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 (

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.

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.

Comparison of oncological outcomes for open and laparoscopic radical nephroureterectomy: results from the Canadian Upper Tract Collaboration.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?Open radical nephroureterectomy (ORNU) with excision of the ipsilateral bladder cuff is a standard treatment for upper tract urothelial carcinoma (UTUC). However, over the past decade laparoscopic RNU (LRNU) has emerged as a minimally invasive surgical alternative. Data comparing the oncological efficacy of ORNU and LRNU have reported mixed results and the equivalence of these surgical techniques have not yet been established. We found that surgical approach was not independently associated with overall or disease-specific survival; however, there was a trend toward an independent association between LRNU and poorer recurrence-free survival (RFS). To our knowledge, this is the first large, multi-institutional analysis to show a trend toward inferior RFS in patients with UTUC treated with LRNU. OBJECTIVE: To examine the association between surgical approach for radical nephroureterectomy (RNU) and clinical outcomes in a large, multi-institutional cohort, as there are limited data comparing the oncological efficacy of open RNU (ORNU) and laparoscopic RNU (LRNU) for upper urinary tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Institutional RNU databases containing detailed information on patients with UTUC treated between 1994 and 2009 were obtained from 10 academic centres in Canada. Data were collected on 1029 patients and combined into a relational database formatted with patient characteristics, pathological characteristics, and survival status. Surgical approach was classified as ORNU (n = 403) or LRNU (n = 446). The clinical outcomes were overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS). The Kaplan-Meier method and Cox proportional regression analysis were used to analyse survival data. RESULTS: Data were evaluable for 849 of 1029 (82.5%) patients. The median (interquartile range) follow-up duration was 2.2 (0.6-5.0) years. The predicted 5-year OS (67% vs 68%, log-rank P = 0.19) and DSS (73% vs 76%, log-rank P = 0.32) rates did not differ between the ORNU and LRNU groups; however, there was a trend toward an improved predicted 5-year RFS rate in the ORNU group (43% vs 33%, log-rank P = 0.06). Multivariable Cox proportional regression analysis showed that surgical approach was not significantly associated with OS (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.63-1.27, P = 0.52) or DSS (HR 0.90, 95% CI 0.60-1.37, P = 0.64); however, there was a trend toward an independent association between surgical approach and RFS (HR 1.24, 95% CI 0.98-1.57, P = 0.08). CONCLUSION: Surgical approach was not independently associated with OS or DSS but there was a trend toward an independent association between LRNU and poorer RFS. Further prospective evaluation is needed.

Association between urinary diversion and quality of life after radical cystectomy.

INTRODUCTION: We examined the association between type of urinary diversion and quality of life (QoL) in patients who underwent radical cystectomy for primary bladder cancer using a validated, disease-specific instrument. MATERIALS AND METHODS: A cohort of 314 consecutive patients treated with radical cystectomy and urinary diversion for primary bladder cancer between January 2000 and December 2006 was analyzed. Participants were mailed the validated Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index (FACT-VCI) questionnaire. Univariable and multivariable linear regression analyses were used to examine the association between type of urinary diversion (ileal conduit versus orthotopic neobladder) and QoL. RESULTS: Eighty-four out of 168 (50% response rate) evaluable patients completed the FACT-VCI questionnaire. The median follow up duration was 5.6 years (range, 2.1 to 9.3 years). ANOVA showed statistically significant differences favoring orthotopic neobladder urinary diversion with more favorable QoL scores on the FACT-VCI (mean difference 5.6 points, p = .03) and radical cystectomy-specific domain (mean difference 2.9 points, p = .05). However, multivariable linear regression analyses showed no statistically significant association between the type of urinary diversion and QoL (FACT-VCI: ß = 4.1 points, p = .177; radical cystectomy-specific: ß = 1.5 points, p = .390). CONCLUSIONS: Type of urinary diversion was not associated with QoL after radical cystectomy. Randomized controlled trials comparing types of urinary diversion using validated, disease-specific QoL instruments are needed.

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.

Associations between body mass index and bladder cancer survival: Is the obesity paradox short-lived?

INTRODUCTION: We investigated the associations of pre-surgical body mass index (BMI) with bladder cancer outcomes in patients treated with radical cystectomy. METHODS: We retrospectively analyzed data from 488 bladder cancer patients treated with radical cystectomy between 1994 and 2007 and followed up until 2016. Cox regression with step function (time-segment analysis) was conducted for overall survival because the proportional hazard assumption was violated. RESULTS: Of 488 bladder cancer patients, 155 (31.8%) were normal weight, 186 (38.1%) were overweight, and 147 (30.1%) were obese. During the median followup of 59.5 months, 363 (74.4%) patients died, including 197 (40.4%) from bladder cancer. In adjusted Cox regression analyses, BMI was not significantly associated with bladder cancer-specific survival for overweight (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.57-1.10, p=0.16) or obese (HR 0.76, 95% CI 0.52-1.09, p=0.13) patients. In the Cox regression with step function for overall survival, the time interaction was significant overall (p=0.020) and specifically for over-weight patients (p=0.006). In the time-segment model, the HR for overweight during the first 63 months was 0.66 (95% CI 0.49-0.90, p=0.008), whereas it was 1.41 (95% CI 0.89-2.23, p=0.14) after 63 months. Although not statistically significant, a similar pattern was observed for obese patients. CONCLUSIONS: Our findings suggest that overweight and obese bladder cancer patients had better outcomes within the first five years after radical cystectomy; however, there were no differences in longer-term survival. These data suggest that the obesity paradox in bladder cancer patients treated with radical cystectomy may be short-lived.

Bladder cancer and exeRcise trAining during intraVesical thErapy-the BRAVE trial: a study protocol for a prospective, single-centre, phase II randomised controlled trial.

INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) accounts for about 75% of newly diagnosed bladder cancers. The treatment for NMIBC involves surgical removal of the tumour followed by 6 weekly instillations of immunotherapy or chemotherapy directly into the bladder (ie, intravesical therapy). NMIBC has a high rate of recurrence (31%-78%) and progression (15%). Moreover, bladder cancer and its treatment may affect patient functioning and quality of life. Exercise is a safe and effective intervention for many patient with cancer groups, however, no studies have examined exercise during intravesical therapy for NMIBC. The primary objective of the Bladder cancer and exeRcise trAining during intraVesical thErapy (BRAVE) trial is to examine the safety and feasibility of an exercise intervention in patients with bladder cancer undergoing intravesical therapy. The secondary objectives are to investigate the preliminary efficacy of exercise on health-related fitness and patient-reported outcomes; examine the social cognitive predictors of exercise adherence; and explore the potential effects of exercise on tumour recurrence and progression. METHODS AND ANALYSIS: BRAVE is a phase II randomised controlled trial that aims to include 66 patients with NMIBC scheduled to receive intravesical therapy. Participants will be randomly assigned to the exercise intervention or usual care. The intervention consists of three supervised, high-intensity interval training sessions per week for 12 weeks. Feasibility will be evaluated by eligibility, recruitment, adherence and attrition rates. Preliminary efficacy will focus on changes in cardiorespiratory fitness and patient-reported outcomes from baseline (prior to intravesical therapy) to pre-cystoscopy (3 months). Cancer outcomes will be tracked at 3 months, and 1-year follow-up by cystoscopy. Analysis of covariance will compare between-group differences at post-intervention (pre-cystoscopy) for all health-related fitness and patient-reported outcomes. ETHICS AND DISSEMINATION: The study was approved by the Health Research Ethics Board of Alberta-Cancer Committee (#20-0184). Dissemination will include publication and presentations at scientific conferences and public channels. TRIAL REGISTRATION NUMBER: NCT04593862; Pre-results.

Effects of Exercise on Cardiorespiratory Fitness and Biochemical Progression in Men With Localized Prostate Cancer Under Active Surveillance: The ERASE Randomized Clinical Trial.

IMPORTANCE: Men with prostate cancer who are undergoing active surveillance are at an increased risk of cardiovascular death and disease progression. Exercise has been shown to improve cardiorespiratory fitness, physical functioning, body composition, fatigue, and quality of life during and after treatment; however, to date only 1 exercise study has been conducted in this clinical setting. OBJECTIVE: To examine the effects of exercise on cardiorespiratory fitness and biochemical progression in men with prostate cancer who were undergoing active surveillance. DESIGN, SETTING, AND PARTICIPANTS: The Exercise During Active Surveillance for Prostate Cancer (ERASE) trial was a single-center, 2-group, phase 2 randomized clinical trial conducted at the University of Alberta, Edmonton, Canada. Eligible patients were recruited from July 24, 2018, to February 5, 2020. Participants were adult men who were diagnosed with localized very low risk to favorable intermediate risk prostate cancer and undergoing active surveillance. They were randomized to either the high-intensity interval training (HIIT) group or usual care group. All statistical analyses were based on the intention-to-treat principle. INTERVENTIONS: The HIIT group was asked to complete 12 weeks of thrice-weekly, supervised aerobic sessions on a treadmill at 85% to 95% of peak oxygen consumption (V̇o2). The usual care group maintained their normal exercise levels. MAIN OUTCOMES AND MEASURES: The primary outcome was peak V̇o2, which was assessed as the highest value of oxygen uptake during a graded exercise test using a modified Bruce protocol. Secondary and exploratory outcomes were indicators of biochemical progression of prostate cancer, including prostate-specific antigen (PSA) level and PSA kinetics, and growth of prostate cancer cell line LNCaP. RESULTS: A total of 52 male patients, with a mean (SD) age of 63.4 (7.1) years, were randomized to either the HIIT (n = 26) or usual care (n = 26) groups. Overall, 46 of 52 participants (88%) completed the postintervention peak V̇o2 assessment, and 49 of 52 participants (94%) provided blood samples. Adherence to HIIT was 96%. The primary outcome of peak V̇o2 increased by 0.9 mL/kg/min in the HIIT group and decreased by 0.5 mL/kg/min in the usual care group (adjusted between-group mean difference (1.6 mL/kg/min; 95% CI, 0.3-2.9; P = .01). Compared with the usual care group, the HIIT group experienced decreased PSA level (-1.1 µg/L; 95% CI, -2.1 to 0.0; P = .04), PSA velocity (-1.3 µg /L/y; 95% CI, -2.5 to -0.1; P = .04), and LNCaP cell growth (-0.13 optical density unit; 95% CI, -0.25 to -0.02; P = .02). No statistically significant differences were found in PSA doubling time or testosterone. CONCLUSIONS AND RELEVANCE: The ERASE trial demonstrated that HIIT increased cardiorespiratory fitness levels and decreased PSA levels, PSA velocity, and prostate cancer cell growth in men with localized prostate cancer who were under active surveillance. Larger trials are warranted to determine whether such improvement translates to better longer-term clinical outcomes in this setting. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03203460.

The increasing use of renal tumor biopsy amongst Canadian urologists: When is biopsy most utilized?

INTRODUCTION: The role of renal tumor biopsy (RTB) in the management of small renal masses (SRMs) is progressively being recognized as a tool to decrease overtreatment. While an increasing number of studies assessing its role in diagnostics are becoming available, RTB remains variably used amongst urologists. Many patient-, tumor-, and institution-related factors may influence urologists on whether to perform a RTB to help guide management. OBJECTIVE: We aimed at identifying factors associated with the use of RTB for localized SRMs within a number of centers contributing data to the Canadian Kidney Cancer information system. MATERIAL AND METHODS: We identified 3,838 patients diagnosed with a localized SRM (≤4 cm) between January 2011 and December 2018. Patients were stratified based on whether a RTB was performed prior to the primary therapeutic intervention. Factors associated with use of RTB were assessed using univariable and multivariable logistic regression models. RESULTS: A total of 993 patients (25.9%) underwent an RTB. There was an overall increase in RTB use over time (P < 0.001), with patients diagnosed between 2015 and 2018 undergoing more RTB than patients diagnosed between 2011 and 2014 (29.8% vs. 22.2%, respectively; P < 0.001). Patients managed in centers with the highest patient-volume had RTB more frequently than patients managed in low-volume centers. On multivariable analysis, increasing year of diagnosis was significantly associated with more RTB use. Patients treated with surgery underwent RTB statistically less often than patients undergoing thermal ablation (P < 0.001) or managed with active surveillance (P < 0.001). Larger SRMs were associated with more RTB use in patients on active surveillance (P = 0.009), but with less RTB in patients undergoing surgery (P = 0.045). CONCLUSION: This large multicenter cohort study reveals an increasing adoption and overall use of RTB amongst Canadian urologists. Patients managed in high-volume centers and those undergoing non-surgical management were associated with greater use of RTB. Tumor size was also associated with RTB use. This study highlights the influence that physician perceptions and clinical factors may have in the decision to use RTB prior to initiating a therapeutic approach.