The effect of cisplatin-based neoadjuvant chemotherapy on the renal function of patients undergoing radical cystectomy.

INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both. METHODS: We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context. RESULTS: We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m2) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m2). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m2), and the proportion of those with stage ≥3 CKD increased from 37% to 51%. CONCLUSIONS: Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.

A Leak in the System: Addressing the Environmental Impact of Urologic Care.

As urologists we have an opportunity to reduce the carbon footprint of the procedures we perform. We highlight some areas of interest in urology and potential initiatives to reduce the energy and waste footprint of urology care. Urologists can and should make an impact on the growing climate crisis.

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

PURPOSE: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort. MATERIALS AND METHODS: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival. RESULTS: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1). CONCLUSIONS: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

Multicenter evaluation of neoadjuvant and induction gemcitabine-carboplatin versus gemcitabine-cisplatin followed by radical cystectomy for muscle-invasive bladder cancer.

PURPOSE: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). METHODS: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC. RESULTS: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. CONCLUSION: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC.

Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer.

PURPOSE: To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age. RESULTS: pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6-37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p < 0.001) and luminal infiltrated (p = 0.002) compared to those with luminal papillary subtype. CONCLUSIONS: While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

Development of robust artificial neural networks for prediction of 5-year survival in bladder cancer.

PURPOSE: When exploring survival outcomes for patients with bladder cancer, most studies rely on conventional statistical methods such as proportional hazards models. Given the successful application of machine learning to handle big data in many disciplines outside of medicine, we sought to determine if machine learning could be used to improve our ability to predict survival in bladder cancer patients. We compare the performance of artificial neural networks (ANN), a type of machine learning algorithm, with that of multivariable Cox proportional hazards (CPH) models in the prediction of 5-year disease-specific survival (DSS) and overall survival (OS) in patients with bladder cancer. SUBJECTS AND METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 18 program database was queried to identify adult patients with bladder cancer diagnosed between 1995 and 2010, yielding 161,227 patients who met our inclusion criteria. ANNs were trained and tested on an 80/20 split of the dataset. Multivariable CPH models were developed in parallel. Variables used for prediction included age, sex, race, grade, SEER stage, tumor size, lymph node involvement, degree of extension, and surgery received. The primary outcomes were 5-year DSS and 5-year OS. Receiver operating characteristic curve analysis was conducted, and ANN models were tested for calibration. RESULTS: The area under the curve for the ANN models was 0.81 for the OS model and 0.80 for the DSS model. Area under the curve for the CPH models was 0.70 for OS and 0.81 for DSS. The ANN OS model achieved a calibration slope of 1.03 and a calibration intercept of -0.04, while the ANN DSS model achieved a calibration slope of 0.99 and a calibration intercept of -0.04. CONCLUSIONS: Machine learning algorithms can improve our ability to predict bladder cancer prognosis. Compared to CPH models, ANNs predicted OS more accurately and DSS with similar accuracy. Given the inherent limitations of administrative datasets, machine learning may allow for optimal interpretation of the complex data they contain.

Neoadjuvant chemotherapy plus radical cystectomy versus radical cystectomy alone in clinical T2 bladder cancer without hydronephrosis.

OBJECTIVES: To assess the efficacy of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in a retrospective multicentre cohort of patients with cT2N0M0 bladder cancer (BCa) without preoperative hydronephrosis. PATIENTS AND METHODS: This was a propensity-based analysis of 619 patients. Of these, 316 were treated with NAC followed by RC and 303 with upfront RC. After multiple imputations, inverse probability of treatment weighting (IPTW) was used to account for potential selection bias. Multivariable logistic regression analysis was performed to evaluate the impact of NAC on pathological complete response and downstaging at RC, while IPTW-adjusted Kaplan-Meier curves and Cox regression models were built to evaluate the impact of NAC on overall survival (OS). RESULTS: After IPTW-adjusted analysis, standardised differences between groups were <15%. A complete response (pT0N0) at final pathology was achieved in 94 (30%) patients receiving NAC and nine (3%) undergoing upfront RC. Downstaging to non-muscle-invasive disease (

Bupivacaine local anesthetic to decrease opioid requirements after radical cystectomy: Does formulation matter?

INTRODUCTION: Reduction of opioids is an important goal in the care of patients undergoing radical cystectomy (RC). Liposomal bupivacaine (LB) has been shown to be a safe and effective pain reliever in the immediate postoperative period and has been reported to reduce postoperative opioid requirements. Since the liposomal formulation is predicated on slow systemic absorption, the amount of bupivacaine administered is notably higher than that typically used with standard bupivacaine (SB) formulations. In addition, LB is costly, not universally available, and studies comparing this formulation to SB are lacking. We sought to determine if there is a difference in postoperative opioid requirements in patients who receive LB vs. high dose SB at the time of RC. METHODS: In May 2019 we transitioned to administration of high-volume SB injected intraoperatively at the time of RC. This prospective cohort was compared to a historical cohort of patients who received injection of LB at the time of surgery. Primary endpoints included postsurgical opioid use measured in morphine equivalent dose (MED) and patient-reported Numeric Rating Scale (NRS) pain scores and length of stay. All patients were managed using principles of enhanced recovery after surgery (ERAS). RESULTS: From May 2019 through August 2019, 28 patients underwent RC and met eligibility criteria to receive SB at the time of surgery. They were compared to a historical cohort of 34 patients who received LB between November 2017 and July 2018. There was no difference in MED exposure either in the postanesthesia care unit (SB 9.0 ± 8.9 MED vs. LB 6.5 ± 9.4 MED, P= 0.29) or during the remainder of the hospital stay (SB 36.8 ± 56.9 MED vs. LB 42.1 ± 102.5 MED, P= 0.81), no difference in NRS pain scores on postoperative day 1 (SB 2.6 ± 1.6 vs. LB 2.1 ± 1.7, P= 0.23), day 2 (SB 2.4 ± 1.8 vs. LB 1.9 ± 1.6, P= 0.19), or day 3 (SB 1.9 ± 1.8 vs. LB 1.7 ± 1.7, P= 0.69) and no difference in length of stay (SB 5.0 ± 1.7 days, LB 4.9 ± 3.3 days, P= 0.93). Subgroup analysis of open RC and robotic-assisted RC showed no significant difference in MED or pain scores between LB and SB patients. CONCLUSIONS: Among patients undergoing RC under ERAS protocol there was no significant difference in postoperative opioid consumption, NRS pain scores, or length of stay among patients receiving SB compared to LB.

Utilizing time-driven activity-based costing to determine open radical cystectomy and ileal conduit surgical episode cost drivers.

OBJECTIVES: Patients undergoing radical cystectomy represent a particularly resource-intensive patient population. Time-driven activity based costing (TDABC) assigns time to events and then costs are based on the people involved in providing care for specific events. To determine the major cost drivers of radical cystectomy care we used a TDABC analysis for the cystectomy care pathway. SUBJECTS AND METHODS: We retrospectively reviewed a random sample of 100 patients out of 717 eligible patients undergoing open radical cystectomy and ileal conduit for bladder cancer at our institution between 2012 and 2015. We defined the cycle of care as beginning at the preoperative clinic visit and ending with the 90-day postoperative clinic visit. TDABC was carried out with construction of detailed process maps. Capacity cost rates were calculated and the care cycle was divided into 3 phases: surgical, inpatient, and readmissions. Costs were normalized to the lowest cost driver within the cohort. RESULTS: The mean length of stay was 6.9 days. Total inpatient care was the main driver of cost for radical cystectomy making up 32% of the total costs. Inpatient costs were mainly driven by inpatient staff care (76%). Readmissions were responsible for 29% of costs. Surgery was 31% of the costs, with the majority derived from operating room staff costs (65%). CONCLUSION: The major driver of cost in a radical cystectomy pathway is the inpatient stay, closely followed by operating room costs. Surgical costs, inpatient care and readmissions all remain significant sources of expense for cystectomy and efforts to reduce cystectomy costs should be focused in these areas.

Impact of sex on response to neoadjuvant chemotherapy in patients with bladder cancer.

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.

Radical cystectomy in women: Impact of the robot-assisted versus open approach on surgical outcomes.

OBJECTIVES: To perform a comparison of complications following open versus robot-assisted radical cystectomy (RC) among women who undergo the procedure. Studies comparing robotic to open RC have been mixed without a clear delineation of which patients benefit the most from one modality vs. the other, leading to continued debate. PATIENTS AND METHODS: This was a retrospective study of women who underwent either open or robotic RC at the MD Anderson Cancer Center from 1/2014 to 6/2018. Co-morbidities, pathologic data, and complications were assessed with descriptive statistics, along with uni- and multivariable logistic regression. RESULTS: 122 women underwent either open (n = 76) or robotic (n = 46) RC. Open RC was associated with greater intraoperative blood loss (median EBL 775 ml vs. 300 ml, P < 0.001). In both uni- and multivariable analyses, open RC was associated with a greater odds of intraoperative transfusion compared to robotic RC (odds ratio 6.49, 95% CI 2.85-14.78, P < 0.001). Women undergoing open RC were also at greater odds of receiving 4 or more units of packed red blood cells (odds ratio 5.46 (1.75-17.02), P = 0.003). Robotic RC conferred a higher median lymph node yield (27 vs. 20 nodes, P, <0.001) and operative times (median 513 min vs. 391.5 min, P < 0.001). There were no differences in margin positivity, length of stay, or readmission rates at 30 and 90 days. CONCLUSIONS: Robotic RC was associated with a significantly lower risk of transfusion and EBL, and a higher median lymph node yield and operative time. Unique anatomic considerations may in part be responsible for these findings.

Critical Appraisal of Quality Improvement Publications in the Urological Literature.

INTRODUCTION: Quality improvement efforts enable rapid improvement in health care by measuring, analyzing and controlling the delivery of patient care. However, publications on quality improvement initiatives often vary in quality, decreasing their impact and restricting adoption by other institutions. We aim to compare the number, quality and trends of quality improvement publications in the urological literature. METHODS: PubMed®/MEDLINE® and EMBASE® were used to identify relevant quality improvement publications in the urological literature since 1999. Critical appraisal of each publication was performed using the Quality Improvement Minimum Quality Criteria Set. RESULTS: Inclusion criteria were met by 34 publications. Mean Quality Improvement Minimum Quality Criteria Set score ± SD was 10.8 ± 2.2 out of 16. Of the publications 44.1% (15) scored 10/16 or lower reflecting low quality. Only 8.8% (3) used the Standards for Quality Improvement Reporting Excellence. The majority of quality improvement publications consist of process rather than outcome or structural measures. The number of publications per year increased dramatically in 2015. However, average Quality Improvement Minimum Quality Criteria Set score before and after this time showed no change (p=0.88). Overall, 70.6% (24) of publications failed to report the quality improvement intervention's penetration/reach and 64.7% failed to report on a patient health related outcome. CONCLUSIONS: Critical appraisal of quality improvement publications in the urological literature indicates that the number of quality improvement publications is increasing over time. However, the reporting quality of quality improvement publications has stagnated. Adherence to reporting guidelines, quality standards and inclusion of all domains of the Quality Improvement Minimum Quality Criteria Set will potentially improve the quality of quality improvement publications and facilitate adoption of best practices in the field of urology.

The Impact of Early Exposure to Urology: Evaluation of an Introductory Preclinical Course.

INTRODUCTION: Early exposure in medical school can increase student interest in urology. The majority of medical students graduate without completing a clinical rotation in this field. The primary objectives of our study were to increase exposure to urology and to facilitate interactions between preclinical students and department faculty. METHODS: A 7-week urology curriculum consisting of a weekly 1-hour class was introduced into the M.D. curriculum. Lectures were taught by faculty, fellows and resident physicians, and focused on the professional trajectory of the speaker, a career in urology, information on urological subspecialties and teaching points relevant to each topic. Pre/post surveys were administered to evaluate the effectiveness of the course. RESULTS: A total of 16 students enrolled in the course. Before this course the majority of students had less than 1 hour of teaching focused on urological topics. Informal exposure to urology was similar between preclinical students and graduating fourth year medical students (p >0.05). Post-course surveys showed that students had increased exposure to urology, greater opportunity to interact with residents, fellows and faculty, and overall they were satisfied with their course experience. Students who attended 4 or more courses reported they understood what a career in urology entails and had acquired the necessary information to decide whether to enroll in a clinical rotation in urology. CONCLUSIONS: This course increased exposure to urology among preclinical students and is a feasible addition to a standard medical school curriculum. Future studies will follow these students longitudinally and determine if this course increases student enrollment in urological clinical rotations and increases urology residency applications.

The prognostic value of the neutrophil-to-lymphocyte ratio in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and radical cystectomy.

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.

ICUD-SIU International Consultation on Bladder Cancer 2017: management of non-muscle invasive bladder cancer.

PURPOSE: To provide a summary of the Third International Consultation on Bladder Cancer recommendations for the management of non-muscle invasive bladder cancer (NMIBC). METHODS: A detailed review of the literature was performed focusing on original articles for the management of NMIBC. An international committee assessed and graded the articles based on the Oxford Centre for Evidence-based Medicine system. The entire spectrum of NMIBC was covered such as prognostic factors of recurrence and progression, risk stratification, staging, management of positive urine cytology with negative white light cystoscopy, indications of bladder and prostatic urethral biopsies, management of Ta low grade (LG) and high risk tumors (Ta high grade [HG], T1, carcinoma in situ [CIS]), impact of BCG strain and host on outcomes, management of complications of intravesical therapy, role of alternative therapies, indications for early cystectomy, surveillance strategies, and new treatments. The working group provides several recommendations on the management of NMIBC. RESULTS: Recommendations were summarized with regard to staging; management of primary and recurrent LG Ta and high risk disease, positive urine cytology with negative white light cystoscopy and prostatic urethral involvement; indications for timely cystectomy; and surveillance strategies. CONCLUSION: NMIBC remains a common and challenging malignancy to manage. Accurate staging, grading, and risk stratification are critical determinants of the management and outcomes of these patients. Current tools for risk stratification are limited but informative, and should be used in clinical practice when determining diagnosis, surveillance, and treatment of NMIBC.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Determining the optimal time for radical cystectomy after neoadjuvant chemotherapy.

OBJECTIVE: To determine whether the recovery window (RW) between neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) affects 90-day postoperative morbidity and incidence of lymph node metastasis. PATIENTS AND METHODS: We reviewed patients treated with NAC and RC from 1995 to 2013 for ≤cT4 N0 M0 bladder cancer. The association of the RW with 90-day perioperative morbidity and lymph node metastasis was determined. Generalised linear models were used to determine predictors of each endpoint. Patients were stratified into four RWs by 21-day intervals (18-42; 43-63; 64-84; and ≥85 days) from last day of NAC to RC. RESULTS: We evaluated 306 patients with RW information during the study period. The median (range) RW was 46 (18-199) days. There was no difference in overall morbidity, re-admission, or major complication rates amongst the four RWs. In the multivariable analysis extravesical disease was an independent predictor of overall morbidity (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.16-3.26; P = 0.011). Age (OR 1.05, 95% CI: 1.02-1.09; P = 0.004), and surgical duration ≥7 h (OR 2.87, 95% CI: 1.52-5.42; P = 0.001) were independent predictors of major complications. Only surgical duration ≥7 h was a predictor of re-admission (OR 2.24; 95% CI: 1.26-3.98; P = 0.006). A RW of ≥85 days had the highest incidence of node-positive disease (pN+; 40%). In a separate multivariable model that included clinical predictors for pN+, a RW of ≥85 days was an independent predictor of nodal metastasis (OR 2.92, 95% CI: 1.20-7.09; P = 0.018). CONCLUSION: Patients treated with NAC for bladder cancer can undergo RC between 18 and 84 days (2.5-12 weeks) after NAC with no difference in the risk of perioperative morbidity. Delaying surgery beyond 12 weeks was associated with a significant risk of lymph node metastasis.

Neurocognitive deficits in older patients with cancer.

OBJECTIVE: To assess cognitive function in older adults undergoing cancer care. MATERIALS AND METHODS: This is a cross-sectional study, in the University of Texas MD Anderson Cancer Center, in older adults undergoing cancer care. Comprehensive geriatric assessments were conducted prior to surgery, chemotherapy or allogeneic stem cell transplantation, at the Program for Healthy Aging from January 1, 2013 through March 31, 2015. Cognitive assessment was conducted through personal and family interview, and the Montreal cognitive assessment (MoCA). Functional, physical, nutritional, social support, comorbidity assessment and medication review were conducted. ANALYSIS: Patients with mild cognitive impairment (MCI) or dementia were compared to patients who were cognitively intact. RESULTS: One hundred and ninety-two patients underwent geriatric assessment, mean (±SD) age was 78 ±â€¯7 years, 121 (63%) had some degree of neurocognitive deficit, with 64 patients (33%) presenting with major neurocognitive deficit (dementia), and 57 cases (30%), minor neurocognitive deficit (MCI). Early stage dementia was evident in 50% of cases, moderate stage in 32%, and severe stage in 18%. The prevalence of dementia and MCI were higher than in the general population studies (70-79 years). Associated factors for neurocognitive deficits as compared to older patients with cancer with normal cognition, included a higher comorbidity index (p = 0.04), stroke (p = 0.03), metastatic disease (p = 0.04), and warfarin use (p = 0.03). CONCLUSION: Neurocognitive deficits (MCI and dementia) are more common in older adults with cancer. Factors associated with neurocognitive deficits include high comorbidity, stroke, warfarin use and metastatic cancer. Identification and management of these conditions is of great relevance in the course of cancer therapy.