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• In 1993 the NIH established guidelines for demographic reporting in clinical trials. • Most clinical trials for BCG-unresponsive bladder cancer do not report race/ethnicity data. • Racial/ethnic minorities are disproportionately underrepresented in these clinical trials. The National Institutes of Health (NIH) Revitalization Act of 1993 established guidelines for the inclusion of racial/ethnic minorities and women in clinical research. However, the reporting rate of such patient demographic data in clinical trials for BCG-unresponsive non-muscle invasive bladder cancer is not well characterized. We identified published clinical trials of all phases (I –III) for BCG-unresponsive non-muscle invasive bladder cancer conducted in the US and/or Canada. We calculated the proportion of studies reporting patient gender and race/ethnicity, tabulating these data when present. We compared reported trial participant race, ethnicity and gender with the number of new bladder cancer cases and deaths using the Centers for Disease Control and Prevention (CDC) and National Cancer Institute (NCI) U.S. Cancer Statistics data from 2013 –2017. We identified 27 trials published from 1998 –2021 enrolling a total of 1673 patients. While all trials included data on patient gender (22% women overall), only 40.7% included any data on patient race/ethnicity. Among those that did, trial participants were reported as white (94%), Black (2.1%), Hispanic (0.6%), Asian (0.9%), and Other (2.3%). Racial/ethnic minorities were underrepresented in clinical trials relative to their proportion of new bladder cancer cases and deaths. Most clinical trials that have been conducted for BCG-unresponsive non-muscle invasive bladder cancer do not report data on patient race or ethnicity despite NIH guidelines advocating for inclusion of such data. Racial/ethnic minorities remain underrepresented in these trials relative to the burden of bladder cancer prevalence and mortality faced by these groups. [ABSTRACT FROM AUTHOR]

Trimodal therapy (TMT) for muscle invasive bladder cancer has become an accepted alternative to radical cystectomy and has become integrated into national guidelines as standard a treatment option. The urologist plays a critical role in proper patient selection, thorough transurethral resection, ongoing cystoscopic surveillance and management of local recurrences. There exists multiple patient related and tumor related factors, which contribute to the selection of TMT vs. radical cystectomy for a patient with muscle invasive bladder cancer. Although the ideal patient for TMT has a tumor which can undergo a visibly complete resection, has no associated hydronephrosis, does not invade the prostatic urethra and is not associated with diffuse carcinoma in situ throughout the bladder, select patients who do not meet all these criteria can still be successfully treated with this approach. A multidisciplinary approach including urology, radiation oncology and medical oncology is paramount with clear communication of tumor location, timing of chemoradiation and repeat cystoscopic resection followed by surveillance. Nonmuscle invasive bladder cancer recurrences can occur in up to 26% of patients after completion of TMT, with many being treated by routine and standard therapy for non-muscle invasive bladder cancer. However, in this population after TMT, early salvage cystectomy should be considered in those with adverse features, including T1 disease, tumor greater than 3 cm, CIS, or lymphovascular invasion. Salvage cystectomy can be performed for local recurrences with acceptable oncologic control and no clear evidence of any greater risk of early complications; however, there may be a slightly increased risk for late complications, namely small bowel obstruction, ureteral stricture, and parastomal hernia. An understanding of these surgical considerations is of utmost importance to the treating urologist in selecting and managing a patient through TMT. [ABSTRACT FROM AUTHOR]

It is estimated that at least 50% of bladder cancer (BC) cases are linked to smoking, while persistent smoking after diagnosis is associated with higher risk of disease recurrence, higher rates of progression, adverse pathological response to neoadjuvant chemotherapy, and higher risk of developing metastatic disease and death. Yet, the association between smoking and mental health in this population is poorly understood. BC patients are usually burdened psychologically by stress, anxiety, and depression, irrespective of the stage of disease or timing and treatment modality. We sought to investigate the association between smoking status and mental health among patients and survivors of BC. Using the CDC national Behavioral Risk Factor Surveillance System (BRFSS) cycles between 2016 and 2021, we conducted a cross-sectional study of participants who self-reported ever being diagnosed with BC. A descriptive analysis of our study cohort was conducted (Table 1). Further, we used a multivariable logistic regression analysis (MVA) to examine the association between smoking status and the outcome of self-reported 14+ days per month when mental health is not good. We hypothesized that smoking is associated with worse mental health. In our MVA (Table 2) we adjusted our analysis for age, time from being diagnosed to undergoing the survey in years, treatment status, income, marital status, exercise and physical activity, BMI, history of depression, history of coronary heart disease or myocardial infraction, and history of chronic kidney disease. An institutional review board waiver was obtained given the use of de-identified data. Two-sided statistical significance was defined as P<0.05. We identified 1,118 BC patients and survivors out of 2,632,647 participants in the 2016 to 2021 BRFSS. 188 (16.9%) were current smokers, 584 (52.5%) were former smokers, and 341 (30.6%) had never smoked. Among the BC cohort, only 104 (9.3%) individuals reported 14+ days per month when mental health was not good. (Table 1). Our MVA showed that being a current smoker is independently associated with worse mental health compared to being a never smoker (OR 2.41, 95% CI 1.06 – 5.50, p=0.04), while being a former smoker was not an independent predictor of worse mental health (OR 0.96, 95% CI 0.46 – 2.00, p=0.91). Other significant predictors of poor mental health can be seen in Table 2. Standard logistic regression diagnostics for our MVA yielded a Hosmer-Lemeshow goodness of fit test p=0.88, and a receiver operating characteristic (ROC) with an area under the curve (AUC) of 0.81. Our results indicate an independent association between being a current smoker and reported poor mental health in BC patients and survivors. Moreover, being a former smoker was not associated with poor mental health. Our results are profound and significant due to the well-known implications of smoking in the development of bladder cancer. Our findings bring a piece of valuable clinical information to this specific population and supports the importance of smoking cessation programs. An important strength of our study is the large national sample size. Limitations include the lack of granularity in staging and treatment-specific data and traditional biases inherited from retrospective studies. Since smoking behavior is modifiable, our findings should encourage the implementation of smoking cessation programs in BC patients and survivors in order to improve mental health and quality of life. [ABSTRACT FROM AUTHOR]

Rationale: Several guidelines exist that address treatment of patients with nonmetastatic muscle-invasive bladder cancer (MIBC). However, most only briefly mention follow-up strategies for patients and hence the treating physician is often left to infer on what the preferred follow-up schema would be for an individual patient. Herein, we aim to synthesize recommendations for follow-up of patients with MIBC for easy reference.Methods: A multidisciplinary MIBC expert panel from the International Bladder Cancer Network was assembled to critically assess currently available major guidelines on surveillance of MIBC patients. Recommendations for follow-up were extracted and critically evaluated. Important considerations for guideline assessment included both aspects of oncological and functional follow-up-frequency of visits, the use of different imaging modalities, the role of cytology and molecular markers, and the duration of follow-up.Outcome: An International Bladder Cancer Network expert consensus recommendation was constructed for the follow-up of patients with MIBC based on the currently available evidence-based data. [ABSTRACT FROM AUTHOR]

• Progressive MIBC has worse outcomes than de novo MIBC, even with neoadjuvant chemotherapy. • Progressive MIBC and de novo MIBC should be considered as distinct entities. • Consideration of additional or innovative systemic therapies should be given for progressive MIBC. To compare survival and pathologic outcomes in patients with progressive muscle-invasive bladder cancer (pgMIBC) and de novo muscle-invasive bladder cancer (dnMIBC) after radical cystectomy (RC), with a focus on the role of neoadjuvant chemotherapy (NAC). A comprehensive literature search was conducted on PubMed and EMBASE databases to identify studies comparing pgMIBC to dnMIBC. Survival outcomes, including cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS), and pathologic outcomes (rates of ≤pT1, pT0, pT3/T4, and pN+ disease) were compared between pgMIBC and dnMIBC. The analysis included 19 cohorts from 16 studies, categorized into 3 groups based on NAC use: 1. patients who underwent RC and were all treated with NAC (RC + NAC only group); 2. patients who underwent RC, with or without NAC (RC +/- NAC group); 3. patients who only underwent RC without NAC (RC only group). Compared to dnMIBC, pgMIBC demonstrated worse outcomes for CSS, OS, and RFS. In the RC + NAC only group (3 cohorts), the hazard ratio (HR) for CSS was 1.52 (95% confidence interval [CI] = 1.05–2.2), while the HR for OS was 1.46 (95%CI = 1.05–2.02). Similarly, in the RC +/- NAC group (6 cohorts for CSS and 3 cohorts for OS), the HR for CSS was 1.27 (95%CI = 1.05–1.55), and the HR for OS was 1.27 (95%CI = 1.08–1.51). There were no significant differences observed in pathologic outcomes, including rates of ≤pT1, pT0, and pT3/T4 disease, across all subgroups. However, pgMIBC was associated with a higher risk of nodal metastatic (pN+) disease in the RC + NAC only group (4 cohorts, relative risk [RR] = 1.43, 95%CI = 1.12–1.84). The findings highlight the potentially worse prognosis in patients with pgMIBC compared to dnMIBC, even with the modern use of NAC. The study emphasizes the importance of careful patient counseling, further classification of patients for treatment selection, and the consideration of additional or innovative systemic therapies for pgMIBC. [ABSTRACT FROM AUTHOR]

Testicular germ cell tumors (TGCT) are one of the most common malignancies in young to middle-aged men. Though highly treatable at all stages, identifying the disease at an early stage is crucial to maximizing quality-of-life for survivors and minimizing treatment toxicity. In the United States (U.S.), access to healthcare is highly dependent on insurance status and insurance quality. Little is known about the effect of insurance providers and the TGCT disease stage in which patients are diagnosed. Herein, we attempt to investigate the relationship between the insurance provider and the TGCT disease stage. We hypothesize that patients who are uninsured or insured under Medicaid are more likely to present with higher-stage TGCT than patients who are privately insured. Using the National Cancer Database (NCDB) from 2004 to 2016, we captured all men aged 18 years or older diagnosed with TGCT. We calculated a descriptive demographic characteristic for our study cohort. Using multivariable logistic regression analysis, we identified significant predictors for the outcome of late-stage presentation. Late-stage presentation was defined as any TGCT of stage II or stage III. Further, we used a multivariable Multinomial (polytomous) logistic regression modeling to calculate the adjusted probability for TGCT stage presentation for each insurance provider. Finally, we conducted an adjusted risk difference analysis to quantify the statistical significance difference between the adjusted probability for stage presentation. We identified 70,757 individuals with TGCT;;significant predictors of presenting with;late stage TGCT;included having non-seminoma;disease compared to seminoma (OR; 3.08, 95%CI; [2.96,3.2], p <0.01), being uninsured compared to;privately insured;(OR; 1.33, 95%CI; [1.25,1.41], p <0.01), and being on Medicaid compared to private insurance (OR; 2.09, 95%CI; [1.97,2.22], p <0.01). Significant predictors are in;Table 1. Multinomial (polytomous) logistic regression modeling adjusted probability showed that Medicaid patients are less likely to present with early stage disease than;privately;insured.(Adjusted risk difference (ARD) = -0.15 [-0.16,-0.14], p <0.01), Medicaid patients are more likely to present at stage II compared to private insurance (ARD = 0.01 [0.009,0.02], p= 0.01), and Medicaid patients are more likely to present at stage III compared to privatly;insured (ARD = 0.14 [0.12,0.15], p <0.01) (figure 1). Our results support the conclusion that U.S. patients who are uninsured, publicly insured, or have unknown insurance status are significantly more likely to present with higher-stage TGCT than privately insured patients. Further, patients insured under Medicaid appear to have the greatest disparity among all these groups. In many cases, insurance status may directly result in diagnosis delay. However, the cause of this relationship is likely multifactorial and worthy of further examination. Medicaid-insured patients may have coverage for primary care. Still, they may be less likely to receive an early diagnosis due to factors not captured in NCDB, such as lower health literacy, higher rates of low English proficiency, higher rates of discrimination, and greater difficulty scheduling appointments. Reducing these disparities would result in improved quality-of-life, reduced patient costs, and lower mortality. For both individual providers and public health organizations, it is imperative to work to ensure earlier diagnosis for these patients. [ABSTRACT FROM AUTHOR]

Radical cystectomy (RC) is associated with high rates of post-operative complications and re-admissions. Prophylactic incisional negative pressure wound therapy (iNPWT) has been adopted as part of Enhanced Recovery After Surgery (ERAS) protocol to lower the incidence of surgical wound complications. This study utilized retrospective data of patients who underwent RC at a high-volume tertiary center to assess the impact;of iNPWT for reducing the rates of wound-related complication and re-admissions. Finally, a major criticism of prophylactic iNPWT has been healthcare associated costs. We set out to estimate the cost of utilizing iNPWT in a hospital setting using previously published estimates. We retrospectively reviewed patients who underwent open RC at our institution from 2014 to 2022. We specifically excluded robotics, as we do not use iNPWT unless high risk for infection. In late 2015, we began to employ iNPWT during abdominal closure as part of our ERAS protocol. We compared 30-day and 90-day surgical site infections (SSIs), surgical site occurrences (SSOs = SSIs + seroma + superficial dehiscence), and readmissions between patients who received iNPWT and a contemporary cohort who received standard skin staple closure. We performed multivariate logistic regression to adjust for potential confounding covariates. We also used cost data from the colorectal and plastic surgery literature to estimate cost of iNPWT vs. staple closure. We identified 242 patients who received iNPWT and 55 patients with staple closure. The iNPWT group had significantly lower 30-day rates of SSI (5.8% vs 16.4%, p=0.01) and SSO (9.5% vs 23.6%, p=0.01), lower 90-day rates of SSI (7.4% vs 18.2%, p=0.02) and SSO (11.2% vs 25.5%, p=0.01). After adjusting for patient and perioperative factors, the difference in 30-day SSI and SSO rates (Table 1) and 90-day SSO rate (Table 2) remained significant. There was no significant difference in the rates of readmissions (23.7% for iNPWT vs 23.6% for standard closure, p=0.96) or SSI-specific readmissions (4.5% vs 10.9%, p=0.08) at 30 days or at 90 days (27.7% vs 25.5%, p=0.74; 6.2% vs 10.9%, p=0.23), when adjusting for covariates. Using the average difference in cost of the closures, combined with reported cost of superficial, ambulatory SSI, we estimated a 37% cost savings in regards to SSI care per patient using iNPWT. Prophylactic iNPWT is associated with reduced rates of 30-day SSI and SSO and 90-day SSO. Our analysis suggests that the direct cost of iNPWT is potentially outweighed by cost savings associated with reduced wound-related complications. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Due to imprecise clinical staging, the finding of extravesical and node-positive disease at the time of radical cystectomy (RC) for patients with clinically localized bladder cancer is not uncommon. Circulating tumor cells (CTCs) have been shown to be present in the peripheral blood of patients with metastatic urothelial carcinoma. The object of this study was to evaluate the ability of CTCs to predict extravesical disease in bladder cancer patients prior to RC. Materials and methods: Peripheral blood samples from 43 patients with bladder cancer were evaluated using the CellSearch (Veridex, LLC, Raritan, NJ) CTC assay prior to RC. The sensitivity, specificity, and positive predictive value (PPV) of CTC status in predicting extravesical disease was calculated. Receiver operating characteristic (ROC) curves were generated to quantify the ability of CTCs to predict extravesical and node-positive disease. Results: CTCs were detected in 9 (21%) patients prior to RC. The sensitivity, specificity, and PPV of CTC status in predicting extravesical disease were 27%, 88% and 78%, respectively. The accuracy of CTC status in predicting extravesical (≥pT3 or node-positive) disease for the entire cohort was 0.576. In a model incorporating preoperative hydronephrosis, CTC status did not improve the predictive accuracy for extravesical disease (0.576 vs. 0.585, P = 0.915). Conclusion: CTCs were detected in low numbers in a small percentage (21%) of patients prior to undergoing RC at our institution. CTC status was not a robust predictor of extravesical or node-positive disease in this cohort. CTC status is not likely to be a clinically useful parameter for directing therapeutic decisions in patients with ≤cT2 bladder cancer. [Copyright &y& Elsevier]

Abstract: Diagnosis of bladder cancer is primarily made based on clinical presentation and then by direct visualization with cystoscopy. Despite the massive investments recently made to identify urinary-based assays that are able to diagnosis urothelial carcinoma, urine cytology and cystoscopy still remain the gold standard. Recently proof of principle studies have shown that noninvasive urine-based metabolomics, using high pressure liquid chromatography (HPLC) and nuclear magnetic resonance (NMR), may be able to accurately diagnosis bladder cancer. This review discuses the published studies investigating metabolomics and bladder cancer and the future potential of this developing field. [Copyright &y& Elsevier]

Prostate cancer (PCa) is the most prevalent non-skin cancer and the second leading cause of death from cancer in men in the United States. Evidence suggests that smoking is associated with higher-grade PCa at diagnosis with increased overall and PCa-specific mortality. Prostate specific antigen (PSA) screening significantly decreases the risk of PCa death. Previous studies indicate smokers are less likely to adhere to guideline-concordant cancer screening. Herein, we investigate the association between smoking;and PSA screening at a national level using the U.S.-based Behavioral Risk Factor Surveillance System (BRFSS) survey. We hypothesize that smokers are less likely to undergo guideline-concordant PSA screening in comparison to non-smokers. Using the 2018 BRFSS survey cycle, we analyzed men aged between 55 and 69 who responded to the cigarette smoking and PSA screening questions. Smoking status was divided into never smoker, former smoker, and current smoker. Current smoker was further divided into daily and non-daily smokers. National PSA screening prevalence was calculated for each group. A complex weighted multivariable Poisson regression modeling adjusted for age, race, marriage status, education, income, health insurance, and having a personal doctor was then used to calculate the adjusted relative risk of undergoing PSA screening. 58,996 individuals representing a national estimate of 27.04 million responded to the smoking and PSA screening questionnaires. The overall national prevalence of PSA screening was 39% [95%CI; 39%-40%]. When categorizing by smoking status, the prevalence of PSA screening for never smokers; 42% [95%CI; 41%-44%], current smokers; 27% [95%CI; 25%-29%], and former smokers 42% [95%CI; 39%-40%] (see Table 1). Among current smokers, the prevalence was 27% [95% CI; 24%-29%] for those who smoke daily and 29% [95% CI; 24%-33%] for those who do not smoke daily. The adjusted relative risk (aRR) for undergoing PSA in comparison to those who never smoked was 0.81 for current smokers (95% CI: 0.75-0.88, P < 0.01) and 0.99 for former smokers (95% CI: 0.94-1.03, P = 0.53) (Table 2). Smokers are less likely to undergo PSA screening. Delay in diagnosis is one mechanism that could explain why smokers are more likely to present with high-grade prostate cancer at diagnosis.; Interventions to increase screening in this population may improve prostate cancer outcomes.; Further quantitative and qualitative studies are needed to further understand the phenomena to aid in developing strategies to tackle the reduced PSA screening rates in smokers. [ABSTRACT FROM AUTHOR]

Patients with Bacillus Calmette-Guerin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) are at significant risk for recurrence and progression and there is an unmet need for local, effective, bladder-preserving treatment options. Nadofaragene firadenovec, a non-replicating recombinant adenovirus vector-based gene therapy that delivers a copy of the human interferon alfa-2b gene into the bladder epithelium, is approved by the FDA for treatment of adult patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with/without papillary tumors (±Ta/T1). The Phase 3 study of nadofaragene firadenovec met its primary endpoint;;53.4% of patients with CIS±Ta/T1 achieved;complete response (CR) at three months. The 24-month follow-up results showed that nadofaragene firadenovec was well tolerated, and 36.4% of the patients with CIS±Ta/T1 who achieved a CR remained high-grade recurrence free (HGRF) at 24 months. Herein, we report 36-month follow-up results from the Phase 3 study for the CIS±Ta/T1 cohort. The open-label Phase 3 study enrolled 107 patients with BCG-unresponsive NMIBC with CIS±Ta/T1 (NCT02773849). The efficacy analysis for this cohort included 103 patients who met the protocol definition of BCG-unresponsive NMIBC. Patients received 75 mL of nadofaragene firadenovec (3×1011 viral particles/mL) once every 3 months for up to 4 doses. The protocol mandated a 5-site biopsy (dome, trigone, right and left lateral walls, posterior wall) at 12 months and patients who were HGRF were offered continued treatment once every 3 months at the investigator's discretion. Assessments beyond 24 months were performed in accordance with usual clinical practice. The study is ongoing, with a planned 5-year treatment and monitoring phase; the follow-up results reported here are based on the 36-month interim data for the CIS±Ta/T1 cohort. Mean (standard deviation) duration of follow-up for the entire cohort was 42.1 (12.6) months*, with a total of 13/107 (12.1%) patients having received 36 months of treatment.At 36 months, 14/55 (25.5%) patients who had achieved a CR at 3 months remained HGRF. For these patients, the Kaplan–Meier (KM)-estimated probability of duration of CR for at least 12, 24 and 36 months was 46.5%, 36.6% and 34.2%, respectively (Figure).In the overall CIS±Ta/T1 cohort (N=103), the KM-estimated median (95% confidence interval [CI]) duration of HGRF survival was 6.0 (3.4, 8.3) months, and probability;(95% CI) of HGRF survival for at least 12 months was 30.1% (21.5, 39.2). Two patients (1.9%) discontinued due to adverse events, while four (3.9%) experienced progression to muscle-invasive disease. The KM-estimated cystectomy-free survival (95% CI) at 36 months was 53.8% (43.3, 63.1), and the three-year overall survival was 90.4% (82.3, 94.9). Intravesical nadofaragene firadenovec, administered once every three months, demonstrated a sustained durability of response in patients with BCG-unresponsive CIS±Ta/T1 papillary disease. Nadofaragene firadenovec represents a novel treatment option for BCG-unresponsive NMIBC with a favorable benefit-to-risk ratio.*All patients had passed 36 months at data cutoff on 09 September 2021.Figure. Kaplan–Meier estimated durability of complete response in patients with CIS±Ta/T1 papillary disease. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) after radical cystectomy (RC) and pelvic lymph node dissection (PLND) represents a significant problem in terms of morbidity, mortality, and cost. Much work has already been done studying the use of extended prophylaxis (EP) to lower VTE rates, and the use of 28 days of EP with enoxaparin is considered;standard of care in many surgical guidelines. Unfortunately there are still significant barriers to adoption of this practice after RC, including patient pain, dissatisfaction, lack of insurance coverage, and costs. Apixaban has emerged as a possible alternative that may alleviate some of the issues with enoxaparin, however data comparing enoxaparin to apixaban in the RC population is limited. We have designed a pragmatic, multi-site, randomized, controlled trial of discharge on EP with apixaban vs enoxaparin to compare patient adherence, patient satisfaction, drug costs, and rates of VTE and bleeding. Inclusion criteria;are patients undergoing RC with PLND for urothelial bladder cancer (any T, N0-1, M0) at the University of Pennsylvania and Vanderbilt University Medical Center. Exclusion criteria include medical contraindication to prophylactic anticoagulation, failure to undergo RC with PLND, failure to be discharged by post-op day (POD) 14, and inability to communicate via telephone in English. Patients will be screened and enrolled pre-op, randomized prior to discharge, and contacted by phone at POD 30 and 90 for study assessments.The primary outcome is adherence, measured as the proportion of days covered (PDC). Secondary outcomes include barriers to adherence, satisfaction, cost, and VTE rates. The trial is designed as a non-inferiority study (H A : PDC of apixaban is non-inferior to that of enoxaparin) with plans to analyze for superiority (H A : PDC of apixaban is superior to that of enoxaparin) if non-inferiority is found. Target sample size is 220 participants. Results: Conclusions: [ABSTRACT FROM AUTHOR]

Purpose: To determine the association of micropapillary urothelial carcinoma (MUC) variant histology with bladder cancer outcomes after radical cystectomy.Materials and Methods: Information on MUC patients treated with radical cystectomy was obtained from five academic centers. Data on 1,497 patients were assembled in a relational database. Tumor histology was categorized as urothelial carcinoma without any histological variants (UC; n = 1,346) or MUC (n = 151). Univariable and multivariable models were used to analyze associations with recurrence-free (RFS) and overall (OS) survival.Results: Median follow-up was 10.0 and 7.8 years for the UC and MUC groups, respectively. No significant differences were noted between UC and MUC groups with regard to age, gender, clinical disease stage, and administration of neoadjuvant and adjuvant chemotherapy (all, P ≥ 0.10). When compared with UC, presence of MUC was associated with higher pathologic stage (organ-confined, 60% vs. 27%; extravesical, 18% vs. 23%; node-positive, 22% vs. 50%; P < 0.01) and lymphovascular invasion (29% vs. 58%; P < 0.01) at cystectomy. In comparison with UC, MUC patients had poorer 5-year RFS (70% vs. 44%; P < 0.01) and OS (61% vs. 38%; P < 0.01). However, on multivariable analysis, tumor histology was not independently associated with the risks of recurrence (P = 0.27) or mortality (P = 0.12).Conclusions: This multi-institutional analysis demonstrated that the presence of MUC was associated with locally advanced disease at radical cystectomy. However, clinical outcomes were comparable to those with pure UC after controlling for standard clinicopathologic predictors. [ABSTRACT FROM AUTHOR]

Introduction: Blue light cystoscopy (BLC) using hexaminolevulinate (HAL/Cysview/Hexvix) has been previously shown to improve detection of non-muscle-invasive bladder cancer (NMIBC). Herein, we evaluated the detection of malignant lesions in a heterogenous group of patients in the real world setting and documented the change in risk category due to upstaging or upgrading.Methods: Prospective enrollment during April 2014 to December 2016 of consecutive adult patients with suspected or known non-muscle-invasive bladder cancer based on prior cystoscopy or imaging, undergoing transurethral resection of bladder tumor at 9 different referral medical centers. HAL was instilled in the bladder for 1 to 3 hours before evacuation and inspection. Sensitivity and specificity of BLC, white light cystoscopy (WLC), and the combination of both BLC and WLC for detection of any malignancy was reported on final pathology. Number of patients with a change in American Urological Association (AUA) risk category based on BLC findings leading to a possible change in management and adverse events were recorded.Results: Overall, 1,632 separate samples from bladder resection or biopsy were identified from 641 BLC procedures on 533 patients: 85 (16%) underwent repeat BLC (range: 2-5). Sensitivity of WLC, BLC, and the combination for diagnosis of any malignant lesion was 76%, 91%, and 98.5%, respectively. Addition of BLC to standard WLC increased detection rate by 12% for any papillary lesion and 43% for carcinoma in-situ. Within the WLC negative group, an additional 206 lesions in 133 (25%) patients were detected exclusively with BLC. In multifocal disease, BLC resulted in AUA risk-group migration occurred in 33 (6%) patients and a change in recommended management in 74 (14%). False-positive rate was 25% for WLC and 30% for BLC. One mild dermatologic hypersensitivity reaction (0.2%).Conclusions: BLC increases detection rates of carcinoma in-situ and papillary lesions over WLC alone and can change management in 14% of cases. Repeat use of HAL for BLC is safe. [ABSTRACT FROM AUTHOR]

Background: The time of cancer diagnosis is a major event during which quality of life (QOL) can be affected and represents a crucial time to identify patients at high risk of decline. We sought to compare the differential effects of the diagnosis of 3 major urologic malignancies on QOL.Methods: The Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey database was queried for patients who completed a QOL questionnaire (SF-36 or VR-12) before and after a diagnosis of bladder, kidney, or prostate cancer. Primary outcome measures were the mental component summary (MCS), and physical component summary (PCS) scores. Mixed effects linear regression was performed with cancer diagnosis as the primary variable of interest, with race and cardiovascular comorbidity status included as potentially confounding independent variables.Results: There were 3,258 patients with urologic cancers. Both MCS and PCS scores dropped after diagnosis in all disease states. Bladder and kidney cancer patients demonstrated the greatest decline in MCS score (-1.762 points, 95% CI-2.571 to -0.952, P < 0.001) and PCS score (-3.769 points, 95% CI-5.042 to -2.496, P < 0.001), respectively, after adjustment for potential confounders. By contrast, prostate cancer patients demonstrated the smallest decline in both domains. Race and cardiovascular comorbidity status were independently associated with QOL, with an association 2 to 3 times greater than that of cancer diagnosis.Conclusions: Diagnosis of a urologic cancer was associated with a decline in patient-reported QOL, particularly in those with bladder or kidney cancer. Changes in physical health were more prominent than in mental health. Race and cardiovascular comorbidity status influenced QOL domains to a greater extent than specific urologic cancer diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: The therapeutic benefit of intravesical instillation of hexaminolevulinate (HAL) at the time of transurethral resection of bladder tumor (TURBT) has been demonstrated in multiple studies. The purpose of this study was to prospectively assess the safety of repeated administration of HAL from a phase III pre-trial planned analysis.Materials and Methods: All patients evaluated in the study received at least 1 dose of HAL at the time of office cystoscopy, and a subset of these patients (n = 103, 33.2%) received a second dose a few weeks later at the time of TURBT. Adverse events (AEs) were recorded, and the safety of repeat use of HAL was determined by comparing the proportion of patients with AEs considered causally related to HAL in the surveillance examination compared to the OR examination. Association between categorical variables was tested using Fisher's Exact Test, and a P < 0.05 was considered statistically significant.Results: HAL-related AEs were experienced by 6 patients (2.2%) during surveillance cystoscopy and 3 patients (3.4%) following TURBT (P = 0.76); 181 patients (59.5%) had prior exposure to HAL before enrolling in the study with no difference in the number of AEs when comparing prior exposure to HAL to no prior exposure (P = 0.76). Of the patients who previously received intravesical therapy, 8 (2.9%) had at least 1 AE during surveillance compared to 3 (9.7%) who had no prior intravesical therapy (P = 0.09).Conclusions: Repeat use of HAL is safe even when administered within a few weeks of receiving a dose of intravesical therapy. [ABSTRACT FROM AUTHOR]

Purpose: To better define surrogate endpoints for neoadjuvant chemotherapy (NAC) trials in patients with muscle-invasive bladder cancer. We compared survival in patients with carcinoma in-situ (CIS) only vs. complete response following NAC and radical cystectomy (RC).Materials and Methods: Patients with cT2-4N0M0 disease treated with NAC and RC between 2001 and 2018 were stratified by response: complete response (CR, pT0N0), partial response (PR, pTaN0, pT1N0+/-CIS), CIS-only (pTisN0), stable disease (SD, pT2N0), or progressive disease (PD, >pT2N0). Primary endpoints were overall survival (OS) and risk of recurrence in patients with CIS-only vs. CR. Multivariable Cox proportional hazards regression model was used for OS and a competing risks proportional hazards model was used for risk of recurrence.Results: Of 1,406 patients in our institution cohort, 340 patients met inclusion criteria. Kaplan-Meier mean estimates of OS for CR and CIS-only were 108.9 months (95% CI 89.7-127.9) and 125.8 months (95% CI 112.3-139.3), respectively (P = 0.13). Cox proportional hazards model found no difference in OS between patients with PR (HR 1.06, 95% CI 0.33-2.58, P = 0.897) or CIS-only (HR 0.422, 95% CI 0.15-1.18, P = 0.101) when compared to CR. The risk of recurrence was similar between patients with CIS-only (HR 0.73, 95% 0.29-1.84, P = 0.49) and PR (HR 1.32, 95% CI 0.54-3.29, P = 0.54) when compared to CR on competing risks analysis.Conclusions: Residual CIS-only after NAC and RC demonstrated similar survival outcomes when compared to patients with pathologic CR. Further study in large multi-institutional cohorts may further validate CIS-only as an additional surrogate endpoint after NAC and may inform future trials. [ABSTRACT FROM AUTHOR]

Abstract: Objective: With the increased diagnosis of low grade, low volume, potentially non-lethal disease, active surveillance (AS) has become an increasingly popular alternative for select men with low-risk prostate cancer. The absence of precise clinical staging modalities currently makes it difficult to predict which patients are most appropriate for AS. The goal of our study was to evaluate the ability of endorectal MRI (eMRI) to predict adverse pathologic features in patients who would otherwise qualify for an AS program. Materials and methods: We retrospectively reviewed our institution''s radical prostatectomy (RP) database from 1991 to 2007 and identified 172 patients who would have qualified for AS and underwent preoperative staging eMRI with T2-weighted (T2W) sequences. MRI findings were correlated to final pathology in order to assess the ability of staging eMRI to predict adverse pathologic features in patients suitable for AS. Results: The mean age of our cohort was 59.8 ± 6.2 years. The mean PSA at the time of diagnosis was 5.2 ± 2.2 ng/ml. In 51% of patients, no discrete tumor was visualized on eMRI and in 49% of patients a discrete tumor was detected. At the time of RP, Gleason score upgrading, extracapsular extension, and a positive surgical margin occurred in 17%, 6%, and 5% of cases, respectively. Patients with documented tumor on eMRI did not have an increased incidence of adverse pathologic findings with regard to tumor volume (P = 0.31), extra-capsular extension (P = 0.82), Gleason upgrading (P = 0.92), seminal vesicle invasion (P = 0.97), or positive surgical margin rate (P = 0.95) compared with those in whom no tumor was seen. Conclusion: Discrete tumor identification on eMRI is not predictive of adverse pathologic features in patients who would otherwise qualify for AS. eMRI likely does not provide additional information when prospectively evaluating patients for AS protocols. [Copyright &y& Elsevier]

Introduction: Repeat BCG induction remains an option for select non-muscle invasive bladder cancer (NMIBC) patients who fail initial therapy. Alternative salvage intravesical regimens such as Gemcitabine and Docetaxel (Gem/Doce) have been investigated. We aimed to compare the efficacy BCG plus interferon a-2b (BCG/IFN) and Gem/Doce in patients with recurrent NMIBC after a single prior BCG course.Methods: The National Phase II BCG/IFN trial database and multi-institutional Gem/Doce database were queried for patients with recurrent NMIBC after one prior BCG induction course, excluding those with BCG unresponsive disease. Stabilized inverse probability treatment weighted survival curves were estimated using the Kaplan-Meier method and compared. Propensity scores were derived from a logistic regression model. The primary outcome was recurrence free survival (RFS); secondary outcomes were high-grade (HG) RFS and risk factors for treatment failure.Results: We identified 197 BCG/IFN and 93 Gem/Doce patients who met study criteria. Patients receiving Gem/Doce were older and more likely to have HG disease, CIS, and persistent disease following induction BCG (all P < 0.01). After propensity score-based weighting, the adjusted 1- and 2-year RFS was 61% and 53% after BCG/IFN versus 68% and 46% after Gem/Doce (P = 0.95). Adjusted 1- and 2-year HG-RFS was 60% and 51% after BCG/IFN versus 63% and 42% after Gem/Doce (P = 0.68). Multivariable Cox regression revealed that Gem/Doce treatment was not associated with an increased risk of failure (HR = 0.97, P = 0.89) as compared to BCG/IFN.Conclusion: Patients with recurrent NMIBC after a single induction BCG failure and not deemed BCG unresponsive had similar oncologic outcomes with Gem/Doce and BCG/IFN in a post-hoc analysis. Additional prospective studies are needed. [ABSTRACT FROM AUTHOR]

Purpose: Metastatic recurrence occurs in over 25% of upper tract urothelial carcinoma patients treated with radical nephroureterectomy. While metastatic recurrence suggests poor prognosis, the impact of the specific site of recurrence on prognosis is not well documented.Materials and Methods: We retrospectively analyzed 188 patients who underwent radical nephroureterectomy for high-grade, node-negative upper tract urothelial carcinoma at our institution from 2003 to 2018 without receiving neoadjuvant or adjuvant chemotherapy. Competing-risks survival analysis was performed to evaluate the cumulative incidence and predictors of metastatic recurrence. The Kaplan-Meier method and log-rank test were used to estimate and compare recurrence site-specific survival probabilities following metastatic recurrence. Cox regression analyses were performed to assess site-specific prognoses.Results: Of the 188 patients, 47 (25%) developed metastatic recurrence over a median follow-up of 30 months (interquartile range: 10.5-58.5 months). The 1- and 2-year cumulative incidences of metastatic recurrence were 13.6% and 23.6%, respectively. On multivariable analysis, lymphovascular invasion was significantly predictive of metastatic recurrence (subhazard ratio: 2.6, P = 0.01). Of the 47 patients who developed recurrence, 38 (80.9%) died over a median follow-up of 10 months (interquartile range: 5-20 months). Metastatic recurrence was most common in the lungs (n= 13, 28%) and at multiple sites (n= 14, 30%). Median time to recurrence was shorter for recurrences at multiple sites (6.5 months) and those in the liver (13 months) and bone (18 months) compared to other sites. Patients who recurred in the liver (hazard ratio: 6.3, P = 0.007), bone (hazard ratio: 4.9, P = 0.02), and multiple sites (hazard ratio: 4.6, P = 0.01) had significantly worse prognosis compared to those who recurred in lymph nodes. Statistical significance persisted after adjusting for treatment with salvage therapy.Conclusions: A significant proportion of high-grade upper tract urothelial carcinoma patients recur systemically after radical nephroureterectomy. Lymphovascular invasion is a predictor of metastatic recurrence and may inform decisions regarding perioperative chemotherapy. Hepatic and osseous recurrences have relatively quicker onset and less favorable prognosis compared to other sites. These findings may benefit future efforts to develop recurrence site-specific treatment plans and highlight the necessity of subsequent endeavors to explore the genetic associations of recurrence in upper tract urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: To report our experience with sequential maintenance intravesical gemcitabine/docetaxel (GEM/DOCE) for patients with nonmuscle-invasive bladder cancer.Materials and Methods: Fifty-nine patients who received full GEM/DOCE for nonmuscle-invasive bladder cancer between 2013 and 2018, per the protocol adapted from University of Iowa, were identified and characterized. Patients were treated with 6 weekly instillations of GEM/DOCE and subsequent monthly maintenance installations for those with no evidence of disease at the first surveillance. Student's t test and χ2 test were used to compare continuous and categorical variables as appropriate. For survival analyses, Kaplan-Meier (KM) curves were created to assess disease-free survival (DFS). Overall comparisons of KM survival analysis were conducted using the Wilcoxon test.Results: Among all patients, median follow-up was 24 months. Sixty-six percent of patients received ≥2 intravesical induction therapies prior to receiving GEM/DOCE. Thirty-one patients (63%) failed ≥2 induction courses of Bacillus Calmette-Guérin (BCG) before receiving GEM/DOCE. Overall DFS was 49% at 1 year and 29% at 2 years. For patients who failed ≥1 induction courses of BCG, overall DFS was 48% at 1 year and 32% at 2 years. GEM/DOCE appears to be effective for therapy naïve and patients who have failed previous intravesical therapies (P = 0.39). There were 41 (69.5%) patients who had no evidence of disease at the first surveillance and were eligible for maintenance therapy. Among these patients, 24 were managed with observation alone and 17 with monthly maintenance. Median follow-up for observed patients was 36 months and 26 months for patients with maintenance. DFS at 1 year was 42% for observed patients and 81% for patients receiving maintenance (P = 0.04). DFS at 2 years was 32% for observed patients and 59% for patients receiving maintenance therapy (P = 0.45). For maintenance eligible patients who received ≥1 induction courses of BCG, DFS was 42% for observed patients and 81% for patients receiving maintenance therapy at 1 year and 34% for observed patients and 59% for patients receiving maintenance therapy at 2 years. Pathologic stage at recurrence was similar between observed patients and those receiving maintenance (P = 0.83). KM analyses showed greater DFS for patients receiving maintenance therapy compared to observed patients (P = 0.04).Conclusion: Patients who demonstrate initial complete response to GEM/DOCE may benefit from maintenance GEM/DOCE. [ABSTRACT FROM AUTHOR]

Purpose: According to the 2016 American Urological Association (AUA) guidelines for nonmuscle invasive bladder cancer (NMIBC), clinicians should offer a 2nd intravesical induction course of Bacillus Calmette-Guérin (BCG) to patients with persistent or recurrent Ta or CIS disease after a 1st BCG induction course. However, evidence for a 2nd course is limited, and some patients forego a 2nd induction of BCG in favor of a clinical trial or alternate intravesical therapy. We sought to investigate contemporary oncologic outcomes of a 2nd induction course of BCG in a multi-institutional cohort.Materials and Methods: Three hundred fifty-three patients who received full induction BCG for NMIBC since 2001 at 2 institutions were identified. Patients were categorized as receiving primary 6-week induction therapy or subsequent 2nd 6-week induction therapy for patients who recurred or persisted. The baseline differences in demographic and tumor characteristics were compared between the 2 groups, and Kaplan-Meier curves were constructed to assess high-grade recurrence free survival (HgRFS) among both groups. Univariable logistic regression was used to determine factors associated with recurrence after 2nd course BCG RESULTS: A total of 353 patients received 1st induction BCG (BCG1) and 116 patients received a 2nd induction course (BCG2). Maintenance therapy was given to 117 (33.1%) patients after BCG1 and 43 (37.1%) patients after BCG2. Both cohorts were similar in demographics including age, sex, and race. Pathologic stage before treatment differed as BCG1 patients were more likely to have T1 (40.8% vs. 25%) and less likely to have CIS (13.9% vs. 33.6%) (P < 0.001). Complete response (CR) 3 months after BCG1 was observed in 276 patients (78.2%) and 104 patients (89.7%) after BCG2. Responses remained durable, with 36-month CR of 54.7% in BCG1 and 65.6% in BCG2. Progression to MIBC was identified in 1.4% of BCG1 patients vs. 3.4% in BCG2 patients (P = 0.17). Pathologic stage before BCG2 does not predict progression to MIBC (P = 0.21) after BCG2. The time interval between the 1st and 2nd induction of BCG was not significantly associated with response to 2nd induction BCG (P = 0.47). Maintenance therapy after BCG2 was associated with decreased recurrence after 2nd induction course of BCG.Conclusion: A 2nd course of BCG is efficacious with a durable HgRFS, validating the recommendations of the 2016 AUA guidelines. [ABSTRACT FROM AUTHOR]

Objective: We ex vivo cultured primary tumor cells from N-methyl-N-nitrosourea (MNU)-induced bladder tumors in rats and established an immortalized cell line from them.Materials and Methods: Bladder tumors in rats were induced by instillation of MNU into the murine bladder. Primary tumor cells were prepared by the cancer-tissue originated spheroid method. An immortalized cell line was established by co-culture with fibroblasts. The cultured tumor cells were molecularly and functionally characterized by quantitative real-time polymerase chain reaction, Western blot, growth assay, and transwell migration assay.Results: Primary tumor cells were successfully prepared as multicellular spheroids from MNU-induced bladder tumors. The differentiation marker expression patterns observed in the original tumors were largely retained in the spheroids. We succeeded in establishing a cell line from the spheroids and named it T-MNU-1. Although basal markers (CK14 and CK5) were enriched in T-MNU-1 compared to the spheroids, T-MNU-1 expressed both luminal and basal markers. T-MNU-1 was able to migrate through a transwell.Conclusions: Tumor cells in MNU-induced bladder tumors were successfully cultured ex vivo as organoids, and an immortalized cell line was also established from them. The ex vivo models offer a platform that enables analysis of intrinsic characteristics of tumor cells excluding influence of microenvironment in MNU-induced bladder tumors. [ABSTRACT FROM AUTHOR]

Background: Patients with bladder cancer undergoing radical cystectomy (RC) experience high rates of perioperative blood transfusions (PBTs) and morbidity. The aim of this study was to evaluate the effect of blood storage duration on the risk of adverse perioperative outcomes in this high-risk patient population.Materials and Methods: In a retrospective review of RC patients from 2010 to 2014 who received PBTs, the average storage duration for all units transfused was used to classify patients as receiving older blood using 3 different definitions (≥21 days,≥28 days, and≥35 days). Multivariable Poisson regression models were used to determine the adjusted relative risk of perioperative infections and overall morbidity in those given older blood compared to fresher blood.Results: Of the 451 patients undergoing RC, 205 (45%) received nonirradiated PBTs. In multivariable modeling, increasing average blood storage duration, as a continuous variable, was associated with an increased risk of infections (risk ratio [RR] = 1.08 per day, 95% CI: 1.01-1.17) and overall morbidity (RR = 1.08 per day, 95% CI: 1.01-1.15). Furthermore, ≥28-day blood storage (vs.<28) was associated with increased infections (RR = 2.69, 95% CI: 1.18-6.14) and morbidity (RR = 2.54, 95% CI: 1.31-4.95), and ≥35-day blood storage (vs.<35) was also associated with increased infections (RR = 2.83, 95% CI: 1.42-5.66) and morbidity (RR = 3.35, 95% CI: 1.95-5.77).Conclusions: Although blood is stored up to 42 days, storage≥28 days may expose RC patients to increased perioperative infections and overall morbidity compared with storage<28 days. Prospective cohort studies are warranted in cystectomy and other high-risk surgical oncology patients to better determine the effect of blood storage duration. [ABSTRACT FROM AUTHOR]

Purpose: We estimated the proportion of patients who received neoadjuvant chemotherapy for muscle-invasive bladder cancer whose tumors were downstaged by transurethral resection.Materials and Methods: We identified patients with cT2 N0 urothelial carcinoma who underwent cystectomy at our institution from 2005 to 2014-overall, 139 underwent transurethral resection without chemotherapy, and 146 underwent transurethral resection with chemotherapy. Pathologic response was defined asResults: Neoadjuvant patients were younger than nonneoadjuvant patients (64.4 vs. 71.4 years, P<0.01), with higher median body mass index (28.4 vs. 26.6kg/m2, P<0.01), lower prevalence of Charlson score≥3 (13.7% vs. 30.2%, P<0.01), and lower prevalence of prior non-muscle-invasive cancer (7.5% vs. 20.9%, P<0.01). More neoadjuvant patients achieved response compared with nonneoadjuvant patients (62.3% vs. 20.1%, RR = 3.10, P<0.01). Adjustment resulted in a RR of pathologic response in neoadjuvant vs. nonneoadjuvant patients of 2.60 (95% CI: 1.81-3.74, P<0.01). This adjusted RR indicates that among patients who receive neoadjuvant chemotherapy and undergo transurethral resection, 38% (95% CI: 27%-55%) of pathologic response can be attributed to transurethral resection.Conclusions: We estimate that in a cohort of patients who receive chemotherapy and undergo transurethral resection before cystectomy, 38% of pathologic response can be attributed to transurethral resection. Understanding who responds to chemotherapy and who responds to transurethral resection is needed to measure the effectiveness of both interventions. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to characterize the contemporary trends in lymphadenectomy for the treatment of upper tract urothelial carcinoma in a population-based cohort and to determine if number of lymph nodes removed and tumor location are predictors of cancer-specific survival in patients undergoing nephroureterectomy.Materials and Methods: Individuals with upper tract urothelial carcinoma undergoing nephroureterectomy in the Surveillance, Epidemiology, and End Results program from 2004 to 2012 were identified. Linear regression was used to assess trends in lymphadenectomy. Patients were stratified based on nodal status, quartiles of nodes removed, and tumor location. Kaplan-Meier analysis, log-rank tests, and Cox proportional hazards models were used to compare cancer-specific survival and overall survival among groups.Results: In the cohort, 25% (721/2,862) of all patients and 27% (566/2,079) of grade 3/4 patients underwent lymphadenectomy. The percentage of patients undergoing lymphadenectomy increased from 20% (60/295) in 2004 to 33% (106/320) in 2012 (P = 0.02). Patients with the highest quartile of lymph nodes removed had improved the 5-year cancer-specific survival of 78% (95% CI: 69%-85%) compared to the second quartile (60%; 95% CI: 51%-67%; P = 0.003) and the third quartile (60%; 95% CI: 51%-68%; P = 0.002) of nodes removed. This trend held for node-negative and node-positive patients. In multivariable modeling, a lower number of lymph nodes dissected (hazard ratio = 0.94, 95% CI: 0.91-0.98) and ureteral tumors (hazard ratio = 1.29, 95% CI: 1.07-1.56) were predictors of worse cancer-specific survival.Conclusions: In patients with upper tract urothelial carcinoma undergoing nephroureterectomy, rates of lymphadenectomy have increased from 2004 to 2012 in the United States. In this contemporary cohort, an increase in the number of nodes removed and renal pelvis tumors are associated with improved cancer-specific survival, which highlights the importance of intentional lymph node dissection with adequate lymph node yield in these patients. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to determine the accuracy of urethral frozen section (FS) by analyzing our clinical experience.Materials and Methods: A total of 298 patients undergoing radical cystectomy for bladder cancer with benign or malignant urethral FS were identified between 2000 and 2012. Urethral FS were compared with rereviewed FS to calculate the positive and negative predictive values of the FS. To assess the ability of the positive FS to be cleared with further sampling/resection, FS were then compared with the final urethral margin. The cases of positive urethral FS were then specifically analyzed to assess rates of urethral recurrence and survival.Results: All negative FS were confirmed to be negative on FS rereview and on final pathology, resulting in a NPV of 100%. Urethral FS were positive in 28 (8.7%) patients, of whom 2 (7%) were negative on FS rereview, yielding a positive predictive value of 93%. Both false positives were because of contamination of detached cancer from the bladder being present in the FS. After additional sampling/resection, the final margin was negative in 13 (46%) patients.Conclusions: A negative urethral FS reliably identifies individuals for whom urethrectomy is unnecessary and provides robust information for decision-making regarding the safety of orthotopic reconstruction. Nearly half of the patients with a positive FS were ultimately determined to have a negative final margin. Accordingly, we recommend that surgeons and pathologists discuss positive FS findings at the time of surgery and consider whether additional tissue should be analyzed in real time. [ABSTRACT FROM AUTHOR]

Objective: To investigate the modified frailty index (mFI) as a preoperative predictor of postoperative complications following radical cystectomy (RC) in patients with bladder cancer.Materials and Methods: Patients undergoing RC were identified from the National Surgical Quality Improvement Program participant use files (2011-2013). The mFI was defined in prior studies with 11 variables based on mapping the Canadian Study of Health and Aging Frailty Index to the National Surgical Quality Improvement Program comorbidities and activities of daily livings. The mFI groups were determined by the number of risk factors per patient (0, 1, 2, and≥3). Univariable and multivariable regression were performed to determine predictors of Clavien 4 and 5 complications, and a sensitivity analysis was performed to determine the mFI value that would be a significant predictor of Clavien 4 and 5 complications.Results: Of the 2,679 cystectomy patients identified, 843 (31%) of patients had an mFI of 0, 1176 (44%) had an mFI of 1, 555 (21%) had an mFI of 2, and 105 (4%) had an mFI≥3. Overall, 1585 (59%) of patients experienced a Clavien complication. When stratified at a cutoff of mFI≥2, the overall complication rate was not different (61.7% vs. 58.3%, P = 0.1), but the mFI2 or greater group had a significantly higher rate of Clavien grade 4 or 5 complications (14.6% vs. 8.3%, P<0.001) and overall mortality rate (3.5% vs. 1.8%, P = 0.01) in the 30-day postoperative period. The multivariate logistic regression model showed independent predictors of Clavien grade 4 or 5 complications were age>80 years (odds ratio [OR] = 1.58 [1.11-2.27]), mFI2 (OR = 1.84 [1.28-2.64]), and mFI3 (OR = 2.58 [1.47-4.55]).Conclusions: Among patients undergoing RC, the mFI can identify those patients at greatest risk for severe complications and mortality. Given that bladder cancer is increasing in prevalence particularly among the elderly, preoperative risk stratification is crucial to inform decision-making about surgical candidacy. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively validate and compare a modified frailty index predicting adverse outcomes and other risk stratification tools among patients undergoing urologic oncological surgeries.Materials and Methods: The American College of Surgeons National Surgical Quality Improvement Program was queried from 2005 to 2013 to identify patients undergoing cystectomy, prostatectomy, nephrectomy, and nephroureterectomy. Using the Canadian Study of Health and Aging Frailty Index, 11 variables were matched to the database; 4 were also added because of their relevance in oncology patients. The incidence of mortality, Clavien-Dindo IV complications, and adverse events were assessed with patients grouped according to their modified frailty index score.Results: We identified 41,681 patients who were undergoing surgery for presumed urologic malignancy. Patients with a high frailty index score of >0.20 had a 3.70 odds of a Clavien-Dindo IV event (CI: 2.865-4.788, P<0.0005) and a 5.95 odds of 30-day mortality (CI: 3.72-9.51, P<0.0005) in comparison with nonfrail patients after adjusting for race, sex, age, smoking history, and procedure. Using C-statistics to compare the sensitivity and specificity of the predictive ability of different models per risk stratification tool and the Akaike information criteria to assess for the fit of the models with the data, the modified frailty index was comparable or superior to the Charlson comorbidity index but inferior to the American Society of Anesthesiologists Risk Class in predicting 30-day mortality or Clavien-Dindo IV events. When the modified frailty index was augmented with the American Society of Anesthesiologists Risk Class, the new index was superior in all aspects in comparison to other risk stratification tools.Conclusion: Existing risk stratification tools may be improved by incorporating variables in our 15-point modified frailty index as well as other factors such as walking speed, exhaustion, and sarcopenia to fully assess frailty. This is relevant in diseases such as kidney and prostate cancer, where surveillance and other nonsurgical interventions exist as alternatives to a potentially complicated surgery. In these scenarios, our modified frailty index augmented by the American Society of Anesthesiologists Risk Class may help inform which patients have increased surgical complications that may outweigh the benefit of surgery although this index needs prospective validation. [ABSTRACT FROM AUTHOR]

Purpose To evaluate gemcitabine-cisplatin (GC) neoadjuvant cisplatin-based chemotherapy (NAC) for pathologic response (pR) and cancer-specific outcomes following radical cystectomy (RC) for muscle-invasive bladder cancer and identify clinical parameters associated with pR. Materials and methods We studied 150 consecutive cases of muscle-invasive bladder cancer that received GC NAC followed by open RC (2000–2013). A cohort of 121 patients treated by RC alone was used for comparison. Pathologic response and cancer-specific survival (CSS) were compared. We created the Johns Hopkins Hospital Dose Index to characterize chemotherapeutic dosing regimens and accurately assess sufficient neoadjuvant dosing regarding patient tolerance. Results No significant difference was noted in 5-year CSS between GC NAC (58%) and non-NAC cohorts (61%). The median follow-up was 19.6 months (GC NAC) and 106.5 months (non-NAC). Patients with residual non–muscle-invasive disease after GC NAC exhibit similar 5-year CSS relative to patients with no residual carcinoma ( P = 0.99). NAC pR (≤pT1) demonstrated improved 5-year CSS rates (90.6% vs. 27.1%, P <0.01) and decreased nodal positivity rates (0% vs. 41.3%, P <0.01) when compared with nonresponders (≥pT2). Clinicopathologic outcomes were inferior in NAC pathologic nonresponders when compared with the entire RC-only–treated cohort. A lower pathologic nonresponder rate was seen in patients tolerating sufficient dosing of NAC as stratified by the Johns Hopkins Hospital Dose Index ( P = 0.049), congruent with the National Comprehensive Cancer Network guidelines. A multivariate classification tree model demonstrated 60 years of age or younger and clinical stage cT2 as significant of NAC response ( P < 0.05). Conclusions Pathologic nonresponders fare worse than patients proceeding directly to RC alone do. Multiple predictive models incorporating clinical, histopathologic, and molecular features are currently being developed to identify patients who are most likely to benefit from GC NAC. [ABSTRACT FROM AUTHOR]

Abstract: Background: Partial cystectomy (PC) is a therapeutic option for select patients with bladder cancer, but its associated perioperative risks and costs are unknown. We estimated annual rates of PC in a nationally representative sample of hospitals, and analyzed whether hospital volume affects postoperative outcomes and costs in patients undergoing PC. Methods: From the Nationwide Inpatient Sample, we selected a weighted cohort of patients with bladder cancer who underwent PC between 2002 and 2008. Differences in length of stay, charges, and clinical outcomes were calculated based on operative volume, and univariate and multivariate regression models were fitted to predict in-hospital mortality (IHM) and hospital-acquired conditions. Results: A total of 10,780 patients with bladder cancer who underwent PC were identified with an annual rate between 1457 and 1628 cases. IHM rates were 1.8%, constituting 195 patients (between 9 and 46 annually). A total of 417 patients (3.9%) experienced a “never event” complication, which Medicare no longer reimburses. The mean annual hospital volume of patients who died was 1.7 cases/y compared with 2.4 cases/y among those without fatal complications. No cases of IHM were identified among hospitals performing at least 5 partial cystectomies/y. In a multivariate regression model increased hospital volume was independently associated with decreased mortality (odds ratio = 0.70, 95% confidence interval; 0.60–0.80). Conclusions: Approximately 1 in 25 patients undergoing PC experience a hospital-acquired complication, and nearly 1 in 50 die as a result of the operation. For each additional case a hospital performs annually, the risk of IHM decreases by 30%. [Copyright &y& Elsevier]

Objective: To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC)., Methods: Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses., Results: A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75-1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71-1.58, P = 0.77)., Conclusion: Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The neutrophil-to-lymphocyte ratio (NLR) is an attractive marker because it is derived from routine bloodwork. NLR has shown promise as a prognostic factor in muscle invasive bladder cancer (MIBC) but its value in patients receiving neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is not yet established. Since NLR is related to an oncogenic environment and poor antitumor host response, we hypothesized that a high NLR would be associated with a poor response to NAC and would remain a poor prognostic indicator in patients receiving NAC., Methods: A retrospective analysis was performed on patients with nonmetastatic MIBC (cT2-4aN0M0) who received NAC prior to RC between 2000 and 2013 at 1 of 19 centers across Europe and North America. The pre-NAC NLR was used to split patients into a low (NLR ≤ 3) and high (NLR > 3) group. Demographic and clinical parameters were compared between the groups using Student's t test, chi-squared, or Fisher's exact test. Putative risk factors for disease-specific and overall survival were analyzed using Cox regression, while predictors of response to NAC (defined as absence of MIBC in RC specimen) were investigated using logistic regression., Results: Data were available for 340 patients (199 NLR ≤ 3, 141 NLR > 3). Other than age and rate of lymphovascular invasion, demographic and pretreatment characteristics did not differ significantly. More patients in the NLR > 3 group had residual MIBC after NAC than the NLR ≤ 3 group (70.8% vs. 58.3%, P = 0.049). NLR was the only significant predictor of response (odds ratio: 0.36, P = 0.003) in logistic regression. NLR was a significant risk factor for both disease-specific (hazard ratio (HR): 2.4, P = 0.006) and overall survival (HR:1.8, P = 0.02)., Conclusion: NLR > 3 was associated with a decreased response to NAC and shorter disease-specific and overall survival. This suggests that NLR is a simple tool that can aid in MIBC risk stratification in clinical practice., (Copyright © 2019 Elsevier Inc. All rights reserved.)