Disparities in prostate cancer screening, diagnoses, management, and outcomes between Indigenous and non-Indigenous men in a universal health care system.

BACKGROUND: Indigenous Peoples have higher morbidity rates and lower life expectancies than non-Indigenous Canadians. Identification of disparities between Indigenous and non-Indigenous men regarding prostate cancer (PCa) screening, diagnoses, management, and outcomes was sought. METHODS: An observational cohort of men diagnosed with PCa between June 2014 and October 2022 was studied. Men were prospectively enrolled in the province-wide Alberta Prostate Cancer Research Initiative. The primary outcomes were tumor characteristics (stage, grade, and prostate-specific antigen [PSA]) at diagnosis. Secondary outcomes were PSA testing rates, time from diagnosis to treatment, treatment modality, and metastasis-free, cancer-specific, and overall survivals. RESULTS: Examination of 1,444,974 men for whom aggregate PSA testing data were available was performed. Men in Indigenous communities were less likely to have PSA testing performed than men outside of Indigenous communities (32 vs. 46 PSA tests per 100 men [aged 50-70 years] within 1 year; p < .001). Among 6049 men diagnosed with PCa, Indigenous men had higher risk disease characteristics: a higher proportion of Indigenous men had PSA ≥ 10 ng/mL (48% vs. 30%; p < .01), TNM stage ≥ T2 (65% vs. 47%; p < .01), and Gleason grade group ≥ 2 (79% vs. 64%; p < .01) compared to non-Indigenous men. With a median follow-up of 40 months (interquartile range, 25-65 months), Indigenous men were at higher risk of developing PCa metastases (hazard ratio, 2.3; 95% CI, 1.2-4.2; p < .01) than non-Indigenous men. CONCLUSIONS: Despite receiving care in a universal health care system, Indigenous men were less likely to receive PSA testing and more likely to be diagnosed with aggressive tumors and develop PCa metastases than non-Indigenous men.

Obesity and Complication Risk From Radical Cystectomy: Identifying a Body Mass Index Threshold.

PURPOSE: There are conflicting reports regarding radical cystectomy complication risk from obesity subcategories, and a BMI threshold below which complication risk is notably reduced is undefined. A BMI threshold may be helpful in prehabilitation to aid patient counseling and inform weight loss strategies to potentially mitigate obesity-associated complication risk. This study aims to identify such a threshold and further investigate the association between BMI subcategories and perioperative complications from radical cystectomy. MATERIALS AND METHODS: Data were extracted from the Canadian Bladder Cancer Information System, a prospective registry across 14 academic centers. Five hundred and eighty-nine patients were analyzed. Perioperative (≤90 days) complications were compared between BMI subcategories. Unconditional multivariable logistic regression and cubic spline analysis were performed to determine the association between BMI and complication risk and identify a BMI threshold. RESULTS: Perioperative complications were reported in 51 (30%), 97 (43%), and 85 (43%) normal, overweight, and obese patients (P = .02). BMI was independently associated with developing any complication (OR 1.04 95% CI 1.01, 1.07). Predicted complication risk began to rise consistently above a BMI threshold of 34 kg/m2. Both overweight (OR 2.00 95% CI 1.26-3.17) and obese (OR 1.98 95% CI 1.24-3.18) patients had increased risk of complications compared to normal BMI patients. CONCLUSIONS: Complication risk from radical cystectomy is independently associated with BMI. Both overweight and obese patients are at increased risk compared to normal BMI patients. A BMI threshold of 34 kg/m2 has been identified, which may inform prehabilitation treatment strategies.

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.

A Randomized Trial of the Effects of Exercise on Anxiety, Fear of Cancer Progression and Quality of Life in Prostate Cancer Patients on Active Surveillance.

PURPOSE: We examined the effects of exercise on prostate cancer-specific anxiety, fear of cancer progression, quality of life and psychosocial outcomes in patients with prostate cancer on active surveillance. MATERIALS AND METHODS: The ERASE (Exercise during Active Surveillance for Prostate Cancer) Trial randomized 52 patients with prostate cancer undergoing active surveillance to high-intensity interval training (HIIT, 26 patients) or usual care (UC, 26 patients). The HIIT group performed a 12-week, thrice weekly, supervised, aerobic HIIT program. The UC group did not exercise. Patient-reported outcomes were assessed at baseline and after intervention, including prostate cancer-specific anxiety (Memorial Anxiety Scale for Prostate Cancer), fear of cancer progression (Fear of Cancer Recurrence Inventory), prostate cancer symptoms (Expanded Prostate Cancer Index Composite), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core) and psychological health outcomes (eg fatigue, stress and self-esteem). Analysis of covariance was used to compare between-group differences. RESULTS: Fifty of 52 participants (96%) completed patient-reported outcome assessments at 12 weeks. Adherence to HIIT was 96%. Compared to UC, HIIT significantly improved total prostate cancer-specific anxiety (adjusted between-group mean difference -2.7, 95% confidence interval, range -5.0 to -0.4, p=0.024), as well as the fear of progression subscale (p=0.013), hormonal symptoms (p=0.005), perceived stress (p=0.037), fatigue (p=0.029) and self-esteem (p=0.007). CONCLUSIONS: A 12-week supervised HIIT program may improve prostate cancer-specific anxiety, fear of cancer progression, hormone symptoms, stress, fatigue and self-esteem in men with prostate cancer on active surveillance. Larger trials are needed to confirm the effects of HIIT on patient-reported outcomes in the active surveillance setting.

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.

Effects of supervised high-intensity interval training on motivational outcomes in men with prostate cancer undergoing active surveillance: results from a randomized controlled trial.

BACKGROUND: Understanding the motivational effects of supervised aerobic high-intensity interval training (HIIT) may help men with prostate cancer undergoing active surveillance initiate and maintain exercise behavior, however, few studies have addressed this question. This report explored exercise motivation in men with prostate cancer undergoing active surveillance participating in a randomized exercise trial. METHODS: The Exercise during Active Surveillance for Prostate Cancer (ERASE) trial randomized 52 men with prostate cancer on active surveillance to the HIIT exercise group or the usual care (UC) group. The exercise program was supervised aerobic HIIT conducted three times per week for 12 weeks. The motivation questions were developed using the Theory of Planned Behavior and included motivational constructs, anticipated and experienced outcomes, and barriers to HIIT during active surveillance. RESULTS: The HIIT group attended 96% of the planned exercise sessions with 100% compliance to the exercise protocol. Motivation outcome data were obtained in 25/26 (96%) participants in the HIIT group and 25/26 (96%) participants in the UC group. At baseline, study participants were generally motivated to perform HIIT. After the intervention, the HIIT group reported that HIIT was even more enjoyable (p < 0.001; d = 1.38), more motivating (p = 0.001; d = 0.89), more controllable (p < 0.001; d = 0.85), and instilled more confidence (p = 0.004; d = 0.66) than they had anticipated. Moreover, compared to UC, HIIT participants reported significantly higher perceived control (p = 0.006; d = 0.68) and a more specific plan (p = 0.032; d = 0.67) for performing HIIT over the next 6 months. No significant differences were found in anticipated versus experienced outcomes. Exercise barriers were minimal, however, the most often reported barriers included pain or soreness (56%), traveling to the fitness center (40%), and being too busy and having limited time (36%). CONCLUSION: Men with prostate cancer on active surveillance were largely motivated and expected significant benefits from a supervised HIIT program. Moreover, the men assigned to the HIIT program experienced few barriers and achieved high adherence, which further improved their motivation. Future research is needed to understand long-term exercise motivation and behavior change in this setting. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03203460 . Registered on June 29, 2017.

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 (

Achieving the "trifecta" with open versus minimally invasive partial nephrectomy.

INTRODUCTION: The "trifecta" is a summary measure of outcome after partial nephrectomy (PN) that encompasses three parameters: negative surgical margin, ≤ 10% decrease in post-operative estimated glomerular filtration rate (eGFR) and absence of urological complications. We assessed trifecta rates in patients undergoing open (OPN), laparoscopic (LPN), and robotic PN (RPN) for a clinical T1 renal mass (≤ 7 cm). METHODS: Clinical and pathologic parameters were extracted from the prospectively maintained Canadian Kidney Cancer Information System for patients treated between January 2011 and October 2018. Comparisons between groups were made using Kruskal-Wallis test for continuous variables and Chi-squared independence test for categorical variables. Multivariable analysis was performed to identify predictors of each component of the trifecta and the trifecta itself. RESULTS: Of 1708 total patients, 746 underwent OPN, 678 LPN, and 284 RPN for a T1 renal mass. A 'trifecta' was achieved in 53% OPN, 52% LPN and 47% RPN (p = 0.194). On multivariable analysis, OPN and LPN were associated with less frequent post-operative decline in eGFR and more frequent trifecta when compared to RPN, but there was no difference between OPN and LPN. OPN also predicted a higher rate of negative margins compared to RPN but not LPN. CONCLUSION: After correction for confounding variables, OPN and LPN were more likely than RPN to achieve the trifecta, which appeared to be due primarily to loss of renal function. No difference was observed between OPN and LPN. Analyses were limited by the lack of nephrometry score.

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.

How I Do It: Technical report on surgically-initiated rectus sheath catheter using catheter-over-needle assembly.

Development of chronic postsurgical pain following major abdominal or pelvic surgeries is increasingly recognized. Multimodal analgesia including regional anesthesia such as rectus sheath block is growing in popularity. While the literature mainly describes ultrasound-guided rectus sheath blocks, there are many advantages to surgically-initiated rectus sheath catheter performed at the end of surgery. In this technical description, we describe the rationale and technique of surgical insertion of rectus sheath catheters following major urologic surgery with midline incision which is routinely performed by urologists at our institution. Furthermore, we would like to highlight the type of catheter used during rectus sheath catheter insertion, namely the catheter-over-needle assembly. It is simple to insert while minimizes complications such as local anesthetic leakage at the insertion site causing dressing disruption and premature catheter dislodgement, as the catheter-over-needle assembly fits snugly with the skin after insertion.

Development and Acceptability Testing of a Patient Decision Aid for Urinary Diversion with Radical Cystectomy.

PURPOSE: The choice of urinary diversion at cystectomy is a life altering decision. Patient decision aids are clinical tools that promote shared decision making by providing information about management options and helping patients communicate their values. We sought to develop and evaluate a patient decision aid for individuals undergoing cystectomy with urinary diversion. MATERIALS AND METHODS: We used the IPDAS (International Patient Decision Aids Standards) to guide a systematic development process. A literature review was performed to determine urinary diversion options and the incidence of outcomes. We created a prototype using the Ottawa Decision Support Framework. A 10-question survey was used to assess patient decision aid acceptability among patients, allied health professionals and urologists. The primary outcome was acceptability of the patient decision aid. RESULTS: Ileal conduit and orthotopic neobladder were included as primary urinary diversion options because they had the most evidence and are most commonly performed. Continent cutaneous diversion was identified as an alternative option. Outcomes specific to ileal conduit were stomal stenosis and parastomal hernia. Outcomes specific to neobladder were daytime and nighttime urinary incontinence and urinary retention. Acceptability testing was completed by 8 urologists, 9 patients and 1 advanced practice nurse. Of the respondents 94% reported that the language was appropriate, 94% reported that the length was adequate and 83% reported that option presentation was balanced. The patient decision aid met all 6 IPDAS defining criteria, all 6 certification criteria and 21 of 23 quality criteria. CONCLUSIONS: We created a novel patient decision aid to improve the quality of decisions made by patients when deciding among urinary diversion options. Effectiveness testing will be performed prospectively.

Effects of high-intensity interval training on fatigue and quality of life in testicular cancer survivors.

BACKGROUND: Testicular cancer survivors (TCS) are at increased risk of cancer-related fatigue (CRF), psychosocial impairment, and poor mental health-related quality of life (HRQoL). Here, we examine the effects of high-intensity interval training (HIIT) on patient-reported outcomes (PROs) in TCS. Secondarily, we explore cardiorespiratory fitness as a mediator of intervention effects and select baseline characteristics as moderators of intervention effects. METHODS: TCS (n = 63) were randomly assigned to 12 weeks of supervised HIIT or usual care (UC). PROs included CRF, depression, anxiety, stress, self-esteem, sleep quality, and HRQoL assessed at baseline, post-intervention, and 3-month follow-up. RESULTS: TCS (median 7 years postdiagnosis) completed 99% of training sessions and achieved 98% of target training intensity. ANCOVA revealed that, compared to UC, HIIT significantly improved post-intervention CRF (p = 0.003), self-esteem (p = 0.029), and multiple HRQoL domains (ps ≤ 0.05). Effects on CRF (p = 0.031) and vitality (p = 0.015) persisted at 3-month follow-up. Cardiorespiratory fitness changes mediated CRF and HRQoL improvements. CRF effects were larger for TCS with an inactive lifestyle, lower fitness, higher testosterone, and clinical fatigue at baseline. CONCLUSIONS: HIIT significantly improves CRF and HRQoL in TCS. Mediation by cardiorespiratory fitness and moderation by clinical characteristics suggests opportunities for targeted exercise interventions to optimise PROs in TCS.

Effects of high-intensity aerobic interval training on cardiovascular disease risk in testicular cancer survivors: A phase 2 randomized controlled trial.

BACKGROUND: Testicular cancer survivors (TCS) have an increased risk of treatment-related cardiovascular disease (CVD), which may limit their overall survival. We evaluated the effects of high-intensity aerobic interval training (HIIT) on traditional and novel CVD risk factors and surrogate markers of mortality in a population-based sample of TCS. METHODS: This phase 2 trial (ClinicalTrials.gov identifier NCT02459132) randomly assigned 63 TCS to usual care (UC) or 12 weeks of supervised HIIT (ie, alternating periods of vigorous-intensity and light-intensity aerobic exercise). The primary outcome was peak aerobic fitness (VO2peak ) assessed via a treadmill-based maximal cardiorespiratory exercise test. Secondary endpoints included CVD risk (eg, Framingham Risk Score), arterial health, parasympathetic nervous system function, and blood-based biomarkers. RESULTS: Postintervention VO2peak data were obtained for 61 participants (97%). HIIT participants attended 99% of the exercise sessions and achieved 98% of the target exercise intensity. Analysis of covariance demonstrated that HIIT was superior to UC for improving VO2peak (adjusted between-group mean difference, 3.7 mL O2 /kg/min; 95% confidence interval, 2.4-5.1 [P<.001]) and multiple secondary outcomes including CVD risk (P = .011), arterial thickness (P<.001), arterial stiffness (P<.001), postexercise parasympathetic reactivation (P = .001), inflammation (P = .045), and low-density lipoprotein (P = .014). Overall, HIIT reduced the prevalence of modifiable CVD risk factors by 20% compared with UC. CONCLUSIONS: This randomized trial provides the first evidence that HIIT improves cardiorespiratory fitness, multiple pathways of CVD risk, and surrogate markers of mortality in TCS. These findings have important implications for the management of TCS. Further research concerning the long-term effects of HIIT on CVD morbidity and mortality in TCS is warranted. Cancer 2017;123:4057-65. © 2017 American Cancer Society.

AXIN2 expression predicts prostate cancer recurrence and regulates invasion and tumor growth.

BACKGROUND: Treatment of prostate cancer (PCa) may be improved by identifying biological mechanisms of tumor growth that directly impact clinical disease progression. We investigated whether genes associated with a highly tumorigenic, drug resistant, progenitor phenotype impact PCa biology and recurrence. METHODS: Radical prostatectomy (RP) specimens (±disease recurrence, N = 276) were analyzed by qRT-PCR to quantify expression of genes associated with self-renewal, drug resistance, and tumorigenicity in prior studies. Associations between gene expression and PCa recurrence were confirmed by bootstrap internal validation and by external validation in independent cohorts (total N = 675) and in silico. siRNA knockdown and lentiviral overexpression were used to determine the effect of gene expression on PCa invasion, proliferation, and tumor growth. RESULTS: Four candidate genes were differentially expressed in PCa recurrence. Of these, low AXIN2 expression was internally validated in the discovery cohort. Validation in external cohorts and in silico demonstrated that low AXIN2 was independently associated with more aggressive PCa, biochemical recurrence, and metastasis-free survival after RP. Functionally, siRNA-mediated depletion of AXIN2 significantly increased invasiveness, proliferation, and tumor growth. Conversely, ectopic overexpression of AXIN2 significantly reduced invasiveness, proliferation, and tumor growth. CONCLUSIONS: Low AXIN2 expression was associated with PCa recurrence after RP in our test population as well as in external validation cohorts, and its expression levels in PCa cells significantly impacted invasiveness, proliferation, and tumor growth. Given these novel roles, further study of AXIN2 in PCa may yield promising new predictive and therapeutic strategies.

Randomized Trial of Studer Pouch versus T-Pouch Orthotopic Ileal Neobladder in Patients with Bladder Cancer.

PURPOSE: The need to prevent reflux in the construction of an orthotopic ileal neobladder is controversial. We designed the USC-STAR trial to determine whether the T-pouch neobladder that included an antireflux mechanism was superior to the Studer pouch in patients with bladder cancer undergoing radical cystectomy. MATERIALS AND METHODS: This single center, randomized, controlled trial recruited patients with clinically nonmetastatic bladder cancer scheduled to undergo radical cystectomy with neobladder. Eligible patients were randomly assigned to undergo T-pouch or Studer ileal orthotopic neobladder. Treatment assignment was not masked. The primary end point was change in renal function from baseline to 3 years. The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation was used to calculate the estimated glomerular filtration rate. RESULTS: Between February 2002 and November 2009, 237 patients were randomly assigned to T-pouch ileal orthotopic neobladder and 247 to Studer ileal orthotopic neobladder. Baseline characteristics did not differ between the groups. Between baseline and 3 years the estimated glomerular filtration rate decreased by 6.4 ml/minute/1.73 m(2) in the Studer group and 6.6 ml/minute/1.73 m(2) in the T-pouch group (p=0.35). Multivariable analysis showed that type of ileal orthotopic neobladder was not independently associated with 3-year renal function (p=0.63). However, baseline estimated glomerular filtration rate, age and urinary tract obstruction were independently associated with 3-year decline in renal function. Cumulative risk of urinary tract infection and overall late complications were not different between the groups, but the T-pouch was associated with an increased risk of secondary diversion related surgeries. CONCLUSIONS: T-pouch ileal orthotopic neobladder with an antireflux mechanism did not prevent a moderate reduction in renal function observed at 3 years compared to the Studer pouch, but did result in an increase in diversion related secondary surgical procedures.

The role of adjuvant chemotherapy for lymph node-positive upper tract urothelial carcinoma following radical nephroureterectomy: a retrospective study.

OBJECTIVE: To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC. PATIENTS AND METHODS: We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models. RESULTS: In all patients (T(all) N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols. CONCLUSIONS: AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial.

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.

Impact of concomitant carcinoma in situ on upstaging and outcome following radical cystectomy for bladder cancer.

PURPOSE: To evaluate the impact of concomitant carcinoma in situ (CIS) on upstaging and outcome of patients treated with radical cystectomy with pelvic lymph node dissection. METHODS: We collected and pooled a database of 1,968 patients who have undergone radical cystectomy between 1998 and 2008 in eight academic centers across Canada. Collected variables included patient's age, gender, tumor grade, histology and the presence of concomitant CIS with either cTa-1 or cT2 disease, dates of recurrence and death. RESULTS: In the presence of concomitant CIS, upstaging following radical cystectomy occurred in 48 and 55 % of patients with cTa-1 and cT2 disease, respectively. On univariate analysis, the presence of concomitant CIS with cT2 disease was associated with upstaging (p < 0.0001), and the presence of concomitant CIS with cTa-1 disease was also associated with upstaging but did not reach statistical significance (p = 0.0526). On multivariate analyses, the presence of concomitant CIS with either cTa-1 or cT2 tumors was independently prognostic of disease upstaging (p = 0.0001 and 0.0186, respectively). However, on multivariate analysis that incorporates pathologic stage, concomitant CIS was not significantly associated with worse overall, recurrence-free or disease-specific survival. CONCLUSION: These results demonstrate that while the presence of concomitant CIS on cystectomy specimens does not independently affect outcomes, its presence is significantly predictive of a higher rate of upstaging at radical cystectomy.