Undergoing Radical Cystectomy For Bladder Cancer Research Articles

Интраоперационные осложнения радикальной цистэктомии с различными вариантами деривации мочи

To investigate the rates, types and risk factors for intraoperative complications in patients with bladder cancer undergoing radical cystectomy with various types of urinary diversions. The study comprised 257 patients, including 241 (93.8%) men and 16 (6.2%) women who underwent radical cystectomy. The mean age of the patients was 58.5 (37-81) years. The analysis included intraoperative blood loss and blood transfusion, the rates of vascular, rectum and nerve injury, and operative time as a function of type of urinary diversion and cystectomy, the type of surgery, tumor stage (pT and pN), body mass index, and the total number of radical cystectomies performed by the surgical team. Intraoperative mortality was 0.4%. Intraoperative complications were registered in 34 (13.2%) patients. The mean blood loss was 597 (100-2500) ml, mean volume of intra- and perioperative blood transfusion was 950 and 310 ml, respectively. Statistically significant predictors of intraoperative blood loss were body mass index (p=0.001), the surgeons experience (p=0.004) and the presence of lymph node metastases (N+) (p=0.033). A significant factor affecting the rate of rectal injury is a stage pT4 disease (p=0.028). Nerve injury rates did not differ statistically significantly depending on the above factors (p>0.05). Patients with locally advanced bladder cancer and high body mass index should be operated on by highly qualified surgeons performing at least 50 radical cystectomies per year.

Colony-stimulating factors detected in tumor cells and voided urine are potential prognostic markers for patients with muscle-invasive bladder cancer undergoing radical cystectomy.

BackgroundThe clinical use of macrophage colony-stimulating factor, granulocyte colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) has improved the safety of cytotoxic chemotherapy. However, the overexpression of these CSFs in cancers has been reported to be associated with a poor prognosis in various malignancies. We evaluated the potential of CSF expression as a predictor of clinical outcome in patients with muscle-invasive bladder cancer (MIBC).MethodsConsecutive patients (n=58) with MIBC who underwent radical cystectomy (RC) were included in this retrospective study. Treatment-naïve tumor specimens obtained by initial transurethral resection of bladder tumors prior to RC were immunostained with antibodies against macrophage colony-stimulating factor, G-CSF, and GM-CSF. We compared the clinicopathological variables and survival between these groups. Baseline levels of CSFs in the serum and voided urine were quantified using an enzyme-linked immunosorbent assay and compared with the expression of CSFs in the tumor lesions.ResultsLow expression of GM-CSF in the tumor cells was significantly correlated with a pathological T4 category (vs T2–3; P=0.02). In univariate survival analysis, high G-CSF and low GM-CSF expression in the tumor lesion were associated with poor outcomes. Furthermore, Cox proportional regression analysis revealed that high G-CSF and low GM-CSF expression in the tumor were independent predictors of shorter recurrence-free survival, cancer-specific survival, and overall survival. The levels of CSFs in voided urine were associated with the expression of CSFs in the tumor lesions.ConclusionGM-CSF and G-CSF expression in the tumor lesions obtained by initial transurethral resection are independent predictors of poor outcome in MIBC after RC. Levels of G-CSF and GM-CSF in urine before treatment could be useful in prognostication.

Patient-Reported Outcomes Are Associated With Enhanced Recovery Status in Patients With Bladder Cancer Undergoing Radical Cystectomy.

Bladder cancer is a disease of the elderly that is associated with high morbidity in those treated with radical cystectomy. In this observational study of patients with bladder cancer undergoing radical cystectomy, we analyzed and compared patient-reported outcomes from those treated with Enhanced Recovery After Surgery (ERAS) methods versus those who received traditional perioperative care. We enrolled patients who underwent radical cystectomy at a high-volume tertiary care referral center from November 2013 to December 2016, when the ERAS concept was being introduced into postoperative care at our institution. Patients reported symptom outcomes using the MD Anderson Symptom Inventory preoperatively and on postoperative days 1 to 5. Mann-Whitney U tests were used to compare symptom burden between the ERAS and traditional-care groups. General linear mixed-effects models were used for longitudinal data; linear regression models were used for multivariable analysis. Patients (N = 383) reported dry mouth, disturbed sleep, drowsiness, fatigue, pain, and lack of appetite as the most severe symptoms. Compared with the traditional-care group, the ERAS group had significantly less pain (est. = -0.98, P = .005), drowsiness (est. = -0.91, P = .009), dry mouth (est. = -1.21, P = .002), disturbed sleep (est. = -0.97, P = .01), and interference with functioning (est. = -0.70, P = .022) (adjusted for age, sex, surgical technique, and neoadjuvant chemotherapy status). These results suggest that ERAS practice significantly reduced immediate postoperative symptom burden in bladder cancer patients recovering from radical cystectomy, supporting the use of patient-reported symptom burden as an outcome measure in perioperative care.

Preoperative Incidence of Deep Venous Thrombosis in Patients With Bladder Cancer Undergoing Radical Cystectomy

To determine the preoperative incidence of subclinical lower-extremity deep vein thrombosis (DVT), as well as to evaluate the utility of preoperative DVT screening in patients with bladder cancer before undergoing radical cystectomy. Beginning in 2014, we prospectively instituted a policy of obtaining a screening lower-extremity duplex ultrasound on all patients within 7 days before undergoing radical cystectomy. We reviewed the electronic medical records of all patients at our institution who underwent radical cystectomy for bladder cancer from January 2012 through December 2015. The screened group (n = 65) underwent preoperative screening; the historical control group (n = 78) did not. Primary outcome was a lower-extremity duplex ultrasound positive screening. Secondary outcome measures included the development of symptomatic venous thromboembolism (VTE) postoperatively, and the rate and severity of complications. DVT was identified in 13.9% of patients before undergoing cystectomy. Univariate analysis demonstrated an increased risk of subclinical DVT in patients who were exposed to neoadjuvant chemotherapy (35.3% vs 5.1%, P = .008). Postoperatively, there was a nonsignificant trend of lower DVT rate in the screened group compared to historical control. Overall complication rate and severity were similar between the groups. Subclinical DVT is present in a significant number of pre-cystectomy patients, especially those exposed to neoadjuvant chemotherapy. Ultrasound screening in patients before undergoing radical cystectomy may identify opportunities for early intervention to reduce morbidity and mortality associated with perioperative DVT or venous thromboembolism in the cystectomy population.

Does the site of the orthotopic neobladder outlet matter? A prospective randomized comparative study

BackgroundTo compare the results of urethral anastomosis to a button hole and to the lowest part of the anterior suture line during orthotopic neobladder substitution. MethodsFrom January 2012 to December 2015, 87 consecutive male patients with invasive bladder cancer underwent radical cystectomy and Hautmann ileal neobladder. Patients were randomly divided into two groups; group I (44 patients), the outlet was created as a button-hole at the most dependent part of the pouch, group II (43 patients), the lowest 1 cm of the anterior suture line of the pouch was left open as an outlet. Patients were randomly assigned to either group using computer-generated random numbers (JMP, Version 12.0.1; SAS Institute, Cary, NC, USA) via a sealed envelope. The functional outcomes of both groups were compared especially at the urethro-enteric anastomosis. ResultsThere were no intraoperative complications. Early postoperative complications occurred in 9 patients (5 in group I and 4 in group II, p = 0.484). Prolonged urinary leakage persisted for 11 and 14 days in 2 patients in group I and 10 and 16 days in 2 patients in group II. Delayed postoperative complications occurred in 11 patients (5 [12.5%] in group I and 6 [15.6%] in group II) (p = 0.711). Three patients developed urethro-enteric strictures (2 in group I and 1 in group II) (p = 0.571). ConclusionThe “non-hole” technique of urethral anastomosis was not associated with a significant increase in the complication rate when compared to the commonly performed “hole” technique.

Outcomes of bladder cancer undergoing radical cystectomy: A single-institution experience

Objectives: The objective of the study is to evaluate the functional outcome and postoperative complications of patients with bladder cancer undergoing radical cystectomy. Methods: This was a prospective, single-center study conducted between January 2013 and October 2016. Patients of either sex, aged more than 18 years, diagnosed with bladder cancer and treated with radical cystectomy and urinary diversion were enrolled in this study. Demographic and clinical characteristics, therapy and functional outcome details, and details of complications were collected. Results: A total of 94 patients were enrolled in the study. Overall, the mean age was 53.11 years and 74 (78.72%) patients were male. Of the 94 patients, 61 patients underwent radical cystectomy with ileal conduit (IC) and 30 patients had orthotopic neobladder. The sigmoid diversion was done in two patients, and one patient had a continent diversion. Four patients succumbed to mortality. Two patients had a recurrence at the urethral margin in IC patients. The functional outcome was found to be better in the neobladder group compared to the IC group. Conclusion: This study provides extensive information on outcomes of bladder cancer undergoing radical cystectomy. Studer's neobladder had slightly improved outcomes than IC.

A Retrospective Study of Patients Undergoing Radical Cystectomy and Receiving Peri-Operative Naloxegol or Alvimopan: Comparison of Length of Stay.

Alvimopan is a μ-opioid receptor antagonist used in the post-operative period to decrease rates of post-operative ileus (POI) following radical cystectomy (RC) and thereby shorten length of stay (LOS). Naloxegol is a much less expensive drug of the same class that has yet to be studied for prevention of POI in the peri-operative period. The purpose of the current study is to evaluate the differences in LOS and development of POI in patients post-RC who take alvimopan versus those who take naloxegol, with the hope that drug efficacy can be evaluated against the significant difference in cost burden between the two drugs. The study population included all adult patients between 18-89 years of age with bladder cancer undergoing radical cystectomy with urostomy at University of Colorado Hospital. Those patients who received usual post-operative care as well as either alvimopan or naloxegol between September 2011 and December 2017 were selected for analysis. Patients who did not take either medication or were switched from one drug to the other were excluded from the study. A zero-truncated binomial regression analysis was used to analyze differences in length of stay in patients who received alvimopan versus those who received naloxegol. Additionally, the incidence of post-operative ileus was compared between treatment groups. 130 patients who underwent RC and received either alvimopan or naloxegol were included in the study: 75 (58%) received alvimopan and 55 (42%) received naloxegol. Baseline characteristics were similar between treatment groups. There was no significant difference in the length of stay between patients who received alvimopan and patients who received naloxegol after adjusting for age, sex, BMI, length of surgical time, or stage of disease (p = 0.41). There was no significant between the two drugs for development of POI (p = 0.85). Development of POI was significantly associated with a longer LOS (p = 0.007). The analysis showed that naloxegol was comparable to alvimopan when it came to length of hospital stay following RC. Therefore, naloxegol may be offered as a less expensive, effective alternative to alvimopan.

A systematic review of exercise and psychosocial rehabilitation interventions to improve health-related outcomes in patients with bladder cancer undergoing radical cystectomy

Objective: Summarizing the evidence on the effects of pre- and postoperative exercise and psychosocial rehabilitation interventions on patient-reported outcomes (PROs) and physical fitness in bladder cancer patients undergoing radical cystectomy. Data sources: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Web of Science and the Physiotherapy Evidence Database were searched independently by two authors from inception until 10 November 2017. Cited references of the studies and citing references retrieved via Web of Science were also checked. Review methods: Randomized controlled trials (RCTs) and non-randomized studies assessing effects of exercise and psychosocial interventions in bladder cancer patients undergoing radical cystectomy were eligible. Primary outcome measures were PROs and physical fitness. Risk of bias was assessed using the Cochrane Collaboration tool and the Newcastle–Ottawa Scale. Results: Five RCTs (three exercise and two psychosocial studies) and one non-randomized psychosocial study comprising 317 bladder cancer patients were included. Timing of the intervention was preoperative (n = 2), postoperative (n = 2) or both pre- and postoperative (n = 2). Positive effects of exercise were found for physical fitness (n = 3), some health-related quality-of-life (HRQoL) domains (n = 2), personal activities in daily living (n = 1) and muscle strength (n = 1). Psychosocial interventions showed positive effects on anxiety (n = 1), fatigue (n = 1), depression (n = 1), HRQoL (n = 1) and posttraumatic growth (n = 1). Quality assessment showed most shortcomings with sample sizes and strong heterogeneity was observed between studies. Conclusion: The evidence relating to the effects of exercise in bladder cancer is very limited and is even less for psychosocial interventions.

Cluster analysis identifies three urodynamic patterns in patients with orthotopic neobladder reconstruction.

PurposeTo classify patients with orthotopic neobladder based on urodynamic parameters using cluster analysis and to characterize the voiding function of each group.Materials and methodsFrom January 2012 to November 2015, 142 patients with bladder cancer underwent radical cystectomy and Studer neobladder reconstruction at our institute. Of the 142 patients, 103 with complete urodynamic data and information on urinary functional outcomes were included in this study. K-means clustering was performed with urodynamic parameters which included maximal cystometric capacity, residual volume, maximal flow rate, compliance, and detrusor pressure at maximum flow rate. Three groups emerged by cluster analysis. Urodynamic parameters and urinary function outcomes were compared between three groups.ResultsGroup 1 (n = 44) had ideal urodynamic parameters with a mean maximal bladder capacity of 513.3 ml and mean residual urine volume of 33.1 ml. Group 2 (n = 42) was characterized by small bladder capacity with low compliance. Patients in group 2 had higher rates of daytime incontinence and nighttime incontinence than patients in group 1. Group 3 (n = 17) was characterized by large residual urine volume with high compliance. When we examined gender differences in urodynamics and functional outcomes, residual urine volume and the rate of daytime incontinence were only marginally significant. However, females were significantly more likely to belong to group 2 or 3 (P = 0.003). In multivariate analysis to identify factors associated with group 1 which has the most ideal urodynamic pattern, age (OR 0.95, P = 0.017) and male gender (OR 7.57, P = 0.003) were identified as significant factors.ConclusionsWhile patients with ileal neobladder present with various voiding symptoms, three urodynamic patterns were identified by cluster analysis. Approximately half of patients had ideal urodynamic parameters. The other two groups were characterized by large residual urine and small capacity bladder with low compliance. Young age and male gender appear to have a favorable impact on urodynamic and voiding outcomes in patients undergoing orthotopic neobladder reconstruction.

Bcl-2 as a predictive marker of neoadjuvant chemotherapy response in patients with urothelial bladder cancer undergoing radical cystectomy

Bcl-2 as a predictive marker of neoadjuvant chemotherapy response in patients with urothelial bladder cancer undergoing radical cystectomy

Postoperative C-reactive protein concentration and clinical outcome: comparison of open cystectomy to robot-assisted laparoscopic cystectomy with extracorporeal or intracorporeal urinary diversion in a prospective study

Objective: This study aimed to compare clinical outcome and postoperative systemic inflammatory response using C-reactive protein (CRP) levels, to quantify the degree of tissue injury in open mini-laparotomy cystectomy (OMC) versus robot-assisted laparoscopic cystectomy with extracorporeal (RALC-EUD) or intracorporeal urinary diversion (RALC-IUD).Materials and methods: From September 2012 to September 2015, 309 patients diagnosed with bladder cancer underwent radical cystectomy with urinary diversion. Of these, 175 patients were eligible for the study and underwent OMC (n = 125), RALC-EUD (n = 12) or RALC-IUD (n = 38). Blood samples were obtained preoperatively and postoperatively on days 1–7. Clinical and perioperative parameters, including demographics, comorbidity, tumour stage and postoperative outcomes, were collected from medical records.Results: Age, American Society of Anesthesiologists score and Charlson score were significantly higher in OMC than in the robotic groups (p = 0.020, 0.012 and 0.008, respectively). Other demographic data showed no significant group differences. Estimated blood loss and blood transfusion volume were higher in OMC (p < 0.001) and operative time was longer in the robotic groups (p < 0.001); no difference was found between RALC groups. Postoperative CRP levels changed over time (p < 0.001) and RALC-IUD appeared to have significantly higher CRP levels on postoperative days 3–7 compared to OMC and RALC-EUD (p < 0.031), but OMC CRP levels were higher than RALC-EUD.Conclusions: In this study, robotic techniques seem less traumatic overall than open surgery, as OMC had higher postoperative CRP levels than RALC-EUD. The higher CRP levels in RALC-IUD may be more reflective of the urinary diversion technique than the true tissue trauma.

Abstract 2752: Liquid biopsy analysis of FGFR3 and PIK3CA hotspot mutations for disease surveillance in bladder cancer

Abstract Background: Disease surveillance in patients with bladder cancer is important for early diagnosis of progression and metastasis and for optimal therapeutic treatment. Experimental procedures: Droplet digital PCR (ddPCR) assays were developed and tumour DNA from two patient cohorts was screened for FGFR3 and PIK3CA hotspot mutations. One cohort (NMIBC cohort) included 363 patients with non-muscle invasive bladder cancer (NMIBC). Another cohort (Cx cohort) included 468 patients with bladder cancer undergoing radical cystectomy. Urine supernatants (NMIBC cohort: n=216, Cx cohort: n=27) and plasma samples (NMIBC cohort: n=39, Cx cohort: n=27) from patients harbouring mutations were subsequently screened using ddPCR assays. Liquid biopsies were collected from 2003-2015 with up to 11.3 years of follow-up for the NMIBC cohort and from 1995-2009 with up to 13.5 years of follow-up for the Cx cohort. Results and limitations: In total, 36% of the patients in the NMIBC cohort (129/363) and 11% of the patients in the Cx cohort (44/403) harboured at least one hotspot mutation in FGFR3 or PIK3CA. Screening of DNA from serial urine supernatants from the NMIBC cohort showed high levels of tumour DNA (tDNA) to be significantly associated with later disease progression (p=0.003). Furthermore, high levels of tDNA in preoperative urine supernatants and plasma samples were associated with recurrence in the Cx cohort (p=0.068 and p=0.016 respectively). A positive correlation between the levels of tDNA in urine and plasma was observed (corr.=0.6). The retrospective study design and the low volumes of plasma available for analysis were limitations of the study. Conclusions: Increased levels of FGFR3 and PIK3CA mutated DNA in urine and plasma is indicative of later progression and metastasis in bladder cancer. Citation Format: Emil Christensen, Karin Birkenkamp-Demtröder, Iver Nordentoft, Søren Høyer, Kirstin Van Der Keur, Kim Van Kessel, Ellen Zwarthoff, Mads Agerbæk, Torben Falck Ørntoft, Jørgen Bjerggaard Jensen, Lars Dyrskjøt. Liquid biopsy analysis of FGFR3 and PIK3CA hotspot mutations for disease surveillance in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2752. doi:10.1158/1538-7445.AM2017-2752

Integrative Assessment of Pretreatment Inflammation-, Nutrition-, and Muscle-Based Prognostic Markers in Patients with Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy

Objective: The present study evaluated the clinical relevance of an integrative preoperative assessment of inflammation-, nutrition-, and muscle-based markers for patients with muscle-invasive bladder cancer (MIBC) undergoing curative radical cystectomy (RC). Methods: The analysis enrolled 117 patients and the variables included age, body mass index (BMI), neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), Controlling Nutritional Status score, psoas muscle index (PMI), and peak expiratory flow (PEF). The correlations among the variables were evaluated and their prognostic values after RC were tested. Results: Three inflammation markers (ratios of blood cell counts) were positively correlated (p < 0.0001). The PNI and the BMI were positively correlated (p = 0.04), although they were inversely correlated with the three inflammation markers (p < 0.0001). Age was not significantly correlated with the inflammation markers and PMI, although older age was associated with lower PNI and lower PEF. The disease-specific survival was independently predicted by T4 tumor, positive N status, and decreased PNI. Overall survival was independently predicted by T4 tumor, mGPS, and pretreatment sarcopenia status. Conclusions: The inflammation-, nutrition-, and muscle-based markers would be useful risk assessment tools for MIBC.

Population-based assessment of racial/ethnic differences in utilization of radical cystectomy for patients diagnosed with bladder cancer.

Radical cystectomy is a surgical treatment for recurrent non-muscle-invasive and muscle-invasive bladder cancer; however, many patients may not receive this treatment. A total of 27,578 patients diagnosed with clinical stage I-IV bladder cancer from 1 January 2007 to 31 December 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry database. We used multivariable regression analyses to identify factors predicting the use of radical cystectomy and pelvic lymph node dissection. Cox proportional hazards models were used to analyze survival outcomes. A total of 1,693 (6.1%) patients with bladder cancer underwent radical cystectomy. Most patients (92.4%) who underwent radical cystectomy also underwent pelvic lymph node dissection. When compared with white patients, non-Hispanic blacks were less likely to undergo a radical cystectomy [odds ratio (OR) 0.79, 95% confidence interval (CI) 0.64-0.96, p=0.019]. Moreover, recent year of surgery 2013 versus 2007 (OR 2.32, 95% CI 1.90-2.83, p<0.001), greater percentage of college education ≥36.3 versus <21.3% (OR 1.23, 95% CI 1.04-1.44, p=0.013), Midwest versus West (OR 1.64, 95% CI 1.39-1.94, p<0.001), and more advanced clinical stage III versus I (OR 29.1, 95% CI 23.9-35.3, p<0.001) were associated with increased use of radical cystectomy. Overall survival was improved for patients who underwent radical cystectomy compared with those who did not undergo a radical cystectomy (hazard ratio 0.88, 95% CI 0.80-0.97, p=0.008). There is significant underutilization of radical cystectomy in patients across all age groups diagnosed with bladder cancer, especially among older, non-Hispanic black patients.

Systemic therapy and overall survival trends in patients with non-urothelial histologic variants of muscle invasive bladder cancer undergoing radical cystectomy.

376 Background: Histological variants of urothelial carcinoma (UC) of the bladder have a poorer prognosis than histologically pure UC, and the role of neoadjuvant chemotherapy (NAC) in this group is unclear. Our objective was to evaluate NAC practice patterns and survival outcomes in patients with histologic variants undergoing radical cystectomy (RC). Methods: Patients with cT2-4N0-3M0 muscle invasive bladder cancer (MIBC) who underwent RC from 2003-2012 were selected from the National Cancer Database (NCDB). Patients were categorized by histology code as pure UC or histologic variants. Adjusting for patient and clinical characteristics, generalized estimating equations were used to test the association between histology and receipt of NAC. The association between receipt of NAC and overall survival (OS) was evaluated using Kaplan Meier curves and Cox regression models. Results: In 19,976 patients meeting inclusion criteria, receipt of NAC in histologic variants was less (11-14%) than in pure UC (22%), with the exception of micropapillary disease (23%) (Table). Median OS was lower in variant histologies than for pure UC (8.4 – 30.2 vs. 37.6 months). Receipt of NAC was associated with improved survival compared to RC or RC+adjuvant chemotherapy in patients with pure UC (HR 0.91, p=0.0016). There was no evidence of a survival benefit for NAC in the variant histologies, or that treatment effects differed by histology (P-val for interaction=0.84). Conclusions: In the NCDB, a substantial proportion of patients (13%) with histologic variants of MIBC undergoing RC receive NAC in the absence of a proven survival benefit. Clinical trials inclusive of patients with variant histologies are necessary to elucidate the role of NAC prior to RC. [Table: see text]

Liquid Biopsy Analysis of FGFR3 and PIK3CA Hotspot Mutations for Disease Surveillance in Bladder Cancer

BackgroundDisease surveillance in patients with bladder cancer is important for early diagnosis of progression and metastasis and for optimised treatment. ObjectiveTo develop urine and plasma assays for disease surveillance for patients with FGFR3 and PIK3CA tumour mutations. Design, setting, and participantsDroplet digital polymerase chain reaction (ddPCR) assays were developed and tumour DNA from two patient cohorts was screened for FGFR3 and PIK3CA hotspot mutations. One cohort included 363 patients with non–muscle-invasive bladder cancer (NMIBC). The other cohort included 468 patients with bladder cancer undergoing radical cystectomy (Cx). Urine supernatants (NMIBC n=216, Cx n=27) and plasma samples (NMIBC n=39, Cx n=27) from patients harbouring mutations were subsequently screened using ddPCR assays. Outcome measurements and statistical analysisProgression-free survival, recurrence-free survival, and overall survival were measured. Fisher's exact test, the Wilcoxon rank-sum test and Cox regression analysis were applied. Results and limitationsIn total, 36% of the NMIBC patients (129/363) and 11% of the Cx patients (44/403) harboured at least one FGFR3 or PIK3CA mutation. Screening of DNA from serial urine supernatants from the NMIBC cohort revealed that high levels of tumour DNA (tDNA) were associated with later disease progression in NMIBC (p=0.003). Furthermore, high levels of tDNA in plasma samples were associated with recurrence in the Cx cohort (p=0.016). A positive correlation between tDNA levels in urine and plasma was observed (correlation coefficient 0.6). The retrospective study design and low volumes of plasma available for analysis were limitations of the study. ConclusionsIncreased levels of FGFR3 and PIK3CA mutated DNA in urine and plasma are indicative of later progression and metastasis in bladder cancer. Patient summaryUrine and plasma from patients with bladder cancer may be monitored for diagnosis of progression and metastasis using mutation assays.

Lymph node yield in node-negative patients predicts cancer specific survival following radical cystectomy for transitional cell carcinoma.

PurposeTo determine the oncological implications of increased nodal dissection in node-negative bladder cancer during radical cystectomy in a contemporary Australian series.Materials and MethodsWe performed a multicenter retrospective study, including more than 40 surgeons across 5 sites over a 10-year period. We identified 353 patients with primary bladder cancer undergoing radical cystectomy. Extent of lymphadenectomy was defined as follows; limited pelvic lymph node dissection (PLND) (perivesical, pelvic, and obturator), standard PLND (internal and external iliac) and extended PLND (common iliac). Multivariable cox proportional hazards and logistic regression models were used to determine LNY effect on cancer-specific survival.ResultsOver the study period, the extent of dissection and lymph node yield increased considerably. In node-negative patients, lymph node yield (LNY) conferred a significantly improved cancer-specific survival. Compared to cases where LNY of 1 to 5 nodes were taken, the hazard ratio (HR) for 6 to 15 nodes harvested was 0.78 (95% confidence interval [CI], 0.43–1.39) and for greater than 15 nodes the HR was 0.31 (95% CI, 0.17–0.57), adjusted for age, sex, T stage, margin status, and year of surgery. The predicted probability of cancer-specific death within 2 years of cystectomy was 16% (95% CI, 13%–19%) with 10 nodes harvested, falling to 5.5% (95% CI, 0%–12%) with 30 nodes taken. Increasing harvest in all PLND templates conferred a survival benefit.ConclusionsThe findings of the current study highlight the improved oncological outcomes with increased LNY, irrespective of the dissection template. Further prospective research is needed to aid LND data interpretation.

Perioperative change in neutrophil-lymphocyte ratio predicts the overall survival of patients with bladder cancer undergoing radical cystectomy.

To assess the prognostic value of perioperative changes in the neutrophil-lymphocyte ratio in patients with bladder cancer undergoing radical cystectomy. We performed a retrospective analysis of 323 patients who had undergone radical cystectomy at our institutions. Overall survival was assessed with the Kaplan-Meier method and Cox regression analysis. Preoperative and postoperative neutrophil-lymphocyte ratios were significantly correlated with overall survival (both P=0.0001). Changes in perioperative neutrophil-lymphocyte ratio stratified the patients into two groups, designated favorable- and poor-risk groups, with significantly different 5-year overall survival rates (75.1% and 41.4%, respectively; P<0.0001). Multivariate Cox regression analyses showed that the perioperative change in neutrophil-lymphocyte ratio was an independent prognostic factor for overall survival (hazard ratio 2.56, 95% confidence interval 1.75-3.73; P<0.001). Moreover, a decrease in neutrophil-lymphocyte ratio after adjuvant chemotherapy was associated with favorable overall survival in patients with high postoperative neutrophil-lymphocyte ratio (P<0.001), indicating that neutrophil-lymphocyte ratio may be a predictive factor for the efficacy of adjuvant chemotherapy. Perioperative changes in neutrophil-lymphocyte ratio are significantly associated with overall survival in patients with bladder cancer undergoing radical cystectomy. Follow-up of the neutrophil-lymphocyte ratio change may be useful for the clinical management of patients after surgery.

Diagnosis of micrometastasis in muscle invasive bladder cancer through immunohistochemistry analysis: is there indication for routine evaluation?

Muscle invasive bladder cancer (BC) has a mortality rate of 50% in 5 years, despite the aggressive treatments currently used. The diagnosis of latent tumor cells in histologically normal lymph nodes (LN) may have prognostic value and may explain the tumoral recurrence in BC. Here we evaluated the use of the AE1AE3 cytokeratin marker through immunohistochemical examination of LNs to diagnose micrometastasis in patients with BC undergoing radical cystectomy (RC) and lymph node dissection. Sixty-one patients with pN0 diseases who were submitted to RC were studied. Conventional histological evaluation indicated that these patients did not have lymph node metastasis. Histological sections were reviewed and analyzed by immunohistochemistry (IHC) using the AE1AE3 antibody in single sections. The total number of removed LNs was 832, averaging 13.64 LNs per patient. The IHC evaluation revealed that LN from 2/61 (3.27%) patients had micrometastasis. At the time of the last follow-up, 41% of all patients were in complete disease remission and 41.1% had died from BC. Our study shows that histological analysis using hematoxylin eosin (HE) method by experienced pathologists is sufficient for the diagnosis of LN metastasis and, therefore, there is no indication for routine IHC evaluation in patients at histopathological pN0 stage.

High-Risk of Adverse Pathologic Features in Patients With Clinical T1 High-Grade Bladder Cancer Undergoing Radical Cystectomy.

Radical cystectomy (RC) is used to treat select patients with T1 high-grade (T1HG) bladder cancer. However, population-level utilization trends and outcomes for these patients are not well-known. We sought to evaluate treatment patterns and clinicopathologic outcomes of RC for T1HG bladder cancer. Using the National Cancer Data Base (NCDB) for 1998-2012, we conducted a retrospective cohort study of patients with clinical T1HG bladder cancer. The prevalence of RC used to treat T1HG bladder cancer from 1998-2012 was determined. For years 2010-2012, demographic and cancer-related factors were described and regression analysis was used to examine associations with RC. Oncologic outcomes of RC were described and related to mortality using Cox proportional hazards regression. Treatment of T1HG bladder cancer with RC nearly doubled, from 5.5% during 1998-2000 to 9.9%, during 2010-2012. For 2010-2012, 18,277 patients with T1HG bladder cancer were analyzed. Patients who underwent RC were younger, had fewer comorbidities, and were more often treated at an academic center than those who did not undergo RC. At the time of RC, 41% of patients with T1HG bladder cancer were upstaged (pT2 or greater) and 12.7% had lymph node metastases. The 1- and 3-year survival rates were 0.89 and 0.68, respectively. Extravesical (T3+) disease at RC had the strongest independent hazard (hazard ratio [HR], 2.32; 95% CI, 1.72-3.11) of death other than age of 82 years or older (HR, 3.40; 95% CI, 2.28-5.07). The use of RC for T1HG bladder cancer has increased in prevalence in recent years but is still not widely used. There are concerning pathologic outcomes in patients with clinical T1HG bladder cancer treated with RC, including high rates of pathologic upstaging and nodal metastases. Future studies are necessary to better risk-stratify patients with T1HG bladder cancer to best select those who will benefit from aggressive therapy with RC.