Trimodal therapy vs. radical cystectomy for muscle-invasive bladder cancer: A Canadian cost-effectiveness analysis.

INTRODUCTION: Trimodal therapy (TMT) is a suitable alternative to neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for patients with muscle-invasive bladder cancer (MIBC). In this study, we conducted a cost-effectiveness evaluation of RC±NAC vs. TMT for MIBC in the universal and publicly funded Canadian healthcare system. METHODS: We developed a Markov model with Monte-Carlo microsimulations. Rates and probabilities of transitioning within different health states (e.g., cure, locoregional recurrence, distant metastasis, death) were input in the model after a scoped literature review. Two main scenarios were considered: 1) academic center; and 2) populational-level. Results were reported in life-years gained (LYG), quality-adjusted life years (QALY), and incremental cost-effectiveness ratio (ICER). A sensitivity analysis was performed. RESULTS: A total of 20 000 patients were simulated. For the academic center model, TMT was associated with increased effectiveness (both in LYG and QALY) at a higher cost compared to RC±NAC at five and 10 years. This resulted in an ICER of $19 746/QALY per patient undergoing the TMT strategy at 10 years of followup. For the populational-level model, RC±NAC was associated with higher effectiveness at 10 years, with an ICER of $3319/QALY per patient. This study was limited by heterogeneity within the studies used to build the model. CONCLUSIONS: In this study, TMT performed in academic centers was cost-effective compared to RC±NAC, with higher effectiveness at a higher cost. On the other hand, RC±NAC was considered cost-effective compared to TMT at the populational-level. Further studies are needed to confirm these results.

Critical analysis of quality of life and cost-effectiveness of enhanced recovery after surgery (ERAS) for patient's undergoing urologic oncology surgery: a systematic review.

PURPOSE: Enhanced recovery after surgery (ERAS) protocols have been implemented across a variety of disciplines to improve outcomes. Herein we describe the impact of ERAS on quality of life (QOL) and cost for patients undergoing urologic oncology surgery. METHODS: A systematic literature search using the MEDLINE, Scopus, Clinictrials.gov, and Cochrane Review databases for studies published between 1946 and 2020 was conducted. Articles were reviewed and assigned a risk of bias by two authors and were included if they addressed ERAS and either QOL or cost-effectiveness for patients undergoing urologic oncology surgery. RESULTS: The literature search yielded a total of 682 studies after removing duplicates, of which 10 (1.5%) were included in the review. Nine articles addressed radical cystectomy, while one addressed ERAS and QOL for laparoscopic nephrectomy. Six publications assessed the impact of ERAS on QOL domains. Questionnaires used for assessment of QOL varied across studies, and timing of administration was heterogeneous. Overall, ERAS improved patient QOL during early phases of recovery within the realms of bowel function, physical/social/cognitive functioning, sleep and pain control. Costs were assessed in 4 retrospective studies including 3 conducted in the United States and one from China all addressing radical cystectomy. Studies demonstrated either decreased costs associated with ERAS as a result of decreased length of stay or no change in cost based on ERAS implementation. CONCLUSION: While limited studies are published on the subject, ERAS implementation for radical cystectomy and laparoscopic nephrectomy improved patient-reported QOL during early phases of recovery. For radical cystectomy, there was a decreased or neutral overall financial cost associated with ERAS. Further studies assessing QOL and cost-effectiveness over the entire global period of care in a variety of urologic oncology surgeries are warranted.

Refining assessment of response to radiation-based therapy for muscle-invasive bladder cancer: Is post-treatment tumor bed biopsy always necessary?

INTRODUCTION: Radiation-based therapy (RT) has emerged as a suitable alternative to radical cystectomy (RC) and pelvic lymph node dissection for muscle-invasive bladder cancer (MIBC) patients. Routine biopsy after RT to rule out residual disease remains inconsistent across guidelines. Our objective was to review the significance of a bladder biopsy in terms of assessment of response post-RT and its potential impact on survival. PATIENTS AND METHODS: This was a single-center retrospective study on patients with MIBC (cT2-4aN0-2M0) treated with curative intent RT. A total of 169 patients with primary urothelial carcinoma were analyzed. Patients' demographic, clinical and pathological variables, imaging, cystoscopy, urine cytology, and biopsy reports after RT were collected and compiled. Whenever urine cytology was positive or cystoscopy showed any malignant-appearing lesion, the first assessment post-RT was considered suspicious for residual disease. A descriptive population analysis was reported. Cox regression multivariable analysis was performed to identify independent variables associated with survival outcomes. RESULTS: Median age was 75 years (interquartile range 66-82) and clinical staging was cT2 in 152 (90%) patients. Cytology and cystoscopy were normal in 140 (83%) after RT. Of patients with a control biopsy, residual MIBC was present in 3 (5%) and non-MIBC in another 6 (11%). On the contrary, a for-cause biopsy due to a suspicious assessment post-RT did not yield residual cancer in 45% of patients. Multivariable analysis showed that age (hazard ratio [HR] 1.04, P< 0.001), lymphovascular invasion (HR 1.68, P = 0.03) and a suspicious assessment after RT (HR 3.21; P< 0.001) were significantly associated with worse OS. This study was limited by its retrospective design. CONCLUSIONS: A routine biopsy after RT may be warranted to assess treatment response. This might be particularly important for patients who may benefit from early surgical intervention for residual MIBC. Further prospective studies are needed to confirm our findings.

Evidence-based Assessment of Current and Emerging Bladder-sparing Therapies for Non-muscle-invasive Bladder Cancer After Bacillus Calmette-Guerin Therapy: A Systematic Review and Meta-analysis.

CONTEXT: Currently, there is no standard of care for patients with non-muscle-invasive bladder cancer (NMIBC) who recur despite bacillus Calmette-Guerin (BCG) therapy. Although radical cystectomy is recommended, many patients decline to undergo or are ineligible to receive it. Multiple agents are being investigated for use in this patient population. OBJECTIVE: To systematically synthesize and describe the efficacy and safety of current and emerging treatments for NMIBC patients after treatment with BCG. EVIDENCE ACQUISITION: A systematic literature search of MEDLINE, Embase, and the Cochrane Controlled Register of Trials (period limited to January 2007-June 2019) was performed. Abstracts and presentations from major conference proceedings were also reviewed. Randomized controlled trials were assessed using the Cochrane risk of bias tool. Data for single-arm trials were pooled using a random-effect meta-analysis with the proportions approach. Trials were grouped based on the minimum number of prior BCG courses required before enrollment and further stratified based on the proportion of patients with carcinoma in situ (CIS). EVIDENCE SYNTHESIS: Thirty publications were identified with data from 23 trials for meta-analysis, of which 17 were single arm. Efficacy and safety outcomes varied widely across studies. Heterogeneity across trials was reduced in subgroup analyses. The pooled 12-mo response rates were 24% (95% confidence interval [CI]: 16-32%) for trials with two or more prior BCG courses and 36% (95% CI: 25-47%) for those with one or more prior BCG courses. In a subgroup analysis, inclusion of ≥50% of patients with CIS was associated with a lower response. CONCLUSIONS: The variability in efficacy and safety outcomes highlights the need for consistent endpoint reporting and patient population definitions. With promising emerging treatments currently in development, efficacious and safe therapeutic options are urgently needed for this difficult-to-treat patient population. PATIENT SUMMARY: We examined the efficacy and safety outcomes of treatments for non-muscle-invasive bladder cancer after bacillus Calmette-Guerin therapy. Outcomes varied across studies and patient populations, but emerging treatments currently in development show promising efficacy.

Evaluation of New Tests and Interventions for Prostate Cancer Management: A Systematic Review.

Background: Inaccurate risk classification and the burden of unnecessary biopsies are a challenge due to the limited ability of current risk assessment tools and modalities to diagnose prostate cancer (PCa) and distinguish indolent from aggressive disease. This systematic review assesses newly developed tests and interventions with high evidence of clinical utility that might be adopted in clinical practice during PCa management before initial and repeat biopsy, after positive biopsy, and after radical treatment. Methods: The Cochrane, Embase, MEDLINE, and Web of Science databases were searched for studies pertaining to the clinical utility of PCa diagnostic tests. Outcomes of interest were (1) a measure of the percentage of altered decision-making, (2) decrease in number of unnecessary biopsies, (3) decrease or increase in treatment intensity, and (4) risk reclassification after test results. Results: The search yielded 2,940 articles, of which 46 met the inclusion criteria. We found clinical utility evidence on the Prostate Health Index (PHI), 4Kscore test, MRI, OncotypeDX, Decipher test, Prolaris, ConfirmMDx, Progensa PCA3, NADiA ProsVue, and ProMark. No evidence was identified for Prostarix, ProstaVysion, Prostate Core Mitomic Test, and Mi-Prostate Score. The interventions demonstrated their clinical utility in terms of change in treatment recommendations, decrease/increase in interventional treatment, decrease in biopsy, and risk reclassification. At diagnosis after a positive biopsy, ProMark, OncotypeDX, Prolaris, and MRI guided the use of active surveillance. Use of NADiA ProsVue, Decipher, and Prolaris aided in the decision to add adjuvant therapy post-prostatectomy. PHI, 4Kscore, and MRI used prior initial and repeat biopsies, and ConfirmMDx and Progensa PCA3 used prior repeat biopsies to improve prediction of biopsy outcome, allowing a decrease in unnecessary biopsies. Conclusions: This systematic review suggests that implementation of these tests in clinical practice could effectuate personalized treatment of PCa. Further clinical and economic evaluation studies of long-term PCa outcomes are warranted to provide further guidance.

Contemporary cost-consequence analysis of blue light cystoscopy with hexaminolevulinate in non-muscle-invasive bladder cancer.

INTRODUCTION: Previous studies have suggested cost-savings using blue light cystoscopy (BLC) with hexaminolevulinate (HAL) compared to white light cystoscopy (WLC) during transurethral resection of bladder tumour (TURBT) for non-muscle-invasive bladder cancer (NMIBC), secondary to improvements in recurrence and progression rates; however, these studies have used 'best case scenario' recurrence rate probabilities, thus decreasing generalizability of the findings. The objective of this study was to perform a contemporary cost-effectiveness assessment of BLC compared to WLC at the time of TURBT. METHODS: A decision and cost-effectiveness model with a five-year time horizon following initial TURBT was used. The model was created from the healthcare payer perspective. Comprehensive literature review was performed to obtain contemporary recurrence and progression rates. These values were meta-analyzed for inclusion into the model. Cost variables included in the model were from three large Canadian bladder cancer centres. Model outputs were number of recurrences prevented, bed days saved, and overall costs. One-way sensitivity and scenario analyses were performed to assess model robustness. RESULTS: The five-year amortized cost of using BLC with HAL on all incident NMIBC compared to WLC assistance was $4 832,908 for Ontario (n=4696; $1372/patient); $1 168 968 for British Columbia (n=1204; $1295/patient); and $2 484, 872 (n=2680; $1236/patient) for Quebec. Use of BLC with HAL would result in 87 338 fewer recurrences annually. On sensitivity/scenario analyses for Ontario data, if BLC with HAL equipment were provided to the province at no cost, five-year costs would be $4 158 814 and $1181 cost per patient. If BLC with HAL were only used for cystoscopically appearing aggressive tumours, the five-year amortized cost would be $3 874 098, with a cost per patient of $1222. If there was a 20% or 50% improvement in progression rates with BLC plus HAL, the five-year amortized cost would be $2 660 529 and -$598 039 (cost-saving), respectively. CONCLUSIONS: TURBT using BLC with HAL for patients with NMIBC is associated with a five-year cost of approximately $1-5 million for jurisdictions of 4-13 million people. Although this translates to a cost of $1200-1400 per patient for their initial TURBT, BLC with HAL improves patients care, reduces recurrences, and decreases the need for hospital beds after TURBT. If this diagnostic procedure eventually improves progression rates, there would be considerably improved cost-effectiveness.

Does teaching of robotic partial nephrectomy affect renal function and perioperative outcomes?

PURPOSE: Partial nephrectomy (PN) represents the treatment of choice for localized renal tumor<7cm. Minimally invasive approaches are considered standard of care in many institutions. Maintaining acceptable warm ischemic time (WIT) while teaching robotic PN (RPN) remains challenging. The goal of the present study was to assess the effect of teaching RPN on WIT and renal function in patients undergoing RPN. METHODS: Patients undergoing RPN for cT1-T2 renal tumors were included. RENAL nephrometry score was used to adjust for tumor complexity. Glomerular filtration rates (GFR) were determined preoperatively, at day 2 and at ≥3-month follow-up. Patients in whom the attending surgeon (staff) performed tumorectomy and renorraphy were compared with those in whom the fellow performed these steps. Primary outcomes were WIT and GFR decrease at follow-up visit. Morbidity and margin positivity represented secondary outcomes. RESULTS: Overall, 69 patients (46 "staff" vs. 23 "fellow") were included. Patient׳s characteristics did not differ significantly between the 2 groups. In particular, RENAL score and preoperative GFR were similar between both groups. Mean WIT was 22±9 in the staff and 24±7 in the fellow group (P = 0.09). At follow-up, a GFR reduction of 9% was observed in the staff group vs. 13% in the fellow group (P = 0.38). Complication rates (13% vs. 17%, P = 0.63) and positive margins (9% vs. 4%, P = 0.47) did not differ significantly between staff and fellow. CONCLUSIONS: In our experience, teaching RPN with a strict supervision and stepwise standardized procedure was oncologically and functionally safe after 3 to 6 months of follow-up.

Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC).

PURPOSE: Upper-tract urothelial carcinoma (UTUC) is a relatively uncommon disease with limited available evidence on specific topics. The purpose of this article was to review the previous literature to summarize the current knowledge about UTUC epidemiology, diagnosis, preoperative evaluation and prognostic assessment. METHODS: Using MEDLINE, a non-systematic review was performed including articles between January 2000 and February 2016. English language original articles, reviews and editorials were selected based on their clinical relevance. RESULTS: UTUC accounts for 5-10 % of all urothelial cancers, with an increasing incidence. UTUC and bladder cancer share some common risk factors, even if they are two different entities regarding practical, biological and clinical characteristics. Aristolochic acid plays an important role in UTUC pathogenesis in certain regions. It is further estimated that approximately 10 % of UTUC are part of the hereditary non-polyposis colorectal cancer spectrum disease. UTUC diagnosis remains mainly based on imaging and endoscopy, but development of new technologies is rapidly changing the diagnosis algorithm. To help the decision-making process regarding surgical treatment, extent of lymphadenectomy and selection of neoadjuvant systemic therapies, predictive tools based on preoperative patient and tumor characteristics have been developed. CONCLUSIONS: Awareness regarding epidemiology, diagnosis, preoperative evaluation and prognostic assessment changes is essential to correctly diagnose and manage UTUC patients, thereby potentially improving their outcomes.

Neoadjuvant chemotherapy-related histologic changes in radical cystectomy: assessment accuracy and prediction of response.

We evaluated the spectrum of histologic changes associated with neoadjuvant chemotherapy (NAC) and compared them with those resulting from transurethral resection (TUR). Twenty-five patients who received NAC were divided based on both their preoperative clinical/radiographic findings (clinical stage, hydronephrosis, palpable mass) and the cystectomy (RC) findings into NAC respondents (advanced clinical stage and

Cost-effectiveness of multiparametric magnetic resonance imaging and targeted biopsy in diagnosing prostate cancer.

INTRODUCTION: Transrectal ultrasound-guided biopsy (TRUSGB) is the recommended approach to diagnose prostate cancer (PCa). Overdiagnosis and sampling errors represent major limitations. Magnetic resonance imaging (MRI)-targeted biopsy (MRTB) detects higher proportion of significant PCa and reduces diagnosis of insignificant PCa. Costs prevent MRTB from becoming the new standard in PCa diagnosis. The present study aimed at assessing whether added costs of MRI outweigh benefits of MRTB in a cost-utility model. MATERIALS AND METHODS: A Markov model was developed to estimate quality-adjusted life-year gained (QALY) and costs for 2 strategies (the standard 12-core TRUSGB strategy and the MRTB strategy) over 5, 10, 15, and 20 years. MRI was used as triage test in biopsy-naive men with clinical suspicion of PCa. The model takes into account probability of men harboring PCa, diagnostic accuracy of both procedures, and probability of being assigned to various treatment options. Direct medical costs based on health care system perspective were included. RESULTS: Following standard TRUSGB pathway, calculated cumulative effects at 5, 10, 15, and 20 years were 4.25, 7.17, 9.03, and 10.09 QALY, respectively. Cumulative effects in MRTB pathway were 4.29, 7.26, 9.17, and 10.26 QALY, correspondingly. Costs related to TRUSGB strategy were $8,027, $11,406, $14,883, and $17,587 at 5, 10, 15, and 20 years, respectively, as compared with $7,231, $10,450, $13,267, and $15,400 for the MRTB strategy. At 5, 10, 15, and 20 years, MRTB was the established dominant strategy. CONCLUSIONS: Incorporation of MRI and MRTB in PCa diagnosis and management represents a cost-effective measure at 5, 10, 15, and 20 years after initial diagnosis.

Predictors of costs associated with radical cystectomy for bladder cancer: A population-based retrospective cohort study in the province of Quebec, Canada.

BACKGROUND AND OBJECTIVES: There is paucity of studies on the predictors of bladder cancer (BC) management costs. We aimed to determine predictors of costs associated with radical cystectomy (RC) for BC. METHODS: We conducted a retrospective analysis in a cohort of 2,759 patients who underwent RC for BC between 2000 and 2009. We analyzed predictors of pre-surgery, RC, post-surgery, and total costs. The following variables were considered as potential predictors: age, gender, hospital/surgeon case load, academic hospital, and geo-administrative region. Multivariate linear regression was used to determine predictors. RESULTS: Predictors of pre-surgery costs were: age (ß = 808.64, P < 0.0001) and having surgery in an academic hospital (ß = 511.42, P = 0.003). Increased RC costs were associated with age (ß = 196.73, P = 0.0006), hospital/surgeon annual load (ß = 484.45 and ß = 254.21, P < 0.0001, respectively). Having surgery in academic hospitals and geographic region were significant predictors of low RC costs (ß = -1085.82 and ß = -449.31, P < 0.0001, respectively). Increasing age and the presence of post-operative complications were predictors of high post-operative costs (ß = 623.48, ß = 5781.44, P = 0.01, respectively), while hospital load was associated with low post-surgery costs (ß = -949.79, P < 0.0001). CONCLUSION: Patients' age and surgery performed by high-volume health providers were predictive factors of high RC costs. Low RC costs were associated with surgeries performed in academic hospitals.

Health-care services utilization and costs associated with radical cystectomy for bladder cancer: a descriptive population-based study in the province of Quebec, Canada.

BACKGROUND: Bladder cancer (BC) has the highest lifetime treatment costs per patient of all cancers. The objective of this study was to characterize the use of health-care services and costs associated with BC among patients who underwent radical cystectomy (RC) in the province of Quebec. METHODS: We conducted a descriptive study in a retrospective cohort of patients who underwent RC for BC between 2000 and 2009. Data was obtained from two health administrative databases (RAMQ and ISQ). We calculated average costs per patient and total costs in 2014 Canadian dollars for the following components of costs: 1) Pre-surgery costs (pre and post-urologist consultations, urologist consultations, cystoscopies, TURBTs, imaging procedures); 2) Costs of radical cystectomy and 3) Post-surgery costs (urologist consultations, post-operative consultations, medical oncologist consultations, imaging procedures and post-operative complication management). ARIMA models were used to evaluate trends in average costs per patient over the study period. RESULTS: Among 2759 patients included in the study (75% men), average pre-surgery costs, RC costs, and post-surgery costs were estimated at 3762$, 18979$ and 4770$, respectively. RC cost was responsible for 69% of total costs, followed by post-operative consultations (7.8%), post-operative complications and TURBTs (6% of total costs, each). Academic hospitals performed RC at a lower average cost, compared to community hospitals (difference of $1000, p < .0001). A decreased trend in post-surgery costs was detected in the year 2009. CONCLUSIONS: Costs of RC, TURBT, consultations and post-operative complications were the most important economic components of total RC cost per patient in Quebec. Academic hospitals performed RC at a lower cost, compared to community hospitals.

Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer.

BACKGROUND: The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. OBJECTIVE: We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. DESIGN, SETTING, AND PARTICIPANTS: Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. INTERVENTION: NAC and RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. RESULTS AND LIMITATIONS: Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p=0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p=0.6). CONCLUSIONS: Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. PATIENT SUMMARY: There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.

Contemporary cost-effectiveness analysis comparing sequential bacillus Calmette-Guerin and electromotive mitomycin versus bacillus Calmette-Guerin alone for patients with high-risk non-muscle-invasive bladder cancer.

BACKGROUND: Sequential bacillus Calmette-Guerin (BCG) and electromotive mitomycin (sequential therapy) have been shown in a randomized prospective trial to be superior to therapy with BCG alone in patients with high-risk non-muscle-invasive bladder cancer. The objective of the current study was to compare the costs and benefits of these 2 treatment strategies by performing a 5-year and 10-year cost-effectiveness study. METHODS: A Markov model was developed to estimate the incremental cost-effectiveness ratio over a 5-year and 10-year period. Estimates of disease progression, death, and treatment efficacy were obtained from what to the authors' knowledge is the only randomized trial comparing the 2 therapies. Costs included: 1) medical costs (physician fees); 2) drug costs (preparation and instillation); and 3) hospital costs (procedure fees, admission fees, and tests and procedures done during surveillance). Patients were allowed a second course of induction therapy. RESULTS: Sequential therapy was found to be associated with a higher initial material cost for induction and maintenance. The average effectiveness for the patients treated with therapy with BCG alone was 4.39 years with a mean cost of $9236 (95% confidence interval, $9118-$9345) per patient. The sequential group resulted in an average effectiveness of 4.65 years, with a mean cost of $16,468 (95% confidence interval, $16,371-$16,527). The 5-year incremental cost-effectiveness ratio of sequential versus BCG-alone therapy was $27,815 per life-year gained. The corresponding figure over a 10-year period was $8618 per life-year gained. CONCLUSIONS: The results of the current study suggest that sequential therapy is a cost-effective treatment for patients with high-risk non-muscle-invasive bladder cancer.

Gender-specific differences in clinicopathologic outcomes following radical cystectomy: an international multi-institutional study of more than 8000 patients.

BACKGROUND: The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood. OBJECTIVE: To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS: Data from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012 were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI). RESULTS AND LIMITATIONS: Female patients were older at the time of RC (p=0.033) and had higher rates of pathologic stage T3/T4 disease (p<0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR (p=0.022 and p=0.11, respectively). Female gender was an independent predictor for CSM (p=0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05). CONCLUSIONS: We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.

Adjuvant chemotherapy for upper-tract urothelial carcinoma treated with nephroureterectomy: assessment of adequate renal function and influence on outcome.

OBJECTIVES: Upper-tract urothelial carcinoma (UTUC) is associated with poor outcomes. Our aim was to assess adequacy of renal function and evaluate the role of adjuvant chemotherapy (AC) in patients with UTUC treated by radical nephroureterectomy (RNU) in a universal health care system. MATERIALS AND METHODS: Retrospective data from 1,029 patients treated with RNU across 10 Canadian academic centers were collected. Tested variables included various clinico-pathological parameters, the use of perioperative chemotherapy, preoperative and postoperative creatinine values, and estimated glomerular filtration rates (eGFR). Univariable and multivariable Cox regression models addressed overall survival and disease-specific survival after surgery. Kaplan-Meier survival curves were used to compare outcomes in patients who received or did not receive AC. RESULTS: Median age of patients was 70 years with a median follow-up of patients who were alive of 26 months. The median preoperative and postoperative eGFR rates were 59 mL/min/1.73 m(2) and 47 mL/min/1.73 m(2), respectively. Using a cutoff eGFR of 60, 49% of all the patients and 48% of the patients with ≥ pT3 or pTxN+ or both diseases would have been eligible for cisplatin-based chemotherapy preoperatively and only 18% and 21% of the patients, respectively remained eligible postoperatively. Of the patients who received AC, 75% had an eGFR<60. On multivariate analysis, AC was not prognostic for improved overall survival or disease-specific survival. CONCLUSIONS: Chronic kidney disease is common in patients with UTUC. Following RNU, 57% of the high-risk patients with good preoperative renal function became ineligible for cisplatin-based chemotherapy. Use of AC did not translate into improved survival. Whether this is due to inherent biases of retrospective analysis, limited efficacy of AC in patients with UTUC, or use of suboptimal regimen or dose because of poor postoperative renal function requires further evaluation.

Human resource assessment of academic urology across Canada: What are the future job prospects?

INTRODUCTION: Our objective was to capture an overview of anticipated staffing needs at Canadian urology academic centres over the next 5 years to help guide and counsel urology residents in their respective programs. METHODS: A 30-question survey was sent by email to all chairmen of academic urology divisions/departments during fall 2012. The first part of the survey solicited basic demographic information regarding number of residents, number of fellows and fellowships, and number of attending staff and affiliated hospitals. The second part of the survey included detailed questions on the number and sub-specialty of urologists needed at each respective institution, as well as the appropriate year of recruitment. RESULTS: The response rate was 100%. There are 13 urology training programs across Canada located in 6 out of the 10 provinces. Robotic surgery is available at 9 out of the 13 centres. A total of 68 urologists need to be recruited by academic institutions throughout Canada within the next 5 years. The greatest need is for general urologists, with a total of 13 required. This is followed by 12 urologic oncologists needed, 11 female urology, 7 reconstructive urologists, 6 pediatric urologists, 6 endourologists, 5 transplant surgeons, 4 infertility/andrology, and 4 experts in advanced laparoscopy/robotics. There was no need for any urologic trauma surgeons in any academic institution surveyed. CONCLUSIONS: A total of 68 urologists need to be recruited into academic urology across Canada within the next 5 years. This crucial information can be used to help guide urology residents in choosing the most appropriate fellowship, in addition to providing them with an overview of future job prospects at academic institutions throughout the country.

Clinical nodal staging scores for bladder cancer: a proposal for preoperative risk assessment.

BACKGROUND: Radical cystectomy (RC) with pelvic lymph node dissection (LND) is the standard of care for refractory non-muscle-invasive and muscle-invasive bladder cancer. Although consensus exists on the need for LND, its extent is still debated. OBJECTIVE: To develop a model that allows preoperative determination of the minimum number of lymph nodes (LNs) needed to be removed at RC to ensure true nodal status. DESIGN, SETTING, AND PARTICIPANTS: We analyzed data from 4335 patients treated with RC and pelvic LND without neoadjuvant chemotherapy at 12 academic centers located in the United States, Canada, and Europe. MEASUREMENTS: We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed clinical (preoperative) nodal staging scores (cNSS), which represent the probability that a patient has LN metastasis as a function of the number of examined nodes. RESULTS AND LIMITATIONS: The probability of missing a positive LN decreased with an increasing number of nodes examined (52% if 3 nodes were examined, 40% if 5 were examined, and 26% if 10 were examined). A cNSS of 90% was achieved by examining 6 nodes for clinical Ta-Tis tumors, 9 nodes for cT1 tumors, and 25 nodes for cT2 tumors. In contrast, examination of 25 nodes provided only 77% cNSS for cT3-T4 tumors. The study is limited due to its retrospective design, its multicenter nature, and a lack of preoperative staging parameters. CONCLUSIONS: Every patient treated with RC for bladder cancer needs an LND to ensure accurate nodal staging. The minimum number of examined LNs for adequate staging depends preoperatively on the clinical T stage. Predictive tools can give a preoperative estimation of the likelihood of nodal metastasis and thereby allow tailored decision-making regarding the extent of LND at RC.

Contemporary cost analysis of single instillation of mitomycin after transurethral resection of bladder tumor in a universal health care system.

OBJECTIVE: Although recommended management strategy for nonmuscle-invasive bladder cancer (NMIBC) involves a single postoperative intravesical therapy with mitomycin C (MMC), it is uncommonly used among urologists, in part because of potential increased costs. Our objective was to perform a 5-year cost analysis of this strategy within a single-provider health care environment. METHODS: A decision-analytic model was used. Input estimates for 5-year recurrence rates (50%) and MMC efficacy (absolute risk reduction of 17% and 12%) were identified via a systematic literature search and data from 2 meta-analyses. Direct costs included physician fees, MMC drug and preparation costs, transurethral bladder tumor resection (TURBT), and cystoscopy, as well as institutional hospital fees. Indirect societal costs such as work absences and productivity loss were not considered. The model was limited to a 5-year follow-up period with the following assumptions: similar rates of progression, constant recurrence rates, and no cross-over between groups. RESULTS: Overall 5-year analysis reveals that TURBT plus MMC strategy is not associated with increased costs; it saves the Medicare system $148/patient compared with TURBT alone. Calculated differences took into account avoidance of cystoscopic surveillance, urinary cytology, and reoperative and follow-up costs associated with multiple recurrences. Analysis revealed dominance of MMC usage over TURBT alone as early as 4 years from surgery. CONCLUSIONS: Routine usage of MMC after TURBT is not associated with increased costs to the health care system. In fact, there is a significant cost savings. Nonquantified patient quality of life benefits and secondary societal advantages of gained wages and productivity owing to decreases in recurrence and surgery would further increase the cost savings.

Assessment of the minimum number of lymph nodes needed to detect lymph node invasion at radical nephroureterectomy in patients with upper tract urothelial cancer.

OBJECTIVES: To determine whether a minimum number of lymph nodes (LNs) exist to detect lymph node invasion (LNI) in patients undergoing radical nephroureterectomy (RNU) for upper tract urothelial carcinoma. METHODS: The study included 551 consecutive patients, from 13 centers worldwide, who underwent RNU and lymphadenectomy (LND) between 1992 and 2006. LND was performed at the discretion of the surgeon. All pathological slides were re-reviewed by uropathologists according to strict criteria. Receiver-operating characteristic curve coordinates were used to determine the probability of diagnosing LNI according to the total number of nodes removed. Additionally, the relationship between the number of nodes removed and the rate of positive LNs was tested in univariate and multivariate logistic regression models. RESULTS: Median patient age was 68 years (range: 27-97). Of 551 patients, 140 (25.4%) had positive lymph nodes. Median number of lymph nodes removed was 5 (mean 6.7, range 1-41). The Receiver-operating characteristic coordinates plot indicated that the removal of 13 nodes yielded a 90% probability to detect >or=1 positive LNs. The removal of 8 nodes resulted in a 75% probability of finding >or=1 positive nodes. Removal of >8 LNs (P = .03; odds ratio 1.49) was independently associated with LNI after adjusting for pathological stage and grade. CONCLUSIONS: Our data indicate that 8 LNs need to be removed at radical nephroureterectomy to achieve a 75% probability of finding >or=1 positive nodes. Further improvement of the specificity of LND will require the removal of more lymph nodes.