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The familial aggregation of bladder cancers has been observed, but the incidence and association of familial bladder cancer with germline pathogenic and likely pathogenic (P/LP) variants is unknown.A retrospective analysis was conducted of patients with bladder cancer treated at the Dana-Farber Cancer Institute to identify those with a first-degree relative with bladder cancer. A second cohort of patients referred to DFCI for suspicion of a cancer predisposition syndrome was analyzed for candidate P/LP germline variants. Descriptive statistics were generated.Among 885 patients with bladder cancer, 38 patients (4.3%) had a family history of bladder cancer in a first-degree relative. No significant association of age of diagnosis was observed between patients with and without a first-degree family history of bladder cancer (P = .3). In the second cohort, 27 of 80 (34%) patients with bladder cancer evaluated for cancer predisposition syndromes harbored a P/LP germline variant. P/LP variants were identified most commonly in the following genes: BRCA1 (n = 5), MSH2 (n = 5), MLH1 (n = 4), ATM (n = 3), and CHEK2 (n = 2). Of the 27 patients with identified germline P/LP variants, 20 (74%) had a family history of a tumor component syndrome in a first- or second-degree relative and 3 were subsequently diagnosed with another genetically-linked associated cancer.Familial bladder cancer defined as bladder cancer in the proband and a first-degree relative, was present in 4.3% of patients with bladder cancer and was not associated with age of diagnosis. Additionally, among patients suspected to have a familial cancer syndrome, one-third harbored a germline P/LP variant. Further study of germline variants in patients with familial bladder cancer including somatic testing for loss of heterozygosity may provide insights regarding disease pathogenesis and inform therapy.

Introduction: The aim of this study was to examine the relationship between duration of surgical intervention and postoperative complications in radical cystectomy (RC). We hypothesized that the complication rate increases with longer operative time. Methods: We analyzed the National Surgical Quality Improvement Program database 2011–2017 to identify all patients who underwent RC. Clinicodemographic characteristics, operative time, and perioperative complications using the Clavien-Dindo Classification (CDC) were abstracted. We fit a generalized linear model with linear splines for operative time to analyze if the relationship between operative time and probability of complication changed over time. Results: A total of 10,520 RC patients were identified with a mean operative time of 5.5 h (standard deviation 2.03). In 55% and 18.2%, any complication and major complications (CDC ≥3) occurred within 30 days postoperatively, respectively. The spline regression model for any complication showed an almost linear relationship between the complication rate and operative time, ranging from 55% at 2.5 h to 82% at 10 h. For major complications, the model revealed the inflection point (knot) at 4.5 h, which corresponds to the lowest complication rate with 15%. Operative times at the extremes of the distribution had higher complication rates: 17.5% if 10 h. Discussion/Conclusion: Operative time of RC is associated with postoperative complications. Though many factors impact the duration of surgery, surgeries that lasted between 4 and 5 h had trend toward the lowest complication rates. Attention to factors impacting operative time may allow surgeons to identify strategies for optimizing surgical care and reducing complications after RC.

Sarcomatoid differentiation in patients diagnosed with renal cell carcinoma (sRCC) imply aggressive behavior and often metastatic disease at the time of diagnosis. We aim to examine the overall survival (OS) in patients with sRCC using the National Cancer Database (NCDB).We identified patients diagnosed with sRCC between 2010-2015. We employed Kaplan-Meier curves and multivariable Cox proportional hazards regression models to examine the impact of several potential risk factors on OS in patients diagnosed with sRCC.In total, 8582 patients with renal cancer were found to have sarcomatoid differentiation, with 4105 patients (47.8%) being diagnosed with AJCC stage IV disease. The median OS was 17.2 months (IQR 5.4, 68.7 months). Compared to patients who did not undergo surgery, OS was significantly longer in patients undergoing partial or total nephrectomy across all stages. This result remained consistent on multivariable Cox proportional hazards regression adjusting for patient and tumor characteristics (Surgery: Hazard ratio 0.54, 95%Confidence interval 0.43 - 0.68, P.001).In our cohort sRCC was found to have an unfavorable median OS, which was mainly caused by the high number of cases diagnosed with late-stage disease. Additionally, surgery was associated with favorable OS across all stages. This study supports the notion that surgical therapy, even in the setting of cytoreductive surgery, provides a survival benefit in patients with sRCC.

Tobacco use is the cause of several urologic cancers. Persistent use after diagnosis is associated with worse cancer-specific, quality of life, and overall mortality outcomes. Cigarette smoking remains the most common form of tobacco use despite significant population-level decline over the past few decades. The burden of smoking-related urologic disease is under appreciated by urologists and patients which has resulted in gaps in clinical care and limitations to research progress. We sought to summarize evidence-based practices and guideline recommendations for assessing and reporting tobacco use in the clinical and research settings. With a focus on smoking, our two primary goals are: 1) to promote the adoption of standardized and validated measures of tobacco use and 2) to highlight evidence-based strategies for urologists to use in clinical practice.

There are many risk factors for bladder cancer. During an initial assessment of a patient with bladder cancer, a careful discussion and history assessment is important. Particular focus should include social history with details regarding occupational background and discussion of any environmental exposure history.

Introduction: There is a scarcity of data on the impact of behavioral habits, such as exercise, on physical health in patients with bladder cancer. We investigated the association of exercise on self-reported physical health status and examined the prevalence of bladder cancer patients with sedentary lifestyle. Methods: We examined cross-sectional data of participants diagnosed with bladder cancer within the Behavioral Risk Factor Surveillance System (BRFSS) from 2016–2020. Patient health status was surveyed using self-reported measures such as the total days per month when their “physical health is not good.” The primary outcome was patient-reported poor physical health for more than 14 days within a one-month period. Results: Out of 2 193 981 survey participants, we identified 936 with a history of bladder cancer. Nearly one in three bladder cancer patients reported being sedentary within the last month, as a total of 307 (32.8%) patients reported no exercise within the last 30 days. The remaining 628 (67.2%) reported exercising for at least one day within the last month. In multivariable logistic regression model analysis, we found that exercise is protective for self-reported poor physical health status (odds ratio 0.37, 95% confidence interval 0.25–0.56, p

BACKGROUND Smoking, the most common risk factor for bladder cancer (BC), is associated with increased complications after radical cystectomy (RC), poorer oncologic outcomes, and higher mortality. The authors hypothesized that the effect of smoking on the probability of major complications increases with increasing age among patients who undergo RC. METHODS The authors analyzed the American College of Surgeons National Surgical Quality Improvement Program database (2011-2017), identified all patients undergoing RC using Current Procedural Terminology codes, and formed two groups according to smoking status (active smoker and nonsmoker [included former and never-smokers]). Patient characteristics and 30-day postoperative complications using the Clavien-Dindo Classification (CDC) were assessed. A multivariable logistic regression model was constructed that included age, sex, race, body mass index, operative time, comorbidities, chemotherapy status, and type of diversion with major complications (CDC ≥III) as the outcome variable, and explored the interaction between age and smoking status. RESULTS A total of 10,528 patients underwent RC, including 22.8% who were active smokers. The authors identified an interaction between age and smoking status (P = .045). Older patients were found to experience a stronger smoking effect than younger patients with regard to the probability of major complications. The risk of a major complication was the same for 50-year-old nonsmokers and smokers, but it increased from 17.8% to 21.7% for 70-year-old nonsmokers and smokers, respectively (P < .001). CONCLUSIONS Up to 20% of patients who undergo RC are active smokers, and these individuals have an increased risk of major complications. The effect of smoking is stronger with increasing age; the difference with regard to complications for smokers versus nonsmokers was found to increase substantially, wherein older smokers are at an especially high risk of complications.

The objective of this study was to examine the overall survival (OS) in patients diagnosed with high-grade T1 non-muscle-invasive bladder cancer treated with early radical cystectomy versus local treatment of the primary tumor, defined as endoscopic management with or without intravesical chemotherapy or immunotherapy.We identified 4900 patients with histologically confirmed, clinically non-metastatic high-grade T1 bladder cancer undergoing surgical intervention using the National Cancer Database for the period 2010 to 2015. Multivariable logistic regression was used to examine predictors for the receipt of early radical cystectomy (defined as radical cystectomy within 90 days of diagnosis). We then employed multivariable Cox proportional hazards regression models and Kaplan-Meier curves to evaluate the OS according to surgical treatment (early radical cystectomy vs. local treatment).A minority (23.7%) of patients underwent early radical cystectomy. Independent predictors of undergoing early radical cystectomy included lower age, White race, and lower comorbidity status. The median OS was 74.0 months for patients diagnosed with high-grade T1 bladder cancer. The 1- and 5-year survival rates of patients undergoing early radical cystectomy were 94.8% and 71.0%, whereas they were 85.2% and 52.4%, for patients undergoing initial local treatment, respectively (P .001). Compared with patients undergoing local treatment, patients undergoing early radical cystectomy had a lower risk of all-cause mortality (hazard ratio, 0.78; 95% confidence interval, 0.67-0.91; P = .002).In this cohort of patients presenting with high-grade T1 non-muscle-invasive bladder cancer, we found that early radical cystectomy was associated with an OS benefit compared with initial local treatment.

Objective To evaluate the impact of alvimopan in patient undergoing radical cystectomy (RC) for bladder cancer. We hypothesize that alvimopan can decrease cost for RC by reducing length of stay (LOS). Methods We identified patients who underwent elective RC for bladder cancer from 2009 to 2015 in the Premier Healthcare Database, a nationwide, all-payer hospital-based database, and compared patients who received and did not receive alvimopan in the perioperative period. Hospitals that had no record of administering alvimopan for patients undergoing RC were excluded. The primary outcomes were LOS and the direct hospital costs. The secondary outcomes were 90-day readmission for ileus and major complications. Results After applying the inclusion criteria, the study cohort consisted of 1087 patients with 511 patients receiving perioperative alvimopan. Alvimopan was associated with a reduction in hospital costs by −$2709 (95% confidence interval: −$4507 to −$912, P = .003), decreased median LOS (7 vs 8 days, P Conclusion Our data show that alvimopan is associated with a substantial cost-saving in patients undergoing RC, and suggest that routine use of alvimopan may be a potential cost-effective strategy to reduce the overall financial burden of bladder cancer.

BACKGROUND Prostate cancer is the most common male cancer, with a wide range of treatment options. Payment reform to reduce unnecessary spending variation is an important strategy for reducing waste, but its magnitude and drivers within prostate cancer are unknown. METHODS In total, 38,971 men aged ≥66 years with localized prostate cancer who were enrolled in Medicare fee-for-service and were included in the Surveillance, Epidemiology, and End Results-Medicare database from 2009 to 2014 were included. Multilevel linear regression with physician and facility random effects was used to examine the contributions of urologists, radiation oncologists, and their affiliated facilities to variation in total patient spending in the year after diagnosis within geographic region. The authors assessed whether spending variation was driven by patient characteristics, disease risk, or treatments. Physicians and facilities were sorted into quintiles of adjusted patient-level spending, and differences between those that were high-spending and low-spending were examined. RESULTS Substantial variation in spending was driven by physician and facility factors. Differences in cancer treatment modalities drove more variation across physicians than differences in patient and disease characteristics (72% vs 2% for urologists, 20% vs 18% for radiation oncologists). The highest spending physicians spent 46% more than the lowest and had more imaging tests, inpatient care, and radiotherapy spending. There were no differences across spending quintiles in the use of robotic surgery by urologists or the use of brachytherapy by radiation oncologists. CONCLUSIONS Significant differences were observed for patients with similar demographics and disease characteristics. This variation across both physicians and facilities suggests that efforts to reduce unnecessary spending must address decision making at both levels.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

Segmental ureterectomy (SU) is an alternative to radical nephroureterectomy (RNU) in the treatment of upper-tract urothelial carcinoma (UTUC) of the ureter. SU generally preserves renal function, at the expense of less intensive cancer control. We aim to assess whether SU is associated with inferior survival compared to RNU. Using the National Cancer Database (NCDB), we identified patients diagnosed with localized UTUC of the ureter between 2004–2015. We used a propensity-score-overlap-weighted (PSOW) multivariable survival model to compare survival following SU vs. RNU. PSOW-adjusted Kaplan–Meier curves were generated and we performed a non-inferiority test of overall survival. A population of 13,061 individuals with UTUC of the ureter receiving either SU or RNU was identified; of these, 9016 underwent RNU and 4045 SU. Factors associated with decreased likelihood of receiving SU were female gender (OR, 0.81; 95% CI, 0.75–0.88; p < 0.001), advanced clinical T stage (cT4) (OR, 0.51; 95% CI, 0.30–0.88; p = 0.015), and high-grade tumor (OR, 0.76; 95% CI, 0.67–0.86; p < 0.001). Age greater than 79 years was associated with increased probability of undergoing SU (OR, 1.18; 95% CI, 1.00–1.38; p = 0.047). There was no statistically significant difference in OS between SU and RNU (HR, 0.98; 95% CI, 0.93–1.04; p = 0.538). SU was not inferior to RNU in PSOW-adjusted Cox regression analysis (p < 0.001 for non-inferiority). In weighted cohorts of individuals with UTUC of the ureter, the use of SU was not associated with inferior survival compared to RNU. Urologists should continue to utilize SU in appropriately selected patients.

559 Background: BLASST-1 is multi-center phase II trial evaluating neoadjuvant nivolumab (N) with gemcitabine-cisplatin (GC) for patients (pts) with MIBC undergoing radical cystectomy (RC) (NCT03294304). 41 pts with MIBC (cT2-T4a, N≤1, M0) were enrolled between Feb 2018 and June 2019; (cT2N0 90%, cT3N0 7%, cT4N1 3%). Pts received C (70mg/m2) IV on D1, G (1000mg/m2) on D1, D8 and N (360 mg) IV on D8 every 21 days for 4 cycles followed by RC within 8 wks. Primary endpoint was pathologic down staging (PaR; ≤pT1N0). Safety, Relapse-free survival (RFS), Progression-free survival (PFS) and biomarker analyses were secondary endpoints. PaR rate was 65.8%, pCR (≤pT is N0) rate was 49% and there were no safety concerns or delays to RC. At a median follow-up of 15.8 mos, 12-month RFS rate was 85.4% and PFS including death from any cause was 83%. We now report correlation of PaR with tumor mutation patterns of responders (R) and non-responders (NR) using Whole Genome Sequencing (WGS). Methods: DNA was extracted from pre-treatment tumor samples and sequenced to an average depth of 150X and DNA extracted from matched normal tissue (peripheral blood) to a mean depth of 50X. We analyzed 32 Tumor/Normal pairs and 6 Tumor only Whole Genome Samples; 26 pts were classified as (R) and 12 as (NR). Raw sequencing data samples were aligned to hg38 genome build using Burrows-Wheeler Aligner (BWA) followed by duplicate-read removal and base-quality score recalibration using the Genome Analysis Toolkit (GATK). Somatic SNV and INDELS were called by combination of 5 callers (Mutect2, Strelka, VarScan, Platypus and SomaticSniper) for Tumor/Normal pairs and Mutect2 for Tumor only samples following the guidelines of GDC DNA-Seq analysis pipeline. Set of genes known to be significantly mutated in MIBC and shown to impact response/resistance to chemotherapy/immunotherapy respectively were selected. Samples were grouped by response status. Results: Median tumor mutational burden (TMB) for the dataset closely matches with TCGA results. Genes ERCC2, ARID1A, DSP, HMCN1, ERBB2, ERBB3, STAG2, BRCA2 present in (R) only, whereas VHL, ERCC4, PALB2, CDKN2A and CSMD3 present in (NR) only. We also grouped genes based on their biological processes by known Oncogenic Signaling Pathways and the 3 most common pathways are Genome Integrity, RTK Signaling and Transcription Factor with the latter two primarily enriched in (R). We identified a SNP rs2853669 in 5 (NR) and 14 (R). Conclusions: The genomic analysis suggests ERCC2, ARID1A, DSP, HMCN1, ERBB2, ERBB3,STAG2, BRCA2 correlated with PaR and VHL, ERCC4, PALB2, CDKN2A and CSMD3 correlated with lack of response. In addition, RTK Signaling and Transcription Factor were primarily enriched in (R). This genomic correlation of response/resistance to neoadjuvant chemo-immunotherapy in MIBC can help guide future biomarker-driven studies. Clinical trial information: NCT03294304 .

PURPOSE: We investigated the association between race and FT among previous patients with cancer. Studies show that patients with cancer experience financial toxicity (FT) because of their cancer treatment. METHODS: Data on individuals with a cancer history were collected in this cross-sectional study during 2012, 2014, and 2017, from the US Health Information National Trends Survey. This survey is conducted by mail with monetary compensation as an incentive. We specifically assessed responses to two questions: Has cancer hurt you financially? Have you been denied health insurance because of cancer? Multivariable logistic regression analyses were used to assess the associations between these questions and race. RESULTS: Of 10,592 individuals participating, 1,328 men and women (12.5%) with a cancer history were assessed. Compared with Blacks, Whites were found to have a higher rate of insurance (95.4% v 90.0%), were more likely to receive cancer treatment (93.9% v 85%), and had a higher rate of surgical treatment than Blacks (77% v 60%), Hispanics (55%), and others (77%, 60%, 55%, and 74.2%, respectively, P < .001). On multivariable analysis, Blacks were more than five times as likely to be denied insurance (odds ratio, 5.003; 95% CI, 2.451 to 10.213; P < .001) and more than twice as likely to report being hurt financially because of cancer (odds ratio, 2.448; 95% CI, 1.520 to 3.941; P < .001) than Whites. Of all cancer groups analyzed (genitourinary, gynecologic, gastrointestinal, and breast), genitourinary malignancies were the only group in which the rate of reporting being hurt financially varied in a statistically significant manner (Whites 36.7%, Hispanics 62.5%, and Blacks 59.3%, P = .004). CONCLUSION: Our data suggest that race is significantly associated with FT because of cancer. Awareness of racial inequality with regards to FT should be raised among health care workers.

INTRODUCTION AND OBJECTIVE:Radiation associated muscle-invasive bladder cancer (RA-MIBC) is a potentially lethal late toxicity following definitive radiation for prostate cancer. RA-MIBC can be dif...

INTRODUCTION AND OBJECTIVE:To examine the relationship between duration of surgical intervention and postoperative complications in radical cystectomy. We hypothesized that the complication rate in...

INTRODUCTION AND OBJECTIVE:Tobacco use has been shown to be an independent risk factor for postoperative morbidity following a variety of major surgeries. While tobacco use is both a risk factor fo...

INTRODUCTION AND OBJECTIVE:Radical cystectomy (RC) can be a challenging procedure associated with a high morbidity. We evaluated healthcare and surgical factors associated with high-quality RC surg...

BACKGROUND Health insurance is a key mediator of health care disparities. Outcomes in bladder cancer, one of the costliest diseases to treat, may be especially sensitive to a patient's insurance status. METHODS The Surveillance, Epidemiology, and End Results registry and the National Cancer Data Base were used to identify individuals younger than 65 years who were diagnosed with bladder cancer from 2007 to 2014. The associations between the insurance status (privately insured, insured by Medicaid, or uninsured) and the following outcomes were evaluated: diagnosis with advanced disease, cancer-specific survival, delay in treatment longer than 90 days, treatment in a high-volume hospital, and receipt of neoadjuvant chemotherapy (NAC). RESULTS Compared with those with private insurance, uninsured and Medicaid-insured individuals were nearly twice as likely to receive a diagnosis of muscle-invasive bladder cancer (odds ratio [OR] for uninsured individuals, 1.90; 95% confidence interval [CI], 1.70-2.12; OR for Medicaid-insured individuals, 2.03; 95% CI, 1.87-2.20). They were also more likely to die of bladder cancer (adjusted hazard ratio [AHR] for uninsured individuals, 1.49; 95% CI, 1.31-1.71; AHR for Medicaid-insured individuals, 1.61; 95% CI, 1.46-1.79). Delays in treatment longer than 90 days were more likely for uninsured (OR, 1.36; 95% CI, 1.12-1.65) and Medicaid-insured individuals (OR, 1.22; 95% CI, 1.03-1.44) in comparison with the privately insured. Uninsured patients had lower odds of treatment at a high-volume facility, and Medicaid-insured patients had lower odds of receiving NAC (P

The prostate biopsy pathology report represents a critical document used for decision-making in patients diagnosed with prostate cancer, yet the content exceeds the health literacy of most patients. We sought to create and compare the effectiveness of a patient-centered prostate biopsy report compared with standard reports. Using a modified Delphi approach, prostate cancer experts identified critical components of a prostate biopsy report. Patient focus groups provided input for syntax and formatting of patient-centered pathology reports. Ninety-four patients with recent prostate biopsies were block randomized to the standard report with or without the patient-centered report. We evaluated patient activation, self-efficacy, provider communication skills, and prostate cancer knowledge. Experts selected primary and secondary Gleason score and the number of positive scores as the most important elements of the report. Patients prioritized a narrative design, non-threatening language and information on risk classification. Initial assessments were completed by 87% (40/46) in the standard report group and 81% (39/48) in the patient-centered report group. There were no differences in patient activation, self-efficacy, or provider communication skills between groups. Patients who received the patient-centered report had significantly improved ability to recall their Gleason score (100% vs. 85%, p = 0.026) and number of positive cores (90% vs. 65%, p = 0.014). In total, 86% of patients who received the patient-centered report felt that it helped them better understand their results and should always be provided. Patient-centered pathology reports are associated with significantly higher knowledge about a prostate cancer diagnosis. These important health information documents may improve patient-provider communication and help facilitate shared decision-making among patients diagnosed with prostate cancer.

Background The practice of overlapping surgery impacts patients, providers, and policy-makers. While several studies have examined the relationship between overlapping surgery and clinical outcomes, a combined analysis of all available data has not been performed. We aimed to evaluate the impact of overlapping surgery on 30-day mortality, morbidity, and length of surgery. Methods A systematic literature review revealed all relevant studies examining outcomes of overlapping versus non-overlapping surgery as of March 2018. A pooled meta-analysis with stratification by study quality grade was performed, and heterogeneity and publication bias were assessed. Results A total of 14 sets of analyses met inclusion and exclusion criteria. Meta-analysis revealed no significant differences in 30-day mortality (OR = 0.84; p = 0.277) or overall morbidity (OR = 0.96; p = 0.632) between patients who underwent overlapping versus non-overlapping surgery. The standardized mean difference for length of surgery between the groups indicated a small statistically significant increase in length of surgery for the overlapping surgery group (SMD = 0.079, p Conclusion While further study is warranted, current literature suggests that overlapping surgery is not associated with increased risk of mortality or morbidity.

To investigate the temporal relationship of hospital charges relative to recorded costs for surgical episodes of care.This retrospective cohort study selected individuals who underwent any of 8 index urologic surgical procedures at 392 unique institutions from January 1, 2005, through December 31, 2015. For each surgical encounter, cost and charge data reported by hospitals were extracted and adjusted to 2016 US dollars. Trend analysis and multivariable logistic regression modeling were used to assess outcomes. The primary outcome was trend in median charge and cost. Secondary outcomes consisted of hospital characteristics associated with membership in the highest quartile of institutional charge-to-cost ratio.Cohort-level median cost per encounter trended down from $6824 in 2005 to $5586 in 2015 (P for trend.001), and charges increased from $20,210 to $25,773 during the same period (P for trend.001). Hospitals in the highest quartile of institutional charge-to-cost ratio were more likely to be safety net, nonteaching, urban, lower surgical volume, smaller, and located outside the Midwest (P.001 for each characteristic).The pricing trends shown herein could indicate some success in cost-containment for surgical episodes of care, although higher hospital charges may be increasingly used to bolster reimbursement from third-party payers and to compensate for escalating costs in other areas.

BACKGROUND Certain patients with intermediate-risk prostate cancer (PCa) may be appropriate candidates for active surveillance (AS). In the current study, the authors sought to characterize AS use and early mortality outcomes for patients with intermediate-risk PCa in the United States. METHODS The novel Surveillance, Epidemiology, and End Results Active Surveillance/Watchful Waiting database identified 52,940 men diagnosed with National Comprehensive Cancer Network intermediate-risk PCa (cT2b-c, Gleason score of 7, or a prostate-specific antigen level of 10-20 ng/mL) and actively managed (AS, radiotherapy, or radical prostatectomy) from 2010 through 2015. The Cuzick test assessed AS time trends, and logistic multivariable regression characterized features associated with AS. Fine-Gray and Cox modeling determined PCa-specific mortality (PCSM) and overall survival, respectively. RESULTS The rate of AS increased from 3.7% in 2010 to 7.3% in 2015, and from 7.2% to 11.7% among men aged ≥70 years. Among men with favorable and unfavorable intermediate-risk disease, the use of AS increased from 7.2% to 14.9% and from 2.2% to 3.8%, respectively (all P value for trend

OBJECTIVE To examine the incidence of perioperative complications after radical cystectomy (RC) and assess their impact on 90-day postoperative mortality during the index stay and upon readmission. PATIENTS AND METHODS A total of 57 553 patients with bladder cancer (unweighted cohort: 9137 patients) treated with RC, at 360 hospitals in the USA between 2005 and 2013 within the Premier Healthcare Database, were used for analysis. The 90-day perioperative mortality was the primary outcome. Multivariable regression was used to predict the probability of mortality; models were adjusted for patient, hospital, and surgical characteristics. RESULTS An increase in the number of complications resulted in an increasing predicted probability of mortality, with a precipitous increase if patients had four or more complications compared to one complication during hospitalisation following RC (index stay; 1.0-9.7%, P

The impact of anemia in postoperative complications following radical cystectomy (RC) is not completely elucidated and its association with direct hospital costs has not been characterized in depth. Our goal is to determine the association between anemia, 90-day surgical complications and the expenditure attributed to preoperative anemia in patients undergoing RC.We captured all patients who underwent RC between 2003 and 2017 using the Premier Hospital Database (Premier Inc, Charlotte, NC). Patient, hospital and surgical characteristics were evaluated. Anemia was defined by a corresponding diagnostic code that was present on admission prior to RC. Unadjusted patients' demographic characteristics with and without anemia, hospital and surgeon characteristics were compared, and multivariable regression models were developed to evaluate 90-day complications and total direct hospital costs.The cohort included 83,470 patients that underwent RC between 2003 and 2017 and 11% were found to be anemic. On multivariable analysis, preoperative anemia more than doubled the odds of having a complication (odds ratio 2.19 (1.89-2.53)) and significantly increased the risk of major complications (odds ratio 1.51 (1.31-1.75)) at 90-days after RC. Anemic patients had significantly higher 90-days total direct costs due to higher laboratory, pharmacologic, radiology and operating room costs.Anemic cystectomy patients face a 50% increase in the risk of major complications within the first 90-days after surgery. This increased risk persisted after adjusting for patient, hospital and surgical factors. Our study suggests hematocrit level prior to RC may be used as a pre-exisitng condition for increased risk of surgical complications.

PURPOSE/OBJECTIVE(S) Radiation associated muscle-invasive bladder cancer (RA-MIBC) is a rare but potentially lethal late toxicity following definitive radiation therapy for prostate cancer. RA-MIBC is associated with worse prognosis compared to primary MIBC, but it remains unknown whether worse outcomes are driven primarily by difficulty with delivering definitive treatment in a previously irradiated pelvis or whether RA-MIBCs harbor specific aggressive biological features. We sought to characterize the genomic features of RA-MIBC to assess whether the underlying genetic alterations differ from primary (non-radiation associated) MIBC. MATERIALS/METHODS We performed whole-exome sequencing of 27 bladder tumors in patients previously treated with definitive radiation therapy for prostate cancer, and we correlated genomic with clinical data. We compared the mutation profile of RA-MIBC with primary MIBC from The Cancer Genome Atlas (TCGA). We used the Kaplan-Meier method to estimate progression-free survival (PFS) and overall survival (OS). RESULTS The median age of included patients was 79.2 years, and the median time from prostate radiation to MIBC diagnosis was 11.5 years. Median PFS was 12.4 months and median OS was 20.2 months. Among RA-MIBCs, we found mutation signatures characteristic of BRCA1/2 mutations, impaired DNA mismatch repair, and microsatellite instability. When compared to de novo MIBC from TCGA, RA-MIBCs also had significantly higher mutation rates of DNA repair genes, such as FANCA (38.1% vs 5.1%, P < 0.001), CHEK2 (26.1% vs 2.5%, P < 0.001) and MSH6 (26.1% vs 2.5%, P < 0.001). The most commonly mutated genes were TP53 (50%) and KDM6A (36%), which harbored mutations at similar rates as de novo MIBC samples from TCGA. CONCLUSION In this study, we characterize the mutational profiles and clinical outcomes of radiation-associated bladder cancer. These patients exhibited significantly worse PFS and OS compared to prior series of de novo MIBC. Genomically, these tumors exhibited higher rates of mutation signatures characteristic of impaired DNA damage repair compared to previously unirradiated tumors. These genomic differences suggest that some RA-MIBCs may represent a biologically distinct entity compared to de novo MIBC and may indicate an opportunity for the use and development of novel therapeutic strategies.

To characterize the presentation, patterns of care, and outcomes of radiation-associated muscle-invasive bladder cancer (RA-MIBC) compared to primary (non-radiation associated) MIBC. RA-MIBC has been suggested to represent a more aggressive disease variant and be more difficult to treat compared to primary (non-radiation associated) MIBC.We identified 60,090 patients diagnosed with MIBC between 1988-2015 using the Surveillance, Epidemiology, and End Results database and stratified patients based on whether radiation had been administered to a prior pelvic primary cancer. We used Fine-Gray competing risks regression to compare adjusted bladder cancer-specific mortality (BCSM) for RA-MIBC compared to primary MIBC.There were 1,093 patients with RA-MIBC and 58,997 patients with primary MIBC. RA-MIBCs were more likely to be T4 at diagnosis (21.0% vs 17.3%, P.001), and less likely to be node-positive (10.3% vs 17.1%, P.001). The rate of 5-year BCSM was significantly higher for patients with RA-MIBC vs primary MIBC (56.1% vs 35.3%, AHR 1.24, P.001), even after stratification by other tumor, treatment and patient-specific factors.RA-MIBCs tended to present with higher grade and T stage disease and were less likely to receive curative treatment. Even when accounting for stage, grade, and receipt of treatment, patients with RA-MIBC had worse survival compared to those with primary MIBC. These findings suggest that RA-MIBC present unique clinical challenges and may also represent a biologically more aggressive disease compared to primary MIBC. Future research is needed to better understand the biology of RA-MIBC and develop improved treatment approaches.

Purpose We performed a systematic review to assess the clinical features of cyclophosphamide-associated bladder cancer. Materials and Methods MEDLINE, Web of Science, and Cochrane Library were searched from inception to August 2020 according to PRISMA guidelines. Studies that associated bladder cancer with prior cyclophosphamide use on an individual level were included. Results We identified 121 studies spanning over a 50-year period with 285 patients. The most common malignant indication for cyclophosphamide was lymphoma (25%), while the most common non-malignant indication was ANCA-associated vasculitides (26%). Hematuria and dysuria were the most prevalent symptoms prior to a cyclophosphamide-associated bladder cancer diagnosis, and median age at diagnosis was 55 years. Conventional urothelial carcinoma (UC) was the most common bladder-associated diagnosis (74%), although a broad range of cancer types were represented, notably leiomyosarcoma and squamous cell carcinoma. About half of bladder cancers were muscle invasive at diagnosis and median latency time was 10.0 years; 33% of patients had a bladder cancer related death. Conclusions We describe the largest pooled analysis of patients with cyclophosphamide-associated bladder cancer. These bladder cancers have a propensity for younger age at diagnosis, more advanced stage at diagnosis, and variant histology. There was a substantial number of patients with latency time of ≥20 years independent of cumulative cyclophosphamide dose. These findings support consideration of screening and long-term surveillance of cancer survivors with a history of cyclophosphamide therapy for bladder cancer.

Assessing perioperative risk is essential for surgical decision-making. Our study compares the accuracy of comorbidity indices to predict morbidity and mortality.Analyzing the National Surgical Quality Improvement Program, 16 major procedures were identified and American Society of Anesthesiologists (ASA), Charlson Comorbidity Index and modified Frailty Index were calculated. We fit models with each comorbidity index for prediction of morbidity, mortality, and prolonged length of stay (pLOS). Decision Curve Analysis determined the effectiveness of each model.Of 650,437 patients, 11.7%, 6.0%, 17.0% and 0.75% experienced any, major complication, pLOS, and mortality, respectively. Each index was an independent predictor of morbidity, mortality, and pLOS (p 0.05). While the indices performed similarly for morbidity and pLOS, ASA demonstrated greater net benefit for threshold probabilities of 1-5% for mortality.Models including readily available factors (age, sex) already provide a robust estimation of perioperative morbidity and mortality, even without considering comorbidity indices. All comorbidity indices show similar accuracy for prediction of morbidity and pLOS, while ASA, the score easiest to calculate, performs best in prediction of mortality.

Background Radical cystectomy (RC) is associated with high morbidity. Objective To evaluate healthcare and surgical factors associated with high-quality RC surgery. Design, setting, and participants Patients within the prospective British Association of Urological Surgeons (BAUS) registry between 2014 and 2017 were included in this study. Outcome measurements and statistical analysis High-quality surgery was defined using pathological (absence of positive surgical margins and a minimum of a level I lymph node dissection template with a minimum yield of ten or more lymph nodes), recovery (length of stay ≤10 d), and technical (intraoperative blood loss, Take Home Message In this UK registry study of bladder cancer patients treated with radical cystectomy, we report that patients treated by a surgeon with a higher annual operative volume and a minimally invasive approach were associated with the receipt of high-quality surgery. Patients treated with high-quality surgery were more likely to be discharged alive following surgery.

OBJECTIVES To evaluate outcomes of patients achieving a post-treatment pathological stage of

Patients with bacillus Calmette-Guérin-unresponsive carcinoma in situ are treated with radical cystectomy or salvage intravesical chemotherapy. Recently, pembrolizumab was approved for bacillus Calmette-Guérin-unresponsive carcinoma in situ.We used a decision-analytic Markov model to compare pembrolizumab, salvage intravesical chemotherapy (with gemcitabine-docetaxel induction+monthly maintenance) and radical cystectomy for patients with bacillus Calmette-Guérin-unresponsive carcinoma in situ who are radical cystectomy candidates (index patient 1) or are unwilling/unable to undergo radical cystectomy (index patient 2). The model used a U.S. Medicare perspective with a 5-year time horizon. One-way and probabilistic sensitivity analyses were performed. Incremental cost-effectiveness ratios were compared using a willingness to pay threshold of $100,000/quality-adjusted life year.For index patient 1, pembrolizumab was not cost-effective relative to radical cystectomy (incremental cost-effectiveness ratios $1,403,008/quality-adjusted life year) or salvage intravesical chemotherapy (incremental cost-effectiveness ratios $2,011,923/quality-adjusted life year). One-way sensitivity analysis revealed that pembrolizumab only became cost-effective relative to radical cystectomy with a93% price reduction. Relative to radical cystectomy, salvage intravesical chemotherapy was cost-effective for time horizons5 years and nearly cost-effective at 5 years (incremental cost-effectiveness ratios $118,324/quality-adjusted life year). One-way sensitivity analysis revealed that salvage intravesical chemotherapy became cost-effective relative to radical cystectomy if risk of recurrence or metastasis at 2 years was less than 55% or 5.9%, respectively. For index patient 2, pembrolizumab required90% price reduction to be cost-effective (incremental cost-effectiveness ratios $1,073,240/quality-adjusted life year). Pembrolizumab was cost-effective in 0% of 100,000 microsimulations in probabilistic sensitivity analyses for both index patients.At its current price, pembrolizumab is not cost-effective for bacillus Calmette-Guérin-unresponsive carcinoma in situ relative to radical cystectomy or salvage intravesical chemotherapy. Although gemcitabine-docetaxel is not cost-effective relative to radical cystectomy at 5 years, further studies may validate its cost-effectiveness if recurrence and metastasis thresholds are met.

Objectives To investigate the impact of high-intensity local treatment (LT) on overall survival (OS) in patients with stage IV upper tract urothelial carcinoma (UTUC). Patients and methods Within the National Cancer Database, we identified 7,357 patients diagnosed with stage IV UTUC from 2004 to 2015. Patients who underwent high-intensity LT, defined as radical surgery of the primary tumor, were compared with those who did not. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Weighted survival analyses were used to test the association between high-intensity LT and OS. Multivariable Cox model was used to assess for independent predictors of OS. Sensitivity analysis was used to account for possible biases. Results Among stage IV patients, 10.6% (n = 779) had locally advanced disease (T4), 32.6% (n = 2,399) had node-positive disease (N+) and 56.8% (N = 4,179) had distant metastases (M+). Fewer than half of the patients underwent high-intensity LT (n = 2,908, 39.5%) while the remainder did not. On IPTW-adjusted survival analysis, high-intensity LT was associated with a prolonged OS (11.17 months [IQR, 5.19 to 24.28] months vs. 6.18 months [IQR, 2.27 to 14.49], P ≤ 0.001). A similar benefit was seen on adjusted survival analyses for each stage IV subgroup, defined according to TNM characteristics. The survival benefit was confirmed at sensitivity analysis. Conclusion High-intensity LT in balanced cohorts of patients with stage IV UTUC is associated with prolonged OS including those with locally advanced (T4), node-positive (N+) or distant metastases (M+).

OBJECTIVES To develop and validate the Preoperative Risk Evaluation for Partial Nephrectomy (PREP) score to predict the probability of major postoperative complications after partial nephrectomy (PN) based on patient comorbidities. PATIENTS AND METHODS The Premier Healthcare Database was used to identify patients who had undergone elective PN. Through review of International Classification of Diseases ninth revision codes, we identified patient comorbidities and major surgical complications (Clavien-Dindo Grade III-V). Multivariable logistic regression was used to identify predictors of major complications. We used half of the set as the training cohort to develop our risk score and the other half as a validation cohort. RESULTS From 2003 to 2015, 25 451 PNs were performed. The overall rate of major complications was 4.9%. The final risk score consisted of 10 predictors: age, sex, congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, chronic kidney disease, diabetes, hypertension, obesity, and smoking. In the training cohort, the area under the receiver operating characteristic curve (AUC) was 0.75 (95% confidence interval [CI] 0.73-0.78), while the AUC for the validation cohort was 0.73 (95% CI 0.70-0.75). The predicted probabilities of major complication in the low- (≤10 points), intermediate- (11-20 points), high- (21-30 points), and very high-risk (>30 points) categories were 3% (95% CI 2.6-3.2), 8% (95% CI 7.2-9.2), 24% (95% CI 20.5-27.8), and 41% (95% CI 34.5-47.8), respectively. CONCLUSIONS We developed and validated the PREP score to predict the risk of complications after PN based on patient characteristics. Calculation of the PREP score can help providers select treatment options for patients with a cT1a renal mass and enhance the informed consent process for patients planning to undergo PN.

Objectives: To examine the temporal association between blood transfusion and 90-day mortality in patients with bladder cancer treated with radical cystectomy.Methods: This represents a retrospecti...