICUD allows for both decreased postoperative narcotic use and reduced need for narcotic prescriptions at discharge with acceptable complication and readmission rates.

Can anesthetics affect bladder cancer recurrence? Total intravenous versus volatile anesthesia in patients undergoing robot-assisted radical cystectomy: A single institution retrospective analysis.

BACKGROUND: Radical cystectomy is standard of care and part of a multidisciplinary approach for long-term survival in patients with muscle-invasive bladder cancer (MIBC) or high-grade non-MIBC. Recent data have suggested that anesthetic technique can affect long-term survival and recurrence in patients undergoing cancer related surgery. METHODS: The records of all patients who underwent robot-assisted radical cystectomy for high-risk non-MIBC or MIBC at a single academic institution from 2014 to 2020 were retrospectively reviewed. Patients were grouped according to whether they received total intravenous (TIVA) or volatile inhalation anesthesia (VIA). Univariable and multivariable cox proportional hazards models were used to compare hazard ratios for distant recurrence. Kaplan-Meier recurrence-free survival curves were constructed from the date of surgery to recurrence. RESULTS: A total of 231 patients were included, of which 126 (55%) received TIVA and 105 (45%) received VIA. Distant recurrence occurred in 8.7% and 26.7% of patients who received TIVA and VIA, respectively (P < 0.001). Kaplan-Meier analysis demonstrated significant improvement in distant recurrence-free survival with TIVA (log-rank P < 0.001). Multivariable analysis revealed a significant increase in recurrence risk with VIA (HR: 3.4, 95%CI: 1.5-7.7, P < 0.01) and increasing tumor pathological stage (pT2, pT3, pT4, all P < 0.05). CONCLUSIONS: The use of volatile inhalation anesthetics during robot-assisted radical cystectomy may be associated with an increased risk of distant recurrence. Further studies will be necessary to validate these findings.

Predicting morbidity and mortality after radical cystectomy using risk calculators: A comprehensive review of the literature.

INTRODUCTION: Radical cystectomy (RC) with urinary diversion is associated with significant perioperative morbidity and mortality, varying between 30% and 70% and between 0.3% and 10.6%, respectively. Risk calculators have been extensively studied in the general surgery literature to predict 30- and 90-day postoperative morbidity and mortality but have not been widely accepted in the RC literature. MATERIALS AND METHODS: We performed a search of MEDLINE and Embase databases during May 2020 to identify all relevant studies using the following keywords: radical cystectomy, surgical complication predictive model, surgical complication predictive equation, surgical complication predictive nomogram, surgical risk calculator, morbidity, and mortality. We determined the existing surgical predictive nomograms, calculators, and indices and their accuracy in predicting morbidity, mortality, and major complications after RC. RESULTS: National Surgical Quality Improvement Program had poor accuracy at predicting 30-day morbidity at mortality (AUC 0.5-0.6). LACE index showed good discrimination at predicting 90-day mortality (AUC 0.7). The various frailty and sarcopenia indices have shown poor to fair accuracy at predicting (AUC 0.5-0.7). The Isbarn and Aziz nomograms have equivalent accuracy at predicting 90-day mortality (AUC 0.7) but are limited by inclusion of tumor histology and presence of metastatic disease as variables. POSSUM and P-POSSUM have poor ability at predicting morbidity and mortality (AUC 0.5) and are cumbersome calculators. The surgical Apgar score has been able to predict 30-day morbidity and mortality but can only be used in the postoperative setting. DISCUSSION: The currently available surgical risk calculators have either poor accuracy at predicting post-RC morbidity and mortality or are limited by types of variables included. An ideal risk calculator would be comprised of preoperative factors only and have a high accuracy to serve as a tool for preoperative patient counseling prior to surgery. CONCLUSION: There exists a strong need to develop a comprehensive and accurate preoperative risk calculator that predicts morbidity and mortality after RC.

Immunotherapy in non-muscle-invasive bladder cancer: current status and future directions.

PURPOSE: Patients harboring high-grade non-muscle-invasive bladder cancer (NMIBC) experience high rates of both recurrence and progression. Currently, few treatment options besides cystectomy exist for this at-risk population, especially those with BCG-unresponsive disease. The purpose of this review is to present the current status and describe future directions of immunotherapy in NMIBC. METHODS: The PubMed and Google Scholar databases were searched for articles pertaining to immunotherapy in NMIBC. Relevant planned and ongoing clinical trials were identified using www.ClinicalTrials.gov . Published randomized control trials, reviews, other retrospective and prospective studies deemed relevant were used in this review paper. RESULTS: Novel immunotherapies used in the treatment of high-grade NMIBC and BCG-unresponsive disease allow patients more options and have the potential to reduce the need for radical cystectomy. Currently, several options target the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) axis as this mechanism of immunotherapy has been shown to be effective in several cancers, including bladder, melanoma, and lung cancers. In addition, other immunotherapy options for the treatment of NMIBC include viral gene therapies, interleukin-15 superagonists, small molecule inhibitors of indoleamine (2,3)-dioxygenase 1, and vaccines. CONCLUSIONS: The current landscape of immunotherapy in bladder cancer is rapidly evolving, with much literature pertaining to muscle-invasive and metastatic disease. However, the implementation of these treatment options in high-grade NMIBC may allow patients to avoid life-altering surgery. Reliable biomarkers for response are needed to further select patients who may benefit from such therapies.